Abstract: In accordance with the present invention, there are provided methods to modulate processes mediated by retinoid receptors, employing high affinity, high specificity ligands for such receptors. In one aspect of the present invention, there are provided ligands which are more selective for the retinoid X receptor than is retinoic acid (i.e., rexoids). In another aspect of the present invention, alternative ligands (other than retinoic acid) have been discovered which are capable of inducing retinoic acid receptor mediated processes. In yet another aspect, methods have been developed for the preparation of such retinoid receptor ligands from readily available compounds.

Abstract: In accordance with the present invention, there are provided composition and methods useful for the in vivo delivery of a pharmaceutically active agent, wherein the agent is associated with a polymeric biocompatible material.

Abstract: In accordance with the invention, there are provided methods, capsules, and delivery systems useful in preparing biological containment systems with properties (e.g., mechanical strength, capsule permeability and porosity, desired controlled release rates of the biologic or components secreted by the biologic, and immunoreactivity) that can be varied to adapt to a broader range of physiological conditions than known biological containment systems. There are also provided methods of making capsules containing cell aggregates therein, as well as the capsules formed thereby, which are useful as a quantitatively plentiful and low cost alternative to usage of freshly harvested cell aggregates (e.g., islets from pancreas), since the latter are usually available only in limited numbers.

Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of ≦10 nM of CRF occupy ≧50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

Abstract: DNA segments have been discovered, and characterized by sequence, which are response elements operative to confer responsiveness to ligands for several members of the steroid/thyroid superfamily of receptors, for the transcriptional activation and/or repression of promoters in cells. By using transcriptional control regions comprising response elements of the present invention in combination with a functional promoter, it is now possible to provide recombinant DNA vectors containing a gene, the transcription (and, thereby, also expression) of which is under the control of a promoter, the transcriptional activity of which is responsive to ligands for members of the steroid/thyroid superfamily of receptors.

Abstract: In accordance with the present invention, there are provided novel receptor interacting factors, referred to herein as “SMRT”, i.e., a silencing mediator (co-repressor) for retinoic acid receptor (RAR) and thyroid hormone receptor (TR). SMRT is a novel protein whose association with RAR and TR both in solution and on DNA response elements is destabilized by ligand. The interaction of SMRT with mutant receptors correlates with the transcriptional silencing activities of receptors. In vivo, SMRT functions as a potent co-repressor. A GAL4 DNA binding domain (DBD) fusion of SMRT behaves as a frank repressor of a GAL4-dependent reporter. Together, these data identify a novel class of cofactor which is believed to represent an important mediator of hormone action.

Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of 10 nM of CRF occupy 50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

Abstract: In accordance with the present invention, there are provided humanized fish insulin genes. Humanized insulin the present invention encode human insulin alpha and/or beta chains while using fish-preferred codons and regulatory sequences. These humanized genes are thus expressible in fish islet cells. Also provided are transgenic fish having islet cells containing and capable of expressing humanized insulin genes. These islet cells (Brockmann Bodies) can be xenotransplanted into subjects having diabetes. In this manner normoglycemia can be achieved in the recipient of the islets.

Abstract: In accordance with the present invention, there are provided novel methods of blocking amyloid protein toxicity in cells using polycylic compounds. Also provided are novel methods of decreasing amyloid protein production in cells and methods of inhibiting cell death. Invention methods can be used to prevent and treat a diverse class of disease conditions, known as amyloidoses, which are all related to the occurrence of amyloid protein deposits. Invention methods further provide methods of identifying compounds that can block amyloid toxicity or block the amyloid protein induced inhibition of MMT reduction.

Abstract: In accordance with the present invention, there are provided methods for the in vivo reduction of free radical levels in mammalian subjects in need thereof. In contrast to the inhibitory approach described in the prior art (i.e., wherein the function of the species responsible for free radical production is inhibited), the present invention employs a scavenging approach whereby overproduced free radical is bound in vivo to a suitable free radical scavenger. An exemplary free radical scavenger contemplated for use in the practice of the present invention is a dithiocarbamate-ferrous iron complex. This complex binds to free radicals, forming a stable, water-soluble free radical-containing complex. When administered to a subject afflicted with a disorder associated with free radical overproduction, the water-soluble free radical-containing complex is produced and then filtered through the kidneys, concentrated in the urine, and eventually excreted by the subject, thereby reducing in vivo free radical levels.

Abstract: Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T3R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T3R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurr1 heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response.

Abstract: The invention provides conjugates of negatively charged peptide oligomers with therapeutic agents, moieties capable of recruiting endogenous bone-affecting agents, or imaging agents, useful for delivering the agents to bone tissue or calcified masses, and the methods of use thereof. The negatively charged peptide oligomers bind strongly but reversibly to bone tissue and calcified masses with a controllable affinity and retention time on the tissue or mass.

Abstract: Targeting molecules for use in delivering biological agents to non-polarized epithelial cells are disclosed. Upon delivery, the biological agent(s) are lethal to the epithelial cell. The targeting molecules may be used, for example, for the eradication of metastatic epithelial cells.

Abstract: In accordance with the present invention, it has been discovered that retinoic acid receptor (RAR) antagonists are capable of modulating processes mediated by other members of the steroid/thyroid hormone receptor superfamily, including permissive receptors such as PPARs (e.g., PPAR&agr;, PPAR&dgr; and PPAR&ggr;). Indeed, it has been discovered that RAR antagonists, in combination with agonists for members of the steroid/thyroid hormone receptor superfamily, are capable of inducing and/or enhancing processes mediated by such members.

Abstract: In accordance with the present invention, there are provided amphiphilic polyamine compounds and derivatives thereof having the property of promoting transfection of polynucleotides and polypeptides into cells, and formulations comprising said compounds.

Abstract: In accordance with the present invention there are provided cycloaliphatic epoxy compounds and thermosetting resin compositions prepared therefrom. Inventive compounds are based on polycyclic hydrocarbon backbones, as illustrated by the following exemplary structure: wherein: each R is independently lower alkyl or halogen, n′″ is 1 up to about 8, and each x is independently 0, 1, or 2. Inventive compounds provide resins with desirable characteristics such as, for example, hydrophobicity, high Tg values, ionic purity, hydrolytic stability, and the like.

Abstract: In accordance with the present invention, there are provided modified forms of nonsteroidal anti-inflammatory drugs (NSAIDs). Modified NSAIDs according to the invention provide a new class of anti-inflammatory agent which provide the therapeutic benefits of NSAIDs while causing a much lower incidence of side-effects then typically observed with such agents.

Abstract: In accordance with the present invention, there is provided a medication delivery container that is preconfigured to administer an infusion therapy upon activation by a pump mechanism. The configuration of the bag can determine the sequence and amount of medication to be delivered. In one embodiment of the invention, the medication delivery container includes a multi-chamber bag, a manifold assembly and an administration set. The manifold assembly is configured with internal conduits and valves to direct output from each chamber of the bag to an output port in the manifold, and into the administration set. In additional embodiments, there are provided structures in the container to alleviate pressure drop during the application of pressure to the container. Invention containers provide improved infusion therapy administration which is particularly advantageous for reducing errors, infections and other complications associated with manual infusion techniques.

Abstract: In accordance with the present invention, there are provided novel fiber reinforced building material formulations, comprised of an inorganic binding agent and synthetic fibers. The fibrous material employed in invention formulations is capable of undergoing progressive fibrillation upon agitation. As a result, tougher building materials, due to higher fiber addition rates than previously possible, are produced. Formulations containing Portland cement-based compositions and fibrillating synthetic fibers are also contemplated. In addition, there are provided methods of producing fiber reinforced building materials, including Portland cement-based compositions, and articles produced therefrom.

Abstract: In accordance with the present invention, there are provided novel heterobifunctional monomers and uses for the same. Invention compounds have many of the properties required by the microelectronics industry, such as, for example, hydrophobicity, high Tg values, low dielectric constant, ionic purity, low coefficient of thermal expansion (CTE), and the like. These properties result in a thermoset that is particularly well suited to high performance applications where typical operating temperatures are often significantly higher than those at which prior art materials were suitable. Invention compounds are particularly ideal for use in the manufacture of electronic components, such as, for example, printed circuit boards, and the like.