Abstract: Provided herein are microfluidic devices that can be used as a 3D bioassay, e.g., for drug screening, personalized medicine, tissue engineering, wound healing, and other applications. The device has a series of channels {e.g., small fluid channels) in a small polymer block wherein one or more of the channels can be filled with a biologically relevant gel, such as collagen, which is held in place by posts. As shown herein, when the device is plated with cells such as endothelial cells, new blood vessels grow in the gel, which is thick enough for the cells to grow in three dimensions. Other channels, e.g., fluid channels, allow drugs or biological material to be exposed to the 3D cell growth. Cells, such as endothelial cells, can be cultured and observed as they grow on the surface of a 3D gel scaffold, where e.g., rates of angiogenesis can be measured, as well as intervascularization and extravascularization of cancerous cells.

Abstract: Methods of modifying, repairing, attenuating and inactivating a gene or other chromosomal DNA in a cell are disclosed. Also disclosed are methods of treating or prophylaxis of a genetic disease in an individual in need thereof. Further disclosed are chimeric restriction endonucleases.

Abstract: The present invention is based upon a surprising finding that stem cells, more particularly neural stem cells, can migrate throughout a brain tumor and track metastatic brain tumor cells. The invention provides a method for treating brain tumors by administering genetically engineered neural stem cells in an individual affected by brain tumors. The invention also provides a method of preparing genetically engineered neural stem cells and a composition comprising genetically engineered neural stem cells in a pharmaceutically acceptable carrier.

Abstract: The present invention provides a method for recombinant production, recovery and purification of endostatin protein. This method may be employed for large scale recovery and purification of recombinantly-produced endostatin protein.

Abstract: A replacement heart valve apparatus. The heart valve apparatus includes a stent and a valve frame having a substantially cylindrical body defining a lumen. The valve frame includes a plurality of curved wire pairs attached to the substantially cylindrical body. Each curved wire pair includes an inner curved wire and an outer curved wire. The wire frame further having a plurality of leaflets. Each leaflet is attached to a respective inner curved wire and extends over a respective outer curved wire, so as to position the body of the leaflet within the lumen of the valve frame.

Abstract: The present invention relates to isolated and/or recombinant nucleic acids which encode a mammalian (e.g., human) receptor protein designated C—C Chemokine Receptor 3 (CKR-3) or Eos L2, and to proteins or polypeptides, referred to herein as isolated, recombinant mammalian CKR-3 receptors. The invention further relates to recombinant nucleic acid constructs, comprising a nucleic acid which encodes a receptor protein of the present invention or a portion thereof; to host cells comprising such constructs, useful for the production of recombinant CKR-3 receptors or polypeptides; and to antibodies reactive with the receptors, which are useful in research and diagnostic applications. Also provided are methods of use of the nucleic acids, proteins, and host cells to identify ligands, inhibitors (e.g., antagonists) or promoters (agonists) of receptor function.

Abstract: Novel packaging cell lines useful for generating viral accessory protein independent HIV-derived retroviral vector particles, methods of constructing such packaging cell lines and methods of using the viral accessory protein independent HIV-derived retroviral vector particles are disclosed.

Abstract: The present invention provides a bipolar coagulator which can be passed through the internal lumen of a ventricular catheter previously implanted into a cranial ventricle of a living subject and engaged in-situ. The bipolar coagulator will provide bipolar electrical arc currents for coagulation cauterization of adherent brain tissues, such as the choroid plexus, which occludes fluid flow into the intake drainage holes in the implanted ventricular catheter and often becomes adherent to the catheter in-situ. The cautery current provided by the bipolar coagulator is direction oriented and spatially controlled; thereby providing a better distribution of electrical current and heat within the surrounding cranial tissues; and thereby avoiding major complications of damage to intracranial structures such as blood vessels as well as avoiding the severe subarachnoid hemorrhages which are typical using other kinds of coagulation instruments.

Abstract: Disclosed are peptides which are peptide derivatives of the HJ loop of a protein tyrosine kinase. The peptides can modulate the activity of the protein tyrosine kinase. Also disclosed are methods of modulating the activity of a protein tyrosine kinase in a subject by administering one of the peptides of the present invention.

Abstract: A minicell display method has been developed which has significant advantages for screening peptide libraries for candidates that can bind and effectively modulate a particular biological process. The method, based on the small, anucleate minicell, has increased versatility in generating unique sequences to screen as well as increasing the size of the peptides to be screened. In vivo mutagenesis, at the level of protein synthesis, as well as DNA replication, increases diversification of the library to be screened and therefore substantially increases the number of potential peptides that can modulate a particular biological response or mechanism. A number of representative peptides have been generated using this methodology and demonstrated to have desirable biological and pharmaceutical activities.

Abstract: Compositions and methods are provided for producing multilayered artificial organs comprising heterogenous polylayers. Polylayers comprising homogenous cell populations are created on one side of a biocompatible substrate such that a chimeric interface is produced between the heterogenous polylayers. Cellular interaction at the chimeric interface produce an interstitial biomaterial with morphological and functional characteristics that resemble the natural in vivo organ. An artificial organ is produced by creating a first cultured polylayer of cells derived from an isolated population of smooth muscle cells on a substrate in the shape of an organ, and creating a second cultured polylayer of cells derived from a cell population different from the smooth muscle cell population.

Abstract: The invention provides improved methods of introducing site-directed mutations into circular DNA molecules of interest by means of mutagenic primer pairs. The mutagenic primer pairs are also selected so as to be either completely complementary or partially complementary to each other, wherein the mutation site (or sites) is located within the region of complementarity. A mutagenic primer pair is annealed to opposite strands of a circular DNA molecule containing the DNA sequence to be mutagenized. After annealing, first and second mutagenized DNA strands, each incorporating a member of the mutagenic oligonucleotide primer pair is synthesized by a linear cyclic amplification reaction. After the linear cyclic amplification mediated synthesis step is completed, the reaction mixture is treated with a selection enzyme that digests the parental template strands. After the digesting step, a double-stranded circular DNA intermediate is formed.

Abstract: Disclosed are peptides which are peptide derivatives of the HJ loop of a serine/threonine kinase. The peptides can modulate the activity of the serine/threonine kinase. Also disclosed are methods of modulating the activity of a serine/threonine kinase in a subject by administering one of the peptides of the present invention.

Abstract: A method is provided whereby cells having a desired function are seeded on and into biocompatible, biodegradable or non-degradable porous polymer scaffolding matrix, previously implanted in a patient and infiltrated with blood vessels and connective tissue, to produce a functional organ equivalent. The resulting organoid is a chimera formed of parenchymal elements of the donated tissue and vascular and matrix elements of the host. The matrix should be compression resistant and a non-toxic, porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, should allow vascular and connective tissue ingrowth throughout approximately 10 to 90% of the matrix, and the injection of cells such as hepatocytes without damage to the cells or patient. The introduced cells attach to the connective tissue and are fed by the blood vessels.

Abstract: Growth factors and/or angiogenic factors are administered in combination with dissociated cells to be transplanted, preferably in microspheres with the cells on or in a polymeric matrix, to enhance survival and proliferation of the transplanted cells. Examples demonstrate that epidermal growth factor (EGF) was incorporated into microspheres fabricated from a copolymer of lactic and glycolic acid using a double emulsion technique, the incorporated EGF was steadily released over one month in vitro, and it remained biologically active, as determined by its ability to stimulate DNA synthesis, division, and long-term survival of cultured hepatocytes. EGF-containing microspheres were mixed with a suspension of hepatocytes, seeded onto porous sponges, and implanted into the mesentery of two groups of Lewis rats, to demonstrate efficacy in vivo.

Abstract: The present invention relates to inhibition of angiogenesis and the treatment of diseases mediated by angiogenesis. Particularly, the invention relates to the inhibition of neovascularization and the treatment of cancer. The invention further relates to the use of cytochalasin derivatives for the inhibition of angiogenesis and the treatment of angiogenesis associated diseases.

Abstract: A formulation for inducing sustained local anesthesia in a patient comprising a substrate comprising a high load of local anesthetic by weight and an effective amount of a biocompatible, controlled release material to obtain a. reversible nerve blockade or anesthesia effect when implanted or injected in a patient, and a non-toxic glucocorticosteroid agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without the glucocorticosteroid agent.

Abstract: Disclosed are peptides which are peptide derivatives of the HJ loop of a serine/threonine kinase. The peptides can modulate the activity of the serine/threonine kinase. Also disclosed are methods of modulating the activity of a serine/threonine kinase in a subject by administering one of the peptides of the present invention.

Abstract: A vented flask cap having a body portion with proximal and distal ends with a generally cylindrical sidewall extending from the proximal end to the distal end of first and second support plates are formed at the proximal end of the body portion and having a plurality of apertures extending therethrough; a filter assembly is also provided which includes a first, lower membrane having a first porosity, a second, upper membrane having a second porosity and a radiation absorbing material disposed between the first and second membranes.

Abstract: The present invention is a spatially aligned conjugated composition which comprises at least one chemically modified substance which is immunologically representative of a prechosen infectious agent and provides a chemical constituent for entering into and forming a thioether bond; a plurality of chemically substituted metallic oxide particles which range from about 10-10,000 nanometers and are able to enter into a thioether bond and covalent linkage; and at least one thioether bond and linkage joining the metallic oxide particles in a controlled and spatially aligned manner to the antigen or hapten. The conjugated composition may be alternatively employed as an immunogen; as a vaccine; as a diagnostic tool and reactant; and as an analytical material suitable for testing the pharmacological activity of new compounds.