Abstract: Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a recently discovered metabolic pathway. According to the normal functioning of this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins). Also disclosed are therapeutic methods of using such inhibitors to alleviate deleterious effects of 3-deoxyglucosone (3DG).

Abstract: Methods for designing a laser-accelerated ion beam are disclosed. The methods include modeling a system including a heavy ion layer, an electric field, and high energy light positive ions having a maximum light positive ion energy, correlating physical parameters of the heavy ion layer, the electric field, and the maximum light positive ion energy using the model, and varying the parameters of the heavy ion layer to optimize the energy distribution of the high energy light positive ions. One method includes analyzing the acceleration of light positive ions, for example protons, through interaction of a high-power laser pulse with a double-layer target using two-dimensional particle-in-cell (PIC) simulations and a one-dimensional analytical model. The maximum energy acquired by the accelerated light positive ions, e.g., protons, in this model depends on the physical characteristics of the heavy-ion layer—the electron-ion mass ratio and effective charge state of the ions.

Abstract: Compact particle selection and collimation devices are disclosed for delivering beams of protons with desired energy spectra. These devices are useful with laser-accelerated proton therapy systems, in which the initial protons have broad energy and angular distributions. Superconducting magnet systems produce a desired magnetic field configuration to spread the protons with different energies and emitting angles for particle selection. The simulation of proton transport in the presence of the magnetic field shows that the selected protons are successfully refocused on the beam axis after passing through the magnetic field with the optimal magnet system. Dose distributions are also provided using Monte Carlo simulations of the laser-accelerated proton beams for radiation therapy applications.

Abstract: A composition having an agent adapted to affect a multimeric protein by binding to a binding site of the multimeric protein and thereby affecting an equilibrium of units, wherein the multimeric protein has an assembly having a plurality of said units, wherein each of the units has a first complementary surface and a second complementary surface and wherein the first complementary surface of one unit is associated with the second complementary surface of another unit, provided that the assembly is at least one of different quaternary isoforms on a condition that in the multimeric protein (1) a structure of each of the units determines a structure of the different quaternary isoforms, (2) the units are in the equilibrium and (3) the structure of the different quaternary isoforms influences a function of the multimeric protein.

Abstract: An isolated nucleic acid molecule encoding a human DNA repair enzyme, MED1, is disclosed. Like other mismatch repair genes which are mutated in certain cancers, MED1, encoding nucleic acids, proteins and antibodies thereto may be used to advantage in genetic or cancer screening assays. MED1, which recognizes and cleaves DNA, may also be used for the diagnostic detection of mutations and genetic variants.

Abstract: A composition having an agent adapted to affect a multimeric protein by binding to a binding site of the multimeric protein and thereby affecting an equilibrium of units, wherein the multimeric protein has an assembly having a plurality of said units, wherein each of the units has a first complementary surface and a second complementary surface and wherein the first complementary surface of one unit is associated with the second complementary surface of another unit, provided that the assembly is at least one of different quaternary isoforms on a condition that in the multimeric protein (1) a structure of each of the units determines a structure of the different quaternary isoforms, (2) the units are in the equilibrium and (3) the structure of the different quaternary isoforms influences a function of the multimeric protein.

Abstract: Novel methods for inhibiting angiogenesis and treating diseases associated with angiogenesis are described. The methods may comprise administering to a patient an effective amount of a 1,2-dithiol-3-thione derivative or metabolite thereof. Preferred compounds for use in the methods include 5-(2-pyrazinyl)-4methyl-1,2-dithiol-3-thione (Oltipraz) and its metabolites.

Abstract: The invention provides a natural killer cell, NK-92, modified to express a CD16 receptor or an inhibitory killer cell immunoglobulin-like receptor (KIR) on a surface of the cell. In examples, the NK-92 cell is further modified to co-express an associated accessory signaling protein such as Fc?RI-? or TCR-?, chemokines, or cytokines such as interleukin-2 (IL-2) or interleukin-15 (IL-15). Additional methods are disclosed for various assays, assessments, and therapeutic treatments with the modified NK-92 cells.

Abstract: Cells and cell lines which replicate HCV of non-hepatic human and non human origin are disclosed. Also provided are methods of using such cells and cell lines to identify anti-HCV agents for the treatment of HCV infection.

Abstract: A combined yeast/bacterial two-hybrid system is disclosed.

Abstract: Bispecific single chain antibody molecules are disclosed which may be used to advantage to treat various forms of cancer associated with the overexpression of members of the EGFR protein family.

Abstract: Bispecific single chain antibody molecules are disclosed which may be used to advantage to treat various forms of cancer associated with the overexpression of members of the EGFR protein family.

Abstract: Devices and methods are provided for generating laser-accelerated high energy polyenergetic positive ion beams that are spatially separated and modulated based on energy level. The spatially separated and modulated high energy polyenergetic positive ion beams are used for radiation therapy. In addition, methods are provided for treating patients in radiation treatment centers using therapeutically suitable high energy polyenergetic positive ion beams that are provided by spatially separating and modulating positive ion beams. The production of radioisotopes using spatially separated and modulated laser-accelerated high energy polyenergetic positive ion beams is also provided.

Abstract: Novel human MOAT genes and their encoded proteins are provided herein. The MRP-related ABC transporters encoded by the disclosed nucleic acid sequences play a pivotal role in the efflux of pharmacologically beneficial reagents from tumor cells. MOAT genes and their encoded proteins provide valuable therapeutic targets for the design of anti-cancer agents which inhibit the aberrant growth of malignant cells.

Abstract: Methods of optimizing a laser-accelerated proton radiation dose to a targeted region are disclosed. Disclosed methods include providing a plurality of modulated polyenergetic proton beamlets and irradiating the targeted region with the plurality of modulated beamlets.

Abstract: An isolated nucleic acid molecule encoding a human DNA repair enzyme, MED1, is disclosed. Like other mismatch repair genes which are mutated in certain cancers, MED1, encoding nucleic acids, proteins and antibodies thereto may be used to advantage in genetic or cancer screening assays. MED1, which recognizes and cleaves DNA, may also be used for the diagnostic detection of mutations and genetic variants.

Abstract: Novel methods for inhibiting angiogenesis and treating diseases associated with angiogenesis are described. The methods may comprise administering to a patient an effective amount of a 1,2-dithiol-3-thione derivative or metabolite thereof. Preferred compounds for use in the methods include 5-(2-pyrazinyl)-4methyl-1,2-dithiol-3-thione (Oltipraz) and its metabolites.

Abstract: This invention relates to the field of cancer therapy. More particularly, the invention relates to the treatment of mammary tumor, clinically manifest mammary tumor (breast cancer) and metastatic mammary tumor by administration of human Chorionic Gonadotropin (hCG). The treatment preferably comprises the administration of hCG in conjunction with an antiestrogen and/or a Type I Interferon.

Abstract: Devices and methods are provided for generating laser-accelerated high energy polyenergetic positive ion beams that are spatially separated and modulated based on energy level. The spatially separated and modulated high energy polyenergetic positive ion beams are used for radiation therapy. In addition, methods are provided for treating patients in radiation treatment centers using therapeutically suitable high energy polyenergetic positive ion beams that are provided by spatially separating and modulating positive ion beams. The production of radioisotopes using spatially separated and modulated laser-accelerated high energy polyenergetic positive ion beams is also provided.

Abstract: Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins). Also disclosed are therapeutic methods of using such inhibitors to treat glycogen storage diseases, including Fanconi's syndrome, as well as other pathological conditions resulting from the formation of AGE-proteins.