SUBSTITUTED N-(3-(PYRIMIDIN-4-YL)PHENYL)ACRYLAMIDE ANALOGS AS TYROSINE RECEPTOR KINASE BTK INHIBITORS (Fri, 11 Apr 2014)
In one aspect, the invention relates to substituted N-(3-(pyrimidin-4- yl)phenyl)acrylamide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the BTK kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the BTK kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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SUBSTITUTED N-(3-(PYRIMIDIN-4-YL)PHENYL)ACRYLAMIDE ANALOGS AS TYROSINE RECEPTOR KINASE BTK INHIBITORS (Fri, 11 Apr 2014)
In one aspect, the invention relates to substituted N-(3-(pyrimidin-4- yl)phenyl)acrylamide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the BTK kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the BTK kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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METHODS AND COMPOSITIONS RELATED TO NEUROACTIVE THIAZOLINE COMPOUNDS (Fri, 17 Jan 2014)
<p id="p-0001" num="0000">In one aspect, the invention relates to compounds having a general structure: and methods of using same to modulate calcium release. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.</p>
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Paclitaxel trihydrates and methods of making thereof (Fri, 06 Dec 2013)
<p id="p-0001" num="0000">Novel paclitaxel trihydrates. The paclitaxel trihydrates described herein are obtained by recrystallizing paclitaxel from a water/alcohol solution. Such recrystallization is known in the art to yield the one previously known paclitaxel crystalline trihydrate polymorph. Formation of the novel paclitaxel trihydrates described herein is induced by subjecting paclitaxel trihydrate crystals to an elevated pressure. As evidenced by NMR spectra, the novel paclitaxel trihydrates described herein have three-dimensional structures and/or water coordination geometry structures that are distinct from any previously known paclitaxel trihydrate.</p>
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COMPOSITIONS AND METHODS FOR PEPTIDE EXPRESSION AND PURIFICATION USING A TYPE lll SECRETION SYSTEM (Fri, 06 Dec 2013)
Disclosed are compositions and methods for expressing and purifying a peptide of interest using a Flagellar Type III secretion system. Disclosed are nucleic acid sequences that contain a FigM nucleic acid sequence, a cleavage site, and a nucleic acid sequence of interest. Also disclosed are polypeptides that contain FigM, a cleavage site and a peptide of interest. Methods of producing polypeptides that have FigM, a cleavage site and a peptide of interest are provided.
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COMPOUNDS WITH TRPV4 ACTIVITY, COMPOSITIONS AND ASSOCIATED METHODS THEREOF (Fri, 15 Nov 2013)
Compounds, compositions and methods useful for treating ocular diseases are provided. In particular, antagonists of TRPV4, their synthesis, pharmaceutical compositions thereof and methods of treating ocular diseases such as glaucoma, are disclosed. Compounds of the invention include N-(3-(trifluoromethyl)phenyl )-2-methyl-1-(3-morpholinopropyl )-5-phenyl-1 H-pyrrole-3-carboxamide, as well as other 2-phenyl-pyrrole carboxamide derivates and indole carboxamide derivatives.
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OZONATION CONVERSION OF HEAVY HYDROCARBONS FOR RESOURCE RECOVERY (Fri, 08 Nov 2013)
<p id="p-0001" num="0000">A method for upgrading heavy hydrocarbons into more usable hydrocarbon products is provided. The method provides for the steps of adding heavy hydrocarbons to a solvent system to form a reaction medium, and ozonating the reaction medium with an ozone containing gas to provide ozonation products. The solvent system can include a first solvent that solubilizes at least a portion of the heavy hydrocarbons and a reactive solvent which reacts with ozonation intermediates. Reactive solvent is maintained at concentrations sufficient to decompose ozonation intermediates.</p>
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APPLICATIONS OF PARTIALLY AND FULLY SULFATED HYALURONAN (Fri, 16 Aug 2013)
<p id="p-0001" num="0000">Described herein is the use of partially and fully sulfated hyaluronan or the pharmaceutically acceptable salt or ester thereof for therapeutic and cosmetic applications as well as the treatment of a number of systemic, dermatological, periodontal, ophthalmic, and urological inflammatory diseases.</p>
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SUBSTITUTED 1H-INDAZOL-1-OL ANALOGS AS INHIBITORS OF BETA CATENIN/TCF PROTEIN-PROTEIN INTERACTIONS (Fri, 16 Aug 2013)
In one aspect, the invention relates to substituted lH-benzo[d][l,2,3]triazol-l-ol analgoues, derivatives thereof, and related compound; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders, e.g. various tumors and cancers, associated with β-catenin/Tcf protein- protein interaction dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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ADHESIVE COMPLEX COACERVATES AND METHOD OF MAKING AND USING THEREOF (Fri, 26 Jul 2013)
<p id="p-0001" num="0000">Described herein is the synthesis of adhesive complex coacervates and their use thereof. The adhesive complex coacervates are composed of a mixture of one or more polycations and one or more polyanions. The polycations and polyanions in the adhesive complex coacervate are crosslinked with one another by covalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applications. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. They have numerous biological applications as bioadhesives and drug delivery devices and are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.</p>
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THE USE OF ALKYLATED SEMI-SYNTHETIC GLYCOSAMINOGLYCOSAN ETHERS FOR THE TREATMENT OF DENTAL DISORDERS (Fri, 26 Jul 2013)
<p id="p-0001" num="0000">Described herein are methods for treating a dental disorder in a subject comprising administering to the subject an effective amount of a modified hyaluronan or a pharmaceutically acceptable salt or ester thereof, wherein said hyaluronan or its pharmaceutically acceptable salt or ester comprises at least one sulfate group and the primary C-6 hydroxyl proton of at least one N-acetyl-glucosamine residue is substituted with a C<sub>1</sub>-C<sub>10 </sub>unsubstituted alkyl group or fluoroalkyl group.</p>
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HIGH MOLECULAR WIEGHT ARGININE-GRAFTED BIOREDUCIBLE POLYMERS (Fri, 26 Jul 2013)
The polymeric carrier for delivering nucleic acid material to a cell is provided herein. The polymeric carrier can include a dendrimer group having 2 to 8 termini, each of the termini having an arginine-grafted bioreducible polymer attached thereto. In one embodiment, only a porition of the termini can have an arginine-grafted bioreducible polymer attached thereto.
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ISOLATION, IDENTIFICATION, AND USED OF ANTIFUNGAL COMPOUNDS (Fri, 28 Jun 2013)
In one aspect, the invention relates to isolated compounds useful as antifungal agents, for example, compounds having a structure represented by a formula: wherein R1 is hydrogen or hydroxyl; wherein R2 is hydrogen, a-xylose or β -xylose; and wherein R3 and R4 are each hydrogen or together oxygen, or a pharmaceutically acceptable salt therof; methods of isolating and puifying same; pharmaceutical compositions comprising same; agricultural compositions comprising same; and methods of treating and/or preventing fungal infections using same. In one aspect, R2 is not hydrogen or β-xylose when R1 is hydroxyl and R3 and R4 are together oxygen This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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POLYMERIC DRUG DELIVERY CONJUGATES AND METHODS OF MAKING AND USING THEREOF (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">Described herein are biodegradable drug delivery conjugates for effectively delivering bioactive agents to a subject. The drug delivery conjugates comprise a water-soluble high molecular weight linear biodegradable polymer backbone comprising a plurality of linear water-soluble polymeric segments connected to one another by a first (main-chain) cleavable linker, wherein a bioactive agent is covalently bonded to at least one water-soluble polymeric segment, at least one cleavable linker, or a combination thereof. The conjugates possess numerous advantages over prior art delivery conjugates. Also described herein are methods for making and using the conjugates.</p>
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POLYMERIC COMPOSITIONS AND METHODS OF MAKING AND USING THEREOF (Fri, 24 May 2013)
<p id="p-0001" num="0000">Described herein are polymeric compositions that comprise at least one polymer residue and at least one crosslinking moiety, wherein the polymer residue is crosslinked by the crosslinking moiety and wherein the crosslinking moiety is formed from a reaction between a boronic acid moiety and a hydroxamic acid moiety. Also, described are methods of making and using such polymeric compositions.</p>
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FLUORESCENT SENSING OF VAPORS USING TUBULAR NANOFIBRIL MATERIALS (Sat, 11 May 2013)
A fluorescence-based sensor can comprise a nanofiber mass of nanofibers having tubular morphology and a fluorescence detector, where fluorescence of the nanofibers decreases upon contact with a nitro-containing compound. The nanofibers can comprise carbazole-cornered, arylene-ethynylene tetracyclic macromolecules of formula I: where R1-R4 are alkyl-containing groups. The tubular morphology allows for highly selective detection of trinitrotoluene over other nitro-based compounds and oxidizing organic compounds.
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METHODS AND COMPOSITIONS RELATED TO MODIFIED ADENOSINES FOR CONTROLLING OFF-TARGET EFFECTS IN RNA INTERFERENCE (Fri, 26 Apr 2013)
<p id="p-0001" num="0000">Disclosed are compositions and methods related to modified nucleobases. Also disclosed are compositions and methods related to modified interfering RNAs. Also disclosed are compositions and methods related to modified adenonsine for controlling off-target effects in RNA interference.</p>
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Device Comprising Deuterated Organic Interlayer (Fri, 19 Apr 2013)
<p id="p-0001" num="0000">The present invention relates to devices that can be manipulated or controlled with a magnetic field, such as a spin-valve device, an organic light-emitting device, a compass, or a magnetometer. The devices of the invention comprise an organic interlayer comprising a deuterated organic material.</p>
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GALACTOKINASE INHIBITORS FOR THE TREATMENT AND PREVENTION OF ASSOCIATED DISEASES AND DISORDERS (Fri, 29 Mar 2013)
Disclosed are inhibitors of human galactokinase of formula (1) that are useful in treating or preventing a galactokinase mediated disease or disorder, e.g., galactosemia. Also disclosed are a composition comprising a pharmaceutically acceptable carrier and at least one inhibitor of the invention, and a method of treating or preventing such disease or disorder in a mammal. Formula (I)
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SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE) BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIITORS (Fri, 22 Feb 2013)
In one aspect, the invention relates to substituted (E)-N'-(1- phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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ANTAGONISTS OF TRPV1 RECEPTOR (Fri, 02 Nov 2012)
TRPVl antagonists and associated methods are provided. A TRPVl channel antagonist can have the structure: Formula (I) wherein R1 can be -CH3, -(CH2)X(CH)YCH3 where x + y = 1-20, an aromatic, a (CH2)n aromatic where n can be less than or equal to 6, a lipid, or a linker, and wherein R2 can be either Formula (II) or Formula (III) Additionally, R3 can be -O-R4 or -NH-R4 and R4 can be -H, -CH3, an ester, a cyclic ester, or an amide.
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SUBSTITUTED N-PHENYLPYRIMIDIN-2-AMINE ANALOGS AS INHIBITORS OF THE AXL KINASE (Fri, 05 Oct 2012)
In one aspect, the invention relates to substituted N-phenylpyrimidin-2-amine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of Axl kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions for treating disorders associated with dysfunction of the Axl kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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SUBSTITUTED N-(3-(PYRIMIDIN-4-YL)PHENYL)ACRYLAMIDE ANALOGS AS TYROSINE RECEPTOR KINASE BTK INHIBITORS (Fri, 05 Oct 2012)
In one aspect, the invention relates to substituted N-(3-(pyrimidin-4- yl)phenyl)acrylamide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the BTK kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the BTK kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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SUBSTITUTED 3-(1H-BENZO{D}IMIDAZOL-2-YL)-1H-INDAZOLE-ANALOGS AS INHIBITORS OF THE PDK1 KINASE (Fri, 05 Oct 2012)
In one aspect, the invention relates to substituted 3-(lH-benzo[d]imidazol-2-yl)-lH- indazole analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the PDK1 kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions for treating disorders associated with dysfunction of the PDK1 kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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METHODS AND COMPOSITIONS RELATED TO INHIBITION OF VIRAL ENTRY (Fri, 05 Oct 2012)
Disclosed herein are compositions and methods for inhibiting viral entry.
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METHODS FOR TREATING OR PREVENTING UROLOGICAL INFLAMMATION (Fri, 28 Sep 2012)
Described herein are methods for treating or preventing urological inflammation in a subject comprising administering to the subject an effective amount of a compound comprising a. a modified hyaluronan or a pharmaceutically acceptable salt or ester thereof, wherein said hyaluronan or its pharmaceutically acceptable salt or ester comprises at least one sulfate group and at least one primary C-6 hydroxyl position of an N-acetyl-glucosamine residue comprising an alky] group or fluoroalkyl group; b. a partially or fully sulfated hyaluronan or the pharmaceutically acceptable salt or ester thereof, or a combination thereof.
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VINYL -ARYL - SULFONES FOR USE IN PERITONEAL CARCINOMATOSIS (Fri, 31 Aug 2012)
Compounds of formula II are described, wherein D, n, Ra, Rb, and Rc are as herein defined, along with pharmaceutical compositions and methods of using compounds of formula II for treating or reducing the risk of peritoneal carcinomatosis in a patient.
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Slice selective MRI excitation with reduced power deposition using multiple transmit channels (Fri, 27 Jul 2012)
<p id="p-0001" num="0000">Described are embodiments for slice-selective excitation for MRI that utilize multiple RF transmit coils, each of which are driven with a separate independent current waveform. These embodiments allow slice-selective excitation with slice profile and excitation time similar to other single-channel excitation, but with reduction in SAR caused by the transverse component of the RF field by a factor up to the number of excitation coils.</p>
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INTRAVAGINAL DEVICES FOR CONTROLLED DELIVERY OF LUBRICANTS (Sat, 19 May 2012)
The present technology provides intravaginal devices designed to deliver lubricants to the vagina for a sustained period of time. The intravaginal devices include a first segment comprising an outer surface and a lumen containing a lubricant, wherein the first segment is configured to deliver the contents of the lumen to the outer surface, and the first segment comprises a polymer selected from the group consisting of a hydrophilic, semi-permeable elastomer and a hydrophobic elastomer. The lubricant may be an aqueous lubricant. The present technology further provides an intravaginal device including a solid first segment that includes a hydrophilic semi-permeable elastomer, an outer surface and an aqueous lubricant, wherein the first segment is configured to deliver the aqueous lubricant to the outer surface.
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NANOFIBER-BASED HETEROJUNCTION APPROACH FOR HIGH PHOTOCONDUCTIVITY ON ORGANIC MATERIALS (Fri, 20 Apr 2012)
The present disclosure provides methods and compositions for an organic nanofiber- based heterojunction material, comprising nano fibers of an acceptor molecule, the nano fibers coated with a donor molecule, where the acceptor molecule contains a group and the donor molecule contains a companion group, wherein the group and companion group enables strong binding between the acceptor molecule and donor molecule, the strong binding providing for efficient forward electron transfer between the acceptor molecule and donor molecule, and wherein the group and companion group minimize charge carrier recombination between the acceptor molecule and the donor molecule.
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METHODS AND COMPOSITIONS RELATED TO NEUROACTIVE THIAZOLINE COMPOUNDS (Fri, 20 Apr 2012)
In one aspect, the invention relates to compounds having a general structure: and methods of using same to modulate calcium release. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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FLUORESCENT CARBAZOLE OLIGOMERS NANOFIBRIL MATERIALS FOR VAPOR SENSING (Fri, 13 Apr 2012)
A fluorescence based sensor (10) is disclosed and described. The sensor (10) can include nanofibril materials (12) fabricated from a linear carbazole oligomer and a fluorescence detector (14). The linear carbazole oligomer can have the formula (I) where n is 3 to 9, Rn are independently selected amine sidegroups, and at least one Rn is a C1 to C14 alkyl. The carbazole-based fluorescence based sensors (10) can be particularly suitable for detection of explosives and volatile nitro compounds.
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Alkylated semi synthetic glycosaminoglycosan ethers, and methods for making and using thereof (Fri, 09 Mar 2012)
<p id="p-0001" num="0000">Described herein are alkylated and semi-synthetic glycosaminoglycosan ethers, referred to herein as “SAGEs.” The synthesis of sulfated and alkylated SAGEs is also described. The compounds described herein are useful in a number of applications including use for ocular or ophthalmic treatment.</p>
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APPLICATIONS OF PARTIALLY AND FULLY SULFATED HYALURONAN (Fri, 16 Dec 2011)
Described herein is the use of partially and fully sulfated hyaluronan or the pharmaceutically acceptable salt or ester thereof for therapeutic and cosmetic applications as well as the treatment of a number of systemic, dermatological, periodontal, ophthalmic, and urological inflammatory diseases.
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BRYOSTATIN ANALOGUES AND METHODS OF MAKING AND USING THEREOF (Fri, 04 Nov 2011)
<p id="p-0001" num="0000">Described herein are tricyclic macrolactones. The macrolactones have a high binding affinity for PKC. The compounds described herein can be used in a number of therapeutic applications including cancer and Alzheimer's prevention and treatment. The compounds described herein can also treat memory loss. Also described herein are methods for producing macrolactones. The methods permit the high-yield synthesis of macrolactones in fewer steps and with a higher degree of substitution and specificity.</p>
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OZONATION CONVERSION OF HEAVY HYDROCARBONS FOR RESOURCE RECOVERY (Fri, 04 Nov 2011)
A method for upgrading heavy hydrocarbons into more usable hydrocarbon products is provided. The method provides for the steps of adding heavy hydrocarbons to a solvent system to form a reaction medium, and ozonating the reaction medium with an ozone containing gas to provide ozonation products. The solvent system can include a first solvent that solubilizes at least a portion of the heavy hydrocarbons and a reactive solvent.
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BIODEGRADABLE POLYDISULFIDE AMINES FOR GENE DELIVERY (Fri, 28 Oct 2011)
<p id="p-0001" num="0000">Poly(disulfide amine)s, methods of making, and methods of use are described. Illustrative embodiments of the poly(disulfide amine)s include poly(N,N′-cystaminebisacrylamide-spermine), poly(N,N′-cystaminebisaciylamide-N,N′-bis(3-aminopropyl)1,3-propanediamine), poly(N,N′-cystaminebisacrylamide-N,N′-bis(3-amino-propyl)ethylenediamine), poly(N,N′-cystaminebisacrylamide-N,N′-bis(2-aminoethyl)-1,3-propanediamine), and poly(N,N′-cystaminebisacrylamide-triethylenetetramine). These compositions are made by Michael addition between N,N′-cystaminebisacrylamide and protected oligoamine monomers, followed by deprotection. Complexes are formed by mixing the poly(disulfide amine)s with a nucleic acid. Delivery of the nucleic acid into cells is carried out by contacting the cells with the nucleic acid/poly(disulfide amine) complexes.</p>
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METHODS AND COMPOSITIONS RELATED TO MODIFIED ADENOSINES FOR CONTROLLING OFF-TARGET EFFECTS IN RNA INTERFERENCE (Fri, 30 Sep 2011)
Disclosed are compositions and methods related to modified nucleobases. Also disclosed are compositions and methods related to modified interfering RNAs. Also disclosed are compositions and methods related to modified adenonsine for controlling off-target effects in RNA interference.
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CLEAVABLE MODIFICATIONS TO REDUCIBLE POLY (AMIDO ETHYLENIMINES)S TO ENHANCE NUCLEOTIDE DELIVERY (Fri, 23 Sep 2011)
Polyplex formulations were prepared using p(TETA/CBA), its PEGylated analog, p(TETA/CBA)-g-PEG2k, and mixtures of the two species at 10/90 and 50/50 wt %, respectively. Increasing PEG wt% inhibited polyplex formation. This work demonstrates the feasibility of preparing homogenous polyplexes by altering the PEG wt% using a mixture of p(TETA/CBA) and p(TETA/CBA)-g-PEG2k products. Further, a single-step method of making p(TETA/CBA)-g-PEG2k is disclosed.
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CLEAVABLE MODIFICATIONS TO REDUCIBLE POLY (AMIDO ETHYLENIMINES)S TO ENHANCE NUCLEOTIDE DELIVERY (Fri, 23 Sep 2011)
Polyplex formulations were prepared using p(TETA/CBA), its PEGylated analog, p(TETA/CBA)-g-PEG2k, and mixtures of the two species at 10/90 and 50/50 wt %, respectively. Increasing PEG wt% inhibited polyplex formation. This work demonstrates the feasibility of preparing homogenous polyplexes by altering the PEG wt% using a mixture of p(TETA/CBA) and p(TETA/CBA)-g-PEG2k products. Further, a single-step method of making p(TETA/CBA)-g-PEG2k is disclosed.</p>
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POLYMERIC DRUG DELIVERY CONJUGATES AND METHODS OF MAKING AND USING THEREOF (Fri, 16 Sep 2011)
Described herein are biodegradable drug delivery conjugates for effectively delivering bioactive agents to a subject. The drug delivery conjugates comprise a water-soluble high molecular weight linear biodegradable polymer backbone comprising a plurality of linear water-soluble polymeric segments connected to one another by a first (main-chain) cleavable linker, wherein a bioactive agent is covalently bonded to at least one water-soluble polymeric segment, at least one cleavable linker, or a combination thereof. The conjugates possess numerous advantages over prior art delivery conjugates. Also described herein are methods for making and using the conjugates.
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Conductivity sensor device comprising diamond film with at least one nanopore or micropore (Fri, 27 May 2011)
<p id="p-0001" num="0000">Sensor device for ion channel recordings; liquid-liquid measurements and resistive pulse particle counting comprising; at least one sensor element; the element comprising a diamond thin film substrate and a pore which is a nanopore or a micropore included in the substrate. This device may be used in analysis, for instance the device may be used for single molecule detection of an apialyte (e.g. DNA), for the analysis of interactions between a sensor element and an analyte, for the detection of pore forming entities, or for the determination of ion transfer.</p>
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Alkylated semi synthetic glycosaminoglycosan ethers, and methods for making and using thereof (Fri, 08 Apr 2011)
<p id="p-0001" num="0000">Described herein is the synthesis of alkylated and semi-synthetic glycosaminoglycosan ethers, referred to herein as “SAGEs.” The synthesis of sulfated alkylated SAGEs is also described. The compounds described herein are useful in a number of applications including wound healing, drug delivery, and the treatment of a number of inflammatory diseases and skin disorders.</p>
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DEVICE COMPRISING DEUTERATED ORGANIC INTERLAYER (Fri, 01 Apr 2011)
The present invention relates to devices that can be manipulated or controlled with a magnetic field, such as a spin-valve device, an organic light-emitting device, a compass, or a magnetometer. The devices of the invention comprise an organic interlayer comprising a deuterated organic material.
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J-SUPERFAMILY CONOTOXIN PEPTIDES (Fri, 18 Mar 2011)
<p id="p-0001" num="0000">The invention relates to relatively short peptides (termed J-Superfamily conotoxin peptides, J-conotoxins or J-conotoxin peptides herein), about 25 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds. The J-conotoxins are useful for treating disorders involving voltage gated ion channels and/or receptors.</p>
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Quinoline-oxazoline compounds and their use in oxidation synthesis (Fri, 04 Mar 2011)
<p id="p-0001" num="0000">A quinoline-oxazoline compound having the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="33.78mm" file="US08263774-20120911-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">where one of X<sub>1 </sub>and X<sub>2 </sub>is N and the other is C and one of R1, R2 and R3 is Z wherein Z is an oxazoline radical having the formula</li> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="17.70mm" wi="22.35mm" file="US08263774-20120911-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> such that when X<sub>1 </sub>is N R2 is Z and R1 is absent, and when X<sub>2 </sub>is N either R1 or R3 is Z and R2 is absent. R1 and R3 through R12 are independently H or a pendant moiety which does not interfere with coordination of either N in the quinoline compound with a coordination center. These compounds can be complexed with a suitable coordination center such as catalytically active palladium and can be highly useful in catalytically oxidizing alkenes with high regioselectivity. </p>
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ADHESIVE COMPLEX COACERVATES AND METHODS OF MAKING AND USING THEREOF (Fri, 28 Jan 2011)
Adhesive complex coacervates are composed of a mixture of one or more polycations and one or more polyanions. The polycations andpolyanions in the adhesive complex coacervate are crosslinked with one another bycovalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applications. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. The adhesive complex coacervates have numerous biological applications as bioadhesives and drug delivery devices. In particular, the adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.
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ADHESIVE COMPLEX COACERVATES AND METHODS OF MAKING AND USING THEREOF (Fri, 28 Jan 2011)
Adhesive complex coacervates are composed of a mixture of one or more polycations and one or more polyanions. The polycations andpolyanions in the adhesive complex coacervate are crosslinked with one another bycovalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applications. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. The adhesive complex coacervates have numerous biological applications as bioadhesives and drug delivery devices. In particular, the adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.</p>
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MODIFIED MACROMOLECULES AND METHODS OF MAKING AND USING THEREOF (Fri, 31 Dec 2010)
<p id="p-0001-en" num="0000">Described herein are composites produced by reacting a first thiolated macromolecule with at least one compound having at least one thiol-reactive electrophilic functional group. The methods described herein permit the cross-linking of a variety of different thiolated macromolecules with one another. The composites described herein have a variety of biomedical and pharmaceutical applications, which are also described herein.</p>
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RADIATION ENHANCED MACROMOLECULAR DELIVERY OF THERAPEUTIC AGENTS FOR CHEMOTHERAPY (Fri, 24 Dec 2010)
Described herein are anti-cancer compounds composed of a macromolecule comprising (1) at least one anti-cancer agent directly or indirectly bonded to the macromolecule and (2) at least one high Z element directly or indirectly bonded to the macromolecule that is capable of producing Auger electrons upon exposure to X-ray energy. When the compounds are exposed to low energy X-ray (e.g., kilo electron volts KeV) Auger electrons are produced by the high Z elements present in the compound. Because lower energy is required when compared to typical radiotherapy, which uses therapeutic X-ray energy in the million electron volt range (MeV), the subject experiences lower collateral damage when compared to radiation therapy. Additionally, the presence of the anti-cancer agent provides a second mechanism for killing cancer cells. Methods for making and using the anti¬ cancer compounds are also described herein.
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ALKYLATED SEMI-SYNTHETIC GLYCOSAMINOGLYCAN ETHERS, AND METHODS OF MAKING AND USING THEREOF (Fri, 17 Dec 2010)
<p id="p-0001-en" num="0000">Described herein is the synthesis of alkylated and semi-synthetic glycosaminoglycosan ethers, referred to herein as “SAGEs.” The synthesis of sulfated alkylated SAGEs is also described. The compounds described herein are useful in a number of applications including wound healing, drug delivery, and the treatment of a number of inflammatory diseases and skin disorders.</p>
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Methods for chelation therapy (Fri, 10 Dec 2010)
<p id="p-0001" num="0000">The invention relates to compositions and methods of treatment using an iron chelator, an antioxidant, estrogen, and/or combinations thereof, optionally, linked to a nanoparticle, to treat a subject in need thereof. The compositions and methods may be used to restore or protect the normal functions of osteoblast and osteoclast by depleting iron and inhibiting oxidative damage. The compositions and methods may also be used to increase the bone formation rate in a subject.</p>
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ADHESIVE COMPLEX COACERVATES AND METHODS OF MAKING AND USING THEREOF (Fri, 03 Dec 2010)
<p id="p-0001-en" num="0000">Described herein is the synthesis of adhesive complex coacervates. The adhesive complex coacervates are composed of a mixture of one or more polycations, one or more poly anions, and one of more multivalent cations. The polycations and polyanions in the adhesive complex coacervate are crosslinked with one another by covalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applications. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. The adhesive complex coacervates have numerous biological applications as bioadhesives and drug delivery devices. In particular, the adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.</p>
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Identification of the hepcidin binding site on ferroportin (Fri, 19 Nov 2010)
<p id="p-0001" num="0000">The invention relates to materials and procedures for the use of the hepcidin binding domain (HBD) on ferroportin. A 20 amino acid peptide of the HBD was synthesized and shown to recapitulate the characteristics and specificity of hepcidin binding to cell surface ferroportin. The affinity of hepcidin for the HBD peptide permits a rapid, sensitive assay of hepcidin in biological fluids.</p>
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POLYMERIC COMPOSITIONS AND METHODS OF MAKING AND USING THEREOF (Fri, 12 Nov 2010)
<p id="p-0001-en" num="0000">Described herein are polymeric compositions that comprise at least one polymer residue and at least one crosslinking moiety, wherein the polymer residue is crosslinked by the crosslinking moiety and wherein the crosslinking moiety is formed from a reaction between a boronic acid moiety and a hydroxamic acid moiety. Also, described are methods of making and using such polymeric compositions.</p>
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PAS Kinase Regulates Energy Homeostasis (Fri, 08 Oct 2010)
<p id="p-0001-en" num="0000">Disclosed are compositions and methods related to PAS Kinase (PASK) and various diseases and disorders associated therewith. Included are methods for treating insulin resistance, cancer, and diabetes comprising administering a composition that inhibits PAS Kinase. Further included are methods, including high throughput screening methods, for identifying test compounds that modulate PAS Kinase.</p>
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METHODS AND COMPOSITIONS RELATED TO MODIFIED GUANINE BASES FOR CONTROLLING OFF-TARGET EFFECTS IN RNA INTERFERENCE (Fri, 01 Oct 2010)
Disclosed are compositions and methods related to modified nucleobases. Also disclosed are compositions and methods related to modified interfering RNAs. Also disclosed are compositions and methods related to modified guanine bases for controlling off-target effects in RNA interference.
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Simultaneous acquisitions of spin- and stimulated-echo planar imaging (Fri, 27 Aug 2010)
<p id="p-0001" num="0000">The disclosure provides echo planar imaging (EPI) based single-shot imaging techniques for acquiring spin-EPI (SEPI) and stimulated-EPI after a single RF excitation. In certain embodiments, the SEPI and STEPI acquired in a singleshot are used to compute a T<sub>1 </sub>map in realtime, which can be used for realtime monitoring of concentrations of paramagnetic-ion based contrast agent in dynamic contrast enhanced MRI. In certain embodiments, B<sub>1 </sub>field inhomogeneity correction is provided for the STEPI. In certain embodiments, a gradient-EPI (GEPI) is also acquired after the single RF excitation providing singleshot SEPI, GEPI and STEPI acquisition. In certain embodiments, the phase difference between the SEPI and GEPI is used to compute temperature-dependent chemical shift in a subject in realtime. The temperature-dependent chemical shift can be used to monitor temperature changes in the subject in realtime, for example, during a heat treatment to control the dosage of heat energy.</p>
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Methods and compositions related to cyclic peptide synthesis (Fri, 20 Aug 2010)
<p id="p-0001" num="0000">Disclosed are compositions and methods for prenylation of polymers such as peptides.</p>
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Methods and Compositions Related to Inhibition of Viral Entry (Fri, 23 Jul 2010)
<p id="p-0001-en" num="0000">Disclosed are compositions and methods for inhibiting viral entry.</p>
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METHOD OF DETECTING OCULAR DISEASES AND PATHOLOGIC CONDITIONS AND TREATMENT OF SAME (Fri, 02 Jul 2010)
<p id="p-0001-en" num="0000">Methods of detecting and treating diseases and pathological conditions of the eye are disclosed. In particular a genetic variant of the HtrA1 gene is correlated to age related macular degeneration (AMD). In addition, biologically active agents capable of inhibiting HtrA1 activity are provided, and methods of treating diseases and pathological conditions of the eye are additionally disclosed.</p>
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BIODEGRADABLE INTRAVAGINAL MEDICAL DEVICE FOR DELIVERY OF THERAPEUTICS (Fri, 02 Jul 2010)
<p id="p-0001-en" num="0000">The present disclosure relates to biodegradable intravaginal rings for the delivery of therapeutic or prophylactic agent, inter alia, antiviral agents. The present disclosure further relates to biodegradable polyurethanes which will allow therapeutic/prophylactic agents to be released in a controlled manner that will not degrade when in use, but will degrade upon disposal. </p>
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Methods and compositions related to continuous flow thermal gradient PCR (Fri, 02 Jul 2010)
<p id="p-0001" num="0000">Disclosed are compositions and a method for amplification and detection of nucleic acid sequences based on continuous flow thermal gradient PCR.</p>
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MONOCHROME MULTIPLEX QUANTITATIVE PCR (Fri, 02 Jul 2010)
Disclosed herein are methods and compositions for determining the copy number of a first target nucleic acid as compared to the copy number of a second target nucleic acid in a single well with a single detection label. For example, disclosed herein are methods and compositions for determining the copy number of a first target nucleic acid as compared to the copy number of a second target nucleic acid by a monochrome multiplex quantitative PCR (MMQPCR) in a single well with a single detection label.
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MONOCHROME MULTIPLEX QUANTITATIVE PCR (Fri, 02 Jul 2010)
Disclosed herein are methods and composi-tions for determining the copy number of a first target nu-cleic acid as compared to the copy number of a second tar-get nucleic acid in a single well with a single detection la-bel. For example, disclosed herein are methods and com-positions for determining the copy number of a first target nucleic acid as compared to the copy number of a second target nucleic acid by a monochrome multiplex quantita-tive PCR (MMQPCR) in a single well with a single detec-tion label. </p>
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Reducing non-target nucleic acid dependent amplifications: amplifying repetitive nucleic acid sequences (Fri, 18 Jun 2010)
<p id="p-0001" num="0000">The present invention provides for compositions and methods for amplifying target nucleic acids using nucleic acid primers designed to limit non-target nucleic acid dependent priming events. The present invention permits amplifying and quantitating the number of repetitive units in a repetitive region, such as the number of telomere repetitive units.</p>
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Phenylthiocarbamide (PTC) taste receptor (Fri, 18 Jun 2010)
<p id="p-0001" num="0000">The invention provides isolated nucleic and amino acid sequences of a taste cell receptor that serves as a sensor for the bitter taste of phenylthiocarbamide (PTC), antibodies to such PTC taste receptor, methods of detecting such nucleic and amino acid sequences, and methods of screening for modulators of such PTC taste receptor.</p>
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Molecular fluorescence sensor for highly sensitive and selective detection of mercury (Fri, 11 Jun 2010)
<p id="p-0001" num="0000">A fluorescent sensor compound based on a perylene core is described and disclosed. The fluorescent sensor compound for detecting mercury can have a structure I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.32mm" wi="73.32mm" file="US08058075-20111115-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> where A and A′ are linking groups, B and B′ are binding ligands which are selective for binding with Hg<sup>2+</sup>, and R1 through R8 are side groups. These fluorescence sensor materials are robust against photobleaching, while still providing exceptional detection sensitivity and selectivity. </p>
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BIODEGRADABLE POLYDISULFIDE AMINES FOR GENE DELIVERY (Fri, 11 Jun 2010)
Poly(disulfide amine)s, methods of making, and methods of use are described. Illustrative embodiments of the poly(disulfide amine)s include poly(N,N'- cystaminebisacrylamide-spermine), poly(N,N'-cystaminebisaciylamide-N,N'-bis(3- aminopropyl)-l,3-propanediamine), poly(N, N'-cystaminebisacrylamide-N, N'-bis(3- aminopropyl)ethylenediamine), poly(N,N'-cystaminebisacrylamide-N,N'-bis(2- aminoethyl)- 1,3-propanediamine), and poly(N, N'-cystaminebisacrylamide- triethylenetetramine). These compositions are made by Michael addition between N,N'- cystaminebisacrylamide and protected oligoamine monomers, followed by deprotection. Complexes are formed by mixing the poly(disulfide amine)s with a nucleic acid. Delivery of the nucleic acid into cells is carried out by contacting the cells with the nucleic acid/poly(disulfide amine) complexes.
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PDE1 AS A TARGET THERAPEUTIC IN HEART DISEASE (Fri, 11 Jun 2010)
Disclosed are compositions and methods related to inhibition of PDE1.
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CARRIERS FOR THE DELIVERY OF NUCLEIC ACIDS TO CELLS AND METHODS OF USE THEREOF (Fri, 04 Jun 2010)
Described herein are compounds and methods useful for the delivery of nucleic acids to cells. The compounds and methods are useful in delivering all types of nucleic acids to cells including sensitive nucleic acids such as, for example, siRNA.
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METHOD OF DETECTING OCULAR DISEASES AND PATHOLOGIC CONDITIONS AND TREATMENT OF SAME (Fri, 28 May 2010)
<p id="p-0001-en" num="0000">Ocular diseases affecting the macula or the vasculature of the eye affect a wide variety of individuals. In particular, Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world and has a significant genetic predisposition. Methods of analyzing one or more mutations in the HtrA1 gene in order to identify individuals with a presusceptability to development of an ocular disease and a pathologic condition of the eye and diagnose those currently suffering from an ocular disease or a pathologic condition of the eye are provided. The methods of the present invention may further include analysis of the CFH gene in order to identify individuals with a presusceptability to development of an ocular disease and a pathologic condition of the eye and diagnose those currently suffering from an ocular disease or a pathologic condition of the eye. Compositions and methods for treating ocular disease and pathologic conditions of the eye are also provided.</p>
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Polymeric carrier for delivery of small interfering RNA (Fri, 28 May 2010)
<p id="p-0001" num="0000">A carrier for delivering small interfering RNA (siRNA) into cells includes a cholesterol residue covalently bonded to oligoarginine. Mixing the siRNA with the carrier produces a complex-containing composition. Contacting a cell with the complex-containing composition results in delivery of the siRNA into the cell. Delivery of an siRNA targeted to vascular endothelial growth factor is a treatment for cancer. Methods of making the carrier and complex are also disclosed.</p>
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ADHESIVE COMPLEX COACERVATES AND METHODS OF MAKING AND USING THEREOF (Fri, 14 May 2010)
<p id="p-0001-en" num="0000">Described herein is the synthesis of adhesive complex coacervates and their use thereof. The adhesive complex coacervates are composed of a mixture of one or more polycations and one or more polyanions. The polycations and polyanions in the adhesive complex coacervate are crosslinked with one another by covalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applications. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. The adhesive complex coacervates have numerous biological applications as bioadhesives and drug delivery devices. In particular, the adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.</p>
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Dynamic composite gradient systems for MRI (Fri, 30 Apr 2010)
<p id="p-0001" num="0000">A composite gradient system is described, including a body gradient system and an insert gradient system, in which the body gradient system and the insert gradient system can be driven independently and simultaneously. The composite gradient system can provide an operator with the flexibility of imaging a subject using the body gradient system alone, the insert gradient system alone, or both gradient systems simultaneously, and therefore enjoy the advantages of each gradient system. In some embodiments, the body gradient system and the insert gradient system may be driven concurrently during an imaging sequence to produce composite magnetic field gradients having high amplitude and/or fast slew rate, resulting in high image resolution and/or fast image acquisition. In some embodiments, a subject may be imaged using the body gradient system alone while leaving the insert gradient system in place.</p>
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PROTECTED ENANTIOPURE TRIFLUOROTHREONINES AND METHODS OF MAKING AND USING SAME (Fri, 23 Apr 2010)
<p id="p-0001-en" num="0000">Disclosed are processes for preparing a protected trifluorothreonine, or salt thereof or carboxylate derivative thereof, the process comprising: dihydroxylation of an alkene to yield a dihydroxyl compound; conversion of the dihydroxyl compound to a monohydroxyl compound; protection of the monohydroxyl compound to yield an azide compound; transformation of the azide compound to yield an amino compound; protection of the amino compound to yield a protected amine compound; and oxidation of the protected amine compound to yield the protected trifluorothreonine. Also disclosed are compounds having the structure:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="16.59mm" wi="52.66mm" file="US20100099845A1-20100422-C00001.TIF" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">or salt thereof or carboxylate derivative thereof, wherein P<sup>2 </sup>is a hydroxyl protecting group, and wherein P<sup>3 </sup>is an amine protecting group. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.</p>
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TYROSINE-RICH CONOPEPTIDES (Fri, 16 Apr 2010)
<p id="p-0001-en" num="0000">The invention relates to relatively short peptides (termed Conopeptide-Y family peptides or CPY family peptides or CPY peptides herein), about 30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which are rich in the amino acid tyrosine.</p>
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Methods and Compositions related to HIF-1 alpha (Fri, 26 Mar 2010)
<p id="p-0001-en" num="0000">Disclosed are compositions and methods related to HIF-1α.</p>
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LABELED PEPTIDES AND METHODS OF USE THEREOF FOR IMPROVED OXIDATION AND MAPPING OF DISULFIDE BRIDGES (Fri, 05 Mar 2010)
Described herein are labeled proteins and methods of use thereof for identifying the position of multiple disulfide bridges present in the peptide. The methods combine the use of diselenide bridges and NMR-based mapping of the disulfide bridges. Also described herein are labeled proteins described above that contain fluorous bridges and spacers that facilitate oxidative folding of the protein. The resulting biorthogonal oxidation strategy for studying disulfide-rich peptides both improves oxidative folding and provides simultaneous determination of the disulfide crosslink connectivity in the peptide. The methods permit routine and facile production of disulfide-rich peptides.
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Methods and Compositions Related to Inhibition of Ceramide Synthesis (Fri, 26 Feb 2010)
<p id="p-0001-en" num="0000">Disclosed are compositions and methods related to the ceramide synthesis pathway and various diseases and disorders associated therewith, such as insulin resistance and inflammation.</p>
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Slice selective MRI excitation with reduced power deposition using multiple transmit channels (Fri, 22 Jan 2010)
<p id="p-0001" num="0000">Described are embodiments for slice-selective excitation for MRI that utilize multiple RF transmit coils, each of which are driven with a separate independent current waveform. These embodiments allow slice-selective excitation with slice profile and excitation time similar to other single-channel excitation, but with reduction in SAR caused by the transverse component of the RF field by a factor up to the number of excitation coils.</p>
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pH-sensitive polymeric micelles for drug delivery (Fri, 15 Jan 2010)
<p id="p-0001" num="0000">Mixed micelles containing poly(L-histidine-co-phenylalanine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.</p>
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Enhanced fill-factor NMR coils and associated methods (Fri, 08 Jan 2010)
<p id="p-0001" num="0000">An NMR probe which includes a probe matrix (<b>24</b>) having a void sample (<b>28</b>) volume therein. A conductive coil (<b>16, 26</b>) can be at least partially embedded in the probe matrix (<b>24</b>). By embedding the conductive coil (<b>16, 26</b>) in the probe matrix (<b>24</b>), the fill-factor can be significantly increased. NMR probes can be formed by a method which includes wrapping a conductive wire (<b>16</b>) around a coil form (<b>18</b>) to produce a coil precursor assembly. The probe matrix (<b>24</b>) can be formed around the conductive wire and coil form with a matrix material using any suitable technique such as soft lithography and/or molding. The coil form can be removed from the probe matrix leaving a void sample volume (<b>28</b>) in the probe matrix. Advantageously, the NMR probes of the present invention allow for fill-factors approaching and achieving 100%.</p>
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MULTIFUNCTIONAL CARRIERS FOR THE DELIVERY OF NUCLEIC ACIDS AND METHODS OF USE THEREOF (Fri, 08 Jan 2010)
<p id="p-0001-en" num="0000">Described herein are multifunctional compounds useful as devices for the delivery of nucleic acids to cells. Also described herein are methods for using the multifunctional compounds.</p>
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METHOD AND APPARATUS FOR MEASURING MAGNETIC FIELDS (Fri, 18 Dec 2009)
A new ultra-sensitive magnetometer is disclosed and described. The ultra- sensitive magnetometer relies on non-tunneling magneto-transport (MT) and control of MT in organic solid state devices. These organic devices can have different active components as magnetic and non-magnetic polymers and self-assembled monolayers (SAMs). Magnetic field sensors can include a pair of electrodes spaced apart from one another. An organic layer can be oriented between the pair of electrodes to form an organic solid state device, wherein at least one of the organic layer and electrodes is magnetic and when the organic layer is not magnetic the organic layer comprises a self assembled monolayer and the magnetic field sensor operates under non-tunneling magnetic spin transport.
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High field strength magentic field generation system and associated methods (Fri, 11 Dec 2009)
<p id="p-0001" num="0000">A magnetic field generation system includes first (<b>28</b><i>a</i>) and second (<b>28</b><i>b</i>) magnetic flux concentrators spaced apart to form a sample volume (<b>30</b>). A first set of auxiliary permanent magnets (<b>10</b><i>a</i><b>, 10</b><i>b</i>) can be symmetrically oriented about and in contact with a portion of the first magnetic flux concentrator (<b>28</b><i>a</i>). Similarly, a second set of auxiliary permanent magnets (<b>10</b><i>c</i><b>, 10</b><i>d</i>) can be symmetrically oriented about and in contact with a portion of the second magnetic flux concentrator (<b>28</b><i>b</i>). The first(<b>10</b><i>a</i><b>, 10</b><i>b</i>) and second (<b>10</b><i>c</i><b>, 10</b><i>d</i>) sets of auxiliary magnets can be magnetically associated via the first (<b>28</b><i>a</i>) and second (<b>28</b><i>b</i>) magnetic flux concentrators. Magnetically soft shunts (<b>38</b>) can be movably oriented to allow variation of the magnetic field strength across the sample volume by disrupting the field flux across the magnetic flux concentrators.</p>
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Highly fluorinated oils and surfactants and methods of making and using same (Fri, 23 Oct 2009)
<p id="p-0001" num="0000">Disclosed are compounds comprising the structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="126.15mm" wi="63.16mm" file="US08252778-20120828-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> In one aspect, the compounds exhibit maximum symmetric branching. Also disclosed are bilayers, micelles, coatings, and nanoparticles comprising the disclosed compounds. Also disclosed are processes for the preparation of the disclosed compounds and methods of using the disclosed compounds. Also disclosed are highly fluorinated dendrons and methods for making same. Also disclosed are methods for Fluorous Mixture Synthesis and tagging. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. </p>
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BRYOSTATIN ANALOGUES AND METHODS OF MAKING AND USING THEREOF (Fri, 23 Oct 2009)
Described herein are tricyclic macrolactones. The macrolactones have a high binding affinity for PKC. The compounds described herein can be used in a number of therapeutic applications including cancer and Alzheimer's prevention and treatment. The compounds described herein can also treat memory loss. Also described herein are methods for producing macrolactones. The methods permit the high-yield synthesis of macrolactones in fewer steps and with a higher degree of substitution and specificity.
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ALKYLATED SEMI-SYNTHETIC GLYCOSAMINOGLYCOSAN ETHERS, AND METHODS FOR MAKING AND USING THEREOF (Fri, 09 Oct 2009)
Described herein is the synthesis of alkylated and fluoroalkylated semi-synthetic glycosaminoglycosan ethers, referred to herein as "SAGEs." The synthesis of sulfated alkylated and fluoroalkylated SAGEs is also described. The compounds described herein are useful in a number of applications including wound healing, drug delivery, and the treatment of a number of inflammatory diseases and skin disorders.
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ALKYLATED SEMI-SYNTHETIC GLYCOSAMINOGLYCOSAN ETHERS, AND METHODS FOR MAKING AND USING THEREOF (Fri, 09 Oct 2009)
Described herein is the synthesis of alkylated and fluoroalkylated semi- synthetic glycosaminoglycosan ethers, re-ferred to herein as "SAGEs." The synthesis of sulfated alkylated and fluoroalkylated SAGEs is also described. The compounds de-scribed herein are useful in a number of applications including wound healing, drug delivery, and the treatment of a number of in-flammatory diseases and skin disorders. </p>
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MICROFLUIDIC FLOW CELL (Sat, 12 Sep 2009)
A microfluidic flow cell having a body with a fluid transport channel disposed therein, the fluid transport channel having a proximal end and a distal end defining a fluid flow path, a fluid inlet port disposed at the proximal end of the fluid transport channel at a central portion of the body and an outlet port disposed at the distal end of the fluid transport channel at an outer portion of the body, and a plurality sample wells disposed in the fluid transport channel substantially perpendicular to the fluid flow path in the fluid transport channel. The microfluidic flow cell may have hundreds or thousands of individual, sub-microliter sample wells. The microfluidic flow cell can be filled by applying a flowable liquid to the inlet port and spinning the flow cell to cause fluid to flow into fluid transport channel. The microfluidic flow cells described herein can be used in a variety of applications where small sample size and/or a large number of replicates are desirable.
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Methods and Compositions Related to Cyclic Peptide Synthesis (Fri, 28 Aug 2009)
<p id="p-0001-en" num="0000">Disclosed are compositions and methods for cyclization of polymers such as peptides.</p>
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ARGININE-CONJUGATED BIOREDUCIBLE POLY (DISULFIDE AMINE) POLYMERS FOR GENE DELIVERY SYSTEMS (Fri, 21 Aug 2009)
An arginine-grafted bioreducible poly (disulfide amine) ('ABP') as a reagent for efficient and nontoxic gene delivery is described. ABP forms positively charged nano-particles of less than 200 nm with plasmid DNA. ABP is biodegraded under reducing conditions, such as the cytoplasm. ABP exhibits much higher transfection efficiency than polyethyleneimine in mammalian cells and exhibits no cytotoxicity.
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METHODS FOR TREATING PAIN AND SCREENING ANALGESIC COMPOUNDS (Fri, 14 Aug 2009)
<p id="p-0001-en" num="0000">The present invention relates to the use of compounds that block the α9α10 subtype of the nicotinic acetylcholine receptor (nAChR) for treating pain, such as neuropathic pain and inflammatory pain, and inflammatory disorders, such as arthritis. The present invention also relates to screening compounds to identify analgesic agents that block the α9α10 subtype of the nAChR.</p>
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LINEAR ORDER RELEASE POLYMER (Fri, 31 Jul 2009)
Intravaginal drug delivery devices, including intravaginal rings, are provided herein. The devices comprise a polyether urethane composition and a pharmaceutically effective amount of at least one vaginally administrable drug homogeneously distributed throughout the polyether urethane. The devices are capable of exhibiting a substantially zero order release profile of drug over extended periods of time. Also disclosed are methods for making the devices and methods of using the devices to prevent or treat a biological condition.
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ADHESIVE COMPLEX COACERVATES AND METHODS OF MAKING AND USING THEREOF (Fri, 31 Jul 2009)
Described herein is the synthesis of adhesive complex coacervates. The adhesive complex coacervates are composed of a mixture of one or more polycations, one or more poly anions, and one of more multivalent cations. The polycations and polyanions in the adhesice complex coacervate are crosslinked with one another by covalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applicatgions. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. The adhesive complex coacervates have numerous biological applications as bioadhesives and drug delivery devices. In particular, the adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.
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ADHESIVE COMPLEX COACERVATES AND METHODS OF MAKING AND USING THEREOF (Fri, 31 Jul 2009)
Described herein is the synthesis of adhesive complex coacervates. The adhesive complex coacervates are composed of a mixture of one or more polycations, one or more poly anions, and one of more multivalent cations. The polycations and polyanions in the adhesice complex coacervate are crosslinked with one another by covalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applicatgions. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. The adhesive complex coacervates have numerous biological applications as bioadhesives and drug delivery devices. In particular, the adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions. </p>
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BIODEGRADABLE POLY(DISULFIDE AMINE)S FOR GENE DELIVERY (Fri, 22 May 2009)
<p id="p-0001-en" num="0000">Poly(disulfide amine)s, methods of making, and methods of use are described. Illustrative embodiments of the poly(disulfide amine)s include poly(CBA-DAE), poly(CBA-DAB), and poly(CBA-DAH). These compositions are made by Michael addition between N,N′-cystaminebisacrylamide and N-Boc-protected diamine monomers, followed by N-Boc deprotection. Complexes are formed by mixing the poly(disulfide amine)s with nucleic acid. Delivery of the nucleic acid into cells is carried out by contacting the cells with the nucleic acid/poly(disulfide amine) complexes.</p>
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Anti-adhesion composites and methods of use thereof (Fri, 15 May 2009)
<p id="p-0001" num="0000">Described herein are composites that inhibit or reduce adhesion between two or more tissues. Also described herein are methods of using the composites.</p>
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Crosslinked compounds and methods of making and using thereof (Fri, 08 May 2009)
<p id="p-0001" num="0000">Described herein are crosslinked compounds useful in numerous treatments. Described herein are methods of making crosslinked compounds via (1) die oxidative coupling of two or more thiol compounds or (2) by the reaction between at least one thiol compound with at least one thiol-reactive compound.</p>
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IDENTIFICATION OF THE HEPCIDIN BINDING SITE ON FERROPORTIN (Fri, 01 May 2009)
The invention relates to materials and procedures for the use of the hepcidin binding domain (HBD) on ferroportin. A 20 amino acid peptide of the HBD was synthesized and shown to recapitulate the characteristics and specificity of hepcidin binding to cell surface ferroportin. The affinity of hepcidin for the HBD peptide permits a rapid, sensitive assay of hepcidin in biological fluids.
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Hyaluronic acid containing bioconjugates: targeted delivery of anti-cancer drugs to cancer cells (Fri, 24 Apr 2009)
<p id="p-0001-en" num="0000">A cell-targeted polymeric drug delivery system was designed based on the specific interaction between hyaluronic acid (HA) and its cell surface receptors overexpressed on cancer cell surface. The invention relates to compounds composed of a carrier molecule, wherein the carrier molecule contains at least one residue of an anti-cancer agent and at least one residue of a hyaluronic acid. The invention also relates to methods of making and using the compounds thereof.</p>
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CROSSLINKED COMPOUNDS AND METHODS OF MAKING AND USING THEREOF (Fri, 24 Apr 2009)
<p id="p-0001-en" num="0000">Described herein are crosslinked compounds useful in numerous treatments. Described herein are methods of making crosslinked compounds via (1) the oxidative coupling of two or more thiol compounds or (2) by the reaction between at least one thiol compound with at least one thiol-reactive compound.</p>
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ANTIBODIES TO HTRA1 AND METHODS OF USING THE SAME (Fri, 10 Apr 2009)
Antibodies to HtrA1 and methods of using such antibodies are described herein. The antibodies described herein are raised against HtrA1 and variants of HtrA1 as defined herein. The antibodies disclosed herein are useful in treating disease or injury of the eye. For example, in one embodiment, HtrA1 antibodies may be used to treat age-related macular degeneration (AMD) in both its wet and dry forms, diabetic retinopathy (DR), retinopathy of prematurity (ROP) or macular edema. In another embodiment, HtrA1 antibodies may be used to treat choroidal or retinal neovascularization associated with or resulting from disease or injury. In another embodiment, the methods of the present invention include use of HtrA1 antibodies to treat ischemia-induced retinal neovascularization resulting from vascular damage, occlusion or leak resulting from disease or injury. The methods described herein include administering a therapeutically-effective amount of one or more HtrA1 antibodies to a subject. Pharmaceutical compositions of antibodies to HtrA1 are also described herein.
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Drug delivery vehicle that mimics viral properties (Fri, 06 Mar 2009)
<p id="p-0001" num="0000">A drug delivery vehicle for targeted delivery of a drug mimics viral properties of size, capsid-like protein capsule, cell-specific entry, toxin release, destruction of infected cells, and migration to neighboring cells. This vehicle, termed a virogel, contains a hydrophobic polymeric core, a hydrophilic inner shell, a hydrophilic outer shell, and a ligand. An illustrative drug-loaded virogel includes poly(L-histidine-co-phenylalanine) as the core, doxorubicin loaded in the core, polyethylene glycol as the inner shell, bovine serum albumin as the outer shell, and folic acid as the ligand.</p>
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DRUG DELIVERY VEHICLE THAT MIMICS VIRAL PROPERTIES (Fri, 06 Mar 2009)
A drug delivery vehicle for targeted delivery of a drug mimics viral properties of size, capsid-like protein capsule, cell-specific entry, toxin release, destruction of infected cells, and migration to neighboring cells. This vehicle, termed a virogel, contains a hydrophobic polymeric core, a hydrophilic inner shell, a hydrophilic outer shell, and a ligand. An illustrative drug-loaded virogel includes poly(L-histidine-co-phenylalanine) as the core, doxorubicin loaded in the core, polyethylene glycol as the inner shell, bovine serum albumin as the outer shell, and folic acid as the ligand.
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α-conotoxin MII analogs (Fri, 02 Jan 2009)
<p id="p-0001" num="0000">The invention relates to novel conopeptides and/or novel uses of conopeptides. The conopeptides of the invention are analogs of α-Conotoxin MII that are selective for α6-containing nAChRs as described herein.</p>
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α-CHLORO AND α-BROMO PHOSPHONATE ANALOGS OF LYSOPHOSPHATIDIC ACID AND METHODS OF MAKING AND USING THEREOF (Thu, 25 Dec 2008)
Described herein is the synthesis and pharmacology of a series of α- substituted methylene phosphonate analogs, in which the α-CH2 moiety is replaced with CHCl or CHBr.
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.ALPHA.-CHLORO AND .ALPHA.-BROMO PHOSPHONATE ANALOGS OF LYSOPHOSPHATIDIC ACID AND METHODS OF MAKING AND USING THEREOF (Thu, 25 Dec 2008)
Described herein is the synthesis and pharmacology of a series of .alpha.- substituted methylene phosphonate analogs, in which the .alpha.-CH2 moiety is replaced with CHCl or CHBr. </p>
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Methods and Compositions Related to Delivery of Chemical Compounds to Invertebrate Embryos (Fri, 07 Nov 2008)
<p id="p-0001-en" num="0000">Disclosed are methods and compositions related to the delivery of chemical compounds to invertebrate embryos.</p>
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DENDRIMERS AND METHODS OF MAKING AND USING THEREOF (Fri, 10 Oct 2008)
Described herein are dendrimers derived from polyhedral silsesquioxanes and methods of making/using thereof.
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Phenylthiocarbamide (PTC) taste receptor (Fri, 19 Sep 2008)
<p id="p-0001-en" num="0000">The invention provides isolated nucleic and amino acid sequences of a taste cell receptor that serves as a sensor for the bitter taste of phenylthiocarbamide (PTC), antibodies to such PTC taste receptor, methods of detecting such nucleic and amino acid sequences, and methods of screening for modulators of such PTC taste receptor.</p>
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PEPTIDES THAT INTERACT WITH TOPOISOMERASE I AND METHODS THEREOF (Fri, 05 Sep 2008)
Disclosed are compositions and methods for treating cancer comprising peptides that can act synergistically with chemotherapeutic agents.
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SYNTHESIS OF NOVEL XYLOSIDES AND POTENTIAL USES THEREOF (Fri, 29 Aug 2008)
The present invention includes a xyloside for use in inducing synthesis of a glycosaminoglycan in a cell, the xyloside having a chemical structure of one of Formula (1), Formula (2), Formula (3), Formula (4), Formula (5), Formula (6), Formula (7), Formula (8), Formula (9), or Formula (10) as shown herein. Also, the present invention includes a method of making a xyloside for use in inducing synthesis of a glycosaminoglycan in a cell, wherein the method is performed with 'Click' chemistry. Additionally, the present invention includes a method of administering a xyloside so as to induce synthesis of a glycosaminoglycan in a cell.
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METHODS AND COMPOSITIONS RELATED TO INHIBITION OF VIRAL ENTRY (Fri, 15 Aug 2008)
Disclosed are compositions and methods for inhibiting viral entry.
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METHODS AND COMPOSITIONS RELATED TO INHIBITION OF VIRAL ENTRY (Fri, 15 Aug 2008)
Disclosed are compositions and methods for inhibiting viral entry.</p>
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Sulfonamide-based oligomers and polymers for destabilization of biological membranes (Fri, 08 Aug 2008)
<p id="p-0001-en" num="0000">Oligomeric sulfonamides for use as endosomolytic reagents for transfection with polymeric or lipid-based vectors are described. A mixture of an oligomeric sulfonamide with a polymeric or lipid-based gene carrier and a nucleic acid results in a polyplex that exhibits 6-12-fold better gene expression than controls. A method of transfecting cells in vitro is carried out by contacting cultured mammalian cells with an effective amount of a polyplex.</p>
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METHOD OF DETECTING OCULAR DISEASES AND PATHOLOGIC CONDITIONS AND TREATMENT OF SAME (Fri, 08 Aug 2008)
Ocular diseases affecting the macula or the vasculature of the eye affect a wide variety of individuals. In particular, Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world and has a significant genetic predisposition. Methods of analyzing one or more mutations in the HtrA1 gene in order to identify individuals with a presusceptability to development of an ocular disease and a pathologic condition of the eye and diagnose those currently suffering from an ocular disease or a pathologic condition of the eye are provided. The methods of the present invention may further include analysis of the CFH gene in order to identify individuals with a presusceptability to development of an ocular disease and a pathologic condition of the eye and diagnose those currently suffering from an ocular disease or a pathologic condition of the eye. Compositions and methods for treating ocular disease and pathologic conditions of the eye are also provided.
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Process and Formulation to Improve Viability of Stored Cells and Tissue (Fri, 25 Jul 2008)
<p id="p-0001-en" num="0000">Methods and compositions for the preservation of cells using glucosaminoglycans and derivatives thereof.</p>
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BIODEGRADABLE INTRAVAGINAL DEVICES FOR DELIVERY OF THERAPEUTICS (Fri, 25 Jul 2008)
The present disclosure relates to biodegradable intravaginal rings for the delivery of therapeutic or prophylactic agent, inter alia, antiviral agents. The present disclosure further relates to biodegradable polyurethanes which will allow therapeutic/prophylactic agents to be released in a controlled manner that will not degrade when in use, but will degrade upon disposal.
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Biodegradable and Biocompatible Peg-Based Poly(Ester-Urethanes) (Fri, 13 Jun 2008)
<p id="p-0001-en" num="0000">The compositions disclosed herein include biodegradable elastomers that provide a material for. medical purposes. They may further provide a drug delivery system for the treatment of a wide variety of medical conditions. In particular, the compositions provide biodegradable elastomers composed of a pre-polymeric block, a degradable sequence and a bis-functional linker. The usefulness of the present invention is that it provides a biodegradable elastomer for use with medical devices.</p>
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METHODS AND COMPOSITIONS RELATED TO HIF-1α (Fri, 13 Jun 2008)
Disclosed are compositions and methods related to HIF-1α.
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METHOD OF DETECTING OCULAR DISEASES AND PATHOLOGIC CONDITIONS AND TREATMENT OF SAME (Fri, 06 Jun 2008)
Methods of detecting and treating diseases and pathological conditions of the eye are disclosed. In particular a genetic variant of the HtrA1 gene is correlated to age related macular degeneration (AMD). In addition, biologically active agents capable of inhibiting HtrA1 activity are provided, and methods of treating diseases and pathological conditions of the eye are additionally disclosed.
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METHODS AND COMPOSITIONS RELATED TO CONTINUOUS FLOW THERMAL GRADIENT PCR (Fri, 23 May 2008)
Disclosed are compositions and a method for amplification and detection of nucleic acid sequences based on continuous flow thermal gradient PCR.
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Obesity gene and use thereof (Fri, 11 Apr 2008)
<p id="p-0001" num="0000">The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human obesity and diabetes predisposing gene, specifically the TBC1D1 gene, some mutant alleles of which cause susceptibility to obesity and/or diabetes. More specifically, the invention relates to germline mutations in the TBC1D1 gene and their use in the diagnosis of predisposition to obesity and diabetes. Finally, the invention relates to the screening of the TBC1D1 gene for mutations/alterations, which are useful for diagnosing the predisposition to obesity.</p>
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MULTIFUNCTIONAL CARRIERS FOR THE DELIVERY OF NUCLEIC ACIDS AND METHODS OF USE THEREOF (Fri, 11 Apr 2008)
Described herein are multifunctional compounds useful as devices for the delivery of nucleic acids to cells. Also described herein are methods for using the multifunctional compounds.
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PROTECTED ENANTIOPURE TRIFLUOROTHREONINES AND METHODS OF MAKING AND USING SAME (Fri, 21 Mar 2008)
Disclosed are processes for preparing a protected trifluorothreonine, or salt thereof or carboxylate derivative thereof, the process comprising: dihydroxylation of an alkene to yield a dihydroxyl compound; conversion of the dihydroxyl compound to a monohydroxyl compound; protection of the monohydroxyl compound to yield an azide compound; transformation of the azide compound to yield an amino compound; protection of the amino compound to yield a protected amine compound; and oxidation of the protected amine compound to yield the protected trifluorothreonine. Also disclosed are compounds having the structure: or salt thereof or carboxylate derivative thereof, wherein P2 is a hydroxyl protecting group, and wherein P3 is an amine protecting group. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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HIGHLY FLUORINATED β-AMINO ACIDS AND METHODS OF MAKING AND USING SAME (Fri, 21 Mar 2008)
Disclosed are compounds having the structure: wherein Rla and Rlb are independently H, alkyl, F, or fluoroalkyl; wherein R2a, R2b, R2a', and R2b are independently H, alkyl, F, fluoroalkyl, aryl, or alkenyl; wherein R3 is OH, alkoxyl, NH2, alkylamino, or dialkylamino; wherein R4a and R4b are independently H, alkyl, acyl, or alkyloxycarbonyl; wherein R11, R12, R13, R21, R22, and R23 are independently H, alkyl, F, or fluoroalkyl; and wherein CO, Cl, C2, and C2' are independently chiral or achiral. Also disclosed are processes for making a fluorinated β-amino acid comprising the steps of: providing a diol; treating the diol with a thionyl halide with oxidative workup; reacting the product with an azide salt to yield an azido group; oxidizing the product to yield a carboxyl group; and reducing the azido group to yield an amino group. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Modified macromolescules and associated methods of synthesis and use (Fri, 01 Feb 2008)
<p id="p-0001" num="0000">Described herein are compounds such as macromolecules that have been modified in order to facilitate crosslinking by introduction of at least one hydrazide-reactive group and/or aminooxy-reactive group, and methods of making and using thereof for scar-free wound healing, for delivering bioactive agents or living cells, for preventing adhesion after a surgical procedure or for bone and cartilage repair. The macromolecule can be an oligonucleotide, a necleic acid, a polypeptide, a lipid, a glycoprotein, a glycolipid, a polysaccharide, a protein or a synthetic polymer, preferably a glycosaminoglycan like hyaluronan.</p>
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METHODS FOR TREATING PAIN AND SCREENING ANALGESIC COMPOUNDS (Fri, 25 Jan 2008)
The present invention relates to the use of compounds that block the α9α10 subtype of the nicotinic acetylcholine receptor (nAChR) for treating pain, such as neuropathic pain and inflammatory pain, and inflammatory disorders, such as arthritis. The present invention also relates to screening compounds to identify analgesic agents that block the α9α10 subtype of the nAChR.
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METHODS FOR TREATING PAIN AND SCREENING ANALGESIC COMPOUNDS (Fri, 25 Jan 2008)
The present invention relates to the use of compounds that block the .alpha.9.alpha.10 subtype of the nicotinic acetylcholine receptor (nAChR) for treating pain, such as neuropathic pain and inflammatory pain, and inflammatory disorders, such as arthritis. The present invention also relates to screening compounds to identify analgesic agents that block the .alpha.9.alpha.10 subtype of the nAChR.</p>
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THIOLATED MACROMOLECULES AND METHODS OF MAKING AND USING THEREOF (Fri, 18 Jan 2008)
Described herein are thiolated macromolecules and methods of making and using thereof.
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MACROMOLECULES MODIFIED WITH ELECTROPHILIC GROUPS AND METHODS OF MAKING AND USING THEREOF (Fri, 18 Jan 2008)
Described herein are macromolecules modified with electrophilic groups and methods of making and using thereof. The preparation of a thiol-reactive, electrophililic derivative of HA in order to prepare 'crosslinker-free' hydrogels are described as well as compounds and methods that are capable of coupling two or more molecules, such as macromolecules, under mild conditions. Specifically disclosed is the introduction of reactive bromo- and iodoacetate functionalities at the hydroxyl groups that are abundantly present on the HA polymer. The 'crosslinker- free' hydrogels described have numerous applications including, but not limited to, drug delivery, small molecule delivery, wound healing, burn injury healing, tissue regeneration/engineering, cell culturing, and bio-artificial materials.
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METHODS AND COMPOSITIONS RELATED TO INHIBITION OF CERAMIDE SYNTHESIS (Fri, 28 Dec 2007)
Disclosed are compositions and methods related to the ceramide synthesis pathway and various diseases and disorders associated therewith, such as insulin resistance and inflammation.
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J-SUPERFAMILY CONOTOXIN PEPTIDES (Sat, 22 Dec 2007)
The invention relates to relatively short peptides (termed J-Superfamily conotoxin peptides, J-conotoxins or J-conotoxin peptides herein), about 25 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds. The J-conotoxins are useful for treating disorders involving voltage gated ion channels and/or receptors.
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PAS KINASE REGULATES ENERGY HOMEOSTASIS (Sat, 22 Dec 2007)
Disclosed are compositions and methods related to PAS Kinase and various diseases and disorders associated therewith. Included are methods for treating insulin resistance, cancer, and diabetes comprising administering a composition that inhibits PAS Kinase and methods, including high throughput screening methods, for identifying test compounds that modulate PAS Kinase.
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PAS KINASE REGULATES ENERGY HOMEOSTASIS (Sat, 22 Dec 2007)
Disclosed are compositions and methods related to PAS Kinase (PASK) and various diseases and disorders associated therewith. Included are methods for treating insulin resistance, cancer, and diabetes comprising administering a composition that inhibits PAS Kinase. Further included are methods, including high throughput screening methods, for identifying test compounds that modulate PAS Kinase.
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PAS KINASE REGULATES ENERGY HOMEOSTASIS (Sat, 22 Dec 2007)
Disclosed are compositions and methods related to PAS Kinase (PASK) and various diseases and disorders associated therewith. Included are methods for treating insulin resistance, cancer, and diabetes comprising administering a composition that inhibits PAS Kinase. Further included are methods, including high throughput screening methods, for identifying test compounds that modulate PAS Kinase.</p>
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METHODS AND COMPOSITIONS RELATED TO EOSINOPHIL REGULATION (Fri, 30 Nov 2007)
Disclosed are compositions and methods for regulating eosinophils.
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METHODS AND COMPOSITIONS RELATED TO GABA RECEPTOR SUBUNITS (Fri, 30 Nov 2007)
Disclosed are compositions and methods related to GABAA receptors.
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MODIFIED MACROMOLECULES AND METHODS OF MAKING AND USING THEREOF (Thu, 29 Nov 2007)
</p> <p>Described herein are compounds such as macromolecules that have been modified in order to facilitate crosslinking by introduction of at least one hydrazide-reactive group and /or aminooxy-reactive group, and methods of making and using thereof for scar-free wound healing, for delivering bioactive agents or living cells, for preventing adhesion after a surgical procedure or for bone and cartilage repair. The macromolecule can be an oligonucleotide, a necleic acid, a polypeptide, a lipid, a glycoprotein, a glycolipid, a polysaccharide, a protein or a synthetic polymer, preferably a glycosaminoglycan like hyaluronan.
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Aliphatically modified biodegradable block copolymers as thermogelling polymers (Fri, 16 Nov 2007)
<p id="p-0001-en" num="0000">A thermogelling, aliphatically modified polymer for use in drug delivery is described. Illustrative embodiments include poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone) hexanoate and poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone) laurate. Another illustrative embodiment includes a composition having a thermogelling amount of an aliphatically modified poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone) and an effective amount of a drug. The thermogelling polymers are made by bonding an aliphatic group to poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone). A method of use includes injecting a warm-blooded individual with a thermogelling amount of the aliphatically modified polymer and a drug.</p>
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POLYMERIC COMPOSITIONS AND METHODS OF MAKING AND USING THEREOF (Fri, 02 Nov 2007)
Described herein are polymeric compositions that comprise at least one polymer residue and at least one crosslinking moiety, wherein the polymer residue is crosslinked by the crosslinking moiety and wherein the crosslinking moiety is formed from a reaction between a boronic acid moiety and a hydroxamic acid moiety. Also, described are methods of making and using such polymeric compositions.
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POLYMERIC COMPOSITIONS AND METHODS OF MAKING AND USING THEREOF (Fri, 02 Nov 2007)
Described herein are polymeric compositions that comprise at least one polymer residue and at least one crosslinking moiety, wherein the polymer residue is crosslinked by the crosslinking moiety and wherein the crosslinking moiety is formed from a reaction between a boronic acid moiety and a hydroxamic acid moiety. Also, described are methods of making and using such polymeric compositions.</p>
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Systems and methods for magnetic resonance imaging (Fri, 26 Oct 2007)
<p id="p-0001" num="0000">Methods and apparatus for operating an MRI system is provided. The disclosure provides a diffusion-prepared driven-equilibrium preparation for an imaging volume and acquiring 3-dimensional k-space data from said prepared volume by a plurality of echoplanar readouts of stimulated echoes. An excitation radio-frequency signal and first and second inversion RF signals are provided to define a field-of-view (FOV).</p>
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HIGH FIELD STRENGTH MAGNETIC FIELD GENERATION SYSTEM AND ASSOCIATED METHODS (Fri, 19 Oct 2007)
A magnetic field generation system can comprise first (28a) and second (28b) magnetic flux concentrators each spaced apart to form a sample volume (30). The first (28a) and second (28b) magnetic flux concentrators can be formed of a material having a magnetic field saturation. A first set of auxiliary permanent magnets (10a, 10b) can be symmetrically oriented about a portion of the first magnetic flux concentrator (28a) and can be in substantial contact with the first magnetic flux concentrator. Similarly, a second set of auxiliary permanent magnets (1 Oc, 1 Od) can be symmetrically oriented about a portion of the second magnetic flux concentrator (28b) and can be in substantial contact with the second magnetic flux concentrator. Generally, the first set (10a,10b) and second set (10c,10d) of auxiliary permanent magnets can be remote from the sample volume (30). Each of the first set and second set of auxiliary permanent magnets can be oriented in a magnetically repulsive orientation with respect to at least one other member of their respective sets. The first (10a,10b) and second (10c,10d) sets of auxiliary magnets can be magnetically associated via the first (28a) and second (28b) magnetic flux concentrators. The present invention can further be configured to allow variation of the magnetic field strength across the sample volume by disrupting the field flux across the magnetic flux concentrators. This can be accomplished by orienting one or more magnetically soft shunts (38) in a sufficient proximity to at least one of the magnetic flux concentrators (28a,28b).
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HIGHLY FLUORINATED OILS AND SURFACTANTS AND METHODS OF MAKING AND USING SAME (Fri, 05 Oct 2007)
Disclosed are compounds comprising the structure (I): In one aspect, the compounds exhibit maximum symmetric branching. Also disclosed are bilayers, micelles, coatings, and nanoparticles comprising the disclosed compounds. Also disclosed are processes for the preparation of the disclosed compounds and methods of using the disclosed compounds. Also disclosed are highly fluorinated dendrons and methods for making same. Also disclosed are methods for Fluorous Mixture Synthesis and tagging. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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INTRACELLULAR ISOTOPE DETECTION AND USES THEREOF (Fri, 21 Sep 2007)
A method is disclosed for measuring the hydrogen and/or oxygen isotope ratio of intracellular water in Escherichia coli cells and correlating the hydrogen and/or oxygen isotope ratio with the metabolic activity of the cell. A method is also disclosed for measuring the hydrogen and/or oxygen ratio of intracellular water via a probe, such as a fatty acid, and correlating the hydrogen and/or oxygen ratio with the metabolic activity of the cell. Methods for measuring the hydrogen and/or oxygen isotope ratio of water from eukaryotic organisms, such as cultured rat fibroblasts and whole mammals, and optionally relating the same to a metabolic rate, are also disclosed.
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METHODS AND COMPOSITIONS RELATED TO CYCLIC PEPTIDE SYNTHESIS (Fri, 14 Sep 2007)
Disclosed are compositions and methods for cyclization of polymers such as peptides.
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ENHANCED FILL-FACTOR NMR COILS AND ASSOCIATED METHODS (Fri, 14 Sep 2007)
An NMR probe which includes a probe matrix (24) having a void sample (28) volume therein. A conductive coil (16, 26) can be at least partially embedded in the probe matrix (24). By embedding the conductive coil (16, 26) in the probe matrix (24), the fill-factor can be significantly increased. NMR probes can be formed by a method which includes wrapping a conductive wire (16) around a coil form (18) to produce a coil precursor assembly. The probe matrix (24) can be formed around the conductive wire and coil form with a matrix material using any suitable technique such as soft lithography and/or molding. The coil form can be removed from the probe matrix leaving a void sample volume (28) in the probe matrix. Advantageously, the NMR probes of the present invention allow for fill-factors approaching and achieving 100%.
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METHODS AND COMPOSITIONS RELATED TO CYCLIC PEPTIDE SYNTHESIS (Fri, 14 Sep 2007)
Disclosed are compositions and methods for cyclization of polymers such as peptides.</p>
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Polymeric carrier for delivery of small interfering RNA (Fri, 07 Sep 2007)
<p id="p-0001-en" num="0000">A carrier for delivering small interfering RNA (siRNA) into cells includes a cholesterol residue covalently bonded to oligoarginine. Mixing the siRNA with the carrier produces a complex-containing composition. Contacting a cell with the complex-containing composition results in delivery of the siRNA into the cell. Delivery of an siRNA targeted to vascular endothelial growth factor is a treatment for cancer. Methods of making the carrier and complex are also disclosed.</p>
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Carrier system for specific artery wall gene delivery (Wed, 05 Sep 2007)
<p id="p-0001-en" num="0000">An artery wall binding peptide (AWBP) based on the artery wall cell-binding domain of apolipoprotein B-100 was conjugated to a cationic backbone configured for forming a complex with a nucleic acid to produce a composition that enhances gene transfer to artery wall cells. An illustrative cationic backbone is poly(ethylene glycol)-grafted-poly(L-lysine) (PEG-g-PLL). Methods of making and using the composition for gene transfer are also described.</p>
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APPARATUS AND METHODS FOR INCREASING LATERAL MASS TRANSFER OVER MOLECULE SENSORS (Fri, 13 Jul 2007)
Described are apparatus and methods allowing measurement of adsorption and desorption of analytes with resins directly using increased lateral mass transport Such increased lateral mass transport may be accomplished through the incorporation of a porous media, such as a fibrous bed or a concentrated bed of spheres, into said flow cell Further descnbed is a method of determining if a flo cell would benefit from increased lateral mass transport compπsing companng the rate of surface reaction to the mass transfer coefficient for a given analyte The detection method for the measurement of adsorption and desorption of analytes may be based on the evanescent wave phenomenon at total internal reflection including surface plasmon resonance (SPR).
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Linear polyethylenimine-sterol conjugates for gene delivery (Fri, 06 Jul 2007)
<p id="p-0001" num="0000">Linear polyethylenimine was modified with sterols, such as cholesterol, in three different geometries: linear shaped (L), T-shaped (T), and a combined linear- and T-shaped (LT), to result in linear polyethylenimine-sterol conjugates. These conjugates were mixed with nucleic acids to form complexes for delivery of the nucleic acids into cells. Mammalian cells transfected with these complexes showed protein expression levels higher than linear polyethylenimine alone, and twice that of branched polyethylenimine, but without any significant loss in cell viability. Methods of making these compositions and methods of using them for gene delivery are also described.</p>
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METHODS AND COMPOSITIONS INVOLVING INTRINSIC GENES (Fri, 01 Jun 2007)
Disclosed are compositions and methods related intrinsic gene sets and methods and compositions related to detecting and classifying cancer. </p>
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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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Noninvasive methods for detecting abnormalities in a subject such as disease or dysfunction (Wed, 16 May 2007)
<p id="p-0001-en" num="0000">The systems, methods and apparatus of the present invention comprise noninvasive methods of measuring temperature changes and rates of temperature change in selected body tissues and fluids as a result of absorption and/or dissipation of externally applied heat for the purpose of detecting and monitoring disease or dysfunction, and for preparing diagnostic images of the tissues and related areas from such measurements. Some embodiments of the present invention monitor temperatures of heated tissues directly while other embodiments may measure temperatures of tissues which are heated through flow of heated fluid therethrough.</p>
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POLYMERIC COMPOSITIONS AND METHODS OF MAKING AND USING THEREOF (Fri, 30 Mar 2007)
Described herein are polymeric compositions having a polymer residue and a crosslinker residue, wherein the polymer residue is bonded to the crosslinker residue with a moiety formed from a cycloaddition reaction. Also, described are methods of making and using such polymeric compositions.
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POLYMERIC COMPOSITIONS AND METHODS OF MAKING AND USING THEREOF (Fri, 30 Mar 2007)
Described herein are polymeric compositions having a polymer residue and a crosslinker residue, wherein the polymer residue is bonded to the crosslinker residue with a moiety formed from a cycloaddition reaction. Also, described are methods of making and using such polymeric compositions. </p>
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ANTI-ADHESION COMPOSITES AND METHODS OF USE THEREOF (Thu, 29 Mar 2007)
are methods of using the composites.
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Managing biological databases (Fri, 02 Feb 2007)
<p id="p-0001" num="0000">Methods and systems for managing biological databases. The methods and systems can comprise creation, organization, and presentation of biological databases. The biological databases can be created using data obtained from a plurality of other databases and periodically updated. An executive summary can be created for a biological sequence using the biological database.</p>
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METHODS AND COMPOSITIONS RELATED TO A BRAF MUTATION AND MICROSATELLITE STABILITY (Fri, 19 Jan 2007)
Disclosed are compositions and methods related to BRAF and microsatellite instability.
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COMPOSITIONS AND METHODS FOR PROVIDING A GRADED RESPONSE IN A PROTEIN (Fri, 12 Jan 2007)
The compositions and methods disclosed herein are of use for the graded control of proteins through modification of the post-translational state of said proteins. In particular, the methods provide for the subtle and gradual control of protein levels in direct contrast to the traditional theory of protein levels merely being 'on' at one consistent level or completely 'off.' The ability to modify protein levels may be useful in the production of a variety of cell types, including whole animals or plants, or for therapeutic or laboratory research purposes. Additionally, the methods of the present invention may be utilized to produce or inhibit particular proteins in patients suffering from diseases caused by the complete lack of a particular protein or an incorrect level of a protein.
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ECHOGENIC MICROBUBBLES AND MICROEMULSIONS FOR ULTRASOUND-ENHANCED NANOPARTICLE-MEDIATED DELIVERY OF AGENTS (Fri, 01 Dec 2006)
Described are methods and compositions for treating tumors, such as drug- sensitive tumors, inoperable tumors, poorly vascularized tumors, and multidrug resistant tumors, by intravenous or direct intratumoral injection of compositions comprising microemulsions and polymeric micelle-encapsulated biologically active agents. The methods and compositions also include microemulsions converting into microbubbles in situ upon injection. The methods disclosed optionally including applying a micelle disruption method such as ultrasound. Also disclosed are methodologies of imaging administration of agents in tissues using streams of microemulsions which create microbubbles in situ upon injection. The methods and compositions also include enhancement of tumor treatment through use of microemulsions which create microbubbles in situ, upon injection, as cavitation nuclei. The methods and compositions are also useful in enhancing intracellular drug delivery.
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ECHOGENIC MICROBUBBLES AND MICROEMULSIONS FOR ULTRASOUND-ENHANCED NANOPARTICLE-MEDIATED DELIVERY OF AGENTS (Fri, 01 Dec 2006)
Described are methods and compositions for treating tumors, such as drug- sensitive tumors, inoperable tumors, poorly vascularized tumors, and multidrug resistant tumors, by intravenous or direct intratumoral injection of compositions comprising microemulsions and polymeric micelle-encapsulated biologically active agents. The methods and compositions also include microemulsions converting into microbubbles in situ upon injection. The methods disclosed optionally including applying a micelle disruption method such as ultrasound. Also disclosed are methodologies of imaging administration of agents in tissues using streams of microemulsions which create microbubbles in situ upon injection. The methods and compositions also include enhancement of tumor treatment through use of microemulsions which create microbubbles in situ, upon injection, as cavitation nuclei. The methods and compositions are also useful in enhancing intracellular drug delivery. </p>
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Kappa-PVIIA-related conotoxins as organ protectants (Fri, 17 Nov 2006)
<p id="p-0001-en" num="0000">The invention relates to κ-PVIIA-related conotoxins and their use as organ protecting agents, i.e., organ protectants. These conotoxins can be used for arresting, protecting or preserving an organ, such as a circulatory organ, a respiratory organ, a urinary organ, a digestive organ, a reproductive organ, an endocrine organ or a neurological organ. These conotoxins can also be used for arresting, protecting or preserving somatic cells. </p>
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Elastin-based compositions (Wed, 25 Oct 2006)
<p id="p-0001-en" num="0000">The present invention provides screening methods that use organisms or cells that lack function in one or both elastin genes. These methods are useful in identifying drugs for the prevention and treatment of obstructive vascular diseases, such as atherosclerosis, vascular restenosis and transplant arteriopathy. Further, the invention provides pharmaceutical compositions containing elastin-based compositions that are particularly potent regulators of proliferation, differentiation, and migration of smooth muscle cells in vitro and in vivo. These pharmaceutical compositions and related methods are useful in the prevention and treatment of disorders characterized by diminished capacity to regulate smooth muscle cell function.</p>
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MOUSE MODEL (Fri, 15 Sep 2006)
The present invention relates to transgenic mice, particularly to knock-in mice, having mutations in the KCNQ2 gene or KCNQ3 gene, as well as sperm of such mice. The present invention also relates to targeting vectors intended for the generation of such mice. Furthermore, the present invention relates to murine embryonic stem cells and cryopreserved sperm comprising said targeting vectors as well as to a screening method for the identification of compounds for the treatment of a human physiological condition, such as benign familial neonatal convulsions (BFNC), partial epilepsies, therapeutically resistant epilepsies, migraine, neuropathic pain, stroke, dementia and anxiety.
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PRODRUGS AND CONJUGATES OF THIOL- AND SELENOL- CONTAINING COMPOUNDS AND METHODS OF USE THEREOF (Fri, 21 Jul 2006)
Disclosed are compounds having the formula (I) wherein R1 is hydrogen, an alkyl group, an aryl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aralkyl group, or =0, R2 is an alkyl group, an aryl group, a cycloalkyl group, an alkenyl group, an alkynyl group, or an aralkyl group, or the pharmaceutically acceptable salt or ester thereof. Also disclosed are methods of using the compounds.
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Particle analysis assay for biomolecular quantification (Fri, 16 Jun 2006)
<p id="p-0001" num="0000">A method is provided for carrying out multi-step separations of objects bearing at least two binding sites. In the first step, a first binder/bead composition is bound to objects that bear the first binding site, and then unbound objects, i.e. objects not bearing the first binding site, are separated from bound objects. In the second step, a second binder/bead composition is bound to the remaining objects that bear the second binding site, and then the objects that are bound to both beads are removed from those objects that are bound to only one bead. The beads can differ in magnetic responsiveness, charge, size, color, and the like, and these differences can be used to carry out the separation steps.</p>
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MRI GUIDED PHOTODYNAMIC THERAPY FOR CANCER (Fri, 09 Jun 2006)
Disclosed is a method of therapy used in combination with a diagnostic tool for enhanced photodynamic therapy using MRI, called (magnetic resonance imaging)-guided photodynamic therapy. The methods of the present invention includes administration of MRI contrast agent labeled polymer photosensitizer conjugates, detection and localization of tumor or cancer tissues with contrast-enhanced MRI and specific illumination and treatment of localized target tissues, such as tumors or cancer cells, using laser energy. The delivered laser energy activates the photosentizer accumulated in the target tissue, resulting in treatment. Also disclosed are novel conjugate compounds, such as PLGA-Mce6-DOTA-Gd complexes, having multi-functionality in that the complex may include an MRI contrasting agent linked to a photosensitizing agent.
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MRI GUIDED PHOTODYNAMIC THERAPY FOR CANCER (Fri, 09 Jun 2006)
Disclosed is a method of therapy used in combination with a diagnostic tool for enhanced photodynamic therapy using MRI, called (magnetic resonance imaging)-guided photodynamic therapy. The methods of the present invention includes administration of MRI contrast agent labeled polymer photosensitizer conjugates, detection and localization of tumor or cancer tissues with contrast-enhanced MRI and specific illumination and treatment of localized target tissues, such as tumors or cancer cells, using laser energy. The delivered laser energy activates the photosentizer accumulated in the target tissue, resulting in treatment. Also disclosed are novel conjugate compounds, such as PLGA-Mce6-DOTA-Gd complexes, having multi-functionality in that the complex may include an MRI contrasting agent linked to a photosensitizing agent. </p>
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Methods of selectively incorporating metals onto substrates (Fri, 17 Mar 2006)
<p id="p-0001-en" num="0000">A method for forming multi-metallic sites on a substrate is disclosed and described. A substrate including active groups such as hydroxyl can be reacted with a pretarget metal complex. The target metal attached to the active group can then be reacted with a secondary metal complex such that an oxidation-reduction (redox) reaction occurs to form a multi-metallic species. The substrate can be a highly porous material such as aerogels, xerogels, zeolites, and similar materials. Additional metal complexes can be reacted to increase catalyst loading or control co-catalyst content. The resulting compounds can be oxidized to form oxides or reduced to form metals in the ground state which are suitable for practical use.</p>
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Methods for chelation therapy (Fri, 10 Feb 2006)
<p id="p-0001-en" num="0000">The invention relates to compositions and methods of treatment using an iron chelator, an antioxidant, estrogen, and/or combinations thereof, optionally, linked to a nanoparticle, to treat a subject in need thereof. The compositions and methods may be used to restore or protect the normal functions of osteoblast and osteoclast by depleting iron and inhibiting oxidative damage. The compositions and methods may also be used to increase the bone formation rate in a subject.</p>
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Particle analysis assay for biomolecular quantification (Wed, 08 Feb 2006)
<p id="p-0001-en" num="0000">A method is provided for carrying out multi-step separations of objects bearing at least two binding sites. In the first step, a first binder/bead composition is bound to objects that bear the first binding site, and then unbound objects, i.e. objects not bearing the first binding site, are separated from bound objects. In the second step, a second binder/bead composition is bound to the remaining objects that bear the second binding site, and then the objects that are bound to both beads are removed from those objects that are bound to only one bead. The beads can differ in magnetic responsiveness, charge, size, color, and the like, and these differences can be used to carry out the separation steps.</p>
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METHOD AND COMPOSITIONS INVOLVING PROTEIN KINASE-δ (Fri, 03 Feb 2006)
Disclosed are methods and compositions relating to the use of PKC-δ activators in the treatment of disease.
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METHODS AND COMPOSITIONS INVOLVING PROTEIN KINASE C.DELTA. (Fri, 03 Feb 2006)
Disclosed are methods and compositions relating to the use of PKC-.delta. activators in the treatment of disease. </p>
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β-Superfamily conotoxins (Fri, 09 Dec 2005)
<p id="p-0001-en" num="0000">The present invention is directed to β-superfamily conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, ligand gated channels and other receptors. The invention is further directed to nucleic acid sequences encoding the β-superfamily conotoxin peptides and encoding β-superfamily conotoxin propeptides, as well as the β-superfamily conotoxin propeptides.</p>
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Prodrugs and conjugates of thiol- and selenol-containing compounds and methods of use thereof (Fri, 02 Dec 2005)
<p id="p-0001-en" num="0000">Disclosed are compounds having the formula</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="15.83mm" wi="27.77mm" file="US07425635-20080916-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> wherein R<sup>1 </sup>is hydrogen, an alkyl group, an aryl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an aralkyl group, or ═O, <ul id="ul0001-en" list-style="none"><li><ul id="ul0002-en" list-style="none"><li>R<sup>2 </sup>is an alkyl group, an aryl group, a cycloalkyl group, an alkenyl group, an alkynyl group, or an aralkyl group, <br/> or the pharmaceutically acceptable salt or ester thereof. Also disclosed are methods of using the compounds. </li></ul></li></ul></p>
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METHODS AND COMPOSITIONS RELATED TO DELIVERY OF CHEMICAL COMPOUNDS TO INVERTEBRATE EMBRYOS (Fri, 02 Dec 2005)
Disclosed are methods and compositions related to the delivery of chemical compounds to invertebrate embryos.
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BIORESPONSIVE POLYMER SYSTEM FOR DELIVERY OF MICROBICIDES (Fri, 28 Oct 2005)
The compositions disclosed herein include biodegradable elastomers that provide a material for. medical purposes. They may further provide a drug delivery ystem for the treatment of a wide variety of medical conditions. In particular, the compositions provide biodegradable elastomers composed of a pre-polymeric block, a degradable sequence and a bis-functional linker. The usefulness of the present invention is that it provides a biodegradable elastomer for use with medical devices.
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BIODEGRADABLE AND BIOCOMPATIBLE PEG-BASED POLY(ESTER-URETHANES) (Fri, 28 Oct 2005)
The compositions disclosed herein include biodegradable elastomers that provide a material for. medical purposes. They may further provide a drug delivery ystem for the treatment of a wide variety of medical conditions. In particular, the compositions provide biodegradable elastomers composed of a pre-polymeric block, a degradable sequence and a bis-functional linker. The usefulness of the present invention is that it provides a biodegradable elastomer for use with medical devices. </p>
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BIORESPONSIVE POLYMER SYSTEM FOR DELIVERY OF MICROBICIDES (Fri, 21 Oct 2005)
The polymer systems of the present invention degrade in the presence of an ejaculate. They may further provide degradable sequences that degrade upon contact with an ejaculate and/or microbicides. The polymer systems of the present invention are of use in the oral, rectal or vaginal cavities of an individual for such purposes as the treatment or prevention of sexually transmitted disease, the prevention or promotion of fertility or for hormone replacement therapy.
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BIORESPONSIVE POLYMER SYSTEM FOR DELIVERY OF MICROBICIDES (Fri, 21 Oct 2005)
The polymer systems of the present invention degrade in the presence of an ejaculate. They may further provide degradable sequences that degrade upon contact with an ejaculate and/or microbicides. The polymer systems of the present invention are of use in the oral, rectal or vaginal cavities of an individual for such purposes as the treatment or prevention of sexually transmitted disease, the prevention or promotion of fertility or for hormone replacement therapy. </p>
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Mice which are +/− or −/− for the elastin gene as models for vascular disease (Fri, 07 Oct 2005)
<p id="p-0001-en" num="0000">Elastin, the main component of arterial extracellular matrix, was thought to have a purely structural role. Consistent with this view, elastin hemizygous mice maintain arterial extensibility by increasing the number of elastic lamellae during development. However, mice lacking elastin die of obstructive arterial pathology. This pathology results from subendothelial proliferation and reorganization of smooth muscle, cellular changes similar to those observed in atherosclerosis. Thus, elastin is a molecular determinant of arterial morphogenesis and likely plays a central role in vascular disease. Mice which are heterozygous and null for the elastin gene have been developed. These mice are extremely useful for screening for drugs useful for treating persons with atherosclerosis, hypertension, SVAS or other vascular diseases.</p>
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Contulakin-G, analogs thereof and uses therefor (Fri, 16 Sep 2005)
<p id="p-0001-en" num="0000">The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr<sub>10</sub>-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders. </p>
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PH-sensitive polymeric micelles for drug delivery (Fri, 26 Aug 2005)
<p id="p-0001-en" num="0000">Mixed micelles containing poly(L-histidine)-poly(ethylene glycol) block copolymer and poly(L-lactic acid)-poly(ethylene glycol) block copolymer are a pH-sensitive drug carrier that release the drug in an acidic microenvironment, but not in the blood. Since the microenvironment of solid tumors is acidic, these mixed micelles are useful for treating cancer, including those cancers exhibiting multidrug resistance. Targeting ligands, such as folate, can also be attached to the mixed micelles for enhancing drug delivery into cells. Methods of treating a warm-blooded animal with such a drug are disclosed.</p>
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COMPOSITIONS AND METHODS FOR MODULATING DHR96 (Fri, 05 Aug 2005)
Disclosed are compositions and methods for modulating DHR96 activity and identifying molecules that modulate DHR96 activity.
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Crystal structure of the 30S ribosome and its use (Fri, 15 Jul 2005)
<p id="p-0001-en" num="0000">The invention provides an X-ray crystal structure of the 30S ribosome, obtained from <i>Thermus thermophilus </i>30S subunit, having a tetragonal space group P4<sub>1</sub>2<sub>1</sub>2 with unit cell dimensions of a=401.4±4.0 Å, b=401.4±4.0 Å, c=175.9±5.0 Å. An advantageous feature of the structure is that it diffracts beyond 3 Å resolution. The invention also provides a crystal of 30S having the three dimensional atomic coordinates of the 30S ribosome, the coordinates being provided in Tables 1A and 1B. The data may be used for the rational design and modelling of inhibitors for the 30S ribosome, which have potential use as antibiotics.</p>
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PROCESS AND FORMULATION TO IMPROVE VIABILITY OF STORED CELLS AND TISSUE (Fri, 24 Jun 2005)
Methods and compositions for the preservation of cells using glucosaminoglycans and derivatives thereof.
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MODIFIED MACROMOLECULES AND METHODS OF MAKING AND USING THEREOF (Fri, 24 Jun 2005)
Described herein are compounds such as macromolecules that have been modified in order to facilitate crosslinking by introduction of at least one hydrazide-reactive group and /or aminooxy-reactive group, and methods of making and using thereof for scar-free wound healing, for delivering bioactive agents or living cells, for preventing adhesion after a surgical procedure or for bone and cartilage repair. The macromolecule can be an oligonucleotide, a necleic acid, a polypeptide, a lipid, a glycoprotein, a glycolipid, a polysaccharide, a protein or a synthetic polymer, preferably a glycosaminoglycan like hyaluronan.
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MODIFIED MACROMOLECULES AND METHODS OF MAKING AND USING THEREOF (Fri, 24 Jun 2005)
Described herein are compounds such as macromolecules that have been modified in order to facilitate crosslinking by introduction of at least one hydrazide- reactive group and /or aminooxy-reactive group, and methods of making and using thereof for scar-free wound healing, for delivering bioactive agents or living cells, for preventing adhesion after a surgical procedure or for bone and cartilage repair. The macromolecule can be an oligonucleotide, a necleic acid, a polypeptide, a lipid, a glycoprotein, a glycolipid, a polysaccharide, a protein or a synthetic polymer, preferably a glycosaminoglycan like hyaluronan. </p>
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Mice which are +/− or −/− for the elastin gene as models for vascular disease (Wed, 08 Jun 2005)
<p id="p-0001-en" num="0000">Elastin, the main component of arterial extracellular matrix, was thought to have a purely structural role. Consistent with this view, elastin hemizygous mice maintain arterial extensibility by increasing the number of elastic lamellae during development. However, mice lacking elastin die of obstructive arterial pathology. This pathology results from subendothelial proliferation and reorganization of smooth muscle, cellular changes similar to those observed in atherosclerosis. Thus, elastin is a molecular determinant of arterial morphogenesis and likely plays a central role in vascular disease. Mice which are heterozygous and null for the elastin gene have been developed. These mice are extremely useful for screening for drugs useful for treating persons with atherosclerosis, hypertension, SVAS or other vascular diseases.</p>
>> read more

Tumor environment-induced ligand-expressing nanocarrier system (Fri, 03 Jun 2005)
<p id="p-0001-en" num="0000">Drug delivery compositions for specific delivery of a drug to a tumor are described. These compositions include a core for sequestering the drug and a shell to which a ligand is attached for delivery of a drug to target cells. Since normal cells may also be targeted by the ligand, the compositions embed the ligand in the shell until the localized conditions surrounding the tumor cause the ligand to be displayed on the surface of the shell. One composition exhibits shrinkage of the shell at tumor pH, whereas another composition exhibits extension of the ligand at tumor pH. Still another composition causes the ligand to be exhibited at an elevated temperature.</p>
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METHODS, ARTICLES, AND COMPOSITIONS FOR IDENTIFYING OLIGONUCLEOTIDES (Fri, 03 Jun 2005)
There are many situations where oligonucleotides that efficiently bind a target DNA or RNA are desired. These oligonucleotides can be used for a variety of purposes, including antisense, diagnostics, and array generation. While researchers have worked for many years to identify algorithms and methods for predicting the oligonucleotides that will bind the target with the highest efficiency, better prediction methods are needed. Disclosed are methods, articles, machines, and compositions that aid in identifying oligonucleotides and sets of oligonucleotides that will efficiently bind a target nucleic acid molecule. Also disclosed are optimized sets of oligonucleotides that bind HIV-1 genomic RNA or DNA,, such as the GAG RNA, and methods of using them.
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MinK-related genes, formation of potassium channels and association with cardiac arrhythmia (Wed, 09 Mar 2005)
<p id="p-00001-en" num="00001">The present invention is directed to genes and gene products related to Min-K which form ion channels and to a process for diagnosis of ion channel disorders, including long QT syndrome (LQT). For example, KCNE2 forms I<sub>Kr </sub>potassium channels and is associated with LQT. LQT is diagnosed in accordance with the present invention by analyzing the DNA sequence of KCNE2 of an individual to be tested and comparing the respective DNA sequence to the known DNA sequence of a normal KCNE2 gene. Alternatively, these MinK-related genes of an individual to be tested can be screened for mutations which cause ion channel disorders, including LQT. Prediction of ion channel disorders, including LQT, will enable practitioners to prevent the disorders using existing medical therapy. This invention is further directed to the discovery that the HERG and KCNE2 (also known as MiRP1) proteins coassemble to form a cardiac I<sub>Kr </sub>potassium channel.</p>
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Chromosome 17P-linked prostate cancer susceptibility gene (Wed, 19 Jan 2005)
<p id="p-00001-en" num="00001">The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human prostate cancer predisposing gene (HPC2), some alleles of which cause susceptibility to cancer, in particular prostate cancer. More specifically, the present invention relates to germline mutations in the HPC2 gene and their use in the diagnosis of predisposition to prostate cancer. The invention also relates to presymptomatic therapy of individuals who carry deleterious alleles of the HPC2 gene. The invention further relates to somatic mutations in the HPC2 gene in human prostate cancer and their use in the diagnosis and prognosis of human prostate cancer. Additionally, the invention relates to somatic mutations in the HPC2 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the HPC2 gene, (including gene therapy, protein replacement therapy, protein mimetics, and inhibitors). The invention further relates to the screening of drugs for cancer therapy. Finally, the invention relates to the screening of the HPC2 gene for mutations, which are useful for diagnosing the predisposition to prostate cancer.</p>
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Measurement of wax precipitation temperature and precipitated solid weight percent versus temperature by infrared spectroscopy (Wed, 12 Jan 2005)
<p id="p-00001-en" num="00001">Disclosed is a FT-IR spectroscopy method for the determination of the wax precipitation temperature, and the estimation of the amount of precipitated solid wax material (both crystalline and amorphous) present in a liquid hydrocarbon, such as a petroleum crude oil.</p>
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Mutations in the KCNE1 gene encoding human minK which cause arrhythmia susceptibility thereby establishing KCNE1 as an LQT gene (Fri, 07 Jan 2005)
<p id="p-0001-en" num="0000">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.</p>
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ANTI-ADHESION COMPOSITES AND METHODS OS USE THEREOF (Fri, 07 Jan 2005)
Described herein are composites that inhibit or reduce adhesion between two or more tissues. Also described herein are methods of using the composites.
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ANTI-ADHESION COMPOSITES AND METHODS OF USE THEREOF (Fri, 07 Jan 2005)
Described herein are composites that inhibit or reduce adhesion between two or more tissues. Also described herein are methods of using the composites. </p>
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Mutations in the KCNE1 gene encoding human minK which cause arrhythmia susceptibility thereby establishing KCNE1 as an LQT gene (Fri, 26 Nov 2004)
<p id="p-a-0001-en">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCAE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome. </p>
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ANALOGS OF LYSOPHOSPHATIDIC ACID AND METHODS OF MAKING AND USING THEREOF (Fri, 29 Oct 2004)
Described herein are analogs of lysophosphatidic acid having the formula (I). Also described herein are methods of making and using analogs of lysophosphatidic acid for improving wound healing, reducing inflammation or allergic response increasing or altering cardiovascular function, eliciting or inhibiting platelet aggregation, maintaining or terminating embryonic development.
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MinK-related genes, formation of potassium channels and association with cardiac arrhythmia (Fri, 08 Oct 2004)
<p id="p-a-0001-en">The present invention is directed to genes and gene products related to Min-K which form ion channels and to a process for diagnosis of ion channel disorders, including long QT syndrome (LQT). For example, KCNE2 forms I<sub>Kr </sub>potassium channels and is associated with LQT. LQT is diagnosed in accordance with the present invention by analyzing the DNA sequence of KCNE2 of an individual to be tested and comparing the respective DNA sequence to the known DNA sequence of a normal KCNE2 gene. Alternatively, these MinK-related genes of an individual to be tested can be screened for mutations which cause ion channel disorders, including LQT. Prediction of ion channel disorders, including LQT, will enable practitioners to prevent the disorders using existing medical therapy. This invention is further directed to the discovery that the HERG and KCNE2 (also known as MiRP1) proteins coassemble to form a cardiac I<sub>Kr </sub>potassium channel. </p>
>> read more

B-superfamily conotoxins (Fri, 10 Sep 2004)
<p id="p-a-0001-en">The present invention is directed to β-superfamily conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, ligand gated channels and other receptors. The invention is further directed to nucleic acid sequences encoding the β-superfamily conotoxin peptides and encoding β-superfamily conotoxin propeptides, as well as the β-superfamily conotoxin propeptides. </p>
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Conus gamma-carboxylase (Fri, 20 Aug 2004)
<p id="p-a-0001-en">The present invention is relates to a γ-carboxylase from Conus snails, a nucleic acid sequence encoding the Conus γ-carboxylase and to a method for using the nucleic acid or protein sequences for preparing γ-carboxylated proteins. </p>
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Linear polyethylenimine-sterol conjugates for gene delivery (Fri, 16 Jul 2004)
<p id="p-0001-en" num="0000">Linear polyethylenimine was modified with sterols, such as cholesterol, in three different geometries: linear shaped (L), T-shaped (T), and a combined linear- and T-shaped (LT), to result in linear polyethylenimine-sterol conjugates. These conjugates were mixed with nucleic acids to form complexes for delivery of the nucleic acids into cells. Mammalian cells transfected with these complexes showed protein expression levels higher than linear polyethylenimine alone, and twice that of branched polyethylenimine, but without any significant loss in cell viability. Methods of making these compositions and methods of using them for gene delivery are also described.</p>
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MANAGING BIOLOGICAL DATABASES (Fri, 07 May 2004)
A method for creating a database for managing multiple types of biological information, includes the steps of: inputing the biological information into the database as a new record, comparing the information in the record to the information already present in the database to determine whether the information already exist in the database; and adding the information to the database if it is not redundant. Creating at least one module for a specific type of biological information that is associated with each unique identifier, obtaining a form of biological information associated with a module in the database. Associating the biological information with the correct module in the database, and associating the biological information with the correct unique identifier.
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CROSSLINKED COMPOUNDS AND METHODS OF MAKING AND USING THEREOF (Fri, 07 May 2004)
Described herein are crosslinked compounds useful in numerous treatments. Described herein are methods of making crosslinked compounds via (1) the oxidative coupling of two or more thiol compounds or (2) by the reaction between at least one tbiol compound with at least one thiol-reactive compound.
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CROSSLINKED COMPOUNDS AND METHODS OF MAKING AND USING THEREOF (Fri, 07 May 2004)
Described herein are crosslinked compounds useful in numerous treatments. Described herein are methods of making crosslinked compounds via (1) the oxidative coupling of two or more thiol compounds or (2) by the reaction between at least one tbiol compound with at least one thiol-reactive compound. </p>
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Mutations in and genomic structure of <i>HERG</i>—a long QT syndrome gene (Fri, 23 Apr 2004)
<p id="p-0001-en" num="0000">The invention relates to the determination of the genomic structure of HERG which is a gene associated with long QT syndrome. The sequences of the 15 intron/exon junctions has been determined and this information is useful in devising primers for amplifying and sequencing across all of the exons of the gene. This is useful for determining the presence or absence of mutations which are known to cause long QT syndrome. Also disclosed are many new mutations in HERG which have been found to be associated with long QT syndrome.</p>
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MODULATING VESICULAR MONOAMINE TRANSPORTER TRAFFICKING AND FUNCTION: A NOVEL APPROACH FOR THE TREATMENT OF PARKINSON’S DISEASE (Fri, 02 Apr 2004)
Disclosed are compositions and methods for treating Parkinson's disease.
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METHODS AND COMPOSITIONS RELATED TO INHIBITING NUCLEAR ENVELOPE BREAKDOWN (Fri, 02 Apr 2004)
Disclosed are compositions and methods for inhibiting nuclear envelope breakdown.
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MODULATING VESICULAR MONOAMINE TRANSPORTER TRAFFICKING AND FUNCTION: A NOVEL APPROACH FOR THE TREATMENT OF PARKINSON'S DISEASE (Fri, 02 Apr 2004)
Disclosed are compositions and methods for treating Parkinson's disease. </p>
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Contulakin-G, analogs thereof and uses therefor (Wed, 25 Feb 2004)
<p id="p-00001-en">The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr<sub>10</sub>-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.</p>
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Characterization of single stranded nucleic acids by melting analysis of secondary structure using double strand-specific nucleic acid dye (Fri, 20 Feb 2004)
<p id="p-0001-en" num="0000">A novel method for characterizing nucleic acids. A nucleic acid is combined with a double stranded nucleic acid-specific dye to form a detectable complex between the dye and one or more double stranded structures within the nucleic acid. The combination is then exposed to varying temperatures and the fluorescence emission of the dye is measured to determine the melting temperature(s) for the double stranded structures. In some embodiments that melting temperature profile is then compared to melting temperature profiles generated for other nucleic acid(s) to discern differences between the compared nucleic acids.</p>
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NOVEL INHIBITORS OF UBIQUITIN ISOPEPTIDASES (Fri, 30 Jan 2004)
A novel class of inhibitors of ubiquitin isopeptidases is disclosed that cause tumor cell death via molecular mechanisms independent of p53. Specifically, compounds containing an a,ß-unsaturated ketone with a sterically accessible electrophilic ß-carbon and related compounds are identified herein. Pharmaceutical compositions comprising the inhibitor compounds and methods of using the compounds for treating a variety of disease states are disclosed.
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NOVEL INHIBITORS OF UBIQUITIN ISOPEPTIDASES (Fri, 30 Jan 2004)
A novel class of inhibitors of ubiquitin isopeptidases is disclosed that cause tumor cell death via molecular mechanisms independent of p53. Specifically, compounds containing an a,.szlig.-unsaturated ketone with a sterically accessible electrophilic .szlig.-carbon and related compounds are identified herein. Pharmaceutical compositions comprising the inhibitor compounds and methods of using the compounds for treating a variety of disease states are disclosed. </p>
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Common polymorphism in scn5a implicated in drug-induced cardiac arrhythmia (Fri, 26 Dec 2003)
<p id="p-0001-en" num="0000">The present invention is directed to a specific mutation in SCN5A which causes drug-induced torsade de pointes or ventricular fibrillation. Persons with the mutation are predisposed to developing drug-induced torsade de pointes or ventricular fibrillation when administered certain drugs. This predisposition can be diagnosed in accordance with the present invention by analyzing the DNA sequence of the SCN5A of an individual. By screening patients for the mutation, drug-induced torsade de pointes or ventricular fibrillation can be avoided. Furthermore, drugs can be tested to determine whether they will cause torsade de pointes or ventricular fibrillation.</p>
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Kappa-PVIIA-related conotoxins as organ protectants (Fri, 05 Dec 2003)
<p id="p-a-0001-en">The invention relates to κ-PVIIA-related conotoxins and their use as organ protecting agents, i.e., organ protectants. These conotoxins can be used for arresting, protecting or preserving an organ, such as a circulatory organ, a respiratory organ, a urinary organ, a digestive organ, a reproductive organ, an endocrine organ or a neurological organ. These conotoxins can also be used for arresting, protecting or preserving somatic cells. </p>
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3D STRUCTURE OF THE TSG101 UEV DOMAIN (Fri, 28 Nov 2003)
Disclosed are compositions and methods for inhibiting interactions of TSG101 and GAG.
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PREBLOCKING WITH NON-HA GAGS INCREASES EFFECTIVENESS OF HA CONJUGATED ANTICANCER AGENTS (Fri, 21 Nov 2003)
A cell-targeted polymeric drug delivery system was designed based on the specific interaction between hyaluronic acid (HA) and its cell surface receptors over-expressed on cancer cell surface. Compounds composed of a carrier molecule, wherein the carrier molecule contains at least one residue of an anti-cancer agent and at least one residue of a hyaluronic acid, are described. Also described are methods comprising pre-administering a non-HA GAG blocking agent before administering the HA conjugate. Also described are methods of making and using the compounds thereof.
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PREBLOCKING WITH NON-HA GAGS INCREASES EFFECTIVENESS OF HA CONJUGATED ANTICANCER AGENTS (Fri, 21 Nov 2003)
A cell-targeted polymeric drug delivery system was designed based on the specific interaction between hyaluronic acid (HA) and its cell surface receptors over-expressed on cancer cell surface. Compounds composed of a carrier molecule, wherein the carrier molecule contains at least one residue of an anti-cancer agent and at least one residue of a hyaluronic acid, are described. Also described are methods comprising pre-administering a non-HA GAG blocking agent before administering the HA conjugate. Also described are methods of making and using the compounds thereof. </p>
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Stabilization and acoustic activation of polymeric micelles for drug delivery (Wed, 19 Nov 2003)
<p id="p-00001-en">Methods are disclosed in which a micelle is stabilized against degradation upon dilution. The micelle comprises molecules of a block polymer having a hydrophobic block and a hydrophilic block. The hydrophobic block forms a core of the micelle with corona from the hydrophilic block. The methods for stabilizing the core are (1) by chemically cross-linking, (2) incorporating a hydrophobic oil (vegetable oil) in the core to render it more hydrophobic and stable, and (3) incorporating a cross-linked interpenetrating network of a stimuli-responsive hydrogel into the core. The hydrogel is responsive to any stimuli, but preferably temperature or pH. A substance such as, drugs, can be incorporated into the dense inner core of the micelles.</p> <p id="p-00002-en">When subjected to ultrasound, the micelles release the substance, and then reversibly revert to a stable dense core and re-encapsulating the substance when the ultrasound is turned off. By pulsing the ultrasound, it is therefore, to controllably release the substance in a pulsed manner corresponding to the ultrasound signal.</p>
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CHARACTERIZATION OF SINGLE STRANDED NUCLEIC ACIDS BY MELTING ANALYSIS USING A DOUBLE STRAND SPECIFIC NUCLEIC ACID DYE (Fri, 07 Nov 2003)
A novel method for characterizing nucleic acids. A nucleic acid is combined with a double stranded nucleic acid-specific dye to form a detectable complex between the dye and one or more double stranded structures within the nucleic acid. The combination is then exposed to varying temperatures and the fluorescence emission of the dye is measured to determine the melting temperature(s) for the double stranded structures. In some embodiments that melting temperature profile is then compared to melting temperature profiles generated for other nucleic acid(s) to discern differences between the compared nucleic acids.
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CHARACTERIZATION OF SINGLE STRANDED NUCLEIC ACIDS BY MELTING ANALYSIS OF SECONDARY STRUCTURE USING DOUBLE STRAND-SPECIFIC NUCLEIC ACID DYE (Fri, 07 Nov 2003)
A novel method for characterizing nucleic acids. A nucleic acid is combined with a double stranded nucleic acid-specific dye to form a detectable complex between the dye and one or more double stranded structures within the nucleic acid. The combination is then exposed to varying temperatures and the fluorescence emission of the dye is measured to determine the melting temperature(s) for the double stranded structures. In some embodiments that melting temperature profile is then compared to melting temperature profiles generated for other nucleic acid(s) to discern differences between the compared nucleic acids. </p>
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HYBRID PHOSPHOINOSITIDE PHOSPHOLIPIDS: COMPOSITIONS AND USES (Fri, 10 Oct 2003)
The methods and compositions disclosed synthesis of a novel class of 'two-headed' phospholipid-phosphoinositide hybrids possessing a carbon backbone, such as 2,3-diacylthreitol, erythritol or a synthetic module. The second phospholipid head group allows introduction of a biochemical or chemical moiety in a position orthogonal in space to those occupied by the phosphoinositide head group and the two acyl chains. The diacyl moieties allow for the incorporation of Pea-PIP2 into a lipid bilayer, while the Ptdlns(4,5)P2 moiety in the aqueous layer is specifically recognized by lipid binding proteins. In alternative embodiments of the invention, reporters, for example biotin, fluorophores and/or spin labels, are attached to the free amino group of the head groups of such molecules to specifically target the reporters to the lipid-water interface. Figure (1) illustrates (at c) an exemplary hybrid lipid of the present invention that possess a phosphatidylethanolamine (PE, or Pea) head group at the 1-position and a Ptdlns(4, 5)P2 head group at the 4-position.
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HYBRID PHOSPHOINOSITIDE PHOSPHOLIPIDS: COMPOSITIONS AND USES (Fri, 10 Oct 2003)
The methods and compositions disclosed synthesis of a novel class of "two- headed" phospholipid-phosphoinositide hybrids possessing a carbon backbone, such as 2,3-diacylthreitol, erythritol or a synthetic module. The second phospholipid head group allows introduction of a biochemical or chemical moiety in a position orthogonal in space to those occupied by the phosphoinositide head group and the two acyl chains. The diacyl moieties allow for the incorporation of Pea-PIP2 into a lipid bilayer, while the Ptdlns(4,5)P2 moiety in the aqueous layer is specifically recognized by lipid binding proteins. In alternative embodiments of the invention, reporters, for example biotin, fluorophores and/or spin labels, are attached to the free amino group of the head groups of such molecules to specifically target the reporters to the lipid-water interface. Figure (1) illustrates (at c) an exemplary hybrid lipid of the present invention that possess a phosphatidylethanolamine (PE, or Pea) head group at the 1-position and a Ptdlns(4, 5)P2 head group at the 4-position. </p>
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KVLQT1—a long QT syndrome gene (Fri, 12 Sep 2003)
<p id="p-0001-en" num="0000">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.</p>
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Beta-superfamily conotoxins (Fri, 12 Sep 2003)
<p id="p-a-0001-en">The present invention is directed to β-superfamily conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, ligand gated channels and other receptors. The invention is further directed to nucleic acid sequences encoding the β-superfamily conotoxin peptides and encoding β-superfamily conotoxin propeptides, as well as the β-superfamily conotoxin propeptides. </p>
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KCNQ2 and KCNQ3—potassium channel genes which are mutated in benign familial neonatal convulsions (BFNC) and other epilepsies (Fri, 05 Sep 2003)
<p id="p-0001-en" num="0000">Generalized idiopathic epilepsies (IGE) cause 40% of all seizures and commonly have a genetic basis. One type of IGE is Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited disorder of newborns. A submicroscopic deletion of chromosome 20q13.3 which co-segregates with seizures in a BFNC family has been identified. Characterization of cDNAs spanning the deleted region identified a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KCNQ1-like class of potassium channels. Nine other BFNC probands were shown to have KCNQ2 mutations including three missense mutations, three frameshifts, two nonsense mutations, and one splice site mutation. A second gene, KCNQ3, was found in a separate BFNC family in which the mutation had been localized to chromosome 8. A missense mutation was found in this gene in perfect cosegregation with the BFNC phenotype in this latter family. This demonstrates that defects in potassium channels can cause epilepsy. Furthermore, some members of one of the BFNC families with a mutation in KCNQ2 also exhibited rolandic epilepsy and one individual with juvenile myoclonic epilepsy has a mutation in an alternative exon of KCNQ3.</p>
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Reducing non-target nucleic acid dependent amplifications: amplifying repetitive nucleic acid sequences (Fri, 29 Aug 2003)
<p id="p-0001-en" num="0000">The present invention provides for compositions and methods for amplifying target nucleic acids using nucleic acid primers designed to limit non-target nucleic acid dependent priming events. The present invention permits amplifying and quantitating the number of repetitive units in a repetitive region, such as the number of telomere repetitive units.</p>
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KAPPA-PVIIA-RELATED CONOTOXINS AS ORGAN PROTECTANTS (Fri, 08 Aug 2003)
The invention relates to k-PVIIA-related conotoxins and their use as organ protecting agents, i.e., organ protectants. These conotoxins can be used for arresting, protecting or preserving an organ, such as a circulatory organ, a respiratory organ, a urinary organ, a digestive organ, a reproductive organ, an endocrine organ or a neurological organ. These conotoxins can also be used for arresting, protecting or preserving somatic cells.
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KAPPA-PVIIA-RELATED CONOTOXINS AS ORGAN PROTECTANTS (Fri, 08 Aug 2003)
The invention relates to k-PVIIA-related conotoxins and their use as organ protecting agents, i.e., organ protectants. These conotoxins can be used for arresting, protecting or preserving an organ, such as a circulatory organ, a respiratory organ, a urinary organ, a digestive organ, a reproductive organ, an endocrine organ or a neurological organ. These conotoxins can also be used for arresting, protecting or preserving somatic cells. </p>
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Diagnostic method for KVLQT1—a long QT syndrome gene (Wed, 25 Jun 2003)
<p id="p-00001-en">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.</p>
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Cone snail peptides (Fri, 13 Jun 2003)
<p id="p-a-0001-en">The present invention is directed to conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, voltage-gated ligand channels and/or receptors. The invention is further directed to nucleic acid sequences encoding the conotoxin peptides and encoding propeptides, as well as the propeptides. </p>
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Screening methods using the crystal structure of ribosomal protein L11/GTPase activating region rRNA complex (Fri, 30 May 2003)
<p id="p-00001-en" num="00001">The present invention is broadly directed to methods of screening ribosomal protein L11/GTPase activating region (GAR) RNA-modulating compounds by using information from the high-resolution structure of the L11/GAR complex. The methods are useful in identifying compounds useful for anti-bacterial treatments.</p>
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HIVGP120-INDUCED BOB/GPR15 ACTIVATION (Fri, 09 May 2003)
Disclosed are compositions and methods for reducing the interaction between gp120 and Bob.
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Mutations in the KCNE1 gene encoding human minK which cause arrhythmia susceptibility thereby establishing KCNE1 as an LQT gene (Fri, 21 Mar 2003)
<p id="p-a-0001-en">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome. </p>
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CONUS η-CARBOXYLASE (Fri, 21 Feb 2003)
The present invention is relates to a η-carboxylase from Conus snails, a nucleic acid sequence encoding the Conus η-carboxylase and to a method for using the nucleic acid or protein sequences for preparing η-carboxylated proteins.
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IN VITRO ASSAYS FOR INHIBITORS OF HIV CAPSID CONFORMATIONAL CHANGES AND FOR HIV CAPSID FORMATION (Fri, 21 Feb 2003)
Disclosed are methods and compositions for assays related to particle formation of the HIV virus.
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IN VITRO ASSAYS FOR INHIBITORS OF HIV CAPSID CONFORMATIONAL CHANGES AND FOR HIV CAPSID FORMATION (Fri, 21 Feb 2003)
Disclosed are methods and compositions for assays related to particle formation of the HIV virus. </p>
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PHENYLTHIOCARBAMIDE (PTC) TASTE RECEPTOR (Fri, 31 Jan 2003)
The invention provides isolated nucleic and amino acid sequences of a taste cell receptor that serves as a sensor for the bitter taste of phenylthiocarbamide (PTC), antibodies to such PTC taste receptor, methods of detecting such nucleic and amino acid sequences, and methods of screening for modulators of such PTC taste receptor. </p>
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HYALURONIC ACID CONTAINING BIOCONJUGATES : TARGETED DELIVERY OF ANTI-CANCER DRUGS TO CANCER CELLS (Fri, 15 Nov 2002)
A cell-targeted polymeric drug delivery system was designed based on the specific interaction between hyaluronic acid (HA) and its cell surface receptors overexpressed on cancer cell surface. The invention relates to compounds composed of a carrier molecule, 5 wherein the carrier molecule contains at least one residue of an anti-cancer agent and at least one residue of a hyaluronic acid. The invention also relates to methods of making and using the compounds thereof.
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HYALURONIC ACID CONTAINING BIOCONJUGATES: TARGETED DELIVERY OF ANTI-CANCER DRUGS TO CANCER CELLS (Fri, 15 Nov 2002)
A cell-targeted polymeric drug delivery system was designed based on the specific interaction between hyaluronic acid (HA) and its cell surface receptors overexpressed on cancer cell surface. The invention relates to compounds composed of a carrier molecule,5 wherein the carrier molecule contains at least one residue of an anti-cancer agent and at least one residue of a hyaluronic acid. The invention also relates to methods of making and using the compounds thereof. </p>
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ASSAY FOR DRUG-INDUCED RECODING (Fri, 04 Oct 2002)
A tissue culture assay for measuring drug-induced recoding in regulating cellular polyamine levels is described. A DNA construct containing the renilla luciferase gene separated by a short cloning site from the firefly luciferase gene, both under the control of a single upstream SV40 promoter is provided. The cloning site contains the portion of an antizyme gene known to contain the mRNA signals for polyamine stimulated frameshifting with the downstream firefly gene in the +1 position relative to the upstream renilla gene. A control construct is also produced with the genes in the same reading frame. Frameshifting efficiencies can be determined by comparing the ratio of firefly to renilla luciferase activity in parallel cell cultures.
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KVLQT1—a long QT syndrome gene (Wed, 18 Sep 2002)
<p id="p-00001-en">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.</p>
>> read more

Bioconjugates and delivery of bioactive agents (Fri, 23 Aug 2002)
<p id="p-00001-en">The present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise a bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively as a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis. Further, if the photolysis takes place in the presence of a magnetic field surrounding the release site, the release of the bioactive agent into surrounding healthy tissue is minimized.</p>
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CONE SNAIL PEPTIDES (Fri, 23 Aug 2002)
The present invention is directed to conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, voltage-gated ligand channels and/or receptors. The invention is further directed to nucleic acid sequences encoding the conotoxin peptides and encoding propeptides, as well as the propeptides.
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Bioconjugates and delivery of bioactive agents (Fri, 16 Aug 2002)
<p id="p-00001-en">The present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise a bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively as a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis. Further, if the photolysis takes place in the presence of a magnetic field surrounding the release site, the release of the bioactive agent into surrounding healthy tissue is minimized.</p>
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Mutations in the KCNE1 gene encoding human mink which cause arrhythmia susceptibility thereby establishing KCNE1 as an LQT gene (Wed, 14 Aug 2002)
<p id="p-00001-en">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.</p>
>> read more

Crystal structure of the 30s ribosome (Fri, 09 Aug 2002)
<p id="p-0001-en" num="0000">The invention provides an X-ray crystal structure of the 30S ribosome, obtained from <i>Thermus thermophilus </i>30S subunit, having a tetragonal space group P4<sub>1</sub>2<sub>1</sub>2 with unit cell dimensions of a=401.4±4.0 Å, b=401.4±4.0 Å, c=175.9±5.0 Å. An advantageous feature of the structure is that it diffracts beyond 3 Å resolution. The invention also provides a crystal of 30S having the three dimensional atomic coordinates of the 30S ribosome, the coordinates being provided in Tables 1A and 1B. The data may be used for the rational design and modelling of inhibitors for the 30S ribosome, which have potential use as antibiotics.</p>
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B-SUPERFAMILY CONOTOXINS (Fri, 09 Aug 2002)
The present invention is directed to B-superfamily conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, ligand gated channels and other receptors. The invention is further directed to the nucleic acid sequences encoding the B-superfamily conotoxin peptides and encoding B-superfamily conotoxin propeptides, as well as the B-superfamily conotoxin propeptides.
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KVLQT1—a long qt syndrome gene (Wed, 17 Jul 2002)
<p id="p-00001-en">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.</p>
>> read more

KCNQ2 and KCNQ3-potassium channel genes which are mutated in benign familial neonatal convulsions (BFNC) and other epilepsies (Wed, 03 Jul 2002)
<p id="p-00001-en">Generalized idiopathic epilepsies (IGE) cause 40% of all seizures and commonly have a genetic basis. One type of IGE is Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited disorder of newborns. A submicroscopic deletion of chromosome 20q13.3 which co-segregates with seizures in a BFNC family has been identified. Characterization of cDNAs spanning the deleted region identified a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KCNQ1-like class of potassium channels. Nine other BFNC probands were shown to have KCNQ2 mutations including three missense mutations, three frameshifts, two nonsense mutations, and one splice site mutation. A second gene, KCNQ3, was found in a separate BFNC family in which the mutation had been localized to chromosome 8. A missense mutation was found in this gene in perfect cosegregation with the BFNC phenotype in this latter family. This demonstrates that defects in potassium channels can cause epilepsy. Furthermore, some members of one of the BFNC families with a mutation in KCNQ2 also exhibited rolandic epilepsy and one individual with juvenile myoclonic epilepsy has a mutation in an alternative exon of KCNQ3.</p>
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METHOD AND APPARATUS FOR MULTI-LAYER GROWTH OF ANCHORAGE-DEPENDENT CELLS (Fri, 07 Jun 2002)
Anchorage-dependent cells are grown in a novel cell culture plate and on a novel substratum which increase the oxygenation of the cells. The cell culture plate is made by enclosing a growth chamber within a shell made of a solid sterilizable. One or more culture wells are positioned within the chamber. An inlet port and outlet port are fashioned within the shell for gas exchange. The wells have a well wall which allows for the diffusion of oxygen from the chamber into the well. A perfluorocarbon is placed within the well. A perfluoro-aldehyde is mixed with the perfluorocarbon, and the perfluoro-aldehyde re-orients so that the aldehyde head groups are at the interface. An attachment factor is bound to the perfluoro-aldehyde, which is sunk into the PFC substratum. Aqueous growth media is then added to the well, and anchorage-dependent cells added and allowed to grow.
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CARRIER SYSTEM FOR SPECIFIC ARTERY WALL GENE DELIVERY (Fri, 31 May 2002)
An artery wall binding peptide (AWBP) based on the artery wall cell-binding domain of apolipoprotein B-100 was conjugated to a cationic backbone configured for forming a complex with a nucleic acid to produce a composition that enhances gene transfer to artery wall cells. An illustrative cationic backbone is poly(ethylene glycol)-grafted-poly(L-lysine) (PEG-g-PLL). Methods of making and using the composition for gene transfer are also described.
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Bioconjugates and delivery of bioactive agents (Fri, 26 Apr 2002)
<p id="p-00001-en">The present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise a bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively as a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis. Further, if the photolysis takes place in the presence of a magnetic field surrounding the release site, the release of the bioactive agent into surrounding healthy tissue is minimized.</p>
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Contulakin-G, analogs thereof and uses therefor (Wed, 10 Apr 2002)
<p id="p-00001-en">The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr<sub>10</sub>-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.</p>
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Contulakin-G, analogs thereof and uses therefor (Wed, 06 Feb 2002)
<p id="p-00001-en">The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr<sub>10</sub>-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.</p>
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COMMON POLYMORPHISM IN SCN5A IMPLICATED IN DRUG-INDUCED CARDIAC ARRHYTHMIA (Fri, 01 Feb 2002)
The present invention is directed to a specific mutation in SCN5A which causes drug-induced torsade de pointes or ventricular fibrillation. Persons with the mutation are predisposed to developing drug-induced torsade de pointes or ventricular fibrillation when administered certain drugs. This predisposition can be diagnosed in accordance with the present invention by analyzing the DNA sequence of the SCN5A of an individual. By screening patients for the mutation, drug-induced torsade de pointes or ventricular fibrillation can be avoided. Furthermore, drugs can be tested to determine whether they will cause torsade de pointes or ventricular fibrillation.
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COMMON POLYMORPHISM IN SCN5A IMPLICATED IN DRUG-INDUCED CARDIAC ARRHYTHMIA (Fri, 01 Feb 2002)
The present invention is directed to a specific mutation in SCN5A which causes drug-induced torsade de pointes or ventricular fibrillation. Persons with the mutation are predisposed to developing drug-induced torsade de pointes or ventricular fibrillation when administered certain drugs. This predisposition can be diagnosed in accordance with the present invention by analyzing the DNA sequence of the SCN5A of an individual. By screening patients for the mutation, drug-induced torsade de pointes or ventricular fibrillation can be avoided. Furthermore, drugs can be tested to determine whether they will cause torsade de pointes or ventricular fibrillation. </p>
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HYDROGEL FILMS AND METHODS OF MAKING AND USING THEREFOR (Fri, 25 Jan 2002)
The present invention provides improved hydrogel films useful for therapeutic treatments. The invention also provides materials and methods for modification and polymerization of polysaccharides into hydrogel films, which swell after exposure to a neutral aqueous solution. The methods may include modification of a polysaccharide having at least one carboxylic acid group into a polysaccharide dihydrazide derivative, which is then crosslinked with a polyaldehyde to create a hydrogel film. The invention also relates pharmaceutical compositions composed of a pharmaceutically-acceptable compound and a hydrogel film of the invention. The invention also relates to using the hydrogel films and pharmaceutical compositions of the invention.
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HYDROGEL FILMS AND METHODS OF MAKING AND USING THEREFOR (Fri, 25 Jan 2002)
The present invention provides improved hydrogel films useful for therapeutic treatments. The invention also provides materials and methods for modification and polymerization of polysaccharides into hydrogel films, which swell after exposure to a neutral aqueous solution. The methods may include modification of a polysaccharide having at least one carboxylic acid group into a polysaccharide dihydrazide derivative, which is then crosslinked with a polyaldehyde to create a hydrogel film. The invention also relates pharmaceutical compositions composed of a pharmaceutically-acceptable compound and a hydrogel film of the invention. The invention also relates to using the hydrogel films and pharmaceutical compositions of the invention. </p>
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CRYSTAL STRUCTURE OF THE 30S RIBOSOME AND ITS USE (Tue, 15 Jan 2002)
The invention provides an X-ray crystal structure of the 30S ribosome, obtained from Thermus thermophilus 30S subunit, having a tetragonal space group P4 1 2 1 2 with unit cell dimensions of a = 401.4 ~ 4Ø.ANG., b = 401.4 ~ 4ØANG., c = 175.9 ~ 5ØANG.. An advantageous feature of the structure is that it diffracts beyond 3.ANG. resolution. The invention also provides a crystal of 30S having the three dimensional atomic coordinates of the 30S ribosome, the coordinates being provided in Tables 1A and 1B. The data may be used for the rational design and modelling of inhibitors for the 30S ribosome, which have potential use as antibiotics. </p>
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Mutations in the KCNE1 gene encoding human mink which cause arrhythmia susceptibility thereby establishing KCNE1 as an LQT gene (Wed, 28 Nov 2001)
<p id="p-00001-en">The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes ARE also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.</p>
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Methods for extracting substances using alternating current (Fri, 23 Nov 2001)
<p id="p-00001-en">A variety of methods for extracting different substances such as endogenous substances, pharmaceutical substances, markers of disease, and their metabolites across a tissue are provided. The methods utilize an AC signal to maintain a substantially constant electrical state in a region of the tissue through which extraction occurs, thereby allowing substances to be transported across the tissue in a controlled and predictable manner. Certain methods include an optional AC or DC prepulse signal to initially achieve the target electrical state. An optional DC offset signal can also be utilized to assist in promoting extraction of the substance. The methods have utility in a variety of different clinical settings and applications.</p>
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Bioconjugates and delivery of bioactive agents (Wed, 14 Nov 2001)
<p id="p-00001-en">The present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise of bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively at a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis. Further, if the photolysis takes places in the presence of a magnetic field surrounding the release site, the release of the bioactive agent into surrounding healthy tissue is minimized.</p>
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METHODS FOR EXTRACTING SUBSTANCES USING ALTERNATING CURRENT (Fri, 24 Aug 2001)
A variety of methods for extracting different substances such as endogenous substances, pharmaceutical substances, markers of disease, and their metabolites across a tissue are provided. The methods utilize an AC signal to maintain a substantially constant electrical state in a region of the tissue through which extraction occurs, thereby allowing substances to be transported across the tissue in a controlled and predictable manner. Certain methods include an optional AC or DC prepulse signal to initially achieve the target electrical state. An optional DC offset signal can also be utilized to assist in promoting extraction of the substance. The methods have utility in a variety of different clinical settings and applications. </p>
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AN ACTIVATED-THIOL POLYMER FOR DRUG DELIVERY (Fri, 11 May 2001)
The synthesis and characterization of an acrylamide copolymer for use as a carrier for the delivery of water soluble drugs. The polymer contains active-sulfhydryl groups for coupling of ligands through a disulfide linkage. The polymer can also be prepared containing pendant amino groups in addition to the active-sulfhydryl moiety. This allows the use of different chemistries to conjugate a variety of ligands to the polymer.
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Variable analog delay line for analog signal processing on a single integrated circuit chip (Wed, 25 Apr 2001)
<p id="p-00001-en">Programmable analog delay line devices for analog signal processing are constructed on a single integrated circuit chip using a switched capacitor storage scheme for short-term storage of the voltage or charge waveform. These devices provide variable maximum delay times without signal attenuation and with delay-to-risetime ratios of up to 10<sup>2</sup>to 10<sup>3</sup>. A vector array of switched capacitor analog storage elements may be arranged in a ring-buffer topology, with the number of switched capacitor elements ranging from between about 10 and about 10<sup>5</sup>. Two internal counters incremented by a common clock keep track of the variable delay between an input signal and an output signal.</p>
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PARTICLE ANALYSIS ASSAY FOR BIOMOLECULAR QUANTIFICATION (Fri, 20 Apr 2001)
A method is provided for carrying out multi-step separations of objects bearing at least two binding sites. In the first step, a first binder/bead composition is bound to objects that bear the first binding site, and then unbound objects, i.e. objects not bearing the first binding site, are separated from bound objects. In the second step, a second binder/bead composition is bound to the remaining objects that bear the second binding site, and then the objects that are bound to both beads are removed from those objects that are bound to only one bead. The beads can differ in magnetic responsiveness, charge, size, color, and the like, and these differences can be used to carry out the separation steps.
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Mutations in and genomic structure of HERG—a long QT syndrome gene (Wed, 28 Mar 2001)
<p id="p-00001-en">The invention relates to the determination of the genomic structure of HERG which is a gene associated with long QT syndrome. The sequences of the 15 intron/exon junctions has been determined and this information is useful in devising primers for amplifying and sequencing across all of the exons of the gene. This is useful for determining the presence or absence of mutations which are known to cause long QT syndrome. Also disclosed are many new mutations in HERG which have been found to be associated with long QT syndrome.</p>
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Methods for purifying and assaying a conus γ-carboxylase (Wed, 07 Mar 2001)
<p id="p-00001-en">The present invention is relates to a method for purifying a γ-carboxylase from Conus snails and to a method for assaying the activity of this γ-glutamyl carboxylase.</p>
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METHODS RELATED TO METABOLISM OF PARASITES AND MYCOBACTERIA (Fri, 22 Dec 2000)
The present invention relates to the field of microorganism metabolism. In one aspect, the present invention relates to parasite and mycobacterial steroid compound biosynthesis, including methods to inhibit the steroid compound biosynthesis. The present invention therefore relates broadly to microbiology, pharmaceutical chemistery, and disease treatments.
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17q-linked breast and ovarian cancer susceptibility gene (Wed, 20 Dec 2000)
<p>The present invention relates generally to the field of human genetics. Specifically, the present invention relates to methods and materials used to isolate and detect a human breast and ovarian cancer predisposing gene (BRCA1), some mutant alleles of which cause susceptibility to cancer, in particular breast and ovarian cancer. More specifically, the invention relates to germline mutations in the BRCA1 gene and their use in the diagnosis of predisposition to breast and ovarian cancer. The present invention further relates to somatic mutations in the BRCA1 gene in human breast and ovarian cancer and their use in the diagnosis and prognosis of human breast and ovarian cancer. Additionally, the invention relates to somatic mutations in the BRCA1 gene in other human cancers and their use in the diagnosis and prognosis of human cancers. The invention also relates to the therapy of human cancers which have a mutation in the BRCA1 gene, including gene therapy, protein replacement therapy and protein mimetics. The invention further relates to the screening of drugs for cancer therapy. Finally, the invention relates to the screening of the BRCA1 gene for mutations, which are useful for diagnosing the predisposition to breast and ovarian cancer.</p>
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STABILIZATION AND ACOUSTIC ACTIVATION OF POLYMERIC MICELLES FOR DRUG DELIVERY (Fri, 24 Nov 2000)
Methods are disclosed in which a micelle is stabilized against degradation upon dilution. The micelle comprises molecules of a block polymer having a hydrophobic block and a hydrophilic block. The hydrophobic block forms a core of the micelle with corona from the hydrophilic block. The methods for stabilizing the core are (1) by chemically cross-linking, (2) incorporating a hydrophobic oil (vegetable oil) in the core to render it more hydrophobic and stable, and (3) incorporating a cross-linked interpenetrating network of a stimuli-responsive hydrogel into the core. The hydrogel is responsive to any stimuli, but preferably temperature or pH. A substance such as drugs can be incorporated into the dense inner core of the micelles. When subjected to ultrasound, the micelles release the substance, and then reversibly revert to a stable dense core and re-encapsulating the substance when the ultrasound is turned off. By pulsing the ultrasound, it is therefore, to controllably release the substance in a pulsed manner corresponding to the ultrasound signal.
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Homozygous mutation in KVLQT1 which causes Jervell and Lange Nielsen syndrome (Wed, 22 Nov 2000)
<p>Jervell and Lange-Nielsen syndrome (JLN) is an autosomal recessive form of long QT syndrome. In addition to QT interval prolongation, this disorder is associated with congenital deafness. JLN is rare, but affected individuals are susceptible to cardiac arrhythmias with a high incidence of sudden death and short life expectancy. A homozygous mutation in KVLQT1, the potassium channel gene responsible for chromosome 11-linked long QT syndrome, is shown to be a cause of JLN. -GOVT PAR This application was made with Government support under Grant No. Pb 50-HL52338-02 (SCOR), funded by the National Institutes of Health, Bethesda, Md. The federal government may have certain rights in this invention.</p>
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MinK-RELATED GENES, FORMATION OF POTASSIUM CHANNELS AND ASSOCIATION WITH CARDIAC ARRHYTHMIA (Fri, 27 Oct 2000)
The present invention is directed to genes and gene products related to Min-K which form ion channels and to a process for diagnosis of ion channel disorders, including long QT syndrome (LQT). For example, KCNE2 forms IKr potassium channels and is associated with LQT. LQT is diagnosed in accordance with the present invention by analyzing the DNA sequence of KCNE2 of an individual to be tested and comparing the respective DNA sequence to the known DNA sequence of a normal KCNE2 gene. Alternatively, these MinK-related genes of an individual to be tested can be screened for mutations which cause ion channel disorders, including LQT. Prediction of ion channel disorders, including LQT, will enable practitioners to prevent the disorders using existing medical therapy. This invention is further directed to the discovery that the HERG and KCNE2 (also known as MiRP1) proteins coassemble to form a cardiac IKr potassium channel.
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NONINVASIVE METHODS FOR DETECTING ABNORMALITIES IN A SUBJECT SUCH AS DISEASE OR DYSFUNCTION (Fri, 27 Oct 2000)
The systems, methods and apparatus of the present invention comprise noninvasive methods of measuring temperature changes and rates of temperature change in selected body tissues and fluids as a result of absorption and/or dissipation of externally applied heat for the purpose of detecting and monitoring disease or dysfunction, and for preparing diagnostic images of the tissues and related areas from such measurements. Some embodiments of the present invention monitor temperatures of heated tissues directly while other embodiments may measure temperatures of tissues which are heated through flow of heated fluid therethrough.
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MINK-RELATED GENES, FORMATION OF POTASSIUM CHANNELS AND ASSOCIATION WITH CARDIAC ARRHYTHMIA (Fri, 27 Oct 2000)
The present invention is directed to genes and gene products related to Min-K which form ion channels and to a process for diagnosis of ion channel disorders, including long QT syndrome (LQT). For example, KCNE2 forms IKr potassium channels and is associated with LQT. LQT is diagnosed in accordance with the present invention by analyzing the DNA sequence of KCNE2 of an individual to be tested and comparing the respective DNA sequence to the known DNA sequence of a normal KCNE2 gene. Alternatively, these MinK-related genes of an individual to be tested can be screened for mutations which cause ion channel disorders, including LQT. Prediction of ion channel disorders, including LQT, will enable practitioners to prevent the disorders using existing medical therapy. This invention is further directed to the discovery that the HERG and KCNE2 (also known as MiRP1) proteins coassemble to form a cardiac IKr potassium channel. </p>
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Amphipathic oligonucleotides and polynucleotides having potent antiviral activity (Wed, 11 Oct 2000)
<p>The present invention provides novel compositions that show potent antiviral activity against both DNA and RNA viruses. In particular, the present invention provides oligo- and polyribonucleotides with potent antiviral activity against HIV and HCMV. These compositions are thought to operate in a novel fashion at an early stage of viral infection, meeting the need for alternatives or synergistic therapies to the toxic treatments currently available. The present invention also discloses methods for synthesizing oligo- and polyribonucleotides showing antiviral activity.</p>
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ELASTIN-BASED COMPOSITIONS (Fri, 01 Sep 2000)
The present invention provides screening methods that use organisms or cells that lack function in one or both elastin genes. These methods are useful in identifying drugs for the prevention and treatment of obstructive vascular diseases, such as atherosclerosis, vascular restenosis and transplant arteriopathy. Further, the invention provides pharmaceutical compositions containing elastin-based compositions that are particularly potent regulators of proliferation, differentiation, and migration of smooth muscle cells in vitro and in vivo. These pharmaceutical compositions and related methods are useful in the prevention and treatment of disorders characterized by diminished capacity to regulate smooth muscle cell function.
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ELASTIN-BASED COMPOSITIONS (Fri, 01 Sep 2000)
The present invention provides screening methods that use organisms or cells that lack function in one or both elastin genes. These methods are useful in identifying drugs for the prevention and treatment of obstructive vascular diseases, such as atherosclerosis, vascular restenosis and transplant arteriopathy. Further, the invention provides pharmaceutical compositions containing elastin-based compositions that are particularly potent regulators of proliferation, differentiation, and migration of smooth muscle cells in vitro and in vivo. These pharmaceutical compositions and related methods are useful in the prevention and treatment of disorders characterized by diminished capacity to regulate smooth muscle cell function. </p>
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ATTACHMENT OF ACID MOIETY-CONTAINING BIOMOLECULES TO ACTIVATED POLYMERIC SURFACES (Fri, 21 Jul 2000)
Compositions comprising an activated polymeric substrate having an acid moiety-containing biomolecule covalently bonded via the acid moiety to the substrate are disclosed. Methods for making such compositions are also provided, including methods that involve plasma processing of the substrate prior to the attachment of the biomolecule. These compositions find use as novel biomaterials, e.g. for tissue engineering and the prevention of adhesions, for selective attachment and growth of specific cell types, for coating surgically-implanted materials, and in coating vessels for storage of blood and blood products.
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Actin mutations in dilated cardiomyopathy, a heritable form of heart failure (Wed, 17 May 2000)
<p>Two mutations in the human cardiac actin gene are disclosed which have been associated with idiopathic dilated cardiomyopathy (IDC) in two families. These mutations cosegregate with IDC in the two families. Both mutations affect universally conserved amino acids in domains of actin that attach to Z bands and intercalated discs. Analysis of the cardiac actin gene can be used to determine the presence in a patient of IDC resulting from mutations in this gene. Such analysis is useful in the diagnosis and prognosis of the disease in patients with mutations in this gene. -GOVT PAR This application was made with Government support under an NIH SCOR grant (Grant No. 5-P50-HL-53773) funded by the National Institutes of Health, Bethesda, Md. and Public Health Services Research Grant M01-RR00064 from the National Center for Research Resources. The U.S. Government has certain rights in this invention.</p>
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CONTULAKIN-G, ANALOGS THEREOF AND USES THEREFOR (Fri, 28 Apr 2000)
The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson"s disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette"s syndrome, Huntington"s chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.
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CONTULAKIN-G, ANALOGS THEREOF AND USES THEREFOR (Fri, 28 Apr 2000)
The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10- contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti- inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti- psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti- arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders. </p>
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DELIVERY OF PHOSPHOINOSITIDE POLYPHOSPHATES INTO CELLS (Fri, 07 Apr 2000)
A method for facilitating delivery of a phosphatidylinositol polyphosphate or derivative thereof into a eukaryotic cell is disclosed. The method includes forming a complex of the phosphatidylinositol polyphosphate or derivative with a polyamine, and then contacting the cell with the complex. Preferred polyamines include aminoglycosides, dendrimeric polyamines, and histones. Compositions of matter for use in the method are also described. A method for screening compounds for minimum toxicity to eukaryotic cells and maximum toxicity to bacterial cells is also disclosed. Also disclosed is a method for monitoring calcium flux in a cell.
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DELIVERY OF PHOSPHOINOSITIDE POLYPHOSPHATES INTO CELLS (Fri, 07 Apr 2000)
A method for facilitating delivery of a phosphatidylinositol polyphosphate or derivative thereof into a eukaryotic cell is disclosed. The method includes forming a complex of the phosphatidylinositol polyphosphate or derivative with a polyamine, and then contacting the cell with the complex. Preferred polyamines include aminoglycosides, dendrimeric polyamines, and histones. Compositions of matter for use in the method are also described. A method for screening compounds for minimum toxicity to eukaryotic cells and maximum toxicity to bacterial cells is also disclosed. Also disclosed is a method for monitoring calcium flux in a cell. </p>
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METHOD FOR PREPARATION OF LOW MOLECULAR WEIGHT POLYETHYLENE GLYCOL-CARBOXYLIC ACIDS (Fri, 10 Mar 2000)
A method of making low molecular weight polyethylene glycol carboxylic acids comprises reacting lower molecular weight polyethylene glycols with monohalogen-substituted aliphatic acid esters in base, and then saponifying the resulting intermediates. The polyethylene glycol carboxylic acids are then extracted with a toluene-containing organic phase for removing unreacted compounds and byproducts. The extracted polyethylene glycol carboxylic acids are then acidified and purified by dialysis, gel filtration, or extraction and precipitation.
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MUTATIONS IN AND GENOMIC STRUCTURE OF HERG - A LONG QT SYNDROME GENE (Fri, 11 Feb 2000)
The invention relates to the determination of the genomic structure of HERG which is a gene associated with long QT syndrome. The sequences of the 15 intron/exon junctions has been determined and this information is useful in devising primers for amplifying and sequencing across all of the exons of the gene. This is useful for determining the presence or absence of mutations which are known to cause long QT syndrome. Also disclosed are many new mutations in HERG which have been found to be associated with long QT syndrome.
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HUMAN MINK GENE MUTATIONS ASSOCIATED WITH ARRHYTHMIA (Fri, 11 Feb 2000)
The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes are also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.
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KVLQT1 - A LONG QT SYNDROME GENE (Fri, 11 Feb 2000)
The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes are also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome.
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MUTATIONS IN AND GENOMIC STRUCTURE OF HERG - A LONG QT SYNDROME GENE (Fri, 11 Feb 2000)
The invention relates to the determination of the genomic structure of HERG which is a gene associated with long QT syndrome. The sequences of the 15 intron/exon junctions has been determined and this information is useful in devising primers for amplifying and sequencing across all of the exons of the gene. This is useful for determining the presence or absence of mutations which are known to cause long QT syndrome. Also disclosed are many new mutations in HERG which have been found to be associated with long QT syndrome. </p>
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KVLQT1 - A LONG QT SYNDROME (Fri, 11 Feb 2000)
The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes are also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome. </p>
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HUMAN MINK GENE MUTATIONS ASSOCIATED WITH ARRHYTHMIA (Fri, 11 Feb 2000)
The genomic structure including the sequence of the intron/exon junctions is disclosed for KVLQT1 and KCNE1 which are genes associated with long QT syndrome. Additional sequence data for the two genes are also disclosed. Also disclosed are newly found mutations in KVLQT1 which result in long QT syndrome. The intron/exon junction sequence data allow for the design of primer pairs to amplify and sequence across all of the exons of the two genes. This can be used to screen persons for the presence of mutations which cause long QT syndrome. Assays can be performed to screen persons for the presence of mutations in either the DNA or proteins. The DNA and proteins may also be used in assays to screen for drugs which will be useful in treating or preventing the occurrence of long QT syndrome. </p>
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HYALURONIC ACID MIMICS AND METHODS RELATED THERETO (Fri, 14 Jan 2000)
HA mimics and methods related thereto are disclosed. In particular, mimics with structures determined by virtue of novel methods, and the novel methods are disclosed. The HA mimics are useful for a variety of HA-related uses. </p>
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HYDROGELS OF WATER SOLUBLE POLYMERS CROSSLINKED BY PROTEIN DOMAINS (Fri, 24 Dec 1999)
A stimuli-responsive, hybrid hydrogel wherein the bulk of the polymer is made up of relatively inexpensive water soluble polymer strands crosslinked by protein domains. The responsiveness of the gel is controlled or modulated by the protein component.
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