Abstract: The present invention relates to the field of biomarkers. More specifically, the present invention relates to biomarkers useful in diagnosing aggressive prostate cancer. In one embodiment, a method for identifying patients as having or likely to have aggressive prostate cancer comprises the steps of (a) obtaining a biological sample from the patient; (b) performing an assay on the biological sample to detect fucosylated fucosylated DPP-4, sTIE-2, sVEGFR-1, and FUT8; and (c) identifying the patient as having or likely to have aggressive prostate cancer if there is a statistically significant difference in the levels of fucosylated TIMP-1, fucosylated DPP-4, sTIE-2, sVEGFR-1 and FUT8.

Abstract: Mucus-penetrating liposomal nanoparticles and methods of making and using thereof are described herein. The nanoparticles contain one or more lipids, one or more PEG-conjugated lipids, and optionally one or more additional materials that physically and/or chemically stabilize the particles. The nanoparticle have an average diameter of about 100 nm to about 300 nm, preferably from about 100 nm to about 250 nm, more preferably from about 100 nm to about 200 nm. The particles are mobile in mucus. The liposomes can further contain one or more therapeutic, prophylactic, and/or diagnostic agent to be delivered to a mucosal surface, such as the CV tract, the colon, the nose, the lungs, and/or the eyes. The liposomes can further contain one or more CEST agents to allow real time imaging of the particles in a live animal. The particles may also further contain an imaging agent, such as a fluorescent label.

Abstract: Methods of using viruses labeled with alkyne-modified biomolecules, such as fatty acids, carbohydrates and lipids, to treat a plant, an insect or an animal infected with a virus or to increase the infectivity of a virus, such as the human immunodeficiency virus, are provided. Also provided are methods of labeling a virus, such as human immunodeficiency virus, with an alkyne-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. The viruses labeled with alkyne-modified biomolecules may be combined with a pharmaceutically acceptable excipient to produce a pharmaceutical composition, optionally containing another anti-viral agent and/or a delivery agent, such as a liposome.

Abstract: The present invention, referred to as Oasis is Automated Statistical Inference for Segmentation (OASIS), is a fully automated and robust statistical method for cross-sectional MS lesion segmentation. Using intensity information from multiple modalities of MRI, a logistic regression model assigns voxel-level probabilities of lesion presence. The OASIS model produces interpretable results in the form of regression coefficients that can be applied to imaging studies quickly and easily. OASIS uses intensity-normalized brain MRI volumes, enabling the model to be robust to changes in scanner and acquisition sequence. OASIS also adjusts for intensity inhomogeneities that preprocessing bias field correction procedures do not remove, using BLUR volumes. This allows for more accurate segmentation of brain areas that are highly distorted by inhomogeneities, such as the cerebellum.

Abstract: An apparatus for neural block determination is provided including processing circuitry configured to receive muscle movement measurements, analyze the muscle movement measurements in a frequency domain, and determine an effectiveness of an anesthetic based on the analysis of the muscle movement measurements in the frequency domain.

Abstract: Disclosed herein are biosensor systems and related methods for detecting analytes in aqueous and biologic environments. A biosensor system for detecting binding of an analyte of interest may include a detector configured to detect a change in an electrical property on a surface thereof. The detector may be a FET. The system also may include a passive layer disposed on a top surface of the detector. Further, the system may include a hydrophobic layer disposed on the passive layer. The system also may include a receptor-attachment material configured for binding to an analyte. A receptor may bind to the analyte, and the receptor may be attached to the receptor-attachment material. The binding of the analyte to the receptor can cause the change of the electrical property at the surface. In response to the change for example, a current may change for indicating the binding of the analyte to the receptor.

Abstract: The present invention provides bivalent and multivalent ligands with a view to improving the affinity and pharmacokinetic properties of a urea class of PSMA inhibitors. The compounds and their synthesis can be generalized to multivalent compounds of other target antigens. Because they present multiple copies of the pharmacophore, multivalent ligands can bind to receptors with high avidity and affinity, thereby serving as powerful inhibitors. The modular multivalent scaffolds of the present invention, in one or more embodiments, contains a lysine-based (?, ?-) dialkyne residue for incorporating two or more antigen binding moieties, such as PSMA binding Lys-Glu urea moieties, exploiting click chemistry and one or more additional lysine residues for subsequent modification with an imaging and/or therapeutic nuclides or a cytotoxic ligands for tumor cell killing.

Abstract: Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure provides significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than commercially available materials, such as LIPOFECTAMINE 2000™, FUGENE®, or polyethylenimine (PEI), for gene delivery to cancerous fibroblasts or human primary fibroblasts. The presently disclosed materials may be useful for cancer therapeutics and regenerative medicine.

Abstract: The present invention relates to the field of extracellular vesicles. More specifically, the present invention provides methods and compositions for using extracellular vesicles as a vector for nucleic acid treatment in vivo of various diseases. In a specific embodiment, the present invention provides an extracellular vesicle isolated from a cell comprising one or more microRNAs (miRNAs) that have been loaded ex vivo into the vesicle so that the miRNAs are present in a higher concentration than when measured in the same extracellular vesicle isolated directly from the cell. In another embodiment, the present invention provides a method for treating cholangiocarcinoma in a subject comprising the step of administering to the subject a plurality of exosomes comprising miR-195.

Abstract: The present invention includes the discovery of a strain of Mycobacterium comprising an expression vector encoding a di-adenylate cyclase enzyme. The Mycobacterium is selected from the group consisting of Mycobacterium tuberculosis, Mycobacterium bovis, or a combination thereof and the preferred strain of Mycobacterium is BCG. The preferred expression vector is a mycobacterial expression vector including an hsp60 promoter and a DNA sequence of diadenylate cyclase (disA), or a functional part thereof. The strains of Mycobacterium are used in therapeutic applications including tuberculosis and cancer.

Abstract: An MRI safe robot for guiding transrectal prostate biopsy comprises a support arm, a robot body operatively connected to the support arm and a transrectal biopsy device operatively connected to the robot body. The transrectal biopsy device includes an endorectal extension and a biopsy needle device, the endorectal extension including an MRI coil for MRI imaging of the prostate. The robot body includes a first driver module for generating rotational motion of the endorectal extension and a second driver module for angulating the biopsy needle device toward a target area of the prostate for biopsy. The biopsy needle device is rotatable relative to the endorectal extension about a fixed axis and translatable through the endorectal extension. Each of the first and second driver modules include at least one pneumatic motor, wherein the MRI images are used by a physician to determine the target area for biopsy.

Abstract: We found that FIZZ1/RELM? is inducible by hypoxia in lung. The hypoxia-upregulated expression of FIZZ1/RELM? was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. Recombinant FIZZ1/RELM? protein stimulates rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibits HIMF-activated Akt phosphorylation. It also inhibits HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. HIMF also has angiogenic and vasoconstrictive activity. Notably, HIMF increases pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

Abstract: The present invention provides pharmaceutical compositions comprising derivatives of NDGA, including M4N (tetra-O-methyl nordihydroguaiaretic acid) and sorafenib and their use in the inhibition and treatment of neoplastic diseases, such as liver cancer, colon cancer, breast cancer, brain cancers and ovarian cancers, for example, in a subject. Compositions comprising derivatives of NDGA, including M4N, sorafenib and additional therapeutic agents are also provided.

Abstract: In one aspect, the present invention relates to a method of identifying compounds useful in modifying the activity of Aldolase.

Abstract: According to some embodiments of the present invention, a cooperatively-controlled robot includes a robotic actuator assembly comprising a tool holder and a force sensor. The cooperatively-controlled robot further includes a control system adapted to communicate with the robotic actuator assembly and the force sensor, and an actuator in communication with the control system and mechanically coupled to a tool. The force sensor is configured to detect a vibrational force applied on the tool and send a signal to the control system based on the vibrational force. The control system is configured to receive the signal and determine a force to apply to the tool to damp the vibrational force. The control system then signals to the actuator to apply the determined force, and the actuator applies the determined force to actively damp a vibration of the tool.

Abstract: A motion-compensated micro-forceps system, including a manually-operable micro-forceps assembly having a plurality of moveable grasping elements; a motor assembly operatively connected to the plurality of moveable grasping elements; an optical detection system having an optical fiber attached to the manually-operable micro-forceps assembly at a fixed axial distance relative to a distal-most end of the plurality of moveable grasping elements; and a motor controller configured to communicate with the optical detection system and the motor assembly to provide motion compensation of the plurality of moveable grasping elements of the manually-operable micro-forceps, wherein the optical detection system is configured to output a signal for the determination of a distance of the plurality of moveable grasping elements of the micro-forceps to a target during operation, and wherein the motor controller is configured to provide feedback control signals to the motor assembly for motion compensation for both hand tremor

Abstract: Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins.

Abstract: A surgical robot including an imaging system comprising at least one camera, a processor in communication with the imaging system, a manipulation system in communication with the processor, and a visual display in communication with the processor. The processor is operable to calculate a mechanical property estimate for an area of an environment based on an environment model of tool-environment interaction data, create a composite image comprising a mechanical property map of the mechanical property estimate overlaid on an environment image from the at least one camera, and output the composite image on the visual display.

Abstract: An image analyzer includes processing circuitry that receives at least one image having a first set of bins and a second set of bins, shifts the first or second set of bins by a number of bins associated with a motion hypothesis to achieve sets of aligned bins, determines a product for each set of aligned bins, compares the products to a product threshold, and identifies an object based on the products that exceed the product threshold.

Abstract: Controlled release dosage formulations for the delivery of active agents, especially for treatment of eye diseases or disorders, such as glaucoma, have been developed. These provide release of the active agent, such as ECA or a derivative thereof, for an effective period of time.