Abstract: Methods for engineering transgenic organisms that synthesize polyhydroxyalkanoates (PHAs) containing 3-hydroxyhexanoate as comonomer have been developed. These processes are based on genetically engineered bacteria such as Escherichia coli or in plant crops as production systems which include PHA biosynthetic genes from PHA producers. In a preferred embodiment of the method, additional genes are introduced in wild type or transgenic polyhydroxybutyrate (PHB) producers, thereby creating new strains that synthesize 3HH monomers which are incorporated into PHAs. The 3HH monomer preferably is derived in microbial systems using butanol or butyrate as feedstocks, which are precursors of 3-hydroxyhexanoyl-CoA. Pathways for in vivo production of butyrol-CoA specifically encompassing butyryl-CoA dehydrogenase activity are provided.

Abstract: Method for controlling the deposition of organic contaminants from the pulp and papermaking systems using water soluble aminoplast ether copolymers is described herein. The aminoplast ether copolymer can be used alone or in combination with one or more additives. The pulps to be treated include mechanical, chemical, semi-chemical pulps; sulfide pulp; recycled old newspapers; mixed office wastes; corrugated boxes; and their combinations. The use of water soluble aminoplast ether copolymers to control or prevent pitch and stickies deposition improves down stream performance of papermaking equipment increasing mill efficiency and improving paper quality.

Abstract: Genetically engineered organisms for production of PHA copolymers containing 2-hydroxyacid monomers and the methods of making and using thereof have been developed. The copolymers containing 2-hydroxyacid monomers can be synthesized via biosynthesis by the action of a PHA polymerase in a living cell. By changing the genetic background of the cells, one can control specific metabolic pathways allowing control of the level of glycolic acid co-monomer in the PHA polymer.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal. Methods for modifying the genome of non-nuclear organelles are also provided.

Abstract: Absorbable polyester fibers, braids, and surgical meshes with prolonged strength retention have been developed. These devices are preferably derived from biocompatible copolymers or homopolymers of 4-hydroxybutyrate. These devices provide a wider range of in vivo strength retention properties than are currently available, and could offer additional benefits such as anti-adhesion properties, reduced risks of infection or other post-operative problems resulting from absorption and eventual elimination of the device, and competitive cost. The devices may also be particularly suitable for use in pediatric populations where their absorption should not hinder growth, and provide in all patient populations wound healing with long-term mechanical stability. The devices may additionally be combined with autologous, allogenic and/or xenogenic tissues to provide implants with improved mechanical, biological and handling properties.

Abstract: It has been discovered that there are at least two significant antigens present on the cells of animal species such as pigs that elicit an immune or inflammatory response immediately upon implantation into humans or contact with human serum. The first is an ?-galactosyl (Gal) epitope, for example, Gal?(1?3)Gal?(1?4)GlcNac (linear B type 2) or Gal? (1?3)Gal?(1?4)Glc (linear B type 6). The second is an N-glycolylneuraminic acid (NeuGc) structure. By eliminating these epitopes, preferably by genetically engineering the animal so that the epitope is either not produced or is greatly reduced, or by chemical or enzymatic treatment of the animal's cells to remove the epitopes, it is possible to produce organs, tissues and cells suitable for xenotransplantation into humans. Cells can be rendered even more compatible by genetically engineering the animal to express a human complement regulatory protein (inhibitor), such as CD59, on its cells, or to express an excess of a pig complement regulatory protein.

Abstract: Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g.

Abstract: Compositions, and methods of use thereof, are provided for the treatment of painful neuropathy by local or topical delivery of compounds that interact with ?-adrenergic receptors, especially an alpha2 adrenergic agonist such as clonidine, to the entire painful area such that the need for systemic dosing is minimized. The compounds are delivered to or adjacent to painful areas in patients with painful length dependent neuropathy, and other neuropathies that affect the pain signaling fibers in the skin. A preferred compound for the treatment of patients with length dependent neuropathy is clonidine applied in a transdermal patch, gel, ointment, lotion, liposomal formulation, cream, or emulsion, wherein the concentration is sufficient to provide an effective dose in the painful area or immediately adjacent areas.

Abstract: Interposition and augmentation devices for tendon and ligament repair, including rotator cuff repair, have been developed as well as methods for their delivery using arthroscopic methods. The devices are preferably derived from biocompatible polyhydroxyalkanoates, and preferably from copolymers or homopolymers of 4-hydroxybutyrate. The devices may be delivered arthroscopically, and offer additional benefits such as support for the surgical repair, high initial strength, prolonged strength retention in vivo, flexibility, anti-adhesion properties, improved biocompatibility, an ability to remodel in vivo to healthy tissue, minimal risk for disease transmission or to potentiate infection, options for fixation including sufficiently high strength to prevent suture pull out or other detachment of the implanted device, eventual absorption eliminating future risk of foreign body reactions or interference with subsequent procedures, competitive cost, and long-term mechanical stability.

Abstract: Clinical studies have been conducted and specific dosage formulations developed using polymeric microparticles having incorporated therein perfluorocarbon gases that provide significantly enhanced images of long duration. The dosage formulation includes microparticles formed of a biocompatible polymer, preferably including a lipid incorporated therein, and containing a perfluorocarbon that is a gas at body temperature. The microparticles are provided to a patient in an amount effective to enhance ultrasound imaging in the ventricular chambers for more than 5 minutes or in the mycocardium for more than a minute, in a dose ranging from 0.025 to 8.0 mg microparticles/kg body weight. Preferably the dose ranges from 0.05 to 4.0 mg microparticles/kg body weight. The dosage formulation typically is provided in a vial.

Abstract: Soluble H4 (sH4) levels have been discovered to correlate with the stage or severity of inflammatory disorders including autoimmune disorders. In particular, circulating levels of sH4 can be used as a diagnostic for determining the severity of an inflammatory disorder or the propensity for developing an inflammatory disorder. The severity of an inflammatory disorder can be determined by assaying the levels of sH4 in a subject and comparing the levels of sH4 to reference sH4 concentrations that correlate to specific stages of an inflammatory disorder. The therapeutic efficacy of treatments for inflammatory disorders can also be determined by comparing levels of sH4 before and during treatment. Methods and devices for measuring sH4 are also provided.

Abstract: A dressing for promoting healing and pain relief of the body of a living organism having a pathologic condition has at least one layer of conductive material having a resistance no greater than 1000 ?/cm2. When placed proximate a portion of the body of the living organism suffering from the pathologic condition, the dressing alters the electrodynamic processes occurring in conjunction with said pathologic condition to promote healing and pain relief in the living organism. When used as a wound dressing, the conductive material is placed in contact with tissue around the periphery of the wound and with the wound, lowering the electrical potential and resistance of the wound and increasing the wound current.

Abstract: The present invention provides a method for determining hair inductive properties of a composition comprising injecting a composition comprising dissociated dermal cells and epidermal cells into skin of a mammal and determining whether at least one hair follicle forms.

Abstract: The invention provides the use of a compound of Formula (I), or metallated derivative thereof, in the preparation of a medicament for killing or attenuating the growth of microorganisms by a method which does not comprise exposing the compound to a photodynamic therapy light source or a sonodynamic therapy ultrasound source Formula (I) wherein X1, X2, X3, X4, Yi, Y2, Y3, Y4 and Z have meanings given in the description. Preferably, the microorganisms are selected from the group consisting off bacteria, mycoplasmas, yeasts, fungi and viruses.

Abstract: A method for reversibly, or irreversibly, altering the permeability of cells, tissues or other biological barriers, to molecules to be transported into or through these materials, through the application of acoustic energy, is provided. The acoustic energy is applied indirectly to the cells or tissue whose permeability is to be altered, at a frequency and intensity appropriate to alter the permeability to achieve the desired effect, such as the transport of endogenous or exogenous molecules and/or fluid, for drug delivery, measurement of analyte, removal of fluid, alteration of cell or tissue viability or alteration of structure of materials. In the preferred embodiment, the method includes applying the ultrasound in combination with devices for monitoring and/or implementing feedback controls.

Abstract: Coexpression of a polyhydroxyalkanoic acid synthase and a either a fatty acid:acyl-CoA transferase or an acyl-CoA synthetase in cells enables the biosynthesis of polyester materials. Plasmids, bacteria, materials, and methods for the preparation of polyesters are disclosed.

Abstract: Highly undifferentiated spore-like cells can be isolated from many different tissues and bodily fluids and used to treat a wide variety of disorders.

Abstract: Unique labels for security or identification purposes, methods of making the labels and uses for the labels are described herein. The label is formed from one or more crystalline materials, optionally in combination with a non-crystalline material, or from a combination of polymers, and has a unique, detectable pattern. In one embodiment, the label is formed from a crystalline material, preferably a metallic material, which naturally contains a unique grain structure, with unique reflective properties. In a preferred embodiment, the label is formed of a metallic material that has been recrystallized to enlarge the size of the grains so that they are visible to the unaided human eye.

Abstract: It has been discovered that improved yields of engineered tissue following implantation, and engineered tissue having enhanced mechanical strength and flexibility or pliability, can be obtained by implantation, preferably subcutaneously, of a fibrous polymeric matrix for a period of time sufficient to obtain ingrowth of fibrous tissue and/or blood vessels, which is the removed for subsequent implantation at the site where the implant is desired. The matrix is optionally seeded prior to the first implantation, after ingrowth of the fibrous tissue, or at the time of reimplantation. The time required for fibrous ingrowth typically ranges from days to weeks. The method is particularly useful in making valves and tubular structures, especially heart valves and blood vessels.

Abstract: The present invention provides compounds that are inducers or inhibitors of apoptosis of apoptosis preceded by cell-cycle arrest. In addition, the present invention provides pharmaceutical compositions and methods for treating mammals with leukemia or other forms of cancer or for treating disease conditions caused by apoptosis of cells.