Johns Hopkins university - organic-reaction.com

ARTICLES COMPRISING TEMPLATED CROSSLINKED POLYMER FILMS FOR ELECTRONIC DETECTION OF NITROAROMATIC EXPLOSIVES (Sat, 11 May 2013)
The present invention provides devices and articles of manufacture comprising a low-voltage operable, highly sensitive, and selectively responsive polymer for the detection of nitroaromatic compounds, including explosives. Resistive devices were fabricated by simple spin-coating on flexible and transparent substrates as well as silicon substrates, and were stable under ambient temperature and oxygen levels before exposure to the nitroaromatics. After exposure to 2,4,6-trinitrotoluene (TNT), the devices showed increased conductance, even with pg quantities of TNT, accompanied by a confirming color change from colorless to deep red. The relative conductance increase per unit exposure is the highest yet reported for TNT. Aromatic anion salts, on the other hand, did not induce any electronic responses. Methods of making the articles and devices, and their use are also provided.
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Novel Phosphorylation of Cardiac Troponin I as a Monitor for Cardiac Injury (Fri, 26 Apr 2013)
This invention relates to novel phosphorylation sites in cardiac Troponin I that are associated with the onset of heart failure. The phosphorylation sites, i.e., serine 5, tyrosine 26, threonine 51, serine 166, threonine 181 and/or serine 199, can be used as biomarkers for (i) identifying subjects at risk for the development of heart failure, (ii) treating subjects having a higher than normal level of the biomarker, and (iii) monitoring therapy of a subject at risk for the development of heart failure. Also described are antibodies, reagents, and kits for carrying out a method of the present invention.
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HIGH AFFINITY BETA LACTAMASE INHIBITORS (Fri, 19 Apr 2013)
Inhibitors of beta lactamases and their use in treating bacterial infections are dicslosed.
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Heterocyclic and carbonate derivatives of NDGA and their use as new anti-HIV and anti-cancer agents (Wed, 17 Apr 2013)
Reaction of nordihydroguaiaretic acid with various alkyl chlorides, 1-piperidinecarbonyl chloride, methyl chloroformate, or 1,1′-carbonyldiimidazole under alkaline conditions produced the corresponding phenol ethers, carbamates and carbonates, respectively, in 67-83% yields (Scheme 1 and Scheme 2). Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found to be stable in aqueous solution. These new compounds exerted potent activities against HIV Tat-regulated transactivation in cos-7 cells. The most active transcription inhibitor compound of this series 5b (P4N, Tetrapiperidino NDGA, meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperidino)ethoxypehnyl])butane tetrakishydrochloride salt) has an IC50 of 0.88 μ<smallcaps>M</smallcaps>.
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BISPHOSPHONAMIDATE PRODRUGS AND USES THEREOF (Fri, 12 Apr 2013)
Bisphosphonamidate prodrugs of therapeutic bisphosphonate compounds and uses thereof to treat diseases are described.
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CANCER-SPECIFIC GENETIC REARRANGEMENTS (Fri, 22 Mar 2013)
The present invention relates to the field of cancer. More specifically, the present invention provides compositions and methods useful for treating cancer characterized by the expression of mutant FAM190A proteins. In a specific embodiment, a method for treating a patient having a cancer characterized by a FAM190A intragenic rearrangement comprises the step of administering to the patient an agent that inhibits a biological function or reduces the level or expression of the FAM190A protein.
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SERINE PROTEASE INHIBITORS (Fri, 22 Mar 2013)
Potent low molecular weight, highly selective, competitive non-peptidic serine protease inhibitors and their use in treating serine protease-associated diseases are disclosed.
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Method for Late Introduction of the (8R)-Hydroxyl Group Carbapenem Beta-Lactam Antibiotic Synthesis (Fri, 15 Mar 2013)
The presently disclosed subject matter demonstrates that ThnG and ThnQ enzymes encoded by the thienamycin gene cluster in Streptomyces cattleya oxidize the C-2 and C-6 moieties of carbapenems, respectively. ThnQ stereospecifically hydroxylates PS-5 giving N-acetyl thienamycin. ThnG catalyzes sequential desaturation and sulfoxidation of PS-5, giving PS-7 and its sulfoxide. The ThnG and ThnQ enzymes are relatively substrate selective, but give rise to the oxidative diversity of carbapenems produced by S. cattleya, and orthologues likely function similarly in allied streptomyces. 
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ITRACONAZOLE ANALOGS AND USE THEREOF (Fri, 15 Mar 2013)
Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.
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CHEMICAL EXCHANGE SATURATION TRANSFER BASED MRI USING REPORTER GENES AND MRI METHODS RELATED THERETO (Fri, 08 Mar 2013)
Featured are a new class of reporter genes including reporter compositions as well as methods, MRI systems and MRI imaging kits related thereto. The genes according to the present invention provide MR contrast when the sample/subject is irradiated at a specific off-resonance radio-frequency (RF frequency), where the contrast mechanism utilizes chemical exchange saturation transfer (CEST) technique for imaging.
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Compositions and Methods for Characterizing Breast Cancer (Fri, 08 Mar 2013)
The invention provides compositions and methods for characterizing breast cancer stem In particular, the invention provides for the identification of cells expressing Twist and CD44 that express little or virtually undetectable levels of CD24 (i.e. a Twist+/CD44+/CD24−/low cell sub-population). The presence of such cells in a breast cancer specimen identifies the breast cancer as having increased metastic potential. Such cancers are identified as requiring aggressive therapies. Accordingly, the invention provides biomarkers suitable for identifying, diagnosing, and monitoring treatment of a subject with breast cancer.
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SYSTEM FOR A THREE-DIMENSIONAL INTERFACE AND DATABASE (Fri, 04 Jan 2013)
An embodiment in accordance with the present invention provides a system and method for a three-dimensional interface for interacting with a database. The three-dimensional interface can include an interactive three-dimensional atlas depicting an element of anatomy, machine, device, or other object. Given the three-dimensional nature of the atlas, a user can zoom in on particular areas to view them with more specificity. Different structural points of the anatomy are labeled with names or coordinates, such that the user can select one of the structural points and search a database for information related to that specific structural point. The user can also use specific keywords to search with respect to the specific structural point selected. The three-dimensional interface and atlas are displayed to the user on a computing device that can either house the database within its memory or alternately communicate with the database over a network.
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COMPOUNDS FOR TREATING PERIPHERAL NEUROPATHIES AND OTHER NEURODEGENERATIVE DISORDERS (Fri, 28 Dec 2012)
Compounds and methods for treating or preventing a neurodegenerative disease, disorder or condition associated with the overall activity of hsp90 but not with the ATPase activity of hsp90, including peripheral neuropathy, such as peripheral neuropathy caused by chemotherapy or diabetes, disorders 5 of the central nervous system, such as Alzheimer's disease and Parkinsons disease, and motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), in a subject are provided.
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GLYCAN AND GLYCOPEPTIDE CAPTURE AND RELEASE USING REVERSIBLE HYDRAZONE-BASED METHOD (Fri, 14 Dec 2012)
Highly specific and novel methods for reversible hydrazone solid-phase extraction (rHSPE) are provided for glycan or glycopeptide isolation from proteins, peptides, and other contaminants for glycan and glycopeptide analysis. Glycans or glycopeptides in complex mixtures can be conjugated onto solid support or affinity or chemical tags via reversible hydrazone bond. The conjugation methods of the present invention are chemically specific and provide unique means for the removal of other non-glycan containing molecules in the complex sample before the glycans or glycopeptides are hydrolyzed and recovered for analysis. The hydrazone formation and hydrolysis of the novel methods allows for the analysis of glycans and glycopeptides. The hydrazide coating on the solid-phase surfaces are useful for surface glycan capture and on target glycan analysis. Uses of the information generated by the inventive methods for diagnosis and treatment are also disclosed.
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CONJUGATES OF NITROIMIDAZOLES AND THEIR USE AS CHEMOTHERAPEUTIC AGENTS (Fri, 07 Dec 2012)
Novel compounds which are derivatives of tetra-O-methyl nordihydroguaiaretic acid (NDGA), as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof are provided. These NDGA derivatives have a nitroimidazole moiety and these derivatives show preferential toxicity to hypoxic cells as hypoxic cytotoxins. Their cytotoxicity toward hypoxic cells is a result of abstraction of hydrogen from target molecules by free radicals formed in the reduction of the nitro group. This makes the disclosed compounds an effective anti cancer drug because hypoxic cells are generally considered to be more resistant to anti cancer drugs than normal cells. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including hepatocellular carcinoma, breast cancer and prostate cancer, are also provided.
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SKIN AND HAIR REGENERATION USING POLYSACCHARIDE-BASED HYDROGELS (Fri, 23 Nov 2012)
Methods for promoting skin regeneration, promoting hair follicle regeneration, and reducing scarring by topically administering polysaccharide-based hydrogel compositions to injured skin are presented.
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MONOMERIC TRIOXANE AMIDE SULFUR COMPOUNDS (Fri, 19 Oct 2012)
Anilide derivatives of the natural trioxane artemisinin were prepared and evaluated for antimalarial efficacy in Plasmodium berghei-infected mice. Selected anilides derivatives administered orally as one single-digit dose combined with mefloquine hydrochloride were completely curative, i.e., all 5 of the mice in the particular treatment group had no detectable parasitemia on day 30 post infection, gained as much weight by day 30 post infection as the control mice (no infection), and behaved normally.
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SYSTEM AND METHOD OF PERFORMING MAGNETIC RESONANCE SPECTROSCOPIC IMAGING (Fri, 28 Sep 2012)
A method of performing spatially localized magnetic resonance spectroscopy includes receiving a magnetic resonance image of an object; identifying a plurality C of compartments that generate magnetic resonance spectroscopy signals in the object including at least one compartment of interest; segmenting in at least one spatial dimension the magnetic resonance image of the object into the C compartments; acquiring magnetic resonance spectroscopy signals from the compartments by applying a plurality of M' phase encodings applied in the at least one spatial dimension, wherein M' ≥ C; calculating a spatially localized magnetic resonance chemical shift spectrum from the at least one compartment of interest; and rendering a spatially localized magnetic resonance spectrum that is substantially equal to a spatial average of magnetic resonance chemical shift spectra from the at least one compartment of interest. A magnetic resonance spectroscopy and imaging system is configured to perform the above method.
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HIGH DYNAMIC RANGE RF POWER MONITOR (Fri, 28 Sep 2012)
A device with at least one channel for measuring high dynamic range, radio frequency (RF) power levels over broad-ranging duty cycles includes a power sensor circuit comprising at least one logarithmic amplifier; at least one directional RF coupler electrically connected to the at least one power sensor; at least one RF attenuator electrically connected to the at least one RF coupler; and at least one sampling circuit electrically connected to the at least one RF attenuator and the at least one RF coupler. The at least one sampling circuit performs analog-to-digital conversion of electrical signals received to provide digitals signals for measuring the RF power level in the at least one channel.
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CHALCONE DERIVATIVES AS NRF2 ACTIVATORS (Fri, 31 Aug 2012)
Compounds and methods for treating or preventing a disease, disorder or condition associated with an Nrf2-regulated pathway, including those associated with an autoimmune disease, comorbidity associated with diabetes, such as retinopathy and nephropathy, bone marrow transplant for leukemia and related cancers, bone marrow deficiencies, inborn errors of metabolism, and other immune disorders, oxidative stress, respiratory infection, ischemia, neurodegenerative disorders, radiation injury, neutropenia caused by chemotherapy, autoimmunity, and congenital neutropenic disorders, and for restoring a corticosteroid responsiveness, in a subject are provided.
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MUCUS PENETRATING GENE CARRIERS (Fri, 17 Aug 2012)
Nanoparticles gene carriers, particularly nanoparticle gene carriers which exhibit increased rates of diffusion through cystic fibrosis (CF) mucus, as well as methods of making and using thereof, are described herein. The nanoparticle gene carriers are formed from a nucleic acid complexed to one or more biocompatible, polycationic polymers. The nanoparticle gene carriers also contain one or more mucus resistant polymers. In a particularly preferred embodiment, the nanoparticle gene carrier is a nanoparticle formed from one or more nucleic acids, PEI, and a mucus-resistant/diffusive graft copolymer composed of a PEI backbone functionalized by one or more PEG side chains. The nanoparticle gene carriers can efficiently diffuse through CF mucus, and can effectively serve as a vehicle to administer one or more nucleic acids to a patient suffering from CF.
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Method of detection using antibodies that specifically bind hedgehog-derived polypeptides (Fri, 06 Jul 2012)
The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G′CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
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USE OF NON-LABELED SUGARS AND DETECTION BY MRI FOR ASSESSING TISSUE PERFUSION AND METABOLISM (Fri, 22 Jun 2012)
A method for magnetic resonance (MR) imaging or spectroscopy on a MR scanner to detect tissue physiological parameters in one or more tissue areas in a human or non-human subject includes administering to the subject a contrast enhancing physiologically tolerable amount of a sugar that is non-labeled, subjecting the subject to an MR procedure capable of generating MR signals encoding at least one tissue area in the subject in which the sugar either passes or is taken up, detecting a temporal variation in the MR signals in the at least one tissue area after the administering the sugar, determining at least one tissue-related parameter from the temporal variation, and ascertaining whether the at least one tissue-related parameter is abnormal.
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SMART POLYMERIC NANOPARTICLES WHICH OVERCOME MULTIDRUG RESISTANCE TO CANCER CHEMOTHERAPEUTICS AND TREATMENT-RELATED SYSTEMIC TOXICITY (Fri, 15 Jun 2012)
Polymeric nanoparticles with a hydrophobic core that encapsulates curcumin and a hydrophilic shell with one or more chemotherapeutic agents (e.g., doxorubicin) associated with the shell surface are formed from N-isopropylacryl amide (NEPAAM), acrylic acid (AA), and at least one vinyl monomer selected from the group consisting of vinyl acetate, 4-vinyl benzoic acid, methylmethacrylate, vinylmethacrylate, N-vinylpyrrolidone, N-vinyl piperidone, N-vinyl caprolacum, N-vinyl carbazole, and styrene, where the ΝΓΡΑΑΜ, the AA, and the vinyl monomer are present at molar ratios of 50-70:10-30: 10-30 for NIPAAM:AA:vmyl monomer. These nanoparticles effectively overcome multidrug resistance and ameliorate cardiomyopathy in vivo.
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HYBRID CYCLIC LIBRARIES AND SCREENS THEREOF (Fri, 08 Jun 2012)
Provided are novel types of hybrid cyclic libraries that contain a known protein binding domain of a natural product. Also provided are synthetic methods to make such libraries and methods for the deconvolution of hits using partially split-pooled library compounds. Such methods are applicable for use with the entire human proteome to screen such libraries that bind and for the identification of hits.
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COMPOSITIONS AND METHODS RELATING TO REDUCED MUCOADHESION (Fri, 11 May 2012)
The present invention generally relates to reducing the mucoadhesive properties of a particle. In some embodiments, the particle is coated with and/or associated with a (poly(ethylene glycol))- (poly(propylene oxide))-(poly(ethylene glycol)) triblock copolymer. Methods for preparing inventive particles using a poly(ethylene glycol)-vitamin E conjugate as a surfactant are also provided. In some embodiments, methods are provided comprising administering to a subject a composition of particles of the present invention. Such particles with reduced mucoadhesive properties are useful in delivering agents to mucosal tissues such as oral, ophthalmic, gastrointestinal, nasal, respiratory, and genital mucosal tissues.
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SMALL MOLECULES AS EPIGENETIC MODULATORS OF LYSINE-SPECIFIC DEMETHYLASE 1 AND METHODS OF TREATING DISORDERS (Fri, 16 Mar 2012)
The invention provides for novel compounds which are inhibitors of lysine- specific demethylase 1 (LSDl). Such compounds may be used to treat disorders, including cancer.
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Detecting and sorting methylated DNA using a synthetic nanopore (Fri, 17 Feb 2012)
Provided are methods for detecting, characterizing or separating DNA based on methylation. Heterogeneous DNA populations are separated based on DNA methylation by providing a membrane having a nanopore through which an electric field is applied. DNA of interest is introduced, and for a given threshold voltage across the nanopore, only DNA having a methylation parameter of interest may transit the pore, thereby facilitating detection, characterization, or separation of DNA based on methylation. The methods are optionally used to detect a disease state that is associated with DNA methylation including, but not limited to, cancer.
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METHODS FOR THE TREATMENT AND PREVENTION OF METABOLIC DISORDERS (Fri, 17 Feb 2012)
Described herein are methods for detecting, characterizing, preventing, and treating metabolic diseases, including obesity and obesity-associated disorders such as diabetes.
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FUNCTIONAL VASCULARIZATION WITH BIOCOMPATIBLE POLYSACCHARIDE-BASED HYDROGELS (Fri, 06 Jan 2012)
Slow vascularization of functional blood limits the transplantation of tissue constructs and the recovery of ischemic and wounded tissues. Blood vessel ingrowth into polysaccharide-based hydrogel scaffolds remains a challenge. A synergistic effect of multiple angiogenic GFs was established; the co-encapsulation of VEGF plus other growth factors induced more and larger blood vessels than any individual GF, while the combination of all GFs dramatically increased the size and number of newly formed functional vessels. Rapid, efficient, and functional neovascularization may be achieved.
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METHODS OF IDENTIFYING THERAPEUTIC AGENTS FOR TREATING PERSISTER AND BACTERIAL INFECTION (Fri, 23 Dec 2011)
The present invention relates to methods, compositions, assays and kits for identifying an antibacterial agent that decreases persister formation or survival, eliminates or reduces bacterial infection or disease and/or increases killing of a bacterial cell.
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N-Hydroxylsulfonamide Derivatives as New Physiologically Useful Nitroxyl Donors (Fri, 16 Dec 2011)
The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives.
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QUINOLINE COMPOUNDS AS INHIBITORS OF ANGIOGENESIS, HUMAN METHIONINE AMINOPEPTIDASE, AND SIRT1, AND METHODS OF TREATING DISORDERS (Fri, 09 Dec 2011)
Described herein are methods of inhibiting methionine aminopeptidase or SirT1, inhibiting angiogenesis, and treating disorders (or symptoms thereof) associated with methionine aminopeptidase, SirT1 and/or angiogenesis, wherein a compound of the invention is administered to a subject.
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BIOCOMPATIBLE POLYSACCHARIDE-BASED HYDROGELS (Fri, 11 Nov 2011)
Modified polysaccharides and crosslinked modified polysaccharide compositions are described. Methods of using the crosslinked modified polysaccharide compositions to deliver proteins, oligonucleotides, or pharmaceutical agents are also disclosed.
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SELF-FOLDING SUB-CENTIMETER STRUCTURES (Fri, 11 Nov 2011)
A sub-centimeter structure includes a first structural component, a second structural component arranged proximate the first structural component, and a joint connecting the first and second structural components. The joint includes a material that has a first phase that is substantially rigid to hold the first and second structural components in a substantially rigid configuration while the material is in the first phase. The material of the joint has a second phase such that the joint is at least partially fluid to allow the first and second structural components to move relative to each other while the material is in the second phase. The joint interacts with the first and second structural components while the material is in the second phase to cause the first and second structural components to move relative to each other. And, the first and second structural components include a polymer.
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BISPHOSPHONAMIDATE PRODRUGS AND USES THEREOF (Fri, 11 Nov 2011)
Bisphosphonamidate prodrugs of therapeutic bisphosphonate compounds and uses thereof to treat diseases are described.
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CHIRALLY PURE ISOMERS OF ITRACONAZOLE AND INHIBITORS OF LANOSTEROL 14A-DEMETHYLASE FOR USE AS ANGIOGENESIS INHIBITORS (Fri, 28 Oct 2011)
Described herein are methods of inhibiting angiogenesis, and treating or preventing a disease or disorder (or symptoms thereof) associated with angiogenesis, wherein an anti-angiogenesis compound is administered to a subject.
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Arrayed Multiple Ubiquitin Binding Domains as Linkage-specific Polyubiquitin Affinity Reagents (Fri, 14 Oct 2011)
Linkage-specific polyubiquitin recognition is thought to make possible the diverse set of functional outcomes associated with ubiquitination. Thus far, mechanistic insight into this selectivity has been largely limited to single domains that preferentially bind to lysine 48-linked polyubiquitin (K48-polyUb) in isolation. A mechanism is proposed herein, linkage-specific avidity, in which multiple ubiquitin-binding domains are arranged in space so that simultaneous, high-affinity interactions are optimum with one polyUb linkage but unfavorable or impossible with other polyUb topologies and monoUb. The model used herein is human Rap80, which contains tandem ubiquitin interacting motifs (UIMs) that bind to K63-polyUb at DNA doublestrand breaks. The sequence between the Rap80 UIMs positions the domains for efficient avid binding across a single K63 linkage, thus defining selectivity. K48-specific avidity is also demonstrated in a different protein, ataxin-3. Using tandem UIMs, the general principles governing polyUb linkage selectivity and affinity in multivalent ubiquitin receptors are established.
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BORON-CONTAINING PI-ELECTRON MATERIALS INCORPORATING FORMALLY AROMATIC AND NEUTRAL BOREPIN RINGS (Fri, 14 Oct 2011)
The synthesis, functionalization and characterization of borepin-based extended pi-electron molecules is disclosed. Bulky substituents shielded the vacant boron p-orbitals thus allowing synthetic manipulation and purification under ambient lab conditions. The presently disclosed borepin-containing compounds displayed reversible cathodic electrochemistry and can be viewed as n-type analogues to bent acene hydrocarbons.
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COMPOSITIONS AND METHODS FOR TREATMENT OF NEURODEGENERATIVE DISEASE (Fri, 30 Sep 2011)
Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.
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METHOD FOR DETERMINING SUBSTANCE NON-TOXICITY (Fri, 23 Sep 2011)
Described herein are methods for establishing the non-toxicity of a substance. For example, described herein are methods for the construction of a comprehensive database of toxicity associated pathways and methods of using such a database.
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COMPOSITIONS AND METHODS FOR CHARACTERIZING BREAST CANCER (Fri, 16 Sep 2011)
The invention provides compositions and methods for characterizing breast cancer stem In particular, the invention provides for the identification of cells expressing Twist and CD44 that express little or virtually undetectable levels of CD24 (i.e. a Twist+/CD44+/CD24-/low cell sub-population). The presence of such cells in a breast cancer specimen identifies the breast cancer as having increased metastic potential. Such cancers are identified as requiring aggressive therapies. Accordingly, the invention provides biomarkers suitable for identifying, diagnosing, and monitoring treatment of a subject with breast cancer.
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TSPO-TARGETING COMPOUNDS AND USES THEREOF (Fri, 02 Sep 2011)
Translocator protein (TSPO) targeting compounds are described. Methods of making the compounds, and uses of the compounds for imaging are also described.
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HYBRID SCFA-HYDROXYL-DERIVATIZED MONOSACCHARIDES, METHODS OF SYNTHESIS, AND METHODS OF TREATING DISORDERS (Fri, 26 Aug 2011)
Described herein are fatty acid carbohydrate-hydroxyl-hybrid compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.
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IMAGING METHODS FOR ASSESSMENT AND QUANTIFICATION OF VACCINATION AND IN VIVO ANTIGEN CAPTURE (Fri, 26 Aug 2011)
The invention provides for labeling, imaging, and quantifying an antigen presenting cell in vivo.
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OXYSTEROLS THAT ACTIVATE LIVER X RECEPTOR SIGNALING AND INHIBIT HEDGEHOG SIGNALING (Fri, 26 Aug 2011)
This invention relates, e.g., to compositions comprising oxysterol compounds represented by Formula I or Formula II, e.g., comprising one or more of Oxy 16, Oxy 22, Oxy30, Oxy 31, Oxy35, Oxy37, Oxy43, Oxy44, Oxy45 or Oxy47. The compounds are shown to be Hedgehog pathway inhibiting, and to act as agonists for liver X receptor (LXR). Also disclosed are methods of using compositions of the invention to inhibit Hedgehog signaling effects, such as cell proliferation, including treating subjects in need thereof, and pharmaceutical compositions and kits for implementing methods of the invention.
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NOVEL PHOSPHORYLATION OF CARDIAC TROPONIN I AS A MONITOR FOR CARDIAC INJURY (Fri, 26 Aug 2011)
This invention relates to novel phosphorylation sites in cardiac Troponin I that are associated with the onset of heart failure. The phosphorylation sites, i.e., serine 5, tyrosine 26, threonine 51, serine 166, threoninel81 and/or serine 199, can be used as biomarkers for (i) identifying subjects at risk for the development of heart failure, (ii) treating subjects having a higher than normal level of the biomarker, and (iii) monitoring therapy of a subject at risk for the development of heart failure. Also described are antibodies, reagents, and kits for carrying out a method of the present invention.
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PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETED NANOPARTICLES FOR THERAPY OF PROSTATE CANCER (Fri, 19 Aug 2011)
The invention provides a nanoparticle composition that is decorated with a urea-based small-molecule peptidomimetic inhibitor of prostate specific membrane antigen (PSMA), which is expressed by almost all solid tumors. This strategy takes advantage of both the avidity of the functionalized nanoparticle for binding to PSMA and the ability of the nanoparticle to be retained for longer periods of time in the tumor due to enhanced leakage via EPR into the tumor interstitium and poor clearance due to underdeveloped or non-existent lymphatics within the tumor.
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USE OF HISTONE ACETYLTRANSFERASE INHIBITORS AS NOVEL ANTI-CANCER THERAPIES (Fri, 15 Jul 2011)
The present invention provides methods for treating cancer comprising inhibiting the activity of p300/CBP histone acetyltransferase (HAT). Also provided are p300/CBP HAT inhibitors for treating a subject having cancer. In addition, the present invention includes biomarkers for p300/CBP HAT inhibition, which are used to i) monitor the effectiveness of cancer therapy, and ii) identify anti-cancer agents for use in combination therapy.
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POLYMER-BASED COMPOSITIONS AND METHODS FOR TREATMENT OF PERITONEAL DISORDERS (Fri, 15 Jul 2011)
The present invention relates to therapeutic compounds encapsulated within polyether-anhydride polymers. Biodegradable particles made from these polymers have a hydrophobic polyanhydride core and a hydrophilic PEG shell. Therapeutic compounds are encapsulated for prolonged drug delivery and are effective for use in treating peritoneal disorders.
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Pyromellitic diimide organic semiconductors and devices (Fri, 08 Jul 2011)
n-type organic semiconductors have a pyromellitic diimide structure and electronic or electro-optic devices include pyromellitic diimide compounds as organic semiconductors. Specific semiconductors include pyromellitic diimide compounds have sidechains comprising fluorine substituted aliphatic or aromatic moieties linked to the pyromellitic diimide structure by an alkylene or heteroalkylene linking group. An electronic or electro-optic device includes a first electrode, a second electrode space apart from the first electrode, and an organic semiconductor layer arranged between the first and second electrodes. The organic semiconductor layer comprises a pyromellitic diimide compound.
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PSMA-BINDING AGENTS AND USES THEREOF (Fri, 17 Jun 2011)
Prostate-specific membrane antigen (PSMA) binding compounds having radioisotope substituents are described, as well as chemical precursors thereof. Compounds include pyridine containing compounds, compounds having phenylhydrazine structures, and acylated lysine compounds. The compounds allow ready incorporation of radionuclides for single photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging, for example, prostate cancer cells and angiogenesis.
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ADIABATIC MULTI-BAND RF PULSES FOR SELECTIVE SIGNAL SUPPRESSION IN MAGNETIC RESONANCE IMAGING (Fri, 17 Jun 2011)
A magnetic resonance imaging (MRI) system, comprising: a magnetic resonance imaging scanner comprising: a main magnet providing a substantially uniform main magnetic field B0 for a subject under observation; and a radio frequency (RF) coil configured to irradiate a radio frequency (RF) pulse into a region of interest of the subject under observation, wherein the RF pulse comprises a base pulse comprising an adiabatic pulse having a first bandwidth time product (BWTP), wherein the RF pulse selectively suppresses magnetic resonance signals from more than one chemical component or more than one spatial region within the region of interest of the subject under observation, and wherein the adiabatic pulse is characterized by an amplitude modulation function and a frequency modulation function.
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ANTI-CYTOMEGALOVIRUS ACTIVITY OF ARTEMISININ-DERIVED DIMERS (Fri, 17 Jun 2011)
Artemisinin-derived monomers and artemisinin dimers are shown to exhibit in-vitro anti-cytomegalovirus (CMV) activity. Artemisinin dimers effectively inhibited CMV replication in human foreskin fibroblasts and human embryonic lung fibroblasts with no cytotxicity at concentrations required for complete CMV inhibition. Artemisinin dimers were found to be potent and non-cytotoxic inhibitors of CMV replication, which indicates their use as therapeutic agents for the treatment of CMV infection in humans.
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METHOD FOR LATE INTRODUCTION OF THE (8R)-HYDROXYL GROUP IN CARBAPENEM BETA-LACTAM ANTIBIOTIC SYNTHESIS (Fri, 17 Jun 2011)
The presently disclosed subject matter demonstrates that ThnG and ThnQ enzymes encoded by the thienamycin gene cluster in Streptomyces cattleya oxidize the C-2 and C-6 moieties of carbapenems, respectively. ThnQ stereospecifically hydroxylates PS-5 giving N-acetyl thienamycin. ThnG catalyzes sequential desaturation and sulfoxidation of PS-5, giving PS-7 and its sulfoxide. The ThnG and ThnQ enzymes are relatively substrate selective, but give rise to the oxidative diversity of carbapenems produced by S. cattleya, and orthologues likely function similarly in allied streptomyces.
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PRODRUG ACTIVATION IN CANCER CELLS USING MOLECULAR SWITCHES (Fri, 10 Jun 2011)
The present invention features a novel protein engineering strategy by combining the domains of two independent proteins into a molecular switch. The invention features polypeptides comprising a prodrug activating enzyme and a protein that binds a cancer specific marker, polynucleotides encoding the polypeptides, and molecular switches for converting a prodrug into a toxin, comprising the polypeptides. The invention also features methods for converting a prodrug into a toxin, methods for treating cancer, and methods for making the molecular switches, as well as kits.
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METHOD FOR INCORPORATING INTERNAL POLAR AND IONIZABLE GROUPS IN PROTEINS (Fri, 10 Jun 2011)
Internal polar and ionizable groups are essential for enzymatic catalysis, proton transport, redox reactions, and many other functional properties of proteins. To engineer novel enzymes or to modify the function of existing ones, and to build switches that can be used to modify the stability of proteins in response to changes in pH, it is necessary to introduce polar or ionizable groups or to modify the properties of existing ones. However, internal polar and ionizable groups usually destabilize proteins. The disclosure provides new methods that allow the introduction of polar and ionizable groups into the interior of proteins, as well as new methods for improving the accuracy of pKa of an internal amino acid of a protein, and methods for mapping the folding free energy landscape of a protein.
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INHIBITORS OF HUMAN METHIONINE AMINOPEPTIDASE 1 AND METHODS OF TREATING DISORDERS (Fri, 27 May 2011)
Described herein are novel pyrimidine-pyridine compounds, methods of inhibiting methionine aminopeptidase and treating disorders (or symptoms thereof) associated with methionine aminopeptidase, wherein a compound of the invention is administered to a subject.
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MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY OF LOW CONCENTRATION SOLUTES WITH EXCHANGEABLE PROTONS USING LABEL TRANSFER MODULES: FREQUENCY TRANSFER, INVERSION TRANSFER, AND DEPHASING TRANSFER (Fri, 20 May 2011)
An embodiment of the current invention provides a method for magnetic resonance (MR) imaging or spectroscopy, comprising: (a) selectively exciting exchangeable solute protons or protons of exchangeable solute-based water molecules within a frequency range in a subject using at least one frequency-selective radio frequency (RF) pulse, wherein the frequency range encompasses characteristic resonance frequencies of the exchangeable solute protons or protons of exchangeable solute-based water molecules, wherein the frequency range is substantially non-overlapping with a characteristic resonance frequency of bulk water protons in the subject, wherein the at least one frequency selective RF pulse performs a substantially minimal excitation on the bulk water protons, and wherein the at least one frequency-selective RF pulse, sometimes in combination with a time period that separates the at least one frequency-selective RF pulse, magnetically labels the exchangeable solute protons or the exchangeable solute-based water molecules; (b) allowing a portion of the magnetically labeled exchangeable solute protons to exchange with the bulk water protons or allowing the magnetically labeled exchangeable solute-based water molecules to exchange with bulk water molecules; (c) repeating (a) and (b) a plurality of times to enhance a population size of the magnetically labeled exchangeable solute protons or the magnetically labeled exchangeable solute-based water molecules; (d) irradiating the subject under observation with a water excitation RF pulse that is adapted to excite the bulk water protons; (e) recording a magnetic resonance (MR) signal from the subject under observation in response to the water excitation RF pulse; and (f) analyzing the recorded MR signal to estimate a quantity associated with the exchangeable solute protons or the exchangeable solute-based water molecules.
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HYDROGEL-BASED VASCULAR LINEAGE CELL GROWTH MEDIA AND USES THEREOF (Fri, 20 May 2011)
A medium for growing vascular lineage cells is described. The vascular lineage cell growth medium includes an oligosaccharide-based hydrogel and a growth factor that promotes vascularization by vascular lineage cells.
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METHODS OF SYNTHESIS AND USE OF CHEMOSPHERES (Fri, 06 May 2011)
The present invention provides, in general, compositions comprising a hydrogel and an agent, for example a therapeutic agent or an imaging agent, for locoregional delivery. In certain preferred embodiments of the invention, the hydrogel compositions are detectable by Magnetic Responance and CT Scan and are used for locoregional delivery of therapeutic agents, for example chemotherapeutic agents. The invention also features polymer matrix compositions comprising nanoparticles that can be loaded after polymerization with bioactive agents, for example a diagnostic agent or therapeutic agent.
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SITE-SPECIFIC MODIFICATION OF PROTEINS (Fri, 29 Apr 2011)
Methods and compositions for site-specific modification of amino acids, peptides, polypeptides and proteins are disclosed.
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LABELED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA), BIOLOGICAL EVALUATION, AND USE AS IMAGING AGENTS (Fri, 18 Mar 2011)
The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.
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(BIS) UREA AND (BIS) THIOUREA COMPOUNDS AS EPIGENIC MODULATORS OF LYSINE-SPECIFIC DEMETHYLASE 1 AND METHODS OF TREATING DISORDERS (Fri, 25 Feb 2011)
The invention provides for novel (bis)urea and (bis)thiourea compounds which are inhibitors of lysine- specific demethylase 1 (LSD1). Such compounds may be used to treat disorders, including cancer.
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Optimized MRI strip array detectors and apparatus, systems and methods related thereto (Fri, 18 Feb 2011)
Featured is a device for NMR or MRI signals from excited nuclei as well as related apparatus, systems and methods. The device includes a strip array antenna including one or more conductor and N reactive tuning components, where N is an integer ≧1 at least one of the N reactive components is electrically coupled to each of the one or more conductors as well as to ground/virtual ground. The apparent electrical length of the conductors is tuned with the reactive tuning components so it is equal to be about nλ/4, where n is an integer ≧1 and λ is the wavelength of the signal to be detected. The length of the strip also is such as to be substantially in the approximate range of 1.3 times the depth of interest. The strip conductors are also combined with loop coils to form quadrature detectors.
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INHIBITORS OF METHIONINE AMINOPEPTIDASES AND METHODS OF TREATING DISORDERS (Fri, 11 Feb 2011)
The invention is directed towards novel naphthoquinone and naphthothiazole compounds, and methods of treating disorders related to MetAP, including tuberculosis and bacterial infection, using various naphthoquinone, hydroxyquinonline, and naphthothiazole compounds.
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LADDER-TYPE OLIGO-P-PHENYLENE-CONTAINING COPOLYMERS WITH HIGH OPEN-CIRCUIT VOLTAGES AND AMBIENT PHOTOVOLTAIC ACTIVITY (Fri, 11 Feb 2011)
Ladder-type oligo-p-phenylene containing donor-acceptor copolymers are disclosed. The ladder-type oligo-p-phenylene can be used as an electron donor unit in the disclosed copolymers to provide a deeper highest occupied molecular orbital (HOMO) level for obtaining polymeric solar cells having a higher open-circuit voltage. Particular electron-accepting units, e.g., a divalent fused-ring heterocyclic moiety selected from the group consisting of a substituted or unsubstituted benzothiadiazole, a substituted or unsubstituted quinoxaline, a substituted or unsubstituted benzobisthiazole, and a substituted or unsubstituted naphthothiadiazole, can be used to tune the electronic band gaps of the polymers for a better light harvesting ability. The disclosed copolymers exhibit field-effect mobilities as high as 0.011 cm2/(V s). Compared to fluorene-containing copolymers with the same acceptor unit, the disclosed ladder-type oligo-p-phenylene containing copolymers have enhanced and bathochromically shifted absorption bands and much better solubility in organic solvents.
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COMPOSITIONS AND METHODS FOR DIAGNOSING, TREATING OR PREVENTING NEOPLASIAS (Fri, 04 Feb 2011)
As described below, the present invention features compositions and methods for diagnosing, treating and preventing neoplasias.
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METHODS FOR IN VIVO IMAGING OF CELLS (Fri, 28 Jan 2011)
The instant invention provides methods for the in vivo imaging of cells using one or more imaging modalities.
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CANCER TREATMENT WITH GAMA-SECRETASE INHIBITORS (Fri, 28 Jan 2011)
Provided are methods for treating cancer in a patient, comprising administering to a patient in need thereof a therapeutically effective regimen, the regimen comprising administering a gamma-secretase inhibitor, wherein the regimen results in a reduction in the cancer cell population in the patient. In some embodiments of the methods, the therapeutically effective regimen stabilizes, reduces or eliminates the cancer stem cell population. Also provided are compounds of the formula I <chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.17mm" wi="66.29mm" file="US20110020232A1-20110127-C00001.TIF" img-content="chem" img-format="tif"/> </chemistry> or a pharmaceutically acceptable salt thereof, wherein R1, R2, and X are as herein described.
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Antibodies that specifically bind hedgehog-derived polypeptides (Fri, 07 Jan 2011)
The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G′CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
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GDE Compositions and Methods (Fri, 17 Dec 2010)
The present invention relates to compositions to treat glycerophosphodiester phosphodiesterase (GDE) related disorders. The invention also relates to methods treating GDE related disorders. The invention further relates to kits for treating GDE related disorders in a subject. The invention further relates to methods of identifying novel treatments for treating GDE related disorders in a subject.
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SR-BI AS A PREDICTOR OF ELEVATED HIGH DENSITY LIPOPROTEIN AND CARDIOVASCULAR DISEASE (Fri, 10 Dec 2010)
The present invention relates to the field of single nucleotide polymorphisms (SNPs) and uses therefore as a predictor of diseases and conditions. Specifically, the present invention provides methods and kits useful in determining whether a subject is at increased risk for developing a cardiovascular disease by screening for the presence of a SNP in the scavenger receptor class B type I (SR-BI) gene of a subject.
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ANTIFUNGAL AGENTS AS NEUROPROTECTANTS (Fri, 26 Nov 2010)
Provided herein are compounds, compositions and methods for protecting neuronal and glial cells.
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TRIOXANE MONOMERS AND DIMERS (Fri, 26 Nov 2010)
Monomeric and dimeric trioxane fluoroaryl amides, 5-carbon-linked, C-10 non-acetal trioxane dimer esters; trioxane silylamides; and trioxane dimer orthoesters and methods of their use for treating subjects infected with malaria or other parasitic infectious diseases including, but not limited to, toxoplasmic infection; subjects afflicted with psychiatric conditions associated with toxoplasmic infection; and subjects afflicted with cancer.
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Hox Compositions and Methods (Fri, 12 Nov 2010)
The present invention relates to compositions to treat HOXB7 related disorders. The invention also relates to methods treating HOXB7 related disorders. The invention further relates to kits for treating HOXB7 related disorders in a subject. The invention further relates to methods of identifying novel treatments for treating HOXB7 related disorders in a subject.
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SELF-ASSEMBLY OF LITHOGRAPHICALLY PATTERNED POLYHEDRAL NANOSTRUCTURES AND FORMATION OF CURVING NANOSTRUCTURES (Fri, 12 Nov 2010)
The self-assembly of polyhedral nanostructures having at least one dimension of about 100 nm to about 900 nm with electron-beam lithographically patterned surfaces is provided. The presently disclosed three-dimensional nanostructures spontaneous assemble from two-dimensional, tethered panels during plasma or wet chemical etching of the underlying silicon substrate. Any desired surface pattern with a width as small as fifteen nanometers can be precisely defined in all three dimensions. The formation of curving, continuous nanostructures using extrinsic stress also is disclosed.
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METHODS, SYSTEMS AND DEVICES FOR LOCAL MAGNETIC RESONANCE IMAGING (Fri, 08 Oct 2010)
Featured are a device with localized sensitivity to magnetic resonance signals, an imaging system using such a device and MRI methods for performing internal MRI or MRI Endoscopy. Such an MRI method includes introducing an MRI antenna or probe into the specimen to be imaged, the antenna being configured in accordance with the devices described herein, so that the spatial coordinate frame of imaging is inherently locked or defined with respect to the introduced antenna thereby providing imaging of the specimen from the point of view of the antenna. Further such imaging is conducted so that the MRI signal is confined substantially to a volume with respect to a particular region of the antenna or probe.
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SELF-ASSEMBLING PEPTIDES BEARING ORGANIC ELECTRONIC FUNCTIONALITY AND APPLICATIONS EMPLOYING THE SAME (Fri, 08 Oct 2010)
The aqueous self-assembly of oligopeptide-flanked π-conjugated molecules into discrete one-dimensional nanostructures is described. Unique to these molecules is the fact that the π-conjugated unit has been directly embedded within the peptide backbone by way of a synthetic amino acid with π-functionality that is compatible with standard Fmoc-based peptide synthesis or by way of a diacid or other bis(electrophile) that can covalently cross-link peptide chains presented on a synthesis support. The peptide-based molecular designs enforce intimate π- π communication within the aggregates after charge-screening and self-assembly, making these nanostructures attractive for optical or electronic applications in biological environments. In other embodiments, a convenient method to incorporate π-electron units into peptides that assemble into amyloid-like supramolecular polymers is disclosed. Self-assembly manipulates these "electronic peptides" into delocalized sub-10 nm one dimensional (1-D) nanostructures under completely aqueous conditions.
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PSMA-TARGETING COMPOUNDS AND USES THEREOF (Fri, 24 Sep 2010)
Prostate-specific membrane antigen (PSMA) targeting compounds are described. Uses of the compounds for imaging, therapy, cell sorting, and tumor mapping are also described.
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METHODS AND COMPOSITIONS FOR THE DETECTION OF CANCER (Fri, 24 Sep 2010)
Various embodiments of this invention relate generally to targeted activation and delivery of therapeutic drugs to cells that produce prostate specific antigen (PSA), prostate specific membrane antigen (PSMA) or human glandular kallikrein (hK2). Various further embodiments relate more specifically to PSMA-specific peptide prodrugs that become activated to yield therapeutic drugs. Further aspects of various embodiments of the present invention also relate to methods and compositions for treating or preventing cancers and methods and compositions for detecting and/or imaging cancers.
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Compositions and methods for enhancing transport through mucus (Fri, 27 Aug 2010)
The invention generally relates to compositions and methods for transporting substances across mucosal barriers. The invention also relates to methods of making and using such substances.
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METHOD FOR THE DIAGNOSIS OF AGE-ASSOCIATED VASCULAR DISORDERS (Fri, 27 Aug 2010)
Methods for determining if a subject has or is susceptible to having an age- associated vascular disorder are disclosed. The method includes determining if the subject exhibits altered expression of a product of one or more of the genes listed in Table 1 relative to a control level of expression of the gene product. Altered expression of one or more of the genes listed in Table 1 indicates that the subject has or is susceptible to having an age- associated vascular disorder. In specific examples the gene product is a product of the MFG-E8 and an increase in expression indicates the subject has or is susceptible to having an age-associated vascular disorder.
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Free human serum IgE immunoenzymetric assay and methods of use (Fri, 20 Aug 2010)
The present invention relates to the development of novel of free blood fluid IgE Immunoenzymetric assay that is specifically designed to evaluate the blood fluid of patients on therapeutic agents designed to reduce free serum IgE levels, such as Omalizumab. The assay displays the robustness required for clinical analysis of serum containing such agents as Omalizumab.
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PhoU (PerF), A PERSISTENCE SWITCH INVOLVED IN PERSISTER FORMATION AND TOLERANCE TO MULTIPLE ANTIBIOTICS AND STRESSES AS A DRUG TARGET FOR PERSISTER BACTERIA (Fri, 20 Aug 2010)
The PhoU protein is a widely expressed protein in bacteria, but not in eukaryotes. The PhoU protein is required for persister formation in bacteria. The invention includes compositions to reduce persister formation and their use as therapeutic agents. The invention further includes methods for identification of compounds to reduce persister formation. The invention further includes kits for the identification of agents that modulate the activity and expression of PhoU.
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DETECTING AND SORTING METHYLATED DNA USING A SYNTHETIC NANOPORE (Fri, 16 Jul 2010)
Provided are methods for detecting, characterizing or separating DNA based on methylation. Heterogeneous DNA populations are separated based on DNA methylation by providing a membrane having a nanopore through which an electric field is applied. DNA of interest is introduced, and for a given threshold voltage across the nanopore, only DNA having a methylation parameter of interest may transit the pore, thereby facilitating detection, characterization, or separation of DNA based on methylation. The methods are optionally used to detect a disease state that is associated with DNA methylation including, but not limited to, cancer.
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BIOCOMPATIBLE POLYSACCHARIDE-BASED HYDROGELS (Fri, 09 Jul 2010)
Modified polysaccharides and crosslinked modified polysaccharide compositions are described. Methods of using the crosslinked modified polysaccharide compositions to deliver proteins, oligonucleotides, or pharmaceutical agents are also disclosed.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME (Fri, 02 Jul 2010)
Compounds having the following general formula, pharmaceutical compositions comprising the compounds, and methods of treating cancer, obesity, and microbial infections using such compositions: wherein: R1=H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, cyanomethyl, —OCH3, OC(O)CH3 or OC(O)CF3 R2=-OCH2C(O)NHNH—R5, where R5 is (a) phenyl, optionally substituted with one or more of halogen, C1-C8 alkyl, optionally substituted with halogen, —OH, —OR6, where R6 is C1-C8 alkyl, optionally substituted with halogen, or (b) 2-, 3-, or 4-pyridyl, optionally substituted with halogen, —OH, —OR6, where R6 is C1-C8 alkyl, optionally substituted with halogen, or (c) a heterocycle selected from the group consisting of imidazole, thiazole, benzimidazole, benzoxazole, benzthiazole, tetrazole, triazole, and aminothiazole; or (d) —C(O)R7, where R7 is a C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, or a heterocycle selected from the group consisting of pyridyl, imidazole, thiazole, benzimidizole, benzoxazole, benzthiazole, tetrazole, triazole, and aminothiazole; and R3 and R4, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="24.38mm" wi="48.60mm" file="US20100168176A1-20100701-C00001.TIF" img-content="chem" img-format="tif"/> </chemistry> 
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Fatty acid carbohydrate hybrid molecules as therapeutic agents and methods thereof (Fri, 11 Jun 2010)
Described herein are fatty acid carbohydrate hybrid compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.
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Methods for diagnosis and optimizing treatment of multiple sclerosis (Fri, 04 Jun 2010)
Biological markers for multiple sclerosis, and their use in the diagnosis and prognosis of the disease, are described. Also described are methods for treating multiple sclerosis by administering an inhibitor of cathepsin B activity or a neuroprotective composition comprising a modified terpenoid compound. Also described are isolated polypeptide biomarkers, polynucleotides encoding the polypeptide biomarkers, and antibodies that bind specifically to the polypeptide biomarkers. Further described are kits that include the above-mentioned isolated polypeptide biomarkers, the polynucleotides encoding them, or specific antibodies against the polypeptide biomarkers.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME (Fri, 14 May 2010)
A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula IV wherein R21=H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —CH2OR25, —C(O)R25, —CO(O)R25, —C(O)NR25R26, —CH2C(O)R25, or —CH2C(O)NHR25, where R25 and R26 are each independently H, C1-C10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R22=—OH, —OR27, —OCH2C(O)R27, —OCH2C(O)NHR27, —OC(O)R27, —OC(O)OR27, —OC(O)NHNH—R5, or —OC(O)NR27R28, where R27 and R28 are each independently H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R27 and R28 can each optionally contain halogen atoms; R23 and R24, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1.
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QUINOLINE COMPOUNDS AS INHIBITORS OF ANGIOGENESIS, HUMAN METHIONINE AMINOPEPTIDASE, AND SIRT1, AND METHODS OF TREATING DISORDERS (Fri, 16 Apr 2010)
Described herein are methods of inhibiting methionine aminopeptidase or SirT1, inhibiting angiogenesis, and treating disorders (or symptoms thereof) associated with methionine aminopeptidase, SirT1 and/or angiogenesis, wherein a compound of the invention is administered to a subject.
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METHODS FOR SYNTHESIS AND USES OF INHIBITORS OF GHRELIN O-ACYLTRANSFERASE AS POTENTIAL THERAPEUTIC AGENTS FOR OBESITY AND DIABETES (Fri, 09 Apr 2010)
The invention provides inhibitors of ghrelin O-acyltransferase, and methods of making and using them. In some embodiments, the invention provides bisubstrate analog inhibitors of ghrelin O-acyltransferase, which can be effective in treating, for example, obesity and diabetes mellitus.
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ANTI-CHOLESTEROLEMIC COMPOUNDS AND METHODS OF USE (Fri, 12 Mar 2010)
The present invention provides novel compounds with hypocholesteremic activity from crude Embilica officinialis (EO) extracts and methods of use. The invention also provides nutraceuticals.
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Transgenic non-human animals expressing a truncated activin type II receptor (Fri, 12 Mar 2010)
The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.
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PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE (Fri, 12 Mar 2010)
This invention relates to new insights into the pathogenesis of pancreatic cancers by analyzing the genes altered in 24 pancreatic tumors. First, we determined the sequences of 23,781 transcripts, representing 20,583 protein-encoding genes, in DNA from these tumors. Second, we searched for homozygous deletions and amplifications using microarrays querying one million single nucleotide polymorphisms in each sample. Third, we analyzed the transcriptomes of the same samples using SAGE and next-generation sequencing-by-synthesis technologies We found that pancreatic cancers contain an average of 63 genetic alterations, of which 49 are point mutations, 8 are homozygous deletions, and 6 are amplifications. Further analyses revealed a core set of 12 regulatory processes or pathways that were each genetically altered in 70 % to 100 % of the samples. The data suggest that dysregulation of this core set of pathways is responsible for the major features of pancreatic tumorigenesis.
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COMBINATION THERAPY FOR TUBERCULOSIS (Fri, 12 Mar 2010)
The present invention relates to methods of treating tuberculosis, including multi¬ drug resistant varieties and latent tuberculosis. More particularly, the present invention relates to a method of treating tuberculosis in a mammal comprising administering to said mammal in need thereof an effective amount of a compound of formula (I), (S)-N- [[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, or a pharmaceutically acceptable salt thereof in combination with at least two agents useful in the treatment of tuberculosis. The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, (ii) a therapeutically effective amount of at least one agent useful in the treatment of tuberculosis and (iii) one or more pharmaceutically acceptable carriers or vehicles.
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Role of limonoid compounds as neuroprotective agents (Fri, 05 Mar 2010)
Disclosed herein are neuroprotective compounds. Methods for the preparation of such compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the compounds disclosed, alone or in combination with other therapeutic agents, for the treatment of neurodegenerative conditions are provided.
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PRODRUG ACTIVATION IN CANCER CELLS USING MOLECULAR SWITCHES (Fri, 19 Feb 2010)
The present invention features a novel protein engineering strategy by combining the domains of two independent proteins into a molecular switch. The invention features polypeptides comprising a prodrug activating enzyme and a protein that binds a cancer specific marker, polynucleotides encoding the polypeptides, and molecular switches for converting a prodrug into a toxin, comprising the polypeptides. The invention also features methods for converting a prodrug into a toxin, methods for treating cancer, and methods for making the molecular switches, as well as kits.
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ADIABATIC MULTI-BAND RF PULSES FOR SELECTIVE SIGNAL SUPPRESSION IN MAGNETIC RESONANCE IMAGING (Fri, 19 Feb 2010)
A magnetic resonance imaging (MRI) system, comprising: a magnetic resonance imaging scanner comprising: a main magnet providing a substantially uniform main magnetic field B0 for a subject under observation; and a radio frequency (RF) coil configured to irradiate a radio frequency (RF) pulse into a region of interest of the subject under observation, wherein the RF pulse comprises a base pulse comprising an adiabatic pulse having a first bandwidth time product (BWTP), wherein the RF pulse selectively suppresses magnetic resonance signals from more than one chemical component or more than one spatial region within the region of interest of the subject under observation, and wherein the adiabatic pulse is characterized by an amplitude modulation function and a frequency modulation function.
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COMPOUNDS, THEIR SYNTHESES, AND THEIR USES (Fri, 19 Feb 2010)
Embodiments of the present invention provide compounds (such as Formula (I) compounds, Formula (II) compounds, and various embodiments thereof). Compositions comprising those compounds are also provided. Methods for their preparation are included. Also, uses of the compounds are included, such as administering and treating diseases (e.g., cancer and infections).
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PSMA-BINDING AGENTS AND USES THEREOF (Fri, 05 Feb 2010)
Prostate-specific membrane antigen (PSMA) binding compounds having radioisotope substituents are described, as well as chemical precursors thereof. Compounds include pyridine containing compounds, compounds having phenylhydrazine structures, and acylated lysine compounds. The compounds allow ready incorporation of radionuclides for single photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging, for example, prostate cancer cells and angiogenesis.
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PYROMELLITIC DIIMIDE ORGANIC SEMICONDUCTORS AND DEVICES (Fri, 29 Jan 2010)
n-type organic semiconductors have a pyromellitic diimide structure and electronic or electro-optic devices include pyromellitic diimide compounds as organic semiconductors. Specific semiconductors include pyromellitic diimide compounds have sidechains comprising fluorine substituted aliphatic or aromatic moieties linked to the pyromellitic diimide structure by an alkylene or heteroalkylene linking group. An electronic or electro-optic device includes a first electrode, a second electrode space apart from the first electrode, and an organic semiconductor layer arranged between the first and second electrodes. The organic semiconductor layer comprises a pyromellitic diimide compound.
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TRIOXANE DIMER SULFUR COMPOUNDS (Fri, 22 Jan 2010)
The disclosure provides novel trioxane sulfur dimers having Formula I: methods for their preparation, pharmaceutical compositions containing these compounds, and methods for treating cancer, proliferative disorders, and/or malaria using these compounds and/or compositions.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, METHODS OF USE FOR SAME, AND METHODS FOR PREPARING SAME (Fri, 15 Jan 2010)
The present invention relates to a novel class of compounds comprising formula I, wherein n is 0 or 1. A is NR1, O, or S, wherein R1 is H, hydroxyl, C1-C10 alkyl, C1-C10 alkoxy, alkenyl, aryl, alkylaryl or arylalkyl. X is a carboxylate, a phosphonate, or a phosphate residue, or a C1-C10 alkyl residue optionally substituted with a carboxylate, phosphonate or phosphate residue. Y is a C1-C20 alkyl, alkenyl, halide, hydroxyl, C1-C20 alkoxy, aryl, alkylaryl, arylalkyl, cycloalkyl, cycloalkenyl, or a heterocyclic ring and is optionally substituted with one or more halides. Z is a H, a hydroxyl group, a halide, an aryl group, an alkylaryl group, an arylalkyl group, a cycloalkyl group, a cycloalkenyl group or a heterocyclic ring and is optionally substituted with one or more C1-C10 alkyl groups, C1-C10alkoxy groups, hydroxyl groups, cyano groups, carboxylate groups, halides, aryl groups, alkylaryl groups, arylalkyl groups, cycloalkyl groups, cycloalkenyl groups or heterocyclic rings.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME (Fri, 11 Dec 2009)
The class compounds of the present invention may be represented by Formula (I), wherein X may be O, S, or N. R1 and R2 are independently either H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. R3 and R4 are independently either H, an aryl group, a heteroaryl group, and a heterocyclic ring group having 4 to 6 carbon atoms, wherein the aryl, heteroaryl, and heterocyclic moieties are optionally substituted with one or more of a first substitution group defined herein. In a further embodiment, R3 and R4 along with the atoms and bonds to which they are attached, form an optionally substituted 5-7 membered ring having at least one nitrogen atom within the ring structure.
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MRI METHODS USING DIFFUSION TENSOR IMAGING TECHNIQUES AND MRI SYSTEMS EMBODYING SAME (Fri, 27 Nov 2009)
Featured is a method for automatically evaluating acquired MRI data, determining the quality of the acquired images and removing the image data when it is determined that an image is corrupted so the imaged data for the corrupted image is removed from the subsequent tensor fitting. In further embodiments, such determining includes judging the quality of the image data to determine if the image data satisfies a quality threshold criteria and if determined not to be satisfied adjudging the image to be corrupted. Such methods include performing said evaluating, determining and removing in real time and in the case where an image is determined to be corrupted, such methods further includes re-acquiring additional image data corresponding to each of the one or more images removed as being corrupted. Also featured are MRI systems embodying such methods.
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Compositions and methods for the treatment of cancer (Fri, 06 Nov 2009)
The instant invention provides methods and compositions for the treatment and diagnosis of cancer, e.g., cancers characterized by the expression of prostate specific membrane antigen (PSMA).
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HIGH AFFINITY INHIBITORS OF HEPATITIS C VIRUS NS3/4A PROTEASE (Fri, 02 Oct 2009)
Compositions and uses thereof that inhibit HCV life cycle by inhibiting action of the HCV NS3/4A protease. An embodiment of the invention comprises a compound designated RS-2-19.
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Imaging agents and methods of using same for detecting multidrug resistance in cancer (Fri, 04 Sep 2009)
Compounds and methods of using such compounds in the imaging and detection of multidrug resistance cancer in a subject are provided. In particular, novel imaging agents are provided which are suitable for the detection and imaging of a multidrug resistance phenotype in cancer cells and/or tissues using non-invasive medical imaging modalities.
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Molecularly imprinted polymer sensor device (Fri, 07 Aug 2009)
A molecularly imprinted polymer sensor device for detecting the presence of a taggant molecular structure in a fluid is disclosed. The molecularly imprinted polymer sensor device comprises a molecularly imprinted crosslinked polymer having a crosslinked core and a plurality of polymer arms attached to the core, wherein the core has molecular sized cavities adapted to selectively receive and bind displacement molecules having the taggant molecular structure and a colorimetric indicator, said displacement molecule being selectively removed from the molecularly imprinted crosslinked polymer and replaced with the taggant molecular structure upon exposure to the fluid containing the taggant molecular structure therein, thereby indicating the presence of the taggant molecular structure in the fluid.
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SR-BI AS A PREDICTOR OF ELEVATED HIGH DENSITY LIPOPROTEIN AND CARDIOVASCULAR DISEASE (Fri, 07 Aug 2009)
The present invention relates to the field of single nucleotide polymorphisms (SNPs) and uses therefore as a predictor of diseases and conditions. Specifically, the present invention provides methods and kits useful in determiming whether a subject is at increased risk for developing a cardiovascular disease by screening for the presence of a SNP in the scavenger receptor class B type I (SR-BI) gene of a subject.
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TRANSGENIC ANIMALS WHOSE GENOME CONTAINS A TRUNCATED ACTIVE TYPE II RECEPTOR GENE (Tue, 04 Aug 2009)

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Promyostatin peptides and methods of using same (Wed, 29 Jul 2009)
The present invention provides substantially purified peptide portions of a promyostatin polypeptide. For example, the invention provides proteolytic fragments of a promyostatin polypeptide such as a myostatin prodomain or a mature myostatin peptide, as well as functional peptide portions a myostatin prodomain an myostatin. Also provided is a mutant promyostatin polypeptide, which is resistant to proteolytic cleavage, for example, cleavage into a myostatin prodomain and a mature myostatin peptide. The present invention also provides a polynucleotide encoding a peptide portion of a promyostatin polypeptide. In addition, antibodies that specifically bind a peptide portion of a promyostatin polypeptide are provided. The invention further provides methods of identifying a functional peptide portion of a promyostatin polypeptide.
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Antibodies that specifically bind hedgehog-derived polypeptides (Fri, 24 Jul 2009)
The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G′CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
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Truncated Activin Type II Receptor and Methods of Use (Fri, 24 Jul 2009)
The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.
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Histone deacetylase inhibitors (Fri, 17 Jul 2009)
The present invention provides novel HDAC inhibitors and methods of treating diseases using the same.
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N-hydroxylsulfonamide derivatives as new physiologically useful nitroxyl donors (Fri, 26 Jun 2009)
The invention relates to N-hydroxylsulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxylsulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxylsulfonamide derivatives.
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Molecular vaccine linking an endoplasmic reticulum chaperone polypeptide to an antigen (Fri, 12 Jun 2009)
This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.
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METHODS OF SYNTHESIS AND USE OF CHEMOSPHERES (Fri, 12 Jun 2009)
The present invention provides, in general, compositions comprising a hydrogel and an agent, for example a therapeutic agent or an imaging agent, for locoregional delivery. In certain preferred embodiments of the invention, the hydrogel compositions are detectable by Magnetic Responance and CT Scan and are used for locoregional delivery of therapeutic agents, for example chemotherapeutic agents. The invention also features polymer matrix compositions comprising nanoparticles that can be loaded after polymerization with bioactive agents, for example a diagnostic agent or therapeutic agent.
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PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETED NANOPARTICLES FOR THERAPY OF PROSTATE CANCER (Fri, 05 Jun 2009)
The invention provides a nanoparticle composition that is decorated with a urea-based small-molecule peptidomimetic inhibitor of prostate specific membrane antigen (PSMA), which is expressed by almost all solid tumors. This strategy takes advantage of both the avidity of the functionalized nanoparticle for binding to PSMA and the ability of the nanoparticle to be retained for longer periods of time in the tumor due to enhanced leakage via EPR into the tumor interstitium and poor clearance due to underdeveloped or non-existent lymphatics within the tumor.
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Genomic Landscapes of Human Breast and Colorectal Cancers (Fri, 15 May 2009)
Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene “mountains” and a much larger number of gene “hills” that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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GENOMIC LANDSCAPES OF HUMAN BREAST AND COLORECTAL CANCERS (Fri, 17 Apr 2009)
Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene 'mountains' and a much larger number of gene 'hills' that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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FREQUENCY REFERENCING FOR CHEMICAL EXCHANGE SATURATION TRANSFER (CEST) MRI (Fri, 03 Apr 2009)
A water saturation shift referencing (WASSR) technique performed using a magnetic resonance scanner comprises: acquiring a spatial map of Z spectra that encompass the water center frequency using sufficiently low saturation power and sufficiently short duration selected such that symmetry of the Z spectra is not obscured by magnetization transfer but dominated by direct water saturation effects so that the spectrum is substantially symmetric; and performing a symmetry analysis on the substantially symmetric Z spectra to generate a spatial map of the water center frequency. WASSR-corrected chemical exchange saturation transfer (CEST) imaging is disclosed as an illustrative example.
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Sir2 products and activities (Fri, 13 Mar 2009)
A novel compound, 2′/3′-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2′ and 3′ regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2′-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2′/3′-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2′/3′-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2′/3′-O-acetyl-ADP-ribose are also provided.
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SAR DOSIMETER FOR RF POWER DEPOSITION IN MRI AND METHODS AND SYSTEMS RELATED THERETO (Fri, 13 Mar 2009)
Featured is a dosimeter device that measures SAR deposited by RF power deposition during MRI of a specimen. Such a dosimeter device includes a transducer that is configured to present a load to the MRI scanner in which the transducer is located and to provide an output representative of signals induced in the transducer. The transducer also is configured so that the presented load is substantially equivalent to another load which would be presented by the specimen during MRI of the specimen. Such a transducer also is configured so as to generate an MRI signal that is sufficient to allow the MRI scanner to adjust the RF power to a value substantially equal to that of the specimen. Also featured are methods for measuring SAR deposited by RF power deposition and apparatuses or system embodying such a dosimeter device.
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PDE5 inhibitor compositions and methods for treating cardiac indications (Fri, 06 Mar 2009)
The invention features methods and compositions featuring a PDE5 inhibitor for treating or preventing a cardiac indication in a subject.
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RATIONALLY IMPROVED ISONIAZID AND ETHIONAMIDE DERIVATIVES AND ACTIVITY THROUGH SELECTIVE ISOTOPIC SUBSTITUTION (Fri, 27 Feb 2009)
The present invention relates to the use of isotopically labeled derivatives of isoniazid, ethionamide and related compounds as effective therapy for the treatment of mycobacterial diseases, including Mycobacterium tuberculosis.
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FOCAL NONINVASIVE STIMULATION OF THE SENSORY CORTEX OF A SUBJECT WITH CEREBRAL PALSY (Fri, 20 Feb 2009)
Disclosed are methods and related devices for use with subjects with cerebral palsy or periventricular leukomalacia. In preferred embodiments, diffusion tensor imaging (DTI) is used to identify neural areas and transcranial magnetic stimulation (TMS) is used to stimulate neural pathways.
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HYBRID SCFA-HYDROXYL-DERIVATIZED MONOSACCHARIDES, METHODS OF SYNTHESIS, AND METHODS OF TREATING DISORDERS (Fri, 13 Feb 2009)
Described herein are fatty acid carbohydrate-hydroxyl-hybrid compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.
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Techniques for identifying molecular structures and treating cell types lining a body lumen using fluorescence (Fri, 06 Feb 2009)
Techniques for detecting fluorescence emitted by molecular constituents in a wall of a body lumen include introducing an autonomous solid support into the body lumen. Cells in a lumen wall of the body lumen are illuminated by a light source mounted to the solid support with a wavelength that excites a particular fluorescent signal. A detector mounted to the solid support detects whether illuminated cells emit the particular fluorescent signal. If the particular fluorescent signal is detected from the illuminated cells, then intensity or position in the lumen wall of the detected fluorescent signal, or both, is determined. These techniques allow the information collected by the capsule to support diagnosis and therapy of GI cancer and other intestinal pathologies and syndromes. For example, these techniques allow diagnostic imaging using endogenous and exogenous fluoroprobes, treating diseased sites by targeted release of drug with or without photoactivation, and determining therapeutic efficacy.
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Method for magnetic resonance imaging using inversion recovery with on-resonant water suppression including MRI systems and software embodying same (Fri, 30 Jan 2009)
Featured are methods for magnetic resonance imaging of a volume, such a volume having susceptibility-generating objects or interfaces having susceptibility mismatches therein. Such a method includes selectively visualizing one of susceptibility-generating objects or interfaces having susceptibility mismatches as hyperintense signals, where such visualizing includes controlling variable imaging parameters so as to control a geometric extent of a signal enhancing effect, m more particular aspects of the present invention, such selectively visualizing includes attenuating or essentially suppressing signals from fat and/or water, namely on-resonant water protons, so as to thereby enhance a signal(s) associated with magnetic susceptibility gradient(s). Also featured are MRI systems, apparatuses and/or applications programs for execution on a computer system controlling the MRI data acquisition process embodying such methods.
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Optimized MRI strip array detectors and apparatus, systems and methods related thereto (Fri, 16 Jan 2009)
Featured is a device for NMR or MRI signals from excited nuclei as well as related apparatus, systems and methods. The device includes a strip array antenna including one or more conductor and N reactive tuning components, where N is an integer ≧1 at least one of the N reactive components is electrically coupled to each of the one or more conductors as well as to ground/virtual ground. The apparent electrical length of the conductors is tuned with the reactive tuning components so it is equal to be about nλ/4, where n is an integer ≧1 and λ is the wavelength of the signal to be detected. The length of the strip also is such as to be substantially in the approximate range of 1.3 times the depth of interest. The strip conductors are also combined with loop coils to form quadrature detectors.
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LABELED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA), BIOLOGICAL EVALUATION, AND USE AS IMAGING AGENTS (Thu, 01 Jan 2009)
The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino- functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.
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Methods for generating hypermutable microbes (Fri, 26 Dec 2008)
Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.
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METHODS AND COMPOSITIONS FOR MODULATING P300/CBP ACTIVITY (Thu, 25 Dec 2008)
The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi -synthetic HAT domain.
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METHODS FOR IN VIVO IMAGING OF CELLS (Fri, 28 Nov 2008)
The instant invention provides methods for the in vivo imaging of cells using one or more imaging modalities.
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Chemical exchange saturation transfer based MRI using reporter genes and MRI methods related thereto (Fri, 21 Nov 2008)
Featured are a new class of reporter genes including reporter compositions as well as methods, MRI systems and MRI imaging kits related thereto. The genes according to the present invention provide MR contrast when the sample/subject is irradiated at a specific off-resonance radio-frequency (RF frequency), where the contrast mechanism utilizes chemical exchange saturation transfer (CEST) technique for imaging.
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CHIRALLY PURE ISOMERS OF ITRACONAZOLE AND INHIBITORS OF LANOSTEROL 14A- DEMETHYLASE FOR USE AS ANGIOGENESIS INHIBITORS (Fri, 17 Oct 2008)
Described herein are methods of inhibiting angiogenesis, and treating or preventing a disease or disorder (or symptoms thereof) associated with angiogenesis, wherein an anti-angiogenesis compound is administered to a subject.
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Device, systems and methods for localized heating of a vessel and/or in combination with mr/nmr imaging of the vessel and surrounding tissue (Fri, 29 Aug 2008)
Featured are devices, systems and methods for localized heating of a vessel as well as devices, systems and methods for MR/NMR imaging of a vessel while locally heating a portion of the vessel. More particularly featured are such devices, systems and methods for use when administering or delivering therapeutic agents including genes and/or drugs to the tissues of the vessel. Such a method includes positioning a thermal energy delivery device proximal a target site within the vessel of a body and activating the thermal energy delivery device so as to heat the target site thereby locally increasing a temperature of tissue at the target site. In further embodiments, the method includes introducing a therapeutic medium to the target site over a predetermined time period, and wherein said activating occurs at least one of before, during or after said step of introducing.
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Growth Differentiation Factor-8 Nucleic Acid and Polypeptide from Aquatic Species, and Transgenic Aquatic Species (Fri, 25 Jul 2008)
A transgenic non-human aquatic organisms, such as piscine, crustacean, mollusks, and the like, having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the aquatic organism is disclosed. Also disclosed are methods for making such organisms and nucleic acid sequences encoding GDF-8 polypeptides from such aquatic organisms.
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MRI METHODS USING DIFFUSION TENSOR IMAGING TECHNIQUES AND MRI SYSTEMS EMBODYING SAME (Fri, 18 Jul 2008)
Featured is a method for automatically evaluating acquired MRI data, determining the quality of the acquired images and removing the image data when it is determined that an image is corrupted so the imaged data for the corrupted image is removed from the subsequent tensor fitting. In further embodiments, such determining includes judging the quality of the image data to determine if the image data satisfies a quality threshold criteria and if determined not to be satisfied adjudging the image to be corrupted. Such methods include performing said evaluating, determining and removing in real time and in the case where an image is determined to be corrupted, such methods further includes re-acquiring additional image data corresponding to each of the one or more images removed as being corrupted. Also featured are MRI systems embodying such methods.
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METHODS, SYSTEMS AND DEVICES FOR LOCAL ENDOSCOPIC MAGNETIC RESONANCE (Fri, 11 Jul 2008)
Featured are a device with localized sensitivity to magnetic resonance signals, an imaging system using such a device and MRI methods for performing internal MRI or MRI Endoscopy. Such an MRI method includes introducing an MRI antenna or probe into the specimen to be imaged, the antenna being configured in accordance with the devices described herein, so that the spatial coordinate frame of imaging is inherently locked or defined with respect to the introduced antenna thereby providing imaging of the specimen from the point of view of the antenna. Further such imaging is conducted so that the MRI signal is confined substantially to a volume with respect to a particular region of the antenna or probe.
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AGENTS FOR REVERSING EPIGENETIC SILENCING OF GENES (Fri, 11 Jul 2008)
The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.
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ANTI-CHOLESTEROLEMIC COMPOUNDS AND METHODS OF USE (Fri, 04 Jul 2008)
The present invention provides novel compounds with hypocholesteremic activity from crude Embilica officinialis (EO) extracts and methods of use. The invention also provides nutraceuticals.
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Polynucleotides encoding promyostatin polypeptides (Wed, 02 Jul 2008)
The present invention provides isolated polynucleotides encoding promyostatin polypeptides or a peptide portion thereof, polynucleotides complementary thereto, and oligonucleotides that can specifically hybridize to such polynucleotides. The present invention also provides an isolated polynucleotide encoding a mature myostatin peptide.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME,AND METHODS OF USE FOR SAME (Thu, 26 Jun 2008)
 A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula (II), wherein R1 and R2, the same or different from each other, are H, Ci-C20 alkyl, cycloalkyl. alkenyl, aryl, arylalkyl, or alkylaryl, -CH2CORs, -CH2C(0)NRs, -C(0)R5, or -CH2OR5, and can optionally contain halogen atoms, where R5 is a C,-C12 alkyl group. R3 and R4, the same or different from each other, are H, Ci-C2o alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl.
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WATER-DISPERSIBLE ORAL, PARENTERAL, AND TOPICAL FORMULATIONS FOR POORLY WATER SOLUBLE DRUGS USING SMART POLYMERIC NANOPARTICLES (Fri, 20 Jun 2008)
Polymeric nanoparticles with a hydrophobic core and a hydrophilic shell are formed from: 1) N-isopropyl acrylamide (NIPAAM), at a molar ratio of about 50% to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral; either water-soluble vinyl derivatives like vinylpyrolidone (VP) or vinyl acetate (VA), or water insoluble vinyl derivatives like methyl methacrylate (MMA) or styrene (ST), at a molar ratio of about 10% to about 30%;, and acrylic acid (AA), at a molar ratio of about 10% to about 30%. The formed nanoparticles may be optionally surface functional using reactive groups present in AA, including PEGylation, or conjugation of moieties such as chemotherapeutics, contrasting agents, antibodies, radionucleides, ligands, and sugars, for diagnostic, therapeutic, and imaging purposes. The polymeric nanoparticles are preferably dispersed in aqueous solutions. The polymeric nanoparticles incorporate one or more types of medicines or bioactive agents in the hydrophobic core; on occasion, the medicine or bioactive agent may be conjugated to the nanoparticle surface via reactive functional groups. The polymeric nanoparticles are capable of delivering the said medicines or bioactive agents through oral, parenteral, or topical routes. The polymeric nanoparticles allow poorly water soluble medicines or bioactive agents, or those with poor oral bioavailability, to be formulated in an aqueous solution, and enable their convenient delivery into the systemic circulation.
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PHOU (PERF), A PERSISTENCE SWITCH INVOLVED IN PERSISTER FORMATION AS A DRUG TARGET FOR PERSISTER BACTERIA (Fri, 20 Jun 2008)
The PhoU protein is a widely expressed protein in bacteria, but not in eukaryotes. The PhoU protein is required for persister formation in bacteria. The invention includes compositions to reduce persister formation and their use as therapeutic agents. The invention further includes methods for identification of compounds to reduce persister formation. The invention further includes kits for the identification of agents that modulate the activity and expression of PhoU.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME (Fri, 16 May 2008)
Compounds having the following general formula, pharmaceutical compositions comprising the compounds, and methods of treating cancer, obesity, and microbial infections using such compositions: wherein: R1 = H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, cyanomethyl, -OCH3, OC(O)CH3 or OC(O)CF3 R2 = -OCH2C(O)NHNH-R5, where R5 is (a) phenyl, optionally substituted with one or more of halogen, C1-C8 alkyl, optionally substituted with halogen, -OH, -OR6, where R6 is C1-C8 alkyl, optionally substituted with halogen, or (b) 2-, 3-, or 4-pyridyl, optionally substituted with halogen, -OH, -OR6, where R6 is C1-C8 alkyl, optionally substituted with halogen, or (c) a heterocycle selected from the group consisting of imidazole, thiazole, benzimidazole, benzoxazole, benzthiazole, tetrazole, triazole, and aminothiazole; or (d) -C(O)R7, where R7 is a C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, or a heterocycle selected from the group consisting of pyridyl, imidazole, thiazole, benzimidizole, benzoxazole, benzthiazole, tetrazole, triazole, and aminothiazole; and R3 and R4, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl.
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Water-dispersible oral, parenteral, and topical formulations for poorly water soluble drugs using smart polymeric nanoparticles (Fri, 09 May 2008)
Polymeric nanoparticles with a hydrophobic core and a hydrophilic shell are formed from: 1) N-isopropyl acrylamide (NIPAAM), at a molar ratio of about 50% to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral; either water-soluble vinyl derivatives like vinylpyrolidone (VP) or vinyl acetate (VA), or water insoluble vinyl derivatives like methyl methacrylate (MMA) or styrene (ST), at a molar ratio of about 10% to about 30%; and acrylic acid (AA), at a molar ratio of about 10% to about 30%. The formed nanoparticles may be optionally surface functionalized using reactive groups present in AA, including PEGylation, or conjugation of moieties such as chemotherapeutics, contrasting agents, antibodies, radionucleides, ligands, and sugars, for diagnostic, therapeutic, and imaging purposes. The polymeric nanoparticles are preferably dispersed in aqueous solutions. The polymeric nanoparticles incorporate one or more types of medicines or bioactive agents in the hydrophobic core; on occasion, the medicine or bioactive agent may be conjugated to the nanoparticle surface via reactive functional groups. The polymeric nanoparticles are capable of delivering the said medicines or bioactive agents through oral, parenteral, or topical routes. The polymeric nanoparticles allow poorly water soluble medicines or bioactive agents, or those with poor oral bioavailability, to be formulated in an aqueous solution, and enable their convenient delivery into the systemic circulation.
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Compositions and methods for neuroprotectin (Fri, 18 Apr 2008)
Disclosed herein are neuroprotective compounds. Methods for the preparation of such compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the compounds disclosed, alone or in combination with other therapeutic agents, for the treatment of neurodegenerative conditions are provided. 
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Authentication of products using molecularly imprinted polymers (Fri, 07 Mar 2008)
A method for identifying a product includes providing a solid body (10) fabricated from at least a molecularly imprinted polymer having molecular sized cavities (12) adapted to selectively receive and bind molecules (50) having a specific taggant molecular structure (51), the molecular sized cavities (12) disposed on a portion of an exterior surface (11) of the body (10), and applying to the surface of the body a composition containing indicator molecules (50) having a taggant moiety (51) at one end and a marking function group (53) tethered to the taggant moiety (51) by a molecular chain the taggant moieties (51) engaging and binding to the molecular sized cavities (12) so as to mark the portion of the surface (11) of the body (10) with the indicator molecules (50) bound thereto, the marking functional groups (53) rendering the marked portion of the surface (11) perceptible with or without detection instrumentation.
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Cancer treatment with gama-secretase inhibitors (Fri, 07 Mar 2008)
Provided are methods for treating cancer in a patient, comprising administering to a patient in need thereof a therapeutically effective regimen, the regimen comprising administering a gamma-secretase inhibitor, wherein the regimen results in a reduction in the cancer cell population in the patient. In some embodiments of the methods, the therapeutically effective regimen stabilizes, reduces or eliminates the cancer stem cell population. Also provided are compounds of the formula I <chemistry id="chem-us-00001-en" num="1"><img id="emi-c00001" he="20.57mm" wi="66.21mm" file="US20080058316A1-20080306-C00001.TIF" img-content="chem" img-format="tif"/></chemistry> or a pharmaceutically acceptable salt thereof, wherein R1, R2, and X are as herein described. 
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COMPOSITIONS AND METHODS FOR NEUROPROTECTION (Fri, 22 Feb 2008)
Disclosed herein are neuroprotective compounds. Methods for the preparation of such compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the compounds disclosed, alone or in combination with other therapeutic agents, for the treatment of neurodegenerative conditions are provided.
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N-hydroxylsulfonamide derivatives as new physiologically useful nitroxyl donors (Fri, 28 Dec 2007)
The invention relates to N-hydroxysulfonamide derivatives that donate nitroxyl (HNO) under physiological conditions and are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure and ischemia/reperfusion injury. Novel N-hydroxysulfonamide derivatives release NHO at a controlled rate under physiological conditions, and the rate of HNO release is modulated by varying the nature and location of functional groups on the N-hydroxysulfonamide derivatives.
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CRYSTAL STRUCTURE OF A SUBSTRATE COMPLEX OF NAMPT/PBEF/VISFATIN (Fri, 30 Nov 2007)
Nicotinamide phosphoribosyltransferase (Nampt) synthesizes nicotinamide mononucleotide (NMN) from nicotinamide in a mammalian NAD+ biosynthetic pathway and is required for SirTl activity in vivo. Nampt has also been presumed to be a cytokine (PBEF) or a hormone (visfatin). The crystal structure of Nampt in the presence and absence of NMN shows that Nampt is a dimeric type II phosphoribosyltransferase and provides insights into the enzymatic mechanism. The structure also reveals the basis of substrate specificity and suggests routes for the development of specific Nampt inhibitors for treatment of Nampt-associated disorders.
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HOX COMPOSITIONS AND METHODS (Fri, 30 Nov 2007)
The present invention relates to compositions to treat HOXB7 related disorders. The invention also relates to methods treating HOXB7 related disorders. The invention further relates to kits for treating HOXB7 related disorders in a subject. The invention further relates to methods of identifying novel treatments for treating HOXB7 related disorders in a subject.
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DIAGNOSTIC AND PROGNOSTIC MARKERS AND TREATMENT STRATEGIES FOR MULTIPLE SCLEROSIS (Fri, 28 Sep 2007)
Biological markers for multiple sclerosis, and their use in the diagnosis and clinical applications of the disease, are described.
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APPARATUS FOR INSERTION OF A MEDICAL DEVICE WITHIN A BODY DURING A MEDICAL IMAGING PROCESS AND DEVICES AND METHODS RELATED THERETO (Fri, 21 Sep 2007)
A device, system, and method for entering a medical device such as a needle into the body inside a medical imager such as a MRI scanner, CT, X-ray fluoroscopy, and ultrasound imaging, from within a body cavity (such as the rectum, vagina, or laparoscopically accessed cavity). A three degree-of- freedom mechanical device translates and rotates inside the cavity and enters a needle into the body, and steers the needle to a target point selected by the user. The device is guided by real-time images from the medical imager. Networked computers process the medical images and enable the clinician to control the motion of the mechanical device that is operated within the imager, outside of the imager or remotely from outside the imager.
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CANCER TREATMENT WITH GAMMA-SECRETASE INHIBITORS (Sat, 08 Sep 2007)
Provided are methods for treating cancer in a patient, comprising administering to a patient in need thereof a therapeutically effective regimen, the regimen comprising administering a gamma-secretase inhibitor, wherein the regimen results in a reduction in the cancer cell population in the patient In some embodiments of the methods, the therapeutically effective regimen stabilizes, reduces or eliminates the cancer stem cell population.
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Processable molecularly imprinted polymers (Fri, 24 Aug 2007)
A process is provided herein for preparing molecularly imprinted polymers for detecting a target analyte by Reversible Addition Fragmentation Chain Transfer (RAFT). The process includes providing a complex having the formula L3M wherein L is a β-diketone ligand containing a chain transfer moiety and L3 can be the same or different ligands, and M is a lanthanide element; reacting the complex with the target analyte to provide an adduct containing the target analyte; co-polymerizing the adduct with a monomer and cross-linking agent to provide a polymer; and removing the target analyte from the polymer to provide the molecularly imprinted polymer.
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Apolipoprotein c-1 induced apoptosis (Fri, 03 Aug 2007)
The present invention provides methods and compositions for identifying compounds which inhibit ApoCI and which are useful in the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction. The invention further provides methods for treating subjects suffering from or at risk of developing atherosclerosis, plaque rupture, apoptosis, or myocardial infarction. The invention further provides methods for diagnosing subjects at suffering from or at risk of developing treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction. 
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PEPTIDE PRODRUGS (Fri, 03 Aug 2007)
Provided herein are a novel class of oligopeptides and prodrugs that include amino acid sequences containing cleavage sites for fibroblast activation protein (FAP). Also provided herein are methods of treating FAP related disorders, including cancer.
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER (Fri, 20 Jul 2007)
The instant invention provides methods and compositions for the treatment and diagnosis of cancer, e.g., cancers characterized by the expression of prostate specific membrane antigen (PSMA).
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Anticancer agents and use (Fri, 29 Jun 2007)
Provided herein are compositions, all related stereoisomers as well as pharmaceutically acceptable salts provided as simplified analogs of pateamine A, in which the analogs generally are devoid of the C3-amino and C5-methyl groups, also referred to as desmethyl, desamino-pateamine A. Suitable analogs provide anticancer and antiproliferative effects in vivo and in vitro by a novel drug mechanism of action described herein for pateamine A, including inhibition of eIF4A-dependent translation initiation. As with pateamine A, as described herein, suitable analogs cause cell cycle arrest or induce apoptosis in transformed cells. However, toxicity of such compounds to slow growing normal cells is low. In addition, such analogs, like pateamine A, target translation initiation factors and are useful as anticancer and antiproliferative agents in subjects in need thereof. Moreover, the analogs, like pateamine A, are valuable molecular probes for evaluation of eukaryotic translation initiation and as lead compounds for development of improved anticancer agents.
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ELECTROSTATICALLY CONTROLLED HYDROGELS (Fri, 25 May 2007)
The compositions and methods disclosed herein pertain to the manufacture and use of hydrogels. The disclosed compositions and methods pertain to hydrogels capable of induction by a variety of methodologies, such as by pH, salt and/or mixing. Such hydrogels are capable of self- or co-assembly and while doing so, may entrap a variety of bioactive agents in their native form, such as proteins, DNA, RNA and the like. The hydrogels of the present invention also demonstrate rapid sheer-responsiveness. The hydrogels of the present invention are biodegradable, biocompatible and useful as a biomaterial or drug-delivery device.
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MOLECULARLY IMPRINTED POLYMER ION EXCHANGE RESINS (Sat, 19 May 2007)
A molecularly imprinted polymer ion exchange resin for selectively removing one or more inorganic ions in a liquid medium is disclosed and described. The exchange resin can include a bead having a porous structure and comprising a cross-linked molecularly imprinted polymer having molecular sized cavities adapted to selectively receive and bind a specific inorganic ion in a liquid medium. A process for preparing a molecularly imprinted polymer ion exchange resin can include (a) polymerizing a polmerizable mixture in the presence of an inorganic ion imprinting complex to form a bead, said inorganic ion imprinting complex including a ligand and an inorganic ion; and (b) removing the inorganic ions from the bead to form the molecularly imprinted polymer ion exchange resin, the bead having a porous structure and comprising a cross-linked molecularly imprinted polymer having molecular sized cavities adapted to selectively receive and bind a specific inorganic ion in an liquid medium.
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COMPOSITIONS COMPRISING GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE (GDE) AND USES THEREOF (Fri, 13 Apr 2007)
The present invention relates to compositions to treat glycerophosphodiester phosphodiesterase (GDE) related disorders. The invention also relates to methods treating GDE related disorders. The invention further relates to kits for treating GDE related disorders in a subject. The invention further relates to methods of identifying novel treatments for treating GDE related disorders in a subject.
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COMPOSITIONS AND METHODS FOR TREATING INFLAMMATION (Fri, 13 Apr 2007)
The present invention relates to compositions to treat inflammation (LIGHT pathway) related disorders, and specifically liver inflammation or hepatitis. The invention also relates to methods of treating LIGHT pathway related disorders by modulating an interaction between LIGHT and LTβR. The invention further relates to kits for treating LIGHT pathway related disorders in a subject. The invention further relates to methods of identifying novel treatments for treating LIGHT pathway related disorders in a subject.
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IMAGING AGENTS AND METHODS OF USING SAME FOR DETECTING MULTIDRUG RESISTANCE IN CANCER (Fri, 09 Mar 2007)
Compounds and methods of using such compounds in the imaging and detection of multidrug resistance cancer in a subject are provided. In particular, novel imaging agents are provided which are suitable for the detection and imaging of a multidrug resistance phenotype in cancer cells and/or tissues using non-invasive medical imaging modalities.
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INHIBITORS OF DNA REPAIR ENZYMES AND METHODS OF USE THEREOF (Fri, 22 Dec 2006)
Compounds are disclosed that inhibit enzymes of the uracil base excision repair (UBER) pathway. Inhibitors of uracil DNA glycosylase, pUTPase and AP endonuclease I are disclosed. The compounds can comprise a uracil substrate fragment and a second binding element joined covalently together by a linker molecule. The compounds are also disclosed comprising a uracil substrate fragment, a second binding element, and a third binding element, which a joined together covalently by a linker molecule. Also disclosed are methods for treating diseases and disorders in a subject in need of treatment where the disorder and/or diseases include cancer and bacterial, viral, and parasitic infections and where the method includes the step of administering the disclosed inhibitors. The administered inhibitors inhibition the enzymes of the UBER pathway, thereby treating the diseases and disorders disclosed herein.
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FATTY ACID CARBOHYDRATE HYBRID MOLECULES AS THERAPEUTIC AGENTS AND METHODS THEREOF (Fri, 01 Dec 2006)
Described herein are fatty acid carbohydrate hybrid compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.
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FREE HUMAN SERUM IGE IMMUNOENZYMETRIC ASSAY AND METHODS OF USE (Fri, 24 Nov 2006)
The present invention relates to the development of novel of free blood fluid IgE Immunoenzymetric assay that is specifically designed to evaluate the blood fluid of patients on therapeutic agents designed to reduce free serum IgE levels, such as Omalizumab. The assay displays the robustness required for clinical analysis of serum containing such agents as Omalizumab.
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Apparatus for insertion of a medical device during a medical imaging process (Fri, 27 Oct 2006)
The end-effector (150) includes a sheath (152) and a medical device or needle carrier (154) that is disposed within the interior compartment (160) of the sheath. Aperture (162) is located in a portion of the sheath proximal a distal end of the sheath that is inserted into a natural or artificial cavity. This device is guided by a real-time imager.
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Methods for generating hypermutable microbes (Fri, 01 Sep 2006)
Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.
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CHEMICAL EXCHANGE SATURATION TRANSFER BASED MRI USING REPORTER GENES AND MRI METHODS RELATED THERETO (Fri, 18 Aug 2006)
Featured are a new class of reporter genes including reporter compositions as well as methods, MRI systems and MRI imaging kits related thereto. The genes according to the present invention provide MR contrast when the sample/subject is irradiated at a specific off-resonance radio-frequency (RF frequency), where the contrast mechanism utilizes chemical exchange saturation transfer (CEST) technique for imaging.
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MRI METHOD OF SELECTIVE VISUALIZATION WITH ON-RESONANT WATER SUPPRESSION (Fri, 11 Aug 2006)
Featured are methods for magnetic resonance imaging of a volume, such a volume having susceptibility-generating objects or interfaces having susceptibility mismatches therein. Such a method includes selectively visualizing one of susceptibility-generating objects or interfaces having susceptibility mismatches as hyperintense signals, where such visualizing includes controlling variable imaging parameters so as to control a geometric extent of a signal enhancing effect, m more particular aspects of the present invention, such selectively visualizing includes attenuating or essentially suppressing signals from fat and/or water, namely on- resonant water protons, so as to thereby enhance a signal(s) associated with magnetic susceptibility gradient(s). Also featured are MRI systems, apparatuses and/or applications programs for execution on a computer system controlling the MRI data acquisition process embodying such methods.
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ANTI-CANCER DNA VACCINE EMPLOYING PLASMIDS ENCODING MUTANT ONCOPROTEIN ANTIGEN AND CALRETICULIN (Fri, 04 Aug 2006)
Novel nucleic acid vectors comprising sequences encoding (a) calreticulin or a domain thereof, and (b) an antigen, such as human papillomavirus oncoproteins E7 or E6 in detoxified form, are disclosed, as are methods for using such vectors to induce antigen-specific immune responses and to treat or prevent development of tumors.
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RNA INTERFERENCE THAT BLOCKS EXPRESSION OF PRO-APOPTOTIC PROTEINS POTENTIATES IMMUNITY INDUCED BY DNA AND TRANSFECTED DENDRITIC CELL VACCINES (Fri, 14 Jul 2006)
An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and/or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC’s transfected with siRNA targeting Bak and/or Bax serve as improved immunogens and tumor immunotherapeutic agents.
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Method of screening for agents that modulate a homer signaling pathway (Fri, 07 Jul 2006)
The invention features a method of identifying, evaluating and screening for compounds or agents for the treatment of disorders involving the Homer signaling pathway in the modulation of immunosupression and neuroprotection. The method includes evaluating the ability of agents to modulate Homer protein activity, Homer protein/immunophilin-peptidylproline cis-trans isomerase interaction, and/or Homer protein/proline-type Homer ligand consensus sequence interaction to identify agents for such treatment. The invention also discloses treatment modalities involving agents identified by such methods.
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Cav2 RELATED COMPOSITIONS AND METHODS (Fri, 23 Jun 2006)
The present invention relates to compositions to treat CaV2 disorders. The invention also relates to methods treating CaV2 disorders. The invention further relates to kits for treating CaV2 disorders in a subject. The invention further relates to methods of identifying novel treatments for treating Cav2 disorders in a subject.
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Olfactory receptor expression libraries and methods of making and using them (Fri, 05 May 2006)
This invention provides novel libraries of olfactory receptor odorant/ligand-binding domains and methods of making and using them. The invention also provides libraries of vectors and cells comprising these nucleic acid constructs. The compositions and methods of the invention are used to identify novel ligand-binding domains for olfactory neuron odorant receptors and their ligands. Thus, the compositions and methods of the invention can be used to generate novel odorants, to screen for toxic odorants, or to manipulate an animal's olfactory response.
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Process for preparing vinyl substituted beta-diketones (Fri, 31 Mar 2006)
A process for preparing vinyl substituted beta-diketones includes reacting a halogen-containing beta-diketone with an olefin in a reaction zone under Heck coupling reaction conditions in the presence of a catalyst, a base, and an organic phosphine to provide a vinyl substituted beta-diketone product.
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IMPLANTABLE MRI COMPATIBLE STIMULATION LEADS AND ANTENNAS AND RELATED SYSTEMS AND METHODS (Fri, 24 Mar 2006)
In vivo medical stimulation probes include an elongate lead having at least one stimulation electrode disposed on a distal portion thereof. The probes may include a plurality of axially spaced apart RF chokes disposed on and/or in an axially extending shielding layer of the lead in advance of the at least one electrode to inhibit induced RF current from forming and/or traveling along the shielding layer.
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Sir2 products and activities (Fri, 17 Mar 2006)
A novel compound, 2′/3′-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2′ and 3′ regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2′-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2′/3′-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2′/3′-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2′/3′-O-acetyl-ADP-ribose are also provided.
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PDE5 INHIBITOR COMPOSITIONS AND METHODS FOR TREATING CARDIAC INDICATIONS (Fri, 03 Mar 2006)
The invention features methods and compositions featuring a PDE5 inhibitor for treating or preventing a cardiac indication in a subject.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME (Fri, 16 Dec 2005)
A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula (II), wherein R1 and R2, the same or different from each other, are H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, -CH2CORS, -CH2C(O)NRS, -C(O)R5, or -CH2OR5, and can optionally contain halogen atoms, where R5 is a C1-C12 alkyl group. R3 and R4, the same or different from each other, are H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl.
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Design and synthesis of renal dipeptidase inhibitors (Fri, 09 Dec 2005)
Aminophosphinic acid derivatives were synthesized as potential inhibitors of renal dipeptidase, an enzyme overexpressed in benign and malignant colon tumors. Several compounds showed potent enzyme-inhibitory activity. These compounds can be used therapeutically and diagnostically for treatment and detection of tumors.
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Methods for generating hypermutable yeast (Fri, 09 Dec 2005)
Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.
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Transgenic non-human animals expressing a truncated activin type II receptor (Fri, 18 Nov 2005)
The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism. 
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REACTIVE OXYGEN GENERATING ENZYME INHIBITOR WITH NITRIC OXIDE BIOACTIVITY AND USES THEREOF (Fri, 11 Nov 2005)
A reactive oxygen generating enzyme inhibitor with NO donor bioactivity, e.g., nitrated allopurinol, is useful to treat heart failure, stable angina, ischemic disorder, ischemic reperfusion injury, atherosclerosis, sickle cell disease, diabetes, Alzheimer's disease, Parkinson's disease, ALS and asthma and to obtain proper contraction of heart, skeletal and smooth muscle.
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PROCESSABLE MOLECULARLY IMPRINTED POLYMERS (Fri, 04 Nov 2005)
A process is provided herein for preparing molecularly imprinted polymers for detecting a target analyte by Reversible Addition Fragmentation Chain Transfer (RAFT). The process includes providing a complex having the formula L?3#191M wherein L is a ß-diketone ligand containing a chain transfer moiety and L?3#191 can be the same or different ligands, and M is a lanthanide element; reacting the complex with the target analyte to provide an adduct containing the target analyte; co-polymerizing the adduct with a monomer and cross-linking agent to provide a polymer; and, removing the target analyte from the polymer to provide the molecularly imprinted polymer.
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Growth differentiation factor-8 nucleic acid and polypeptide from aquatic species, and transgenic aquatic species (Fri, 30 Sep 2005)
Purified GDF-8 polypeptides of aquatic organisms.
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DNA VACCINES TARGETING ANTIGENS OF THE SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS (SARS-CoV) (Sat, 10 Sep 2005)
This invention provides compositions and methods for inducing and enhancing immune responses, particularly antigen-specific CD8+ T cell mediated responses, against antigens of the SARS coronavirus. These antigens include epitopes of the Membrane (M), Envelope (E), Spike (S) and Nucleocapsid (N) proteins of the virus. Such responses are induced using DNA constructs as an immunogens or vaccines, which encode chimeric polypeptides comprising endoplasmic reticulum chaperone polypeptides, such as human calreticulin (CRT) and an antigenic peptide or polypeptide. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. Such enhanced immunity, whether T cell mediated or antibody-mediated protects an infected subject from infection or spread of the SARS CoV in vivo.
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Bioactivation of alkylating agents for cancer treatment (Fri, 12 Aug 2005)
A rapid screening method for identifying acylfulvenes and acylfulvene analogs with improved chemotherapeutic properties has been developed. The mechanism of toxicity of irofulven, a potentially clinically useful member of the acylfulvene class, has been elucidated and provides guidance for design and testing of a new class of alkylating agents with structures related to irofulven. The role of alkenal/one oxidoreductase (AOR) is shown to be important in cancer cell susceptibility to this class of alkylating agent.
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Protein encoded by a nucleic acid (Fri, 29 Jul 2005)
A method is provided for identifying a compound that modulates a cellualr response associated with Homer and mediated by a cell-surface or an intracellular receptor. A method is further provided for identifying a compound that modulates receptor activated calcium mobilization associated with Homer. A method is provided for identifying a compound that inhibits Homer protein activity based on the crystal structure coordinates of Homer protein binding domain. A method is also provided for identifying a compound that affects the formation of cell surface receptors into clusters. Also provided are nucleic acids encoding Homer proteins as well as Homer proteins, and Homer interacting proteins.
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Hedgehog-derived polypeptides (Wed, 29 Jun 2005)
The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G↓CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
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AUTHENTICATION OF PRODUCTS USING MOLECULARLY IMPRINTED POLYMERS (Fri, 29 Apr 2005)
A method for identifying a product includes providing a solid body (10) fabricated from at least a molecularly imprinted polymer having molecular sized cavities (12) adapted to selectively receive and bind molecules (50) having a specific taggant molecular structure (51), the molecular sized cavities (12) disposed on a portion of an exterior surface (11) of the body (10), and applying to the surface of the body a composition containing indicator molecules (50) having a taggant moiety (51) at one end and a marking function group (53) tethered to the taggant moiety (51) by a molecular chain (52), the taggant moieties (51) engaging and binding to the molecular sized cavities (12) so as to mark the portion of the surface (11) of the body (10) with the indicator molecules (50) bound thereto, the marking functional groups (53) rendering the marked portion of the surface (11) perceptible with or without detection instrumentation.
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Molecular vaccine linking an endoplasmic chaperone polypeptide to an antigen (Fri, 11 Mar 2005)
This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.
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Methods for multiple acquisitions with global inversion cycling for vascular-space-occupancy dependant and apparatuses and devices related thereto (Fri, 11 Feb 2005)
Featured are methods for magnetic resonance imaging in which MR signals of selected tissues, fluid or body components in a target area are desired to be essentially eliminated, which method includes applying an initial RF inversion pulse to invert the magnetization of the selected tissues or to apply any other T1 preparation aimed at nulling one or more tissue species and successively applying one or more RF inversions pulses thereafter. More particularly, the successively applied RF inversion pulses are applied so as to essentially maintain the magnetization of the selected tissues at or about the zero-crossing point of the longitudinal magnetization. Such methods further include interleaving a plurality of excitation pulses for acquiring image data and the RF inversion pulses so that at least one of the plurality of excitation pulses follows in a time sequence the application of one of the applied RF inversion pulses such that the image data is acquired following an inversion pulse.
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METHOD OF SCREENING FOR AGENTS THAT MODULATE IMMUNOPHILIN/PEPTIDYLPROLINE CIS-TRANS ISOMERASE (PPIASE)-HOMER INTERACTION (Fri, 28 Jan 2005)
The invention features a method of identifying, evaluating and screening for compounds or agents for the treatment of disorders involving the Homer signaling pathway in the modulation of immunosupression and neuroprotection. The method inlcudes evaluating the ability of agents to modulate Homer protein activity, Homer protein/immunophilin-peptidylproline cis-trans isomerase interaction, and/or Homer protein/proline-type Homer ligand consensus sequence interaction to identify agents for such treatment. The invention also discloses treatment modalities involving agents identified by such methods.
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β-LACTAMASE INHIBITORS AND METHODS OF USE THEREOF (Fri, 21 Jan 2005)
The invention provides novel non-β-lactam inhibitors of β-lactamases. In particular, the invention provides boronic acid-based compounds set forth in the specification. These compounds may be used with β-lactam antibiotics to bacterial infection, particularly β-lactam-antibiotic-resistant bacterial infections. These compounds are also antibacterial agents by themselves. The invention further provides methods of using such compounds. Finally, the invention provides a pharmaceutical composition comprising these compounds.
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Antimicrobial compounds (Fri, 24 Sep 2004)
This invention provides compounds and methods for treating, with said compound, a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R—SOn-Z-CO—Y, where R is an alkyl groups having 6-20 carbon atoms, unsaturated hydrocarbon groups having 6-20 carbon atoms, or alkyl groups having 6-20 carbon atoms interrupted by at least one aromatic ring; Z is —CH2—, —CH2CH2—, —NH—NH—, —O—, ——NH—, —O—NH—, —CH2—NH—, —CH2—O—, —NH—O—, —NH—CH2—, —O—CH2—, and —CH═CH—; Y is —NH2, —O—CH2—C6H5, —CO—CO—O—CH3, and —O—CH3; and n is 1 or 2. It has been discovered that these compounds treat microbially-based infections caused by corynebacteria, nocardiae, rhodococcus, and mycobacteria. These compounds may be used to treat mycobacterial cells, such as Mycobacteria tuberculosis, drug resistant M. tuberculosis, M. avium intracellulare, M. leprae, M. paratuberculosis, and pathogenic Mycobacteria sp.
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Compounds that release nitric oxide at controlled rates upon photolysis (Fri, 13 Aug 2004)
Chemical compounds which release nitric oxide in a controlled manner upon photolysis with light are provided. These compounds are O2-benzyl, O2-naphthylmethyl and O2-naphthylallyl substituted diazeniumdiolates. Also provided are methods of preparing these novel compounds in high chemical yields as well as methods of using these compounds.
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ELIMINATION OF MR SIGNALS OF SELECTED COMPONENTS IN A TARGET AREA OF AN IMAGED OBJECT (Fri, 18 Jun 2004)
Featured are methods for magnetic resonance imaging in which MR signals of selected tissues, fluid or body components in a target area are desired to be essentially eliminated, which method includes applying an initial RF inversion pulse to invert the magnetization of the selected tissues or to apply any other T1 preparation aimed at nulling one or more tissue species and successively applying one or more RF inversions pulses thereafter. More particularly, the successively applied RF inversion pulses are applied so as to essentially maintain the magnetization of the selected tissues at or about the zero-crossing point of the longitudinal magnetization. Such methods further include interleaving a plurality of excitation pulses for acquiring image data and the RF inversion pulses so that at least one of the plurality of excitation pulses follows in a time sequence the application of one of the applied RF inversion pulses such that the image data is acquired following an inversion pulse.
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Methods for generating hypermutable yeast (Fri, 14 May 2004)
Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.
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Techniques for identifying molecular structures and treating cell types lining a body lumen using fluorescence (Fri, 14 May 2004)
Techniques for detecting fluorescence emitted by molecular constituents in a wall of a body lumen include introducing an autonomous solid support into the body lumen. Cells in a lumen wall of the body lumen are illuminated by a light source mounted to the solid support with a wavelength that excites a particular fluorescent signal. A detector mounted to the solid support detects whether illuminated cells emit the particular fluorescent signal. If the particular fluorescent signal is detected from the illuminated cells, then intensity or position in the lumen wall of the detected fluorescent signal, or both, is determined. These techniques allow the information collected by the capsule to support diagnosis and therapy of GI cancer and other intestinal pathologies and syndromes. For example, these techniques allow diagnostic imaging using endogenous and exogenous fluoroprobes, treating diseased sites by targeted release of drug with or without photoactivation, and determining therapeutic efficacy.
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Design and synthesis of renal dipeptidase inhibitors (Fri, 14 May 2004)
Aminophosphinic acid derivatives were synthesized as potential inhibitors of renal dipeptidase, an enzyme overexpressed in benign and malignant colon tumors. Several compounds showed potent enzyme-inhibitory activity. These compounds can be used therapeutically and diagnostically for treatment and detection of tumors.
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TECHNIQUES FOR IDENTIFYING MOLECULAR STRUCTURES AND TREATING CELL TYPES LINING A BODY LUMEN USING FLUORESCENCE (Fri, 23 Apr 2004)
A fluorescent-labeled probe is taken up selectively by a population of cells in the lumen (102). The capsule is introduced into the body lumen (110). The lumen wall is illuminated (120) and if a particular fluorescent signal is detected (130) then determination of the appropriate diagnosis or therapy is performed (170), otherwise the capsule is moved to a new position in the lumen (140).
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Nucleic acid molecule encoding homer 1B protein (Wed, 14 Apr 2004)
A method is provided for identifying a compound that modulates a cellular response associated with Homer and mediated by a cell-surface or an intracellular receptor. A method is further provided for identifying a compound that modulates receptor activated calcium mobilization associated with Homer. A method is provided for identifying a compound that inhibits Homer protein activity based on the crystal structure coordinates of Homer protein binding domain. A method is also provided for identifying a compound that affects the formation of cell surface receptors into clusters. Also provided are nucleic acids encoding Homer proteins as well as Homer proteins, and Homer interacting proteins.
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Antimicrobial compounds (Wed, 31 Mar 2004)
This invention provides methods for treating a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R—SOn—Z—CO—Y, where R is an alkyl group having 6-20 carbons; Z is a radical selected from —CH2—, —O—, and —NH—, two of these radicals coupled together, or —CH2═CH2—; Y is —NH2, O—CH2—C6H5, —CO—CO—O—CH3, or O—CH3; and n is 1 or 2. It has been discovered that these compounds inhibit growth of microbial cells which synthesize α-substitued, β-hydroxy fatty acids, particularly corynemycolic acid, nocardic acid, and mycolic acid. These compounds may be used to inhibit growth of mycobacterial cells, such asMycobacterium tuberculosis,drug-resistantM. tuberculosis, M. avium intracellulare,andM. leprae.
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Non-invasive diagnostic imaging technology for mitochondria dysfunction using radiolabeled lipophilic salts (Fri, 20 Feb 2004)
The invention provides a series of lipophilic phosphonium cations (PhCs) labeled with 18F for non-invasive assessment of ΔΨm, lipophilic ammonium cation analogs of the PhCs, and methods of using same for imaging and detection of mitochondrial-related pathologies in patients using PET or SPECT.
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Method for MR/NMR imaging (Fri, 13 Feb 2004)
The present invention features an MRI/NMR methodology or process for detecting exogenous amide protons in a region of interest of a body or sample via the water signal. Such methods and processes can be used for any of a number of purposes including determining and assessing the delivery and/or content of a molecular or cellular target(s), such as ligands, oglionucleotides, and RNA/DNA (including plasmids) tagged or labeled by an exogenous contrast agent sourcing such amide protons; detecting and assessing pH effects, more particularly the pH of the liquid pool (e.g., blood); and as a mechanism for MR/NMR signal enhancement (e.g., providing another mechanism for developing contrast between tissues, etc. of the region of interest. 
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Device, systems and methods for localized heating of a vessel and/or in combination with MR/NMR imaging of the vessel and surrounding tissue (Fri, 06 Feb 2004)
Featured are devices, systems and methods for localized heating of a vessel as well as devices, systems and methods for MR/NMR imaging of a vessel while locally heating a portion of the vessel. More particularly featured are such devices, systems and methods for use when administering or delivering therapeutic agents including genes and/or drugs to the tissues of the vessel. Such a method includes positioning a thermal energy delivery device proximal a target site with the vessel of a body and activating the thermal energy delivery device so as to heat the target site thereby locally increasing a temperature of tissue at the target site. In further embodiments, the method includes introducing a therapeutic medium to the target site over a predetermined time period, and wherein said activating occurs at least one of before, during or after said step of introducing.
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Antibodies that specifically bind hedgehog-derived polypeptides (Fri, 30 Jan 2004)
The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G↓CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
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NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME (Fri, 23 Jan 2004)
Pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula (IX): R29 = H, or CI-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, =CHR31, -C(O)OR31, - C(O)R31, -CH2C(O)OR31, CH2C(O)NHR31, where R31 is H or C1-C10 alkyl, cycloalkyl, or alkenyl; R30 = C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl; X5 = -OR32, or NHR32, Where R32 is H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, the R32 group optionally containing a carbonyl group, a carboxyl group, a carboxyamide group, an alcohol group, or an ether group, the R32 group further optionally containing one or more halogen atoms; with the proviso that when R29 is =CH2, then X5 is not OH. Also disclosed are compounds within the scope of the formula (IX), as well as uses of the pharmaceutical compositions for weight loss, anti-microbial and anti-cancer applications, inhibition of fatty acid synthase and neuropeptide-Y, and the stimulation of the activity of carnitine palmitoyl transferase-1.
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METHODS OF TREATING MICROBIAL INFECTIONS IN HUMANS AND ANIMALS (Fri, 16 Jan 2004)
A method of treating a subject with a microbially-based infection, comprising the administration of a compound to the subject. The compound is able to decrease ATP levels in the microbe by at least 10% compared to controls after 24 hours in an in vitro test, without killing mammalian cells during the same time period. The decrease in ATP levels is measured by: (1) removing the cells from the testing location and putting them on ice; (2) harvesting the cells at 4 degrees C by centrifugation and disrupting it with bead-beating in an ATP extraction buffer; (3) removing cellular debris by centrifugation at 4 degrees C, leaving an ATP-containing supernatant; (4) measuring the amount of ATP present in the supernatant by a bioluminescence assay at 4 degrees C.
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NOVEL COMPUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME (Fri, 16 Jan 2004)
A pharmaceutical composition comprising a phamaceurtical diluent and a compound of formula IV wherein R21= H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, -CH2OR25, -C(O)R25, -CO(O)R25, -C(O)NR25R26, -CH2C(O)R25, or -CH2C(O)NHR25, where R25 and R26 are each independently H, C1-C10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R22 = -OH, -OR27, -OCH2C(O)R27, -OCH2C(O)NHR27, -OC(O)R27, -OC(O)OR27, -OC(O)NHNH-R5, or -OC(O)NR27R28, where R27 and R28 are each independentlyH, C1 -C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R27 and R28 can each optionally contain halogen atoms; R23 and R24, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1.
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AGENTS CAPABLE OF INHIBITING RAS AND USES THEREOF (Fri, 09 Jan 2004)
This invention provides an agent capable of blocking the interaction between GTP-Ras and ERI1, wherein ERI1 is a protein comprising amino acids, the sequence of which amino acids is set forth in SEQ ID NO:7. In one embodiment, the agent comprises at least a portion of the ERI1 sequence. This invention provides a nucleic acid which encodes such agent. This invention also provides uses of the agent for treating cancer.
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Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same (Wed, 03 Dec 2003)
The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.
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APPARATUS FOR INSERTION OF A MEDICAL DEVICE DURING A MEDICAL IMAGING PROCESS (Fri, 31 Oct 2003)
The end-effector (150) includes a sheath (152) and a medical device or needle carrier (154) that is disposed within the interior compartment (160) of the sheath. Aperture (162) is located in a portion of the sheath proximal a distal end of the sheath that is inserted into a natural or artificial cavity. This device is guided by a real-time imager.
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DEVICE, SYSTEMS AND METHODS FOR HEATING OF A VESSEL IN COMBINATION WITH MR/NMR IMAGING (Fri, 17 Oct 2003)
Featured are devices, systems and methods for localized heating of a vessel as well as devices, systems and methods for MR/NMR imaging (500) of a vessel while locally heating a portion of the vessel. More particularly featured are such devices, systems and methods for use when administering or delivering therapeutic agents including genes and/or drugs to the tissues of the vessel. Such a method includes positioning a thermal energy delivery device (100) proximal a target site of an internal vessel of a body and activating the thermal energy delivery device so as to heat the target site thereby locally increasing a temperature of tissue at the target site. In further embodiments, the method includes introducing a therapeutic medium to the target site over a predetermined time period, and wherein said activating occurs at least one of before, during or after said step of introducing.
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MAGNETIC RESONANCE METHOD FOR ASSESING AMIDE PROTON TRANSFER EFFECTS BETWEEN AMIDE PROTONS OF ENDOGENOUS MOBILE PROTEINS AND PEPTIDES AND TISSUE WATER IN SITU AND ITS USE FOR IMAGING PH AND MOBILE PROTEIN/PEPTIDE CONTENT (Fri, 29 Aug 2003)
Featured is an MRI/NMR methodology or process to detect amide protons of endogenous mobile proteins and peptides via the water signal. Such methods and processes can be used for the purposes of detection of pH effects and labile amide proton content of mobile proteins/peptides or content changes thereto using MRI Also featured are methods whereby assessment of determined pH effects and amide proton content or content changes and related mobile protein and/or peptide content or content changes can be used in connection with diagnosis, program and treatment of brain related disorders and diseases, cardiac disorders and diseases, and cancer and to use such methods for monitoring, detecting and assessing protein and peptide content in vivo and pathologically for any of a number of diseases or disorders of a human body, including but not limited to cancers, ischemia, Alzheimers and Parkinsons.
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NON-INVASIVE DIAGNOSTIC IMAGING TECHNOLOGY FOR MITOCHONDRIA USING RADIOLABELED LIPOPHILIC SALTS (Fri, 15 Aug 2003)
The invention provides a series of lipophilic phosphonium cations (PhCs) labeled with 18F for non-invasive assessment of ΔΨm, lipophilic ammonium cation analogs of the PhCs, and methods of using same for imaging and detection of mitochondrial-related pathologies in patients using PET or SPECT.
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MOLECULES INTERACTING WITH CASL (MICAL) POLYNUCLEOTIDES, POLYPEPTIDES, AND METHODS OF USING THE SAME (Fri, 15 Aug 2003)
The present invention provides MICAL and MICAL-Like polypeptides and polynucleotides. Also provided are methods that for identifying agents that affect axon growth and placement. Furthermore, provided herein are methods for affecting axon growth and placement.
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MRI TUNABLE ANTENNA AND SYSTEM (Fri, 18 Jul 2003)
A strip array antenna including a number of conductors (14) that are connected to ground or virtual ground though at least one reactive component (150). The apparent electrical length of conductors (140) is tuned so that it equals an integer multiple of a quarter wavelength at the operating frequency.
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METHOD FOR MR/NMR IMAGING (Fri, 20 Jun 2003)
The present invention features an MRI/NMR methodology or process for detecting exogenous amide protons in a region of interest of a body or sample via the water signal. Such methods and processes can be used for any of a number of purposes including determining and assessing the delivery and/or content of a molecular or cellular target(s), such as ligands, oligonucleotides, and RNA/DNA (including plasmids) tagged or labeled by an exogenous contrast agent sourcing such amide protons; detecting and assessing pH effects, more particularly the pH of the liquid pool (e.g., blood); and as a mechanism for MR/NMR signal enhancement (e.g., providing another mechanism for developing contrast between tissues, etc. of the region of interest.
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METHODS AND COMPOSITIONS FOR TREATING VASCULAR LEAK USING HEPATOCYTE GROWTH FACTOR (Fri, 09 May 2003)
News methods are provided for treating vascular leak, including acute lung injury. Therapies of the invention include administration of hepatocyte growth factor to a subject in need thereof, such as a subject suffering from or susceptible to pneumonia or sepsis, or chronic conditions that can result from vascular leak.
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Tissue specific prodrug (Wed, 09 Apr 2003)
The invention provides novel peptide prodrugs which contain cleavage sites specifically cleaved by prostate specific antigen (PSA). These prodrugs are useful for substantially inhibiting the non-specific toxicity of a variety of therapeutic drugs. PSA is secreted by prostatic glandular cells. Upon cleavage of the prodrug by PSA, the therapeutic drugs are activated and exert their toxicity. Novel sesquiterpene-γ-lactones are also provided by the invention, and are designed to be linked to carrier moieties such as the peptides of the invention. Methods for treating cell proliferative disorders are also featured in the invention.
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Structural prediction of allosterism (Fri, 10 Jan 2003)
The present invention provides a computer-assisted method for creating and displaying a model of a molecule in which residues that are affected by the binding of a ligand to the molecule are highlighted, making it possible to trace the path of propagation of a binding signal through the molecule. In order to carry out the method, the binding site determinants of the molecule are determined and the binding constant for the ligand is calculated. The states of a conformational ensemble that are binding competent are identified, and the Gibbs energy and probability of each state and the stability constant per residue of the molecule are calculated in the presence and absence of the ligand. Those residues that display a difference in stability constant in the presence vs absence of ligand are those which are affected by the binding of the ligand.
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Therapeutic suppression of specific immune responses by administration of oligomeric forms of antigen of controlled chemistry (Fri, 13 Dec 2002)
The present invention relates to a method of specifically suppressing an undesired immune response in a mammal suffering from such a response. The method comprises: <ul id="ul0001-en" list-style="none"><li><ul id="ul0002-en" list-style="none"><li>i) preparing a construct comprising at least one discrete antigenically recognizable moiety corresponding to an antigenic determinant of an antigen causing the undesired immune response bound to a pharmacologically acceptable carrier</li><li>wherein the number of the moieties bound to the carrier and the spacing of the moieties on the carrier are such that the construct does not elicit an immune response to the moieties but does directly compete with the antigen for receptors on an immunocompetent cell that recognizes the determinant, and thereby the construct specifically suppresses the undesired immune response; and</li><li>ii) administering the construct to the mammal in an amount such that suppression of the undesired immune response is effected. The invention further relates to constructs suitable for use in the above method and to methods of making same.</li></ul></li></ul>
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METHOD FOR TREATING NERVE INJURY CAUSED BY SURGERY (Fri, 06 Dec 2002)
The present invention relates generally to methods for treating or preventing nerve injury in a warm-blooded animal caused as a consequence of surgery by administering neurotrophic compounds described below. The invention relates more specifically to methods for treating or preventing nerve injury caused as a consequence of prostate surgery as well as erectile dysfunction.
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USE OF FOLLISTATIN TO INCREASE MUSCLE MASS (Fri, 01 Nov 2002)
The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.
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Transgenic non-human animals expressing a truncated activintype II receptor (Fri, 25 Oct 2002)
The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.
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Antiviral compositions and methods of use (Fri, 18 Oct 2002)
Purified antiviral compounds, pharmaceutical formulations containing the compounds, and methods of use of the compounds are provided. The compositions of the invention are isolated antiviral components from plant extracts derived from, for example, Salvia miltiorrhiza, that find use in the treatment of viral infections, such as by inhibiting the activity of viral integrase. Methods for isolation and purification of the antiviral compounds are additionally provided.
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IMAGING NUCLEIC ACID DELIVERY (Fri, 18 Oct 2002)
The invention provides compositions and methods to monitor delivery of nucleic acids (e.g., such as genes) to a target cell. The compositions comprise a nucleic acid delivery vehicle and a contrast agent. Preferably, the contrast agent is suitable for use in magnetic resonance imaging (MRI). The compositions can be used to monitor the efficacy and selectivity of gene delivery. The invention also provides a medical access device for delivering compositions according to the invention to a target tissue. Preferably, the medical access device comprises a perfusion-porous nucleic acid delivery balloon catheter which can be used in an interventional vascular procedure.
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Engineering intracellular sialylation pathways (Fri, 04 Oct 2002)
Methods for manipulating carbohydrate processing pathways in cells of interest are provided. Methods are directed at manipulating multiple pathways involved with the sialylation reaction by using recombinant DNA technology and substrate feeding approaches to enable the production of sialylated glycoproteins in cells of interest. These carbohydrate engineering efforts encompass the implementation of new carbohydrate bioassays, the examination of a selection of insect cell lines and the use of bioinformatics to identify gene sequences for critical processing enzymes. The compositions comprise cells of interest producing sialylated glycoproteins. The methods and compositions are useful for heterologous expression of glycoproteins.
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Human glycosylation enzymes (Fri, 27 Sep 2002)
The present invention relates to novel human glycosylation enzyme polypeptides and isolated nucleic acids containing the coding regions of the genes encoding such polypeptides. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human glycosylation enzyme polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human glycosylation enzyme polypeptides.
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Methods for generating hypermutable yeast (Fri, 06 Sep 2002)
Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be be rendered genetically stable by restoring the mismatch repair system to proper functionality.
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Tissue specific prodrug (Wed, 26 Jun 2002)
The invention provides novel peptide prodrugs which contain cleavage sites specifically cleaved by prostate specific antigen (PSA). These prodrugs are useful for substantially inhibiting the non-specific toxicity of a variety of therapeutic drugs. PSA is secreted by prostatic glandular cells. Upon cleavage of the prodrug by PSA, the therapeutic drugs are activated and exert their toxicity. Novel sesquiterpene-γ-lactones are also provided by the invention, and are designed to be linked to carrier moieties such as the peptides of the invention. Methods for treating cell proliferative disorders are also featured in the invention.
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Transesophageal magnetic resonance analysis method and apparatus (Wed, 19 Jun 2002)
A method of transesophageal magnetic resonance analysis of a patient, such as an animal or human, includes providing a loopless antenna formed from a flexible coaxial cable having an extended center conductor at the distal end thereof. A distal portion of the loopless antenna is secured within a Levin-type gastric tube. The gastric tube which receives the loopless antenna is inserted in the esophagus of the patient. A tuning, matching and decoupling circuit for the loopless antenna is employed external to the patient. The tuning, matching and decoupling circuit is electrically connected to a magnetic resonance imaging scanner. The magnetic resonance imaging scanner is employed to display an image of the aorta of the patient.
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Methods for generating hypermutable microbes (Fri, 07 Jun 2002)
Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.
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TISSUE SPECIFIC PRODRUGS (Fri, 07 Jun 2002)
The invention provides novel peptide prodrugs which contain cleavage sites specifically cleaved by prostate specific membrane antigen (PSMA). These prodrugs are useful for substantially inhibiting the non-specific toxicity of a variety of therapeutic drugs. PSMA is secreted by prostatic glandular cells. Upon cleavage of the prodrug by PSMA, the therapeutic drug are activated and exert their toxicity. Sesquiterpene-η-lactones form part of the prodrugs, and are designed to be linked to carrier moieties such as the peptides of the invention. Methods for treating cell proliferative disorders are also featured in the invention.
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Non-calcemic, antiproliferative, transcriptionally active sulfur-containing analogs of 1α, 25-dihydroxy vitamin D3 (Wed, 01 May 2002)
Novel sulfur-containing analogs of 1α,25-dihydroxy vitamin D3are provided. These analogs are synthesized in a convergent manner by joining A-ring and C,D ring fragments. Each analog with 1α,3β-substituent stereochemistry shows a pharmacologically desirable combination of high antiproliferative and high transcriptional activities in vitro and also low calcemic activity in vivo.
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ANTIVIRAL COMPOSITIONS AND METHODS OF USE (Fri, 05 Apr 2002)
Purified antiviral compounds, pharmaceutical formulations containing the compounds, and methods of use of the compounds are provided. The compositions of the invention are isolated antiviral components from plant extracts derived from, for example, Salvia milriorrhiza, that find use in the treatment of viral infections, such as by inhibiting the activity of viral integrase. Methods for isolation and purification of the antiviral compounds are additionally provided.
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Compounds for the suppression of HIV TAT transactivation (Wed, 03 Apr 2002)
The present invention reveals the isolation, purification and characterization from the creosote bush Larrea tridentata of compounds of the structural formula:<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06365787-20020402-C00001.TIF" img-content="chem" alt="embedded image"/></chemistry> where R1, R2, R3and R4are each selected from the group consisting of HO—, CH3O— and CH3(C═O)O—, provided that R1, R2, R3and R4are not each HO—0 simultaneously. Each compound is a derivative of 1,4-bis-(3,4-dihydroxyphenyl)-2,3-dimethylbutane (nordihydroquaiaretic acid, NDGA). In addition, NDGA and each derivative can be used in a method to suppress Tat transactivation of a lentivirus, including the HIV virus, in a cell by administering NDGA or a derivative of NDGA to the cell.
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PROMYOSTATIN PEPTIDES AND METHODS OF USING SAME (Fri, 08 Feb 2002)
The present invention provides substantially purified peptide portions of a promyostatin polypeptide. For example, the invention provides proteolytic fragments of a promyostatin polypeptide such as a myostatin prodomain or a mature myostatin peptide, as well as functional peptide portions a moystatin prodomain a myostatin. Also provided is a mutant promyostatin polypeptide, which is resistant to proteolytic cleavage, for example, cleavage into a myostatin prodomain and a mature myostatin peptide. The present invention also provides a polynucleotide encoding a peptide portion of a promyostatin polypeptide. In addition, antibodies that specifically bind a peptide portion of a promyostatin polypeptide are provided. The invention further provides methods of identifying a functional peptide portion of a promyostatin polypeptide.
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GROWTH DIFFERENTIATION FACTOR RECEPTORS, AGONISTS AND ANTAGONISTS THEREOF, AND METHODS OF USING SAME (Fri, 08 Feb 2002)
The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development of metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.
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A PH SENSOR SYSTEM AND METHOD FOR USING SAME (Fri, 14 Dec 2001)
A pH sensor system (10) and method capable of monitoring the pH level of a medium based on the characteristics of a chromatic pH sensitive material employed in the pH sensor system is provided. The pH sensor system includes at least a housing (12) having at least one transparent surface (14); a light sensitive circuitry (15), e.g., a LED (16) and photo-detector (18), enclosed within the housing; and, a chromatic pH sensitive material (20) overlaying at least a portion of the transparent surface having the characteristic of becoming saturated when an ambient pH level reaches a predetermined level such that the light sensitive circuitry detects a different intensity of incident light when the chromatic pH sensitive material is saturated than when the chromatic pH sensitive material is not saturated. As the pH level of the medium, e.g., concrete, storage tanks containing chemical reagents, etc., to be monitored steadily decreases, the pH sensitive material on the transparent surface of the housing will gradually become saturated with hydrogen ions and colorless. When the pH level reaches the predetermined level, the pH sensitive material will be unable to absorb any light being emitted from the LED such that the light is reflected back to the photo-detector.
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BIOLOGICALLY USEFUL POLYPHOSPHATES (Fri, 07 Dec 2001)
The present invention provides biodegradable polymers, polymer compositions, particles composed thereof and methods of using same for the controlled release of a biologically active substance to a specified tissue or cells. Preferred polymers include biodegradable, amphiphilic polyphosphates which are capable of complexing one or more biologically active substances. Preferred methods include the controlled release of biologically active substances and gene therapy using polymers and nanoparticles composed thereof.
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BISUBSTRATE INHIBITORS OF KINASES (Fri, 28 Sep 2001)
Protein kinase inhibitors have applications as anti-cancer therapeutic agents and biological tools in cell signalling. Potent and selective bisubstrate inhibitors for the insulin receptor tyrosine kinase are based on a phosphoryl transfer mechanism involving a dissociative transistion state. One such inhibitor is synthesized by linking ATPηS to a peptide substrate analog via a two-carbon spacer. The compound is a high-affinity competitive inhibitor against both nucleotide and peptide substrate and shows a slow off-rate. A crystal structure of this inhibitor bound to the tyrosine kinase domain of the insulin receptor confirms the key design features inspired by a dissociative transition state, and reveal that the linker takes part in the octahedral coordination of an active site Mg2+ ion.
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METHODS FOR GENERATING HYPERMUTABLE YEAST (Fri, 31 Aug 2001)
Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.
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METHODS FOR GENERATING HYPERMUTABLE BACTERIA (Fri, 17 Aug 2001)
Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficinecy and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch reparir activity to the bacteria.
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Tissue specific prodrug (Wed, 25 Jul 2001)
The invention provides novel peptide prodrugs which contain cleavage sites specifically cleaved by prostate specific antigen (PSA). These prodrugs are useful for substantially inhibiting the non-specific toxicity of a variety of therapeutic drugs. PSA is secreted by prostatic glandular cells. Upon cleavage of the prodrug by PSA, the therapeutic drugs are activated and exert their toxicity. Novel sesquiterpene-γ-lactones are also provided by the invention, and are designed to be linked to carrier moieties such as the peptides of the invention. Methods for treating cell proliferative disorders are also featured in the invention.
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Method for prediction of binding targets and the design of ligands (Fri, 04 May 2001)
A computer-based method for the identification of binding targets in proteins and other macromolecules is provided. More particularly, the invention includes an algorithm aimed at predicting binding targets in proteins. This algorithm, named Woolford, requires knowledge of the high resolution structure of the protein but no knowledge of the location or identity of natural binding sites or ligands. Binding targets in the protein are identified and classified according to their expected optimal affinities. Binding targets can be located at the protein surface or at internal surfaces that become exposed as a result of partial unfolding, conformational changes, subunit dissociation, or other events. The entire protein is mapped according to the binding potential of its constituent atoms. Once binding targets are identified, optimal ligands are designed and progressively built by the addition of individual atoms or chemical groups that complement structurally and energetically the selected target. This algorithm is expected to have significant applications in structure-based drug design since it allows: 1) identification of binding targets in proteins; 2) identification of additional targets if the primary target is known; 3) design of ligand molecules with optimal binding affinities for the selected target; and 4) refinement of lead compounds by defining the location and nature of chemical groups for optimal binding affinity.
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Method for the prediction of binding targets and the design of ligands (Wed, 02 May 2001)
A computer-based method for the identification of binding targets in proteins and other macromolecules. More particularly, the invention includes an algorithm aimed at predicting binding targets in proteins. This algorithm, named Woolford, requires knowledge of the high resolution structure of the protein but no knowledge of the location or identity of natural binding sites or ligands. Binding targets in the protein are identified and classified according to their expected optimal affinities. Binding targets can be located at the protein surface or at internal surfaces that become exposed as a result of partial unfolding, conformational changes, subunit dissociation, or other events. The entire protein is mapped according to the binding potential of its constituent atoms. Once binding targets are identified, optimal ligands are designed and progressively built by the addition of individual atoms that complement structurally and energetically the selected target.
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CHIMERIC IMMUNOGENIC COMPOSITIONS AND NUCLEIC ACIDS ENCODING THEM (Fri, 27 Apr 2001)
The invention provides chimeric nucleic acids encoding a chimeric polypeptide, constructs for expressing these polypeptides both in vitro and in vivo, isolated chimeric polypeptides, pharmaceutical compositions and methods of making and using these compositions. These compositions and methods are particularly useful for stimulating or enhancing the immunogenicity of a selected antigen or stimulating or enhancing a cellular immune response specific for that antigen. The nucleic acid of the invention comprises a first polypeptide domain comprising a carboxy terminal fragment of a heat shock protein (HSP), an Flt-3 ligand (FL), a cytoplasmic translocation domain of a Pseudomonas exotoxin A (ETA dII), or a granulocyte-macrophage-colony stimulating factor (GM-CSF) sequence, and a second polypeptide domain comprising an antigenic polypeptide.
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METHODS FOR IDENTIFYING AN AGENT THAT CORRECTS DEFECTIVE PROTEIN FOLDING (Fri, 30 Mar 2001)
The present invention relates to a method of identifying an agent that corrects a defective three dimensional conformation of a polypeptide, by contacting in a cell-free system a peptide portion of the polypeptide with a test agent, wherein the peptide is representative of a region of the polypeptide containing the defective conformation; and determining that the test agent decreases the defective conformation of the peptide. The present invention also relates to a virtual representation of a peptide portion of a polypeptide, wherein the peptide is representative of a region of a polypeptide having a defective three dimensional conformation.
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IMPROVEMENT OF CLAVULANIC ACID PRODUCTION (Fri, 23 Mar 2001)
The invention methods for the enhancement of clavulanic acid production. In particular, the invention provides a method for increasing the production of clavulanic acid by: gene dosage with orf2 from the clavulanic acid biosynthetic pathway in Streptomyces clavuligerus; and by manipulation of fermentation conditions, especially the concentration of DG3P, a substrate of N2(carboxyethyl)arginine synthase, the protein encoded by orf2. A method for preparing N2(carboxyethyl)arginine synthase is also provided, as is an assay for identifying its substrates.
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GROWTH DIFFERENTIATION FACTOR-8 NUCLEIC ACID AND POLYPEPTIDE FROM AQUATIC SPECIES, AND TRANSGENIC AQUATIC SPECIES (Fri, 23 Feb 2001)
A transgenic non-human aquatic organisms, such as piscine, crustacean, mollusks, and the like, having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the aquatic organism is disclosed. Also disclosed are methods for making such organisms and nucleic acid sequences encoding GDF-8 polypeptides from such aquatic organisms.
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Magnetic resonance imaging method and apparatus and method of calibrating the same (Wed, 14 Feb 2001)
The invention provides a method of magnetic resonance imaging. A magnetic resonance imaging apparatus having a plurality of gradient axes is employed. A plurality of imaging planes are employed with respect to the gradient axes. A plurality of gradient referencing pre-scans are executed for the imaging planes to provide a plurality of calibration correction values for the imaging planes. A specimen is employed with respect to the gradient axes. An imaging plane is selected with respect to the specimen, and a main magnetic field is established with respect to the specimen. Radio frequency pulses are applied to the specimen to produce magnetic resonance signals. The calibration correction values for the selected imaging plane are employed to adjust a plurality of gradient waveforms. The gradient waveforms are output as a plurality of magnetic field gradients with respect to the gradient axes. Magnetic resonance information is acquired from the magnetic resonance signals corresponding to the radio frequency pulses. The magnetic resonance information is employed to display an image of the specimen. Associated apparatus and calibration method are also disclosed.
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METHOD OF MAGNETIC RESONANCE IMAGING AND SPECTROSCOPIC ANALYSIS AND ASSOCIATED APPARATUS (Fri, 02 Feb 2001)
The invention provides a method for magnetic resonance imaging, and spectroscopic analysis of a specimen which includes positioning the specimen within a main magnetic field, introducing an antenna having a non-loop antenna portion (22) in close proximity to the specimen. Radio frequency pulses are provided to the region of interest to excite magnetic resonance signals. Gradient magnetic pulses are applied to the region of interest with the antenna receiving magnetic resonance signals, and emitting responsive output signals. A processor processes the responsive output signals to provide image information for display in a desired manner. The method in the preferred form employs a flexible antenna. The method in another preferred form involves employing an impedance matching circuit (30) electrically interposed between the non-loop antenna, and the processor to enhance radio frequency power transfer; and magnetic resonance signal to noise ratio from the non-loop antenna (22) to the processor.
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Compounds for stimulating nerve growth (Wed, 06 Sep 2000)
Compounds which can stimulate neuronal growth by inhibiting the neuronal inhibitory activity of myelin-associated glycoprotein (MAG), and a method of using the compounds for stimulating neuronal growth are provided. The invention further provides a method of identifying compounds which inhibit myelin-associated glycoprotein inhibition of axonal outgrowth of injured nerve cells. The method involves contacting the compound with myelin-associated glycoprotein under conditions which allow myelin-associated glycoprotein and the compound to bind and detecting the binding.
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OLFACTORY RECEPTOR EXPRESSION LIBRARIES AND METHODS OF MAKING AND USING THEM (Fri, 23 Jun 2000)
This invention provides novel librairies of olfactory receptor odorant/ligand-binding domains and methods of making and using them. The invention also provides libraries of vectors and cells comprising these nucleic acid constructs. The compositions and methods of the invention are used to identify novel ligand-binding domains for olfactory neuron odorant receptors and their ligands. Thus, the compositions and methods of the invention can be used to generate novel odorants, to screen for toxic odorants, or to manipulate an animal's oflactory response.
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MINIATURE MAGNETIC RESONANCE CATHETER COILS AND RELATED METHODS (Fri, 26 May 2000)
An electrically insulate generally rectangular flexible circuit board (200) has a first surface (202) on which an electrically conductive path containing a first coil (204) consisting of a first coil segment (210), a generally parallel second coil segment (212), and an end electrically connecting portion (214) are provided. A first capacitor (220), and a second capacitor (222) are provided in the circuit.
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Method and apparatus for determining or imaging longitudinal spin relaxation time or producing images which substantially reflect longitudinal spin relaxation time contrast (Wed, 17 May 2000)
The invention provides a method of determining longitudinal spin relaxation time or imaging longitudinal spin relaxation time or producing images which substantially reflect longitudinal spin relaxation time contrast. The method includes establishing a main magnetic field with respect to a specimen and employing a plurality of magnetic resonance (MR) gradients to spatially encode magnetic resonance signals from at least one position within the specimen. A plurality of pairs of pulses including a first radio frequency (RF) pulse having a first predetermined flip-angle and second RF pulse having a second predetermined flip-angle, which is different from the first predetermined flip-angle, are employed. One of the first RF pulses is applied to the specimen to produce a corresponding first MR signal and first MR information is acquired from the first MR signal corresponding to the first RF pulse. The first MR signal is dephased and one of the second RF pulses is applied to the specimen to produce a corresponding second MR signal. Second MR information is acquired from the second MR signal corresponding to the second RF pulse and the first and second MR information is delivered to a processor. The processor determines a ratio from the first and second MR information and determines the longitudinal spin relaxation time from the ratio. Associated apparatus is also disclosed.
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TRANSESOPHAGEAL MAGNETIC RESONANCE ANALYSIS METHOD AND APPARATUS (Fri, 12 May 2000)
A method of trans-esophageal magnetic resonance analysis of a patient, such as an animal or human, includes providing a non-loop antenna (84), such as a coil or solenoid coil. The non-loop antenna is received within a Levin-type gastric tube (62). The gastric tube which receives the non-loop antenna is inserted in the esophagus of the patient. A tuning, matching and de-coupling circuit (12) is electrically connected to a magnetic resonance imaging scanner (18). The magnetic resonance imaging scanner (18) is employed to provide magnetic resonance imaging or spectroscopic analysis of an intra-Thoracic structure, such as the aorta, of the patient.
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Method of identifying compounds affecting hedgehog cholesterol transfer (Wed, 03 May 2000)
The present invention provides two novel polypeptides, referred to as the "N" and "C" fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G.sup..dwnarw. CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
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HOMER INTERACTING PROTEINS (Fri, 03 Mar 2000)
A method is provided for identifying a compound that modulates a cellular response associated with Homer and mediated by a cell-surface or an intracellular receptor. A method is further provided for identifying a compound that modulates receptor-activated calcium mobilization associated with Homer. A method is provided for identifying a compound that inhibits Homer protein activity based on the crystal structure coordinates of Homer protein binding domain. A method is also provided for identifying a compound that affects the formation of cell-surface receptors into clusters. Also provided are nucleic acids encoding Homer proteins as well as Homer proteins, and Homer-interacting proteins.
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COMPOUNDS FOR ALTERING CELL SURFACE SIALIC ACIDS AND METHODS OF USE THEREFOR (Fri, 18 Feb 2000)
The present invention is based on the identification of compounds in the form of biosynthetic precursors which can be used to modulate neuronal growth, inhibit cellular entry by pathogens and modulate immune responses. The invention further describes acylated mannosamines, and derivatives thereof, which can be used to alter the sialic acid substituents of sialoglycoconjugates.
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Compounds for stimulating nerve growth (Wed, 06 Oct 1999)
Compounds which can stimulate neuronal growth by inhibiting the neuronal inhibitory activity of myelin-associated glycoprotein (MAG), and a method of using the compounds for stimulating neuronal growth are provided. The invention further provides a method of identifying compounds which inhibit myelin-associated glycoprotein inhibition of axonal outgrowth of injured nerve cells. The method involves contacting the compound with myelin-associated glycoprotein under conditions which allow myelin-associated glycoprotein and the compound to bind and detecting the binding. -GOVT PAR This invention was made with government support under NIH Grant/Control number HD14010 awarded by the National Institutes of Health. The government nay have certain rights in this invention.
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Method of magnetic resonance imaging and spectroscopic analysis and associated apparatus employing a loopless antenna (Wed, 28 Jul 1999)
The invention provides a method for magnetic resonance imaging and spectroscopic analysis of a specimen which includes positioning the specimen within a main magnetic field and introducing an antenna having a loopless antenna portion in close proximity to the specimen. Radio frequency pulses are provided to the region of interest to excite magnetic resonance signals, gradient magnetic pulses are applied to the region of interest with the antenna receiving magnetic resonance signals and emitting responsive output signals. A processor processes the responsive output signals to provide image information for display in a desired manner. The method in a preferred form involves employing a flexible antenna. The method in another preferred form involves employing an impedance matching circuit electrically interposed between the loopless antenna and the processor to enhance radio frequency power transfer and magnetic resonance signal-to-noise ratio from the loopless antenna to the processor. The method may be used on a wide variety of specimens and in a preferred use is introduced into small blood vessels of a patient to facilitate determination of atherosclerotic plaque. Medical intervention procedures, such as plaque removal, may be employed generally simultaneously with the imaging of the present invention. Corresponding apparatus and magnetic resonance antenna assembly are provided.
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Oligonucleoside alkyl or arylphosphonate derivatives capable of crosslinking with or cleaving nucleic acids (Wed, 16 Jun 1999)
A composition for inactivating a target nucleic acid which comprises an oligonucleoside alkyl or arylphosphonate analogue which is complementary to the sequence of the target nucleic acid and includes a functional group which reacts with the target nucleic acid to render the target nucleic acid inactive or nonfunctional. -GOVT PAR The work disclosed herein was supported by grants from the National Institute of Health and the Department of Energy.
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Anti-inflammatory compounds (Wed, 16 Jun 1999)
This invention relates to the novel pharmaceutical compositions of Formulas (I) and (II) each of which comprises a compound of Formula (I) or (II) and a pharmaceutically acceptable diluent or carrier. This invention also relates to a method of treating or reducing inflammation in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound or composition of Formula (I) or (II).
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ANTIMICROBIAL COMPOUNDS (Fri, 05 Mar 1999)
This invention provides methods for treating a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R-SOn-Z-CO-Y, where R is an alkyl group having 6-20 carbons; Z is a radical selected from -CH2-, -O-, and -NH-, two of these radicals coupled together, or -CH2=CH2-; Y is -NH2, O-CH2-C6H5, -CO-CO-O-CH3, or O-CH3; and n is 1 or 2. It has been discovered that these compounds inhibit growth of microbial cells which synthesize α-substitued, β-hydroxy fatty acids, particularly corynemycolic acid, nocardic acid, and mycolic acid. These compounds may be used to inhibit growth of mycobacterial cells, such as Mycobacterium tuberculosis, drug-resistant M. tuberculosis, M. avium intracellulare, and M. leprae.
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COMPUTER METHOD UTILIZING FREE ENERGY CALCULATIONS FOR LIGAND DESIGN AND THE PREDICTION OF BINDING TARGETS (Fri, 04 Dec 1998)
A computer-based method for the identification of binding targets in proteins and other macromolecules. More particularly, the invention includes an algorithm aimed at predicting binding targets in proteins. This algorithm, named Woolford, requires knowledge of the high resolution structure of the protein but no knowledge of the location or identity of natural binding sites or ligands. Binding targets in the protein are identified and classified according to their expected optimal affinities. Binding targets can be located at the protein surface or at internal surfaces that become exposed as a result of partial unfolding, conformational changes, subunit dissociation, or other events. The entire protein is mapped according to the binding potential of its constituent atoms. Once binding targets are identified, optimal ligands are designed and progressively built by the addition of individual atoms that complement structurally and energetically the selected target. This algorithm is expected to have significant applications in structure-based drug design since it allows: 1) identification of binding targets in proteins; 2) identification of additional targets if the primary target is known; 3) design of ligand molecules with optimal binding affinities for the selected target; and 4) refinement of lead compounds by defining the location and nature of chemical groups for optimal binding affinity.
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MAGNETIC RESONANCE METHOD AND APPARATUS FOR DETERMINING OR IMAGING LONGITUDINAL SPIN RELAXATION TIME OR PRODUCING IMAGES WHICH SUBSTANTIALLY REFLECT LONGITUDINAL SPIN RELAXATION TIME CONTRAST (Fri, 27 Nov 1998)
The invention provides a method of determining longitudinal spin relaxation time or imaging longitudinal spin relaxation time or producing images which substantially reflect longitudinal spin relaxation time contrast. The method includes establishing a main magnetic field with respect to a specimen and employing a plurality of magnetic resonance (MR) gradients to spatially encode magnetic resonance signals from at least one position within the specimen. A plurality of pairs of pulses including a first radio frequency (RF) pulse having a first predetermined flip-angle and second RF pulse having a second predetermined flip-angle, which is different from the first predetermined flip-angle, are employed. One of the first RF pulses is applied to the specimen to produce a corresponding first MR signal and first MR information is acquired from the first MR signal corresponding to the first RF pulse. The first MR signal is dephased and one of the second RF pulses is applied to the specimen to produce a corresponding second MR signal. Second MR information is acquired from the second MR signal corresponding to the second RF pulse and the first and second MR information is delivered to a processor. The processor determines a ratio from the first and second MR information and determines the longitudinal spin relaxation time from the ratio. Associated apparatus is also disclosed.
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TISSUE SPECIFIC PRODRUG (Fri, 27 Nov 1998)
The invention provides novel peptide prodrugs which contain cleavage sites specifically cleaved by prostate specific antigen (PSA). These prodrugs are useful for substantially inhibiting the non-specific toxicity of a variety of therapeutic drugs. PSA is secreted by prostatic glandular cells. Upon cleavage of the prodrug by PSA, the therapeutic drugs are activated and exert their toxicity. Novel sesquiterpene-η-lactones are also provided by the invention, and are designed to be linked to carrier moieties such as the peptides of the invention. Methods for treating cell proliferative disorders are also featured in the invention.
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Antiproliferative vitamin D.sub.3 hybrids (Wed, 04 Nov 1998)
Vitamin D.sub.3 analogues of formula ##STR1## wherein R represents a 1-hydroxyalkyl group or 1-fluoroalkyl group in a trans- configuration with a 3-hydroxyl group on the A ring and R.sup.2 represents the substituents completing a vitamin D.sub.3 analogue. These novel compounds are potent anti-proliferative substances with activities comparable to that of calcitriol but with vitamin D.sub.3 receptor binding ratings of less than 10.sup.-3 compared to that of calcitriol. -GOVT PAR The invention described and claimed herein was made in part under a grant from the National Institutes of Health. The Government has certain rights in the invention.
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Endoperoxides useful as antiparasitic agents (Wed, 07 Oct 1998)
The present invention relates to novel biologically-active organic peroxides and to novel uses of both known and new organic peroxides. More specifically, this invention details organic endoperoxides having antiparasitic activity, methods for their preparation and methods for treating malaria and cerebral toxoplasmic encephalitis with the organic endoperoxides. -GOVT PAR The invention described and claimed herein was made in part under a grant from the National Institutes of Health, NIH-AI-34885. The Government has certain rights in the invention.
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METHOD OF TREATING A LACTATE DEHYDROGENASE-A (LDH-A)-ASSOCIATED DISORDER (Fri, 28 Aug 1998)
Methods of inhibiting proliferation of cells associated with a cell proliferative disorder by contacting the cells with a glucose antimetabolite where the cells have reduced levels of a member of the anti-apoptotic gene family, such as Bcl-2 are provided. Methods for identifying compounds which inhibit such cells are also disclosed.
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NOVEL HEDGEHOG-DERIVED POLYPEPTIDES (Fri, 17 Jul 1998)
The present invention provides two novel polypeptides, referred to as the 'N' and 'C' fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G↓CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
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Method of internal magnetic resonance imaging and spectroscopic analysis and associated apparatus (Wed, 24 Dec 1997)
The invention provides a method for magnetic resonance imaging and spectroscopic analysis of the interior of a specimen which includes positioning the specimen within a main magnetic field, introducing an invasive probe having an elongated receiver coil into or adjacent to the specimen with the coil having at least one pair of elongated electrical conductors, preferably, generally parallel to each other disposed within a dielectric material and having a pair of ends electrically connected to each other. RF pulses are provided to the region of interest to excite magnetic resonance signals, gradient magnetic pulses are applied to the region of interest with the receiver coil receiving magnetic resonance signals and emitting responsive output signals which may be processed by a computer to provide image information for display in a desired manner. The method in a preferred form involves employing a flexible receiver coil which has uniform sensitivity along the coil and may be operated even when the magnetic resonance signal is in an oblique position. Tuning capacitance may be distributed along the length of the coil and/or a Faraday screen provided to minimize dielectric losses between the coil and the surrounding material of the specimen. The method may be used on a wide variety of specimens and in a preferred use is introduced into small blood vessels of a patient to facilitate determination of atherosclerotic plaque. Medical intervention procedures, such as plaque removal, may be employed generally simultaneously with the imaging of the present invention. Corresponding apparatus is provided.
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VITAMIN D3 ANALOGUES (Fri, 21 Nov 1997)

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METHOD OF MAGNETIC RESONANCE IMAGING AND SPECTROSCOPIC ANALYSIS AND ASSOCIATED APPARATUS (Fri, 31 Oct 1997)
The invention provides a method for magnetic resonance imaging and spectroscopic analysis of a specimen which includes positioning the specimen within a main magnetic field and introducing an antenna having a loopless antenna portion in close proximity to the specimen. Radio frequency pulses are provided to the region of interest to excite magnetic resonance signals, gradient magnetic pulses are applied to the region of interest with the antenna receiving magnetic resonance signals and emitting responsive output signals. A processor processes the responsive output signals to provide image information for display in a desired manner. The method in a preferred form involves employing a flexible antenna. The method in another preferred form involves employing an impedance matching circuit electrically interposed between the loopless antenna and the processor to enhance radio frequency power transfer and magnetic resonance signal-to-noise ratio from the loopless antenna to the processor. The method may be used on a wide variety of specimens and in a preferred use is introduced into small blood vessels of a patient to facilitate determination of atherosclerotic plaque. Medical intervention procedures, such as plaque removal, may be employed generally simultaneously with the imaging of the present invention. Corresponding apparatus and magnetic resonance antenna assembly are provided.
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Hierarchical protein folding prediction (Wed, 22 Oct 1997)
A computer-assisted method for predicting the three-dimensional structure of a protein fragment from its amino acid sequence. A hierarchic procedure ascends the folding hierarchy in discrete stages with concomitant accretion of structure. The protein fragment may be represented by a simplified geometry and folds under the influence of a primitive energy function.
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Endoperoxides useful as antiparasitic agents (Wed, 01 Oct 1997)
The present invention relates to novel biologically-active organic peroxides and to novel uses of both known and new organic peroxides. More specifically, this invention details organic endoperoxides having antiparasitic activity, methods for their preparation and methods for treating malaria and cerebral toxoplasmic encephalitis with the organic endoperoxides. -GOVT PAR The invention described and claimed herein was made in part under a grant from the National Institutes of Health, NIH-AI-34885. The Government has certain rights in the invention.
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Inhibition of inflammatory lipid mediators (Wed, 03 Sep 1997)
Coenzyme A-independent transacylase is required for the release of free arachidonic acid, and the production of arachidonic acid metabolites and platelet activation factor. Blocking of this enzyme inhibits the production of these inflammatory mediators and will be of therapeutic utility in a broad range of allergic and inflammatory diseases and disorders. Compounds are described herein which inhibit the action of CoA-IT and are therefore useful in the treatment of disease states caused thereby.
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Compounds for the suppression of HIV Tat transactivation (Wed, 03 Sep 1997)
The present invention reveals the isolation, purification and characterization from the creosote bush Larrea tridentata of compounds of the structural formula: ##STR1## where R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of HO--, CH.sub.3 O-- and CH.sub.3 (C.dbd.O)O--, provided that R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are not each HO-- simultaneously. Each compound is a derivative of 1,4-bis-(3,4-dihydroxyphenyl)-2,3-dimethylbutane (nordihydroquaiaretic acid, NDGA). In addition, NDGA and each derivative can be used in a method to suppress Tat transactivation of a lentivirus, including the HIV virus, in a cell by administering NDGA or a derivative of NDGA to the cell.
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Synthesis of high mannose glycopolymers (Wed, 03 Sep 1997)
Neoglycoconjugates and new intermediates for the synthesis thereof are synthesized by use of Endo-.beta.-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) in a medium containing an organic solvent.
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CoA-IT and PAF inhibitors (Wed, 16 Jul 1997)
Coenzyme A-independent transacylase is required for the release of free arachidonic acid, and the production of arachidonic acid metabolites and platelet activation factor. Blocking of this enzyme inhibits the production of these inflammatory mediators and will be of therapeutic utility in a broad range of allergic and inflammatory diseases and disorders. Compounds are described herein which inhibit the action of CoA-IT and are therefore useful in the treatment of disease states caused thereby.
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INHIBITION OF FATTY ACID SYNTHASE AS A MEANS TO REDUCE ADIPOCYTE MASS (Fri, 30 May 1997)
Weight loss was noted in nude mice treated with cerulenin, a non-competitive inhibitor of FAS. Sustained reduction of adipocyte mass in humans without toxicity would significantly impact disease prevention worldwide. Aside from psychological and self-esteem improvement, weight loss via reduction of adipocyte mass may: (1) ameliorate hyperglycemia associated with non-insulin-dependent diabetes mellitus thereby reducing diabetic complications such as arterial disease, blindness, cataracts, etc., (2) reduce hypertension, (3) reduce risk of coronary artery vascular disease and stroke, and (4) reduce the risk of other complications of massive obesity such as osteoarthritis, surgical complications, etc. There is also potential use in livestock and poultry to reduce the saturated fat content of meat products. Therefore FAS inhibitors are disclosed herein as novel agents for weight reduction. A family of compounds (η-substituted-α-methylene-β-carboxy-η-butyrolactones) whose synthesis was based on the cerulenin motif is shown herein to inhibit fatty acid synthesis, inhibit growth in certain susceptible tumor cells, and induce weight loss.
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Living cells microencapsulated in a polymeric membrane having two layers (Wed, 16 Apr 1997)
A biocompatible microcapsule containing living cells encapsulated in a membrane is disclosed. The membrane is a complex formed by the cohesion of two polymer layers. An inner layer comprises a substrate biopolymer and an outer layer comprises a synthetic polyelectrolyte having an electrolytic charge opposite that of the substrate biopolymer. Droplets of a solution of substrate biopolymer containing a suspension of living cells can be added to a solution comprising the synthetic polyelectrolyte to form the encapsulates. The membrane is formed by the cohesion of the oppositely-charge polymer layers to form a complex of substrate biopolymer and synthetic polyelectrolyte. Preferably, the inner layer contains a cationic biopolymer, such as collagen modified to have a pKI of 9, or an anionic biopolymer such as esterified or modified hyaluronic acid. Further, the membrane is permeable to materials which are able to maintain normal metabolic functions of bioactive cells which are encapsulated in the inner layer of the membrane. In addition the membrane is permeable to products released by the bioactive cells and impermeable to agents of the immune system which are responsible for immunological reactions that result in an immune rejection of bioactive cells and products thereof.
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TUMOR TYPE II HEXOKINASE TRANSCRIPTION REGULATORY REGIONS (Fri, 07 Feb 1997)
The present invention relates to a tumor promoter involved in the regulation of glucose catabolism in neoplastic tissues. In particular, this promoter region contains numerous response elements that are involved in regulation of transcription of the Type II hexokinase gene in tumor cells. Such elements are of value for diagnostic and therapeutic applications, such as in controlling tumor growth. In addition, the entire promoter region (about 4.3 kbp) or regulatory segments (response elements) contained therein may be used for expression of naturally-occurring or foreign proteins. Such proteins may be derived from mammalian cells and expressed under the control of transcription factors that bind to specific response elements within the tumor Type II hexokinase promoter. Finally, the promoter is useful in gene therapeutic approaches to diseases including diabetes and cancer.
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USE OF SPECIFIC ACPA DERIVATIVE (NPC-17742) FOR THE TREATMENT OF ISCHEMIA (Fri, 20 Dec 1996)
A method of treating a mammal for a disease selected from the group consisting of focal ischemia, global ischemia and neuronal cell ischemia associated with spinal injuries and head trauma; said method comprising administering to the mammal a therapeutically effective amount of the 2R, 4R, 5S isomer of the compound 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid or any pharmaceutically acceptable salt or hydrate of the isomer wherein the isomer or salt or hydrate of the isomer is substantially free from other stereoisomers of the compound.
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METHOD OF INTERNAL MAGNETIC RESONANCE IMAGING AND SPECTROSCOPIC ANALYSIS AND ASSOCIATED APPARATUS (Fri, 06 Dec 1996)
The invention provides a method for magnetic resonance imaging and spectroscopic analysis of the interior of a specimen (4) which includes positioning the specimen within a main magnetic field, introducing an invasive probe having an elongated receiver coil (22) into or adjacent to the specimen with the coil having at least one pair of elongated electrical conductors (24, 26), preferably, generally parallel to each other disposed within a dielectric material (30) and having a pair of ends electrically connected to each other (32). The method involves employing a flexible receiver coil which has uniform sensitivity along the coil. Tuning capacitance may be distributed along the length of the coil and/or a Faraday screen provided to minimize dielectric losses between the coil and the surrounding material of the specimen. In a preferred use the probe is introduced into small blood vessels of a patient to facilitate determination of atherosclerotic plaque. A corresponding apparatus is provided.
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SYNTHESIS OF GLYCOPOLYMERS (Fri, 29 Nov 1996)
Neoglycoconjugates and new intermediates for the synthesis thereof are synthesized by use of Endo-β-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) in a medium containing organic solvent. Such methods allow for the synthesis of novel glycoconjugates including high mannose glycopolymers.
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HIERARCHICAL PROTEIN FOLDING PREDICTION (Fri, 29 Nov 1996)
A computer-assisted method (32, 34, 36, 38) for predicting a three-dimensional structure of a protein fragment from its amino acid sequence. A hierarchic procedure ascends the folding hierarchy in discrete stages with concomitant accretion of structure. The protein fragment may be represented by a simplified geometry and folds under the influence of a primitive energy function.
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INTRACELLULAR MARKER FOR PURIFICATION OF STEM CELLS (Fri, 22 Nov 1996)
An intracellular enzyme, cytosolic aldehyde dehydrogenase, expressed at high levels in primitive stem cells, appears to play an important role in allowing these cells to be resistant to cyclophosphamide. A fluorescent cell-permeable, non-polar aldehyde oxidized intracellularly by ALDH is used to identify human stem cells that are then isolated. For instance, a non-polar aldehyde, such as dansyl aminoacetaldehyde, serves as a substrate for an intracellular ALDH. Bone marrow progenitor stem cells treated with DAAA proliferate normally. Bone marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA and sorted based upon dansyl fluorescence, preferably using an automated fluorescence cell sorting technique such as FACS, are substantially enriched for pluripotent hematopoietic progenitor stem cells. By this method, an enriched cellular composition comprising human lymphohematopoietic stem cells can be obtained. The cell population is capable of self-regeneration in a co-culture medium and of differentiation into various lymphoid hematopoietic lineages.
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