Modulators of Nuclear Hormone Receptor Activity: Novel Compounds, Diverse Applications for Infectious Diseases, Including Anthrax (<i>B. anthracis</i>)

Nuclear hormones such as glucocorticoids dampen inflammatory responses, and thus provide protection to mammals against inflammatory disease and septic shock. The Anthrax lethal factor represses nuclear hormone receptor activity, and thus may contribute to the infectious agent causing even more damage to the host. This observation can be exploited to find new means of studying and interfering with the normal function of nuclear hormone receptors.

HIV-Dependent Expression Vector

This invention provides a DNA construct that can be useful for both diagnostics and AIDS therapeutics. The construct can be incorporated into a retrovirus or into a cell line. This construct mediates the expression of a selected gene in the presence of HIV replication, but is silent in the absence of HIV. The cell line with the incorporated construct can be used as an indicator line for the presence of replication-competent HIV. The virus containing the construct can be used to co-infect a population of HIV-infected cells.

Neuronal Decoding Algorithm for Prosthetic Limbs

The invention is a new algorithm for decoding neuronal responses based on the discovery that neuronal spike trains can be described using order statistics. The device has applications in the direct control of prosthetic limbs by neuronal signals originating from electrodes placed in the brain. The method allows for decoding neuronal responses by monitoring sequences of potentials from neurons while specific motor tasks are carried out.

A Novel Reagent for Labeling PET Tracers at Trifluoromethyl Groups

The molecular imaging technique of positron emission tomography (PET) is an increasingly important tool in biomedical research and in drug discovery and development. Many small molecule drugs and potential PET radiotracers carry trifluoromethyl (CF3) groups. Because CF3 groups are generally considered to be metabolically stable, there is a strong interest in developing drugs with these groups.

Novel Magnetic Resonance Spectroscopy (MRS) Technique to Quantify Brain Metabolites

With respect to quantification of metabolites in the brain, conventional methods of magnetic resonance spectroscopy (MRS) yield results that are highly variable and highly dependent on the sequence type being applied. This invention describes a novel MRS technique that involves preparing longitudinal steady states at different flip angles using trains of RF pulses interspersed with field gradients to quantify metabolites.

Magnetic Resonance Magnification Imaging

With conventional MRI, it is inherently time-consuming to generate high dimensional images with high spatial resolution. This invention, inspired by optical magnification, uses a fundamentally different approach to MRI image formation. It uses specially designed radiofrequency pulses to interact with the magnetic field gradient, wherein the region of interest is filled with more pixels resulting in increased spatial resolution and reduced overall scan times. Currently, 3-fold magnification has been achieved in vivo.

Rat Model for Alzheimer's Disease

The present invention is directed to a transgenic rat model of Alzheimer's Disease (AD) termed TgF344-19+/-. The invention rat overexpresses two human genes (APPswe and PS1deltaE9 genes), each of which are believed to be independent dominant causes of early-onset AD. The hemizygote exhibits major features of AD pathology (i.e., dense and diffuse amyloid plaques, neurofibrillary tangles, cerebral amyloid angiopathy, hyperphosphorylated tau, paired-helical filaments, Hirano bodies, granulovacuolar degeneration, cognitive impairment, and cortical neuronal loss).

Novel Radio-labeled Agents for Imaging Alzheimer's Disease-associated Amyloid

This technology introduces novel radio-labeled agents for imaging amyloid deposits in the brains of Alzheimer's Disease patients. These are small molecule, radio-ligand compounds that are analogs of benzo[d]thiazole. They are highly specific to amyloid, have low background noise, do not undergo rapid defluoridation and do not produce residual radioactivity in the brain. In addition, the compounds are stable and may be readily synthesized from commercially available starting materials.

PTH2 and PTH1 Receptor Ligands

Parathyroid hormone receptors found on osteoblasts in bone and renal tubule cells in kidney elevate blood calcium levels when stimulated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Excessive secretion of PTH from the parathyroid gland results in primary hyperparathyroidism. Production of PTHrP by various tumors results in humoral hypercalcemia of malignancy. In both of these conditions, excessive blood calcium levels lead to clinically significant morbidity. A parathyroid hormone antagonist could therefore have therapeutic value.

Radiotracers for Imaging P-glycoprotein Transporter Function

This invention offers technology to help treat certain brain diseases, such as Alzheimer's disease and Parkinson's, and may lead to more effective and personalized treatments. P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established/prospective chemotherapeutics (a phenomenon known as multidrug resistance; MDR).