OCR 4444

The present invention relates to the risk assessment, detection, diagnosis, or prognosis of prostate cancer. More specifically, this invention relates to the detection of certain polymorphism in the promoter region of the MIF gene to determine the risk, detect, diagnose, or prognosticate prostate cancer. Applicants have discovered that the presence of a -173C and/or -749 (CATT).sub.7 or more repeat predispose an individual to prostate cancer.

OCR 4445

The recent discovery of a role for SEMA 7A in fibrosis using mouse models provides a new therapeutic target for the treatment of fibrosis in lung disease and may be suitable for the treatment of other fibrotic diseases.

OCR 4659

The invention includes methods of preventing and reversing prefrontal cortical decline in normal aged subjects by providing a protein kinase C inhibitor to the subject. The protein kinase C inhibitor can be a phenanthridinium alkaloids or other closely related compound. The inventors have found that when such compounds are administered to normal aged subjects the cognitive performance, including including performance in tasks that utilizing working memory, of the subjects improves.

OCR 4662

ROCK1, or Rho kinase, is a protein kinase activated by Rho that plays a signaling role in cell morphology, transformation, motility, focal adhesion, and cytokinesis. Inhibition of this pathway may prevent tumor cell motility and metastasis. Novel small-molecule inhibitors of ROCK1 have been synthesized and assayed for activity in vitro, and are candidates as anti-cancer drugs.

OCR 4699

Adoptive T cell transfer, involving the ex vivo expansion of T lymphocytes, is a viable therapeutic approach for both infectious diseases and cancer, with demonstrated efficacy in treating melanoma, Epstein-Barr virus, and HIV-related infections. However, T cell transfer by clonal expansion is not clinically feasible as it does not consistently generate therapeutic quantities of T cells. Efforts to develop a reproducible "off-the-shelf" means of stimulating and expanding T cells in vitro have focused on bead-based systems. This novel approach involves single walled carbon nanotubes (SWNT) coupled to anti-CD3 antibodies, a known stimulant for T-cell proliferation. SWNTs have a much higher surface area to volume ratio than previous artificial antigen-presenting cells (aAPCs), which facilitates the high density clusters of T cell antigen receptors that are critical for T-cell activation. Anti-CD3 antibodies adsorbed onto SWNT bundles activate T-cells at antibody concentrations at least an order of magnitude less than antibody alone. Furthermore, similar activation is not achieved with other high surface area materials such as activated carbon, polystyrene nanoparticles, and buckyballs. This novel method thus utilizes the unique properties of SWNTs for enhanced stimuli presentation.

OCR 4715

Yale scientists have discovered that the level of IL-18 and its downstream targets were increased in patients with COPD, as well as in the lungs of smokers. Furthermore, it was found that treating mice with antibody against IL-18Rα significantly decreased Cigarette Smoke (CS) - induced inflammation. IL-18 signaling contributes to the pathogenesis of CS-induced emphysema, pulmonary inflammation and apoptosis. Therefore, the levels of circulating IL-18 represent a readily accessible biomarker for the diagnosis of COPD, and blocking IL-18Rα would be an effective therapy against COPD.

OCR 4744

Virtual screening of the Maybridge library of over 70,000 compounds was performed using a similarity filter, docking and MM-GB/SA post-processing to seek potential non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) and a novel oxadiazole compound was found and several analogs were developed and studied. They showed anti-HIV effects with EC50 values as low as 310 nM.

OCR 4832

Methods for increasing the patency of biodegradable, synthetic vascular grafts are provided. The methods include administering one or more cytokines and/or chemokines that promote outward tissue remodeling of the vascular grafts and vascular neotissue formation. The disclosed methods do not require cell seeding of the vascular grafts, thus avoiding many problems associated with cell seeding. Biodegradable, polymeric vascular grafts which provide controlled release of cytokines and/or chemokines at the site of vascular graft implantation are also provided.

OCR 61904921

OCR 6190 & OCR 4921 have remarkable anti-HIV activity profiles with high potency and anti-viral activity. OCR 6190 is an optimized non-nucleoside reverse transcriptase inhibitors (NNRTI) with 100-fold greater solubility than currently FDA-approved drugs.
OCR 4921 is a proof-of-concept bifunctional chimeric NRTI/NNRTI, as shown below, targeting HIV-1 viral replication.

OCR 4924

Frontotemporal dementia (FTD) is known to be caused by loss of function mutations in the secreted protein progranulin but the physiological role of progranulin the brain is not known. Yale investigators found that Progranulin binds the cell surface protein Sortilin as a receptor. Progranulin/sortilin interaction regulates BDNF secretion. Thus, sortilin receptor agonists are predicted to ameliorate deficits in Fronto-Temporal dementia.