Abstract: The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.

Abstract: Apparatus for simulating microlaryngeal surgery. In one embodiment, the apparatus includes a larynx model that emulates an actual larynx, the larynx model including an inner passage that includes a vocal fold model support that emulates a portion of an actual vocal fold, and a vocal fold model that emulates tissues of an actual vocal fold, the vocal fold model being adapted to be received by the vocal fold model support of the larynx model.

Abstract: Methods and devices are provided for targeted administration of a drug to a patient's eye. In one embodiment, the method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. The fluid drug formulation may flow circumferentially toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye.

Abstract: Provided herein are pharmaceutical and transplant compositions and methods related to the treatment and prevention of diabetes. More specifically, the compositions and methods are related to activation of glial derived neurotrophic factor (GDNF) receptors or overexpression of the GFR-?1/c-Ret receptor complex in insulin secreting cells so as to promote cell survival and proliferation.

Abstract: Reduced dyes, such as hydrocyanines, deuterocyanines, and/or other deuterated dyes capable of detecting one or more reactive oxygen species are described herein. The reduced dyes exhibit little or no fluorescence due to the disrupted ? conjugation. However, upon reaction with ROS, the reduced dyes are oxidized, regenerating the extended ? conjugation and causing a substantial increase in fluorescence intensity. In many case, the oxidized dye is generally membrane impermeable. However, upon reduction, many of the reduced dyes are membrane permeable. Thus, reduced dyes can accumulate in cells and/or tissue to amplify the signal. Once inside the cell or tissue, the reduced dye is reoxidized upon reaction with ROS, and the oxidized dye again becomes membrane impermeable, trapping the dye within the cell. The reduced dyes can be used to image ROS, such as hydroxide radical and superoxide, in serum, cell cultures, tissue explants, and in vivo.

Abstract: We have developed DNA and viral vectors that can be used, alone or in combination, as a vaccine against one HIV clade, subtype, or recombinant form of HIV or against multiple HIV clades, subtypes, or recombinant forms. Moreover, the vectors can encode a variety of antigens, which may be obtained from one clade or from two or more different clades, and the antigens selected and/or the manner in which the vectors are formulated (e.g., mixed) can be manipulated to generate a protective immune response against a variety of clades (e.g., the clades to which a patient is most likely to be exposed; with the proportions of the components of the vaccine tailored to the extent of the patient's risk to a particular clade or clades).

Abstract: Compositions and methods of treatment or prophylaxis of fragile-X associated disorders are provided, as well as methods of screening compounds and kits to screen a library of compounds.

Abstract: The present invention provides methods for the treatment or the prevention of neuronal damage in the CNS. Specifically, the methods of the invention provide for the administration of a therapeutically effective amount of a progestin or progestin metabolite following a traumatic or ischemic injury to the CNS such that, prior to termination of administration of the progestin or progestin metabolite the administration is tapered to avoid withdrawal. The drug taper employed can involve a linear taper, an exponential taper, progressively dividing administered doses by 50%, or can be determined based on the treating physician's assessment of the patient's response to therapy. The tapered administration methods of the present invention may be used in combination with any therapeutic protocol or regimen for the administration of a therapeutically effective amount of a progestin or progestin metabolite to treat a traumatic or ischemic CNS injury.

Abstract: The present invention is directed to compounds, compositions and methods for treating or preventing cancer and viral infections, in particular, HIV, HCV, Norovirus, Saporovirus, HSV-1, HSV-2, Dengue virus, Yellow fever, and HBV in human patients or other animal hosts. The compounds are certain 6-substituted purine monophosphates, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HIV-1, HIV-2, HCV, Norovirus, Saporovirus, HSV-1, HSV-2, Dengue virus, Yellow fever, and HBV.

Abstract: Novel compounds and methods for activating the TrkB receptor are provided. The methods include administering in vivo or in vitro a therapeutically effective amount of a compound containing four six-membered rings and a substituted or unsubstituted C5 or C6 heteroaryl or heterocycloalkyl ring and pharmaceutically acceptable salts, prodrugs, and derivatives thereof. Specifically, methods and compounds for the treatment of disorders including neurologic, neuropsychiatric, and metabolic disorders are provided. For example, a method is provided of treating or reducing the risk of depression, anxiety, or obesity in a subject, which includes selecting a subject with or at risk of developing depression, anxiety, or obesity, and administering to the subject a therapeutically effective amount of the described compounds.

Abstract: User intent may be inferred from mouse movements made within a user interface. Client-side instrumentation may be provided that collects mouse movement data that is provided to a classification engine. The classification engine receives the mouse movement data and creates a mouse trajectory. The mouse trajectory may be split into segments, and features associated with each segment may be determined. Features representing the context of the search, that is, content of the search result page, previous queries submitted, and interaction features such as scrolling, may be included. By examining the features associated with the mouse trajectories within the context of a search session, the user intent may be classified into categories using machine learning classification techniques. By inferring user intent, Web search engines may be able to predict whether a user's intent is commercial and tailor advertising accordingly.

Abstract: The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing CXCR4 related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.

Abstract: The present invention relates to methods of treatment for Parkinson Disease (PD) in a person by identifying gene variants which may indicate a more favorable response to specific medicaments, thereby allowing for personalized or individualized treatment. The present invention relates to a method of screening for a genetic predisposition to PD in a person. The present invention is also directed to a method of testing a person for the presence of particular gene variants, wherein the presence of a gene variant indicates a higher predisposition to PD, and the absence of a gene variant indicates a lower predisposition to PD, compared to a control sample. The present invention further relates to methods and kits for treating, or inhibiting the development of, PD in a person. The present invention is also directed to a method of identifying the heritage of an individual based on the genetic profile of the individual.

Abstract: The present invention relates to the use of PDGF receptor tyrosine kinase or bcr-abl tyrosine kinase inhibitors, especially of N-phenyl-2-pyrimidine-amine derivatives of formula I, in which the symbols and substituents have the meaning as defined herein in free form or in pharmaceutically acceptable salt form, in the manufacture of a pharmaceutical composition for the treatment of tuberous sclerosis associated neoplasms; to a method of treatment of warm-blooded animals, including humans, suffering from a tuberous sclerosis associated neoplasms.

Abstract: Cognitive assessment systems and methods that provide an integrated solution for evaluating the presence or absence of cognitive impairment. The present invention is used to test cognitive functions of an individual including information processing speed, working memory, work list learning and recall, along with variations of these tasks. Immersive and non-immersive systems and methods are disclosed. Testing and results feedback using the present invention may be completed in real time, typically in less than 15 minutes.

Abstract: High efficient methods for producing an antibody molecule that binds an antigen are described. The methods include obtaining a population of PBMC enriched for CD19highCD3negCD20low to negCD38highCD27high cells from a mammal exposed to an antigen from sample of cells enriched for PBMC. The cells are isolated from a sample obtained at a time that the fraction of PBMC expressing antibody reactive to the antigen is at a high level. Sequences encoding heavy and light chain variable domains are prepared in a manner that allow production of molecules with natural heavy and light chain pairing.

Abstract: The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infectious diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.

Abstract: Briefly described, embodiments of this disclosure include compounds as described herein, labeled compounds as described herein, pharmaceutical composition including compounds described herein, methods of imaging, method of forming a compound as described herein, and the like. In particular, embodiments of the disclosure include a series of triamino-pyridine derivatives and labeled triamino-pyridine derivatives, methods of synthesizing these compounds, intermediate compounds, methods of treatment using these compounds, methods of imaging, diagnosing, localizing, monitoring, and/or assessing a condition (e.g., corticotropin releasing factor type-1 (CRF1)) and/or related biological events, using triamino-pyridine derivatives, and the like. In addition, the present disclosure includes compositions (e.g., labeled triamino-pyridine derivatives that are ligands for the CRF1 receptor) used in and methods relating to non-invasive imaging (e.g., positron emission tomography (PET) imaging or SPECT imaging).

Abstract: The methods of the disclosure provide fluorescence-based assays for calcineurin activity, especially in isolated T cells. The methods include the stimulation of the T cells with agents that specifically target the TCR with or without influencing co-stimulatory pathways. One TCR agonist is monoclonal antibodies specific for CD3, which more precisely distinguish the inducible activity of calcineurin than does an alternative method targeting the T cell receptor (CD3) combined with CD28 costimulation. This method more accurately distinguishes between the measured level of calcineurin activity of T cells from immunosuppressed transplant recipients and normal individuals, and thus has improved diagnostic accuracy with respect to the response of an individual to immunosuppressant therapy following an organ transplant.