Abstract: The present invention relates to novel therapies for cancer and, in particular, to therapies that are particularly suited to tumor cells resistant to other types of therapies such as radiation, chemotherapy, or combinations of both approaches. The invention provides methods for identifying and implementing strategies to inhibit a transcription factor which, in combination with other factors, renders the cells resistant and inhibits apopotosis of the cells. The invention provides an inhibitory ATF2 N-terminal fragment, specifically a fragment corresponding to amino acid residues 50-100 of ATF2 (termed peptide II). The invention provides methods for inhibiting tumor cell growth with such peptides.

Abstract: A chemical genus of sulfated cholestanes attached to an oligomer through amide or ester bonds is disclosed. The compounds are useful as anti human immunodeficiency virus (HIV) and anti-herpes simplex virus (HSV) agents. The compounds have the general formula in which CPS (the structure within the square brackets) is a cholanic acid derivative. R1 to R16 are chosen independently from H, OH and OSO3?A+. W is a direct bond or a deshydrogen residue of a C3-C6 diol or triol. A is chosen from H+, a quaternary ammonium species and the cation of an alkali or alkaline earth metal. Z is a direct bond or a residue of an amino acid, a peptide or an aminosulfonic acid. ? is a moiety having n or more —NH and —OH groups separated by 6 or fewer carbons; and n is an integer from 6 to 200.

Abstract: The present invention relates to non-invasive and minimally invasive techniques for evaluating the physical state of a subject, including diagnosing a disease, disorder, or physical state of the subject, determining the prognosis of the subject, determining a subject's susceptibility for a disease, disorder, or physical state and determining, developing and monitoring treatment for the same. The invention also relates to identifying genetic alterations contributing to, or susceptibility for, development of a disease, disorder, or physical state, and for diagnosis, prognosis and treatment of the disease, disorder, or physical state.

Abstract: Method for enhancing in a mammalian cell the activity of an enzyme associated with Gaucher Disease by administering a competitive inhibitor of glucocerebrosidase in an amount effective to enhance the activity of the enzyme. Preferred compounds for use in the method are imino sugars and related compounds. In particular, C8-12-alkyl derivatives of N-alkyl-deoxynojirimycin, isofagomine compounds, and calystegine compoiunds are effective to enhance glucocerebrosidase activity.

Abstract: Methods to improve the tropism or other features of a virus is disclosed. Such methods can be used to prepare, e.g., DNA or plasmid libraries of variants of a gene encoding a viral capsid or envelope restriction site, libraries of viral clones with such variant genes with a randon-dy inserted restriction site or polypeptide sequence targeting a receptor expressed by a specific type of mammalian cells. Described are also methods to prepare mosaic viruses, i.e., viral particles wherein copies of one or more capsid or envelope proteins originate from different sources. These methods can be used to prepare mosaic viruses of a specific mixture of wild-type and mutant proteins, or of different types of mutant proteins.

Abstract: This application provides methods of improving protein replacement therapy by combining protein replacement therapy with active site-specific chaperones (ASSC) to increase the stability and efficiency of the protein being administered. The application further provides stable compositions comprising the purified protein and an ASSC, and methods of treatment by administering the compositions.

Abstract: The present invention pertains to methods to promote outgrowth of, or extension across a substrate of, neuronal cells by inhibiting the interaction between the cytoplasmic tail of the L1-CAM cell surface adhesion molecule and the cytoskeletal protein ankyrin. The invention also pertains to a method to treat diseases characterized by axonal damage such as spinal cord injury, traumatic brain injury, stroke, and neurodegenerative disease by administration of novel peptides that inhibit the binding of the L1-CAM cytoplasmic tail to ankyrin, and to pharmaceutical compositions comprising such peptides. The present invention pertains to the regulation of neuronal signal propagation. Addition of the peptide of the invention disrupts the interaction between the cytoplasmic tail of the cell surface adhesion molecule L1-CAM, the cytoskeletal protein ankyrin, and voltage-gated calcium channels at the presynaptic surface of a neuron leading to a transient redistribution of the calcium channels to cytoplasmic vesicles.

Abstract: Provided is a method for inhibiting growth of a tumor cell which comprises oncogenically activated BRAF and defective p16INK4A by inhibiting activated BRAF and restoring functional p16INK4A. Also provided is a method for sensitizing the foregoing tumor cell to cytotoxic or cytostatic effect of a chemotherapeutic agent or radiation by further contacting the cell with such an agent. Also provided is a method for treating cancer, especially melanoma, by simultaneously inhibiting expression or activity of activated BRAF and restoring or mimicking the activity of wild-type p16INK4A.

Abstract: Disclosed herein is a method for treating hepatic fibrosis comprising administering to a patient in need of such treatment an amount effective to treat hepatic fibrosis of imatinib mesylate. This is based on the ability of imatinib mesylate to down regulate stellate cell activation in culture and in vivo. Hepatic fibrosis is not limited to patients with chronic Hepatitis B, Hepatitis C, non-alcoholic steatophepatitis (NASH), alcoholic liver disease, metabolic liver diseases (Wilson's disease, hemochromatosis), biliary obstruction (congenital or acquired) or liver diseases associated with fibrosis of unknown cause.

Abstract: The present invention relates, in general, to a screening method for identifying novel viral proteins with interferon antagonizing function using a transfection-based assay, and the use of such proteins in isolating various types of attenuated viruses for the development of vaccine and pharmaceutical formulations. The invention also relates to the use of viral interferon antagonists in screening assays to identify potential anti-viral agents. The invention further relates to protocols utilizing interferon antagonists, e.g., NS1, to enhance gene therapy or DNA vaccination based on their ability to increase gene expression.

Abstract: A new circulating form of soluble human tissue factor was identified. This new form of human tissue factor appears to be the result of alternative splicing and is therefore referred to as “alt-hTF.” Alt-hTF mRNA was detected in a cell line, HL-60. The cDNA region encoding the entire open reading frame of alt-hTF was cloned. The sequence encoding the alt-hTF mature peptide was expressed in bacteria. alt-hTF consists of the first 166 amino acids of membrane bound TF, and a 40 amino acid C-terminal region unique to alt-hTF. Alt-hTF is likely to be a useful target for compounds to inhibit clotting and to treat disorders associated with elevated TF. It may also be useful as a target for antibodies selectively reactive with alt-hTF, to remove it from the circulation for treatment of clotting or other disorders associated with elevated or abnormal levels of TF, including thrombotic conditions, cardiovascular disorders, DVT, DIC, and possibly metastatic cancers.

Abstract: Provided is a method for enhancing the activity of a protein, which protein when mutated, folds in an incorrect conformation in the endoplasmic reticulum, by contacting the protein with an effective amount compound which specifically binds to the protein and induces the protein to fold into a proper conformation (a specific chaperone). Also provided are methods for enhancing the stability and preventing the degradation of a protein by contacting the protein with an effective amount of a specific chaperone for the protein which stabilizes the protein in a proper conformation.

Abstract: This invention relates to methods of distinguishing among various types of differentiated and undifferentiated epithelial carcinomas, and non-epithelial carcinomas, by detecting the presence of p63 nucleic acid or protein expression. The invention also provides methods for detecting p63 nucleic acids and proteins, as well as methods for diagnosing and treating certain tumors based on whether the tumors express p63.

Abstract: Methods of maintaining or enhancing memory or learning in a mammal by activating the receptor tyrosine kinase muscle-specific kinase (MuSK) in the brain are disclosed. Also disclosed are methods of treating a disease or condition associated with memory loss or a neurological impairment by administering an effective amount of a MuSK-activating agent to a subject, such as a human, in need of such treatment. The invention also pertains to methods of identifying compounds that maintain or enhance memory or learning or that enhance the recovery from a neurological impairment such as stroke. MuSK, an agrin receptor known to be important in neuromuscular junction formation and function, was isolated from the brain and determined to play an essential role to memory consolidation and learning.

Abstract: Disclosed herein is a novel method of treating vitiligo by using an excimer laser that emits light in the UVB range. The invention includes a method of incrementally increasing exposure of affected vitiligo areas with UVB laser light from an excimer laser to restore pigmentation to skin areas afflicted with vitiligo.

Abstract: This invention relates to methods of distinguishing among various types of differentiated and undifferentiated epithelial carcinomas, and non-epithelial carcinomas, by detecting the presence of p63 nucleic acid or protein expression. The invention also provides methods for detecting p63 nucleic acids and proteins, as well as methods for diagnosing and treating certain tumors based on whether the tumors express p63.

Abstract: A device for presenting content to a user is utilized in combination with a general purpose computer. The computer has a processor, a computer communications interface, a computer memory and an operating system. The operating system has one or more file management tools. The device has a housing, a device communications interface and a device memory. The device memory comprises a boot partition which includes boot software. The boot software is copied from the device into the computer memory and is executed from the computer memory by the processor. The device memory also comprises a secure partition inaccessible by the file management tools and having content stored thereon. The device memory also comprises content delivery software, which is copied to the computer memory, and when executed by the processor from the computer memory can access the content from the secure partition and present it to the user as sensory data.

Abstract: Mutations and polymorphisms in a particular gene, the capillary morphogenesis gene-2 (CMG-2) have been identified. The mutations have been associated with infantile systemic hyalinosis (ISH) and juvenile hyaline fibromatosis (JHF), as well as conditions associated with these disorders. Described herein are variant CMG-2 nucleic acids and variant CMG-2 polypeptides; cells comprising such variant CMG-2 nucleic acids and/or expressing variant CMG-2 polypeptides; and methods of diagnosing and treating such disorders and conditions. Variant CMG-2 proteins include those comprising one or more of E220X, G105D, L329, P257insC, 1189T, A357P, and A322S. Variant CMG-2 nucleic acids include those encoding these mutant CMG-2 proteins, as well as silent mutations or polymorphisms.

Abstract: The present invention relates to identification of tumor suppressor activity of a protein, KLF6 (KLF6), and to related diagnostic and therapeutic compositions and methods. The discovery of this tumor suppressor activity provides screening targets as well, particularly screening for compounds that overcome gene inactivation or alteration.

Abstract: The present invention relates to the use of 8-iso prostaglandins and their derivatives for decreasing intraocular pressure, for example in the treatment of glaucoma It is based, at least in part, on the discovery that 8-iso prostaglandin E2 effectively decreased intraocular pressure by a trabecular meshwork outflow mechanism.