Abstract: Accumulating evidence indicates that the lysosomal Ragulator complex is essential for full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in several developmental neurological disorders, including Angelman syndrome (AS), which is caused by maternal deficiency of the ubiquitin E3 ligase UBE3A. Here, it is reported that Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity. p18 knockdown in hippocampal CA1 neurons of AS mice reduces elevated mTORC1 activity and improves dendritic spine maturation, long-term potentiation (LTP), as well as learning performance.

Abstract: iFormative Feedback (iFF) is an electronic formative feedback acquisition and analytics system which leverages mobile technology, QR codes, and web-based dashboards to provide users with meaningful, real-time, 360-degree assessments of performance. iFF is designed to record the spirit of a user's observations without increasing the administrative burden of data entry, security, collation, interpretation, and dissemination. Through iFF, organizations can efficiently track individual performance through downstream (supervisor to supervisee) and upstream (supervisee to supervisor) analyses of standardized observations recorded in the system.

Abstract: Disclosed herein are, inter alia, inhibitors of protein arginine methyltransferase 9 and pharmaceutical compositions thereof, and methods comprising the use of protein arginine methyltransferase 9 inhibitors for the treatment of a protein arginine methyltransferase 9-modulated disease or disorder, such as a hematological cancer.

Abstract: Disclosed herein are lipid emulsified systems containing antihistamines. Also disclosed herein are pharmaceutical compositions containing the lipid emulsified systems and other chemotherapeutic agents, and methods of chemoprevention and cancer treatment with compositions containing the lipid emulsified systems.

Abstract: Compositions and methods for making and using proliposomal and liposomal formulations of chemotherapeutic agents are disclosed. The proliposomal and liposomal formulations of chemotherapeutics, as well as medicaments and dosage forms that include such formulations, can be used with treatment regimens for bladder cancer and urothelial cancer. Hence, the formulations, medicaments, and dosage forms of the invention are suitable to treat bladder cancers by intravesical administration and to treat urothelial cancers. The formulations according to the invention include (a) a taxane (e.g., paclitaxel, docetaxel) or cisplatin, (b) a first phospholipid, dipalmitoyl phosphatidylcholine (DMPC), and (c) a second phospholipid, dimyrsityl phosphatidyl glycerol sodium (DMPG). The proliposomal formulations form liposomes upon contact with an aqueous vehicle.

Abstract: Compositions and methods for making and using proliposomal and liposomal formulations of chemotherapeutic agents are disclosed. The proliposomal and liposomal formulations of chemotherapeutics, as well as medicaments and dosage forms that include such formulations, can be used with treatment regimens for bladder cancer and urothelial cancer. Hence, the formulations, medicaments, and dosage forms of the invention are suitable to treat bladder cancers by intravesical administration and to treat urothelial cancers. The formulations according to the invention include (a) a taxane (e.g., paclitaxel, docetaxel) or cisplatin, (b) a first phospholipid, dipalmitoyl phosphatidylcholine (DMPC), and (c) a second phospholipid, dimyrsityl phosphatidyl glycerol sodium (DMPG). The proliposomal formulations form liposomes upon contact with an aqueous vehicle.

Abstract: Clostridium perfringens can cause food poisoning and is a major agent in necrotic enteritis. As laws banning the use of antibiotics in animal feed become more common, the need for alternatives to antibiotics becomes greater. Peptidoglycan hydrolases that target the cell wall of specific bacteria are one such alternative. Genes for four endolysins, PlyCP10, PlyCP18, PlyCP33, and PlyCP41, were found within clusters of phage associated genes, likely prophages from strains Cp10, Cp18, Cp33, and Cp41. PlyCP18 and PlyCP33 harbor L-alanine amidase catalytic domains, and PlyCP10 and PlyCP41 have glycosyl hydrolase catalytic domains as predicted by BlastP and PFAM searches. All four genes were synthesized with E. coli codon optimization, expressed in E. coli expression vectors with a 6×His tag for nickel column purification, and the recombinant proteins purified. The four endolysins were capable of lysing the 66 C. perfringens strains tested but not the other bacteria tested.

Abstract: Novel testosterone undecanoate (TU) formulations are disclosed in which TU is incorporated into proliposomal powder dispersions of TU and distearoyl phosphatidylcholine (DSPC). The proliposomal powder dispersions of the invention can also be combined with pharmaceutically acceptable excipients, and incorporated into enterically coated oral dosage forms that are useful for testosterone replacement therapy.

Abstract: This invention is directed to a novel method of treating an individual suffering from a bacterial infection, such as bacterial infections of various tissues or organs of an individual. In general, the method of treatment involves administering to an individual a pharmaceutical formulation that comprises a liposome-encapsulated antimicrobial agent, wherein polyethylene glycol (PEG) molecules are covalently attached to the surface of the liposomes.

Abstract: The invention provides compositions comprising wilforlide A for overcoming drug resistance in cancer therapy, particularly in the treatment of cancers which have exhibited resistance to treatment by chemotherapeutic drugs. Methods and compositions for treating a cancer are disclosed. The method administers to a patient in need thereof a combination of wilforlide A and a chemotherapeutic drug. Wilforlide A and chemotherapeutic drug are administered in a combined amount effective to treat the cancer. The cancer being treated is at least in part resistant to treatment by the chemotherapeutic drug alone.

Abstract: Molecules that selectively inhibit or stimulate the activity of isoforms of calpains are presented. Methods for screening and characterizing such molecules are also presented. Specific functions of calpain-1 calpain-2 in long term potentiation (LTP), learning and memory, neurodegeneration and diseases of synaptic dysfunction are characterized using novel calpain inhibitors, substrates and related methods. The compounds, compositions, and methods described herein are expected to be useful, for treating neurodegenerative diseases and other diseases of synaptic function, and for modulating cognition in patients in need thereof.

Abstract: The invention provides extracts and compositions derived from Tripterygium wilfordii for overcoming drug resistance in cancer therapy. This invention relates to organic solvent extracts of T. wilfordii and their use in cancer treatment, particularly in the treatment of cancers which have exhibited resistance to treatment by chemotherapeutic drugs. Methods of treating a cancer are disclosed. The method administers to a patient in need thereof a combination of (a) an organic solvent extract of T. wilfordii and (b) a chemotherapeutic drug. The organic solvent extract of T. wilfordii (a) and chemotherapeutic drug (b) are administered in a combined amount effective to treat the cancer. The cancer being treated is at least in part resistant to treatment by the chemotherapeutic drug (b) alone. Also disclosed are chemotherapeutic compositions comprising a combination of (a) an organic solvent extract of T.

Abstract: The invention relates to a novel free-flowing powder pharmaceutical formulation for the delivery of a poorly-water-soluble drug substance that increases the solubility and bioavailability of the poorly-water soluble drug substance, as well as to a method of making the free-flowing powder pharmaceutical formulation. The invention also relates to dispersed particles that disperse instantaneously from the free-flowing powder formulation when the formulation is added to water, aqueous solvent, or organic solvent, wherein the bulk distribution of the poorly-water soluble drug substance of the free-flowing powder formulation in the dispersed particles is uniform. Such dispersed particles increase the bioavailable surface area of the poorly water-soluble drug substance and facilitate the drug substance's dissolution.

Abstract: Novel testosterone formulations are disclosed where testosterone is incorporated into a phospholipid/cholesterol system to produce a proliposomal powder dispersion. The proliposomal powder dispersions of the invention may be formulated with pharmaceutically acceptable excipients to form pharmaceutical compositions. Enterically coated oral dosage forms are disclosed as are methods of treatment for testosterone replacement therapy.

Abstract: The invention relates to methods, peptides, nucleic acids and cells for use in isolating and expanding human T cell populations in an antigen-specific manner for immunodiagnostic or therapeutic purposes. The invention also relates to professional antigen presenting cells derived from pluripotent human stem cells, and to customizable antigen presentation by the antigen presenting cells.

Abstract: Novel testosterone formulations are disclosed where testosterone is incorporated into a phospholipid/cholesterol system to produce a proliposomal powder dispersion. The proliposomal powder dispersions of the invention may be formulated with pharmaceutically acceptable excipients to form pharmaceutical compositions. Enterically coated oral dosage forms are disclosed as are methods of treatment for testosterone replacement therapy.

Abstract: The invention relates to a novel free-flowing powder pharmaceutical formulation for the delivery of a poorly-water-soluble drug substance that increases the solubility and bioavailability of the poorly-water soluble drug substance, as well as to a method of making the free-flowing powder pharmaceutical formulation. The invention also relates to dispersed particles that disperse instantaneously from the free-flowing powder formulation when the formulation is added to water, aqueous solvent, or organic solvent, wherein the bulk distribution of the poorly-water soluble drug substance of the free-flowing powder formulation in the dispersed particles is uniform. Such dispersed particles increase the bioavailable surface area of the poorly water-soluble drug substance and facilitate the drug substance's dissolution.

Abstract: The invention provides pharmaceutical compositions containing a vehicle for the targeted delivery of therapeutic and diagnostic agents for the treatment of hyperproliferative diseases. The targeting component of the vehicle is a cystine molecule that is coupled to the cargo component, which can be either a therapeutic or diagnostic agent or to a nanoparticle composition that contains the therapeutic agent or diagnostic. The invention also provides methods of treating hyperproliferative disorders by targeting hyperproliferative disease cells for the targeted delivery of a therapeutic or diagnostic agent.

Abstract: In the setting of chronic infection with a pathogen, the immune system must adapt to the ongoing presence of inflammatory responses driven by the pathogen in order to control the replication of the infecting agent at an acceptable level while limiting immune-mediated damage (immunopathology) (1). A complex interaction is required to accomplish this using a balance of immune related cytokines to stimulate and control the immune response. A particular formulation of reduced glutathione of high concentration in a liposome is proposed. In cooperation with the immune system, the liposomally formulated reduced glutathione according to the invention surprisingly achieves the balance between over-reduction of IL-10 and its necessary bodily function and signaling.

Abstract: This invention is directed to a novel method of treating an individual suffering from a bacterial infection, such as bacterial infections of various tissues or organs of an individual. In general, the method of treatment involves administering to an individual a pharmaceutical formulation that comprises a liposome-encapsulated antimicrobial agent, wherein polyethylene glycol (PEG) molecules are covalently attached to the surface of the liposomes.