Abstract: The present invention is directed to novel phenyloin derivative compounds and the use of such compounds as sodium channel blockers. Such compositions have utility as anti-cancer agents and can be used to limit or prevent PCa growth and/or metastasis.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface and an immunostimulatory moiety. In some embodiments, the immunostimulatory moiety is an adjuvant. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface. The nanocarriers are capable of targeting antigen presenting cells when administered to a subject. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract: Fluid activatable adhesive compositions and activating fluid(s) for activating the adhesive composition are described herein. The adhesive compositions contain at least two polymers with different hydrophilicities. The hydrophilic polymer has quick tack when exposed to a hydrophilic solvent, such as water or other aqueous solvent, while the hydrophobic polymer provides strong adhesion to a paper or polymeric substrate. The adhesive composition may contain particulate fillers which enable fast exhaustion of the activation fluid out of the adhesive when applied to a substrate, thereby allowing the hydrophobic polymers of the adhesive composition to achieve strong adhesion of the liner-free label to the paper or polymeric substrate. The particulate fillers may also function as anti-blocking agents when liner-free label media are tightly wound in a roll.

Abstract: A hydrophilic vehicle-based dual controlled-release matrix system, suitable for encapsulation in hard or soft capsules, has been developed. The matrix is in the form of a solution or a suspension, which allows for easier formulation of low dose compounds. The matrix includes two rate controlling barriers for the controlled release of one or more pharmaceutically active agents. The primary rate controlling barrier includes a hydrophilic vehicle. The primary rate controlling barrier can further comprise one or more solvents which are miscible with the hydrophilic vehicle. The secondary rate controlling barrier includes a hydrogel-forming polymeric material dissolved or dispersed in the hydrophilic vehicle. The presence of the hydrogel-forming polymeric material makes extraction of the drug from the dosage form more difficult. This feature could be beneficial in preventing or minimizing the misuse of dosage forms which contain drugs which are prone to abuse.

Abstract: Fluid activatable adhesive compositions and activating fluid(s) for activating the adhesive composition are described herein. The adhesive compositions contain at least two polymers with different hydrophilicities. The hydrophilic polymer has quick tack when exposed to a hydrophilic solvent, such as water or other aqueous solvent, while the hydrophobic polymer provides strong adhesion to a paper or polymeric substrate. The adhesive composition may contain particulate fillers which enable fast exhaustion of the activation fluid out of the adhesive when applied to a substrate, thereby allowing the hydrophobic polymers of the adhesive composition to achieve strong adhesion of the liner-free label to the paper or polymeric substrate. The particulate fillers may also function as anti-blocking agents when liner-free label media are tightly wound in a roll.

Abstract: Compositions and methods of using scorpion venom peptide that is a ligand for ClC channels are provided. One aspect provides a pharmaceutical composition containing an amount of GaTx2 effective to inhibit ClC activity. Methods of treating a disorder or symptom of a disorder related to aberrant ClC channel activity are also provided.

Abstract: The present invention generally relates to polymers and macromolecules, in particular, to block polymers useful in particles such as nanoparticles. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. In some cases, the nanoparticle may contain a drug. The moiety, in some embodiments, may have a molecular weight greater than about 1000 Da; for example, the moiety may include a polypeptide or a polynucleotide, such as an aptamer. The moiety may also be a targeting moiety, an imaging moiety, a chelating moiety, a charged moiety, or a therapeutic moiety.

Abstract: A method of local treatment of specific bone defects such as osteoporosis or bone cysts comprises the step of local administration of a formulation comprising a fusion peptide containing a first domain comprising PTH or BMP 2 or BMP 7, and a second domain comprising a covalently crosslinkable substrate domain; and a material suitable of forming a biodegradable matrix suitable for cellular growth or in-growth, wherein the fusion peptide is covalently linked to the matrix. In one embodiment, the matrix contains one or more contrast agents, and is preferably formed in the absence of a growth factor. The matrix may be used in the treatment of fluid-filled cysts such as Tarlov cysts, ovarian cysts, arachnoid cysts, aneurysmal bone cysts or hepatic cysts.

Abstract: A system has been constructed that recapitulate the features of a capillary bed through normal human tissue. The system facilitates perfusion of three-dimensional (3D) cell monocultures and heterotypic cell co-cultures at the length scale of the capillary bed. A major feature is that the system can be utilized within a “multiwell plate” format amenable to high-throughput assays compatible with the type of robotics commonly used in pharmaceutical development. The system provides a means to conduct assays for toxicology and metabolism and as a model for human diseases such as hepatic diseases, including hepatitis, exposure-related pathologies, and cancer. Cancer applications include primary liver cancer as well as metastases. The system can also be used as a means of testing gene therapy approaches for treating disease and inborn genetic defects.

Abstract: Disclosed herein are methods and compositions related to the detection of conformational changes and interactions with trigger molecules in riboswitches.

Abstract: Pharmaceutical compositions containing an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methyl transferase inhibito to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control are provided. It has been discovered that ligands for GPR109 can be used to treat one or more symptoms of cancer, inflammatory disorders, and diarrhea. Representative CPR109 ligands include, but are not limited to butyrate, ?-hydroxybutyrate, nicotinic acid, acifran, and octanoate. Suitable DNA methyl transferase inhibitors include 5-azacytidine, 5-aza-2?-deoxytidine, 1-?-D-arabinfarnosyl-5-azacytosine and dihydro-5-azacytidine. Typically, the compositions are formulated to achieve a GPR109 ligand serum blood level of about 1 to about 1000 ?M. The compositions are useful for the treatment of one or more symptoms of cancer.

Abstract: Compositions and methods for targeted gene therapy are disclosed. Compositions containing double duplex-forming pseudocomplementary oligonucleotides are administered in combination with a donor oligonucleotide that is homologous to a target sequence on a double-stranded DNA molecule in need of repair or replacement. By activating cellular mechanisms involved in DNA synthesis, repair and recombination, the double duplex-forming pseudocomplementary oligonucleotides can introduce one or more mutations at a site of interest by increasing the efficiency of targeted recombination of the donor oligonucleotide. The pseudocomplementary oligonucleotides/donor oligonucleotide compositions may be administered in combination with a second therapeutic agent that enhances access of the pseudocomplementary oligonucleotides and/or the donor oligonucleotide to the target site, an agent that enhances or increases DNA repair or recombination, or an agent that enhances uptake or delivery of the oligonucleotides.

Abstract: Bioactive molecules are entrapped within a matrix for the controlled delivery of these compounds for therapeutic healing applications. The matrix may be formed of natural or synthetic compounds. The primary method of entrapment of the bioactive molecule is through precipitation of the bioactive molecule during gelation of the matrix, either in vitro or in vivo. The bioactive molecule may be modified to reduce its effective solubility in the matrix to retain it more effectively within the matrix, such as through the deglycosylation of members within the cystine knot growth factor superfamily and particularly within the TGF? superfamily. The matrix may be modified to include sites with binding affinity for different bioactive molecules, for example, for heparin binding.

Abstract: Liquid orlistat-containing fill materials suitable for encapsulating in hard or soft capsules are described herein. The fill material contains orlistat dissolved in one or more medium chain triglycerides or medium chain partial triglycerides, one or more citrate esters, and combinations thereof. The fill material can also contain one or more pharmaceutically acceptable excipients. In one embodiment, the fill material is substantially free of surfactants. The fill material can be encapsulated in hard or soft, gelatin or non-gelatin capsules. The capsules may be coated to modify release of orlistat from the capsule. Alternatively, the fill material can be encapsulated in an enteric capsule, wherein the enteric polymer is a component of the capsule shell, rather than a coating over the capsule shell. The fill materials are stable at elevated temperatures over an extended period of time and allow for high loadings of orlistat (e.g., 20% w/w or higher).

Abstract: This invention relates to an improved semi-synthetic process for the preparation of taxane derivatives like paclitaxel, docetaxel, canadensol and its derivatives, the process, which has shorten reaction route, simple procedure, high yield and low materials cost, therefore facilitates the commercial manufacture of these derivatives.

Abstract: A flexible, multilayer wound dressing with antibacterial and antifungal properties, together with methods for making the dressing. The dressing includes a layer of silver-containing fabric, a layer of absorbent material, and (optionally) a layer of flexible air-permeable and/or water-impermeable material. The dressing can be used for prophylactic and therapeutic care and treatment of skin infections and surface wounds (including surgical incisions), as a packing material, and as a swab for surface cleaning.

Abstract: Methods and constructs for the introduction of multiple genes into plants using a single transformation event are described. Constructs contain a single 5? promoter operably linked to DNA encoding a modified intein splicing unit. The splicing unit is expressed as a polyprotein and consists of a first protein fused to an intein fused to a second protein. The splicing unit has been engineered to promote excision of all nonessential components in the polyprotein but prevent the ligation reactions normally associated with protein splicing. A single 3? termination sequence, such as a polyadenylation sequence when the construct is to be expressed in eucaryotic cells, follows the last coding sequence. These methods and constructs are particularly useful for creating plants with stacked input traits, illustrated by glyphosate tolerant plants producing BT toxin, and/or value added products, illustrated by the production of polyhydroxyalkanoates in plants.

Abstract: A lipophilic vehicle-based dual controlled-release matrix, suitable for encapsulation in hard or soft capsules, has been developed. The matrix is in the form of a suspension, which allows for easier formulation of low dose compounds and/or compounds which are moisture sensitive. The matrix includes two rate controlling barriers for the controlled release of one or more pharmaceutically active agents. The primary rate controlling barrier includes a relatively lipophilic oily vehicle. The primary rate controlling barrier may further comprise or more excipients, dissolved in the lipophilic vehicle, which themselves have rate controlling properties. The secondary rate controlling barrier is a hydrogel-forming polymeric material which is dispersed in the primary rate controlling barrier. As the primary rate controlling barrier breaks down, the pharmaceutically active agent is slowly released and the surrounding aqueous media begins to percolate into the polymer matrix.

Abstract: Green tea polyphenol compositions and methods of their use are provided. Certain aspects provide methods for modulating expression of one or more autoantigens using the disclosed green tea polyphenol compositions. Representative green tea polyphenols include, but are not limited to (?)-epigallocatechin-3-gallate. Other aspects provide methods for treating autoimmune disease.