Abstract: The present invention provides a means for transferring a therapeutic gene of interest into a nervous system cell by a highly-efficient and simpler means. More specifically, the present invention provides a recombinant vector that uses an adeno-associated virus (AAV), a method for manufacturing the recombinant vector, and a method for using the recombinant vector. More specifically, recombinant adeno-associated virus virions, which are capable of passing through the brain-brain barrier, for transferring a therapeutic genes of interest into a nervous system cell in a highly-efficient manner, a drug composition containing the recombinant adeno-associated virus virions, a method for manufacturing the recombinant adeno-associated virus virions, and a kit or the like are provided.

Abstract: Provided in the present invention are highly stable D-configuration polypeptides DVAP and SVAP having a high binding activity to the GRP78 protein, and also provided are an L-configuration polypeptide LVAP and a DVAP-or SVAP-modified model drug and a macromolecule carrier material, and the use thereof in the construction of a tumour image and a drug-delivery system for targeted treatment.

Abstract: Devices, materials, compounds, systems, and processes for Cherenkov-Activated Nuclear-Targeted Photodynamic Therapy that involves generating Cherenkov light within the tissue of a target volume and using this light to activate photosensitizing material that is located in the nucleus of cells of the target volume.

Abstract: This invention relates to a topical gel drug product preparation containing a composition comprising an isolated polypeptide having a carboxy-terminal amino acid sequence of an alpha connexin (ACT peptide), peptide stabilizers, excipients, buffering agents, and the like. A formulation and preparation steps are disclosed for the manufacturing of a stable, elegant, and pourable topical gel. The resulting formulation possesses long term stability suitable for aesthetic as well as therapeutic applications including the prevention of scaring and accelerated healing of wounds. Methods for treatment of chronic wounds, including chronic ulcers, are also provided.

Abstract: Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

Abstract: A carrier molecule composition. Specific implementations may include: a carrier molecule including at least one cell penetrating peptide (CPP) where the carrier molecule may include at least one hydrophobic domain and where the carrier is non-covalently associated with a biologically active molecule in one of a micelle and a liposome.

Abstract: The invention pertains to methods and vaccines suitable for preventing or reducing malaria transmission. The vaccines block the interaction between ?-tubulin from a malarial parasite and FREP-1 from the mid-gut of a malaria carrier mosquito, for example, Anopheles gambiae.

Abstract: The composition of the present invention can inhibit homologous human T cell reaction and the phenomenon of infiltration which reduces skin graft damage in vivo, thereby enabling prompt, rapid and effective graft rejection prevention or treatment effects at a low concentration. In addition, the present invention has advantages of successfully controlling in vivo human T cell reactions, as compared with conventional therapeutic agents, thus providing few side effects, the possibilities of local high-dose administration of therapeutic agents and potentially new treatments and prescriptions.

Abstract: The present disclosure provides a large combinatorial library of cell-permeable bicyclic peptides. The bicyclic peptides described herein include the first ring consisted of randomized peptide sequences for potential binding to a target of interest while the second ring featured a family of different cell-penetrating motifs, for both cell penetration and target binding. The library was screened against the I?B kinase ?/? (IKK?/?)-binding domain of NF-?B essential modulator (NEMO), resulting in the discovery of several cell-permeable bicyclic peptides which inhibited the NEMO-IKK? interaction, thereby selectively inhibiting canonical NF-?B signaling in mammalian cells and the proliferation of cisplatin-resistant ovarian cancer cells.

Abstract: A subject of the present invention is to provide an anti AQP3 antibody specifically recognizing the extracellular domain of aquaporin 3 (AQP3), which is one type of a water channel protein. By selecting a monoclonal antibody which specifically binds to an oligopeptide included in loop C as one of the extracellular domains of AQP3, an anti AQP3 antibody that is desired in the present invention is provided. An anti AQP3 monoclonal antibody of the present invention can directly bind, from the outside of a cell, to AQP3 present in a cell membrane. Furthermore, as an anti AQP3 monoclonal antibody of the present invention can have an inhibitory activity, the function of permeating a low molecular weight molecule or the like, which is carried by AQP3, can be suppressed.

Abstract: Disclosed is a method of modulating the Sct/SR axis in a mammalian subject in need thereof, including in a subject suffering from a liver disease, such as but not limited to, Early Stage PBC, Primary Sclerosing Cholangitis, Primary Biliary Cholangitis, Biliary Altresia, NASH, NAFLD, or Alcohol induced liver injury. A method of treating Late Stage PBC in a mammalian subject in need thereof is also disclosed; further disclosed is a method of ameliorating PBC-induced biliary damage in a mammalian subject in need thereof. Pharmaceutical compositions for modulating the Sct/SR axis, comprising a SR antagonist or a SR agonist, and a pharmaceutically acceptable carrier or excipient are also disclosed.

Abstract: The present invention relates to novel peptides, composition comprising such peptides including nutritional supplements and methods for inducing satiation and satiety, for weight management and preventing or reducing the incidence of obesity, or for preventing or reducing cardiovascular diseases, atherosclerosis, hypertension, hepatosteatosis, cancer and/or diabetes.

Abstract: The nerve growth promoter of the invention contains a valine in which the hydrogen atom of the amino group may be substituted with a substituent. The nerve growth promoter of the invention has a high effect of promoting differentiation of stem cells into nerve cells and formation of neurites in nerve cells, and the active ingredient therein is hardly degraded by digestive enzymes.

Abstract: The invention relates to an enzyme composition, a process for the preparation thereof and the use of the enzyme composition in enzymatic hydrolysis.

Abstract: The invention relates to the field of antibiotics, more specifically to peptide antibiotics, such as antimicrobial peptides and their use in the treatment of diseases associated with microbial infections. In particular, the invention provides a peptide with antimicrobial activity comprising an amino acid sequence RRWVQRWIRRWR (SEQ ID NO: 24) or an analogue thereof.

Abstract: The present invention refers to the use of protein kinase inhibitors and more specifically to the use of inhibitors of the protein kinase c-Jun amino terminal kinase, JNK inhibitor (poly-)peptides, chimeric peptides, or of nucleic acids encoding same as well as pharmaceutical compositions containing same, for the treatment of non-chronic or chronic inflammatory eye diseases, such as inflammatory diseases of the blephara, conjunctiva, cornea, sclera, the vitreous body, uvea, ciliary body, choroid, orbital bone, lacrimal gland, or iris, in particular wherein the inflammatory disease is selected from hordeolum, chalazion, conjunktivitis, keratitis, scieritis, episcleritis, endophthalmitis, panophtalmitis, irititis, uveitis, cyclitis, chorioiditis, orbital phlegmon, and myositis of the eye muscle etc.

Abstract: Disclosed herein are lipid compositions comprising a cationic lipid of formula (I), a neutral lipid, a sterol and a PEG or PEG-modified lipid, wherein formula (I) is Also disclosed are methods of producing the cationic lipid of formula (I).

Abstract: The invention relates to pharmaceutical compositions comprising a conjugate of a porphyrin (e.g., PpIX) and a recombinant protein. The pharmaceutical compositions of the invention may be used in photodynamic therapy. The invention also relates to methods of producing such pharmaceutical compositions and to methods of using such pharmaceutical compositions in the treatment of diseases, such as cancer.

Abstract: The present invention provides a method for enhancing the specific uptake of a neurotoxin polypeptide into cells, the method comprising: incubating cells susceptible to neurotoxin intoxication with a neurotoxin polypeptide for a time and under conditions which allow for the neurotoxin polypeptide to exert its biological activity, the incubation comprising at least one of the following steps: (i) K+-mediated depolarization of the cells, (ii) a reduced neurotoxin polypeptide exposition time and/or (iii) agitation of the cells during neurotoxin polypeptide exposition, thereby enhancing the specific uptake of the neurotoxin polypeptide into said cells.

Abstract: The present invention relates to a method for preventing or treating multiple sclerosis, particularly relapsing-remitting multiple sclerosis using arsenic trioxide.

Abstract: The invention provides compositions and methods for preventing or treating an ischemia-reperfusion injury, such as occurs during acute myocardial infarction and organ transplant in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof, and one or more additional active agents such as cyclosporine.

Abstract: The invention relates to LAH4 peptides and functional derivatives thereof and their use for improving transduction efficiency of viruses into target cells.

Abstract: The present invention relates to the discovery that a secretory phospholipase A2 (sPLA2-IIA) plays an active role in mediating cellular signaling leading to an inflammatory response or cell proliferation by way of its specific binding with integrin ? at site 2 of integrin ?. More specifically, the invention provides a method for identifying inhibitors of inflammatory or proliferative signaling by screening for compounds that interrupt the specific binding of sPLA2 and integrin ? at site 2. The invention also provides the novel use of a substance that suppresses the specific binding between sPLA2 and site 2 of integrin? for the purpose of treating or preventing a condition involving an undesired inflammatory response or cell proliferation.

Abstract: Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of a therapeutic biological molecule, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to a therapeutic biological molecule and uses of the same. In some embodiments, the aromatic-cationic peptide comprises 2?,6?-dimethyl-Tyr-D-Arg-Phe-Lys-NH2, Phe-D-Arg-Phe-Lys-NH2, or D-Arg-2?,6?-Dmt-Lys-Phe-NH2.

Abstract: A pharmaceutical composition for promoting nerve injury restoration and a use thereof are disclosed. Each unit of the pharmaceutical composition contains 0.5 to 8 g of L-ornithine, 1 to 5 g of aspartic acid, 3 to 10 g of arginine and 3 to 10 g of vitamin B6. The pharmaceutical composition can significantly promote recovery of the spinal nerve function, and particularly has a good therapeutic effect on acute myelitis.

Abstract: The present invention provides compounds represented by Formula I, or pharmaceutically acceptable salts, stereoisomers, solvates, hydrates or combination thereof, The invention also provides pharmaceutical compositions comprising these compounds and methods of using this compounds for treating FXR-mediated or TGR5-mediated diseases or conditions.

Abstract: The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A “therapeutic peptide composition” comprises a “carrier peptide” and a “cargo peptide.” A “carrier peptide” is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The “cargo peptide” is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

Abstract: A therapeutic composition for treating brain injury comprising a polyarginine peptide of from 5 to 9 arginines (SEQ ID NO: 1), and further comprising 1 or more terminal cysteines. The composition is administered in therapeutically effective dosages prophylactically or as soon as possible post-injury in treating neuronal injury.

Abstract: The inventions describe here cover therapeutic compositions, and methods of use, for neutralizing Type I interferons in a mammal. The compositions contain a soluble Orthopoxvirus IFN-binding protein that is modified to remove the cell-binding region, and that specifically binds to Type I IFNs, and a pharmaceutically acceptable carrier or excipient. Another variation of the invention entails a novel IFN-binding protein that is modified to remove the cell-binding region and the signal sequence.

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: Disclosed are novel bioactive peptides derived as antagonists to a fire ant receptor for a pheromone biosynthesis-activating neuropeptide/pyrokinin (PBAN/pyrokinin) gene derived neuropeptide ligand. Also disclosed are methods of controlling fire ants with the bioactive peptides disclosed herein. Methodological approaches to screening peptide libraries for the presence of PBAN/pyrokinin ligands are also provided herein.

Abstract: A method of delivering a cargo agent into cytosol of a cell can include: providing the delivery system of one of the embodiments described herein having the first and second delivery platforms; and administering the delivery system to a cell so as to cause targeting of two features on the cell so as to: cause endocytosis of the first and second delivery platforms of the delivery system into a common endosome, destabilize the endosome of the cell having the delivery system, release the cargo agent from the second linker; and release the cargo agent from the destabilized endosome into cytosol of the cell. A method of treating a disease can include: performing the method of method of delivering a cargo agent into cytosol of a cell in a subject having a disease, wherein the cargo agent is a therapeutic agent for the disease.

Abstract: The invention provides compositions and methods for preventing or treating an ischemia-reperfusion injury, such as occurs during acute myocardial infarction and organ transplant in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof, and one or more additional active agents such as cyclosporine.

Abstract: The present invention relates to compositions and methods for treating autoimmune, microbial, metabolic, neoplastic, and posttraumatic diseases mediated by inflammation in a subject. Compositions and methods including at least one importin beta-selective nuclear transport modifier (NTM) and/or at least one importin alpha-selective NTM, and/or at least one importin alpha-specific NTM, and/or at least one inhibitor of importin alpha and importin beta complex formation may be administered to a subject to modulate the transport of transcription factors, mediated by nuclear import adaptors, into the nucleus of a cell resulting in a decrease or abrogation of inflammation.

Abstract: The invention provides a method for producing an orexin neuron by culturing a pluripotent stem cell or a neural progenitor cell in the presence of N-acetyl-D-mannosamine and optionally in the presence of at least one inhibitor selected from the group consisting of a Sirtuin 1 inhibitor and an O-linked ?-N-acetylglucosamine transferase inhibitor. The invention also provides a therapeutic agent for narcolepsy or eating disorders, such as anorexia, containing N-acetyl-D-mannosamine, which is based on the induction of orexin neuron in vivo.

Abstract: The present disclosure provides peptides and peptide compositions, which facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells.

Abstract: Nuclear Transport Modifiers such as cSN50 and cSN50.1, afford in vivo islet protection following a 2-day course of intense treatment in autoimmune diabetes-prone, non-obese diabetic (NOD) mice, a widely used model of Type 1 diabetes (T1D), which resulted in a diabetes-free state for one year without apparent toxicity and the need to use insulin. cSN50 precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from NOD mice. cSN50 attenuated pro-inflammatory cytokine and chemokine production in immune cells in this model of human T1D. cSN50 also provides cytoprotection of beta cells, therefore preserving residual insulin-producing capacity. Because intracellular delivery of a Nuclear Transport Modifier peptide such as cSN50 and cSN50.1 can result in lowering of fasting blood glucose levels and may ameliorate (e.g.

Abstract: System and method for enhanced interaction processing in a contact center that includes dynamically determining customer segmentation. A processor detects a pending interaction with a customer. The processor retrieves, in response to detecting the pending interaction, identification of a first customer segment to which the customer belongs. The first customer segment is associated with a first objective of the contact center. The processor predicts an outcome of the pending interaction, and identifies a second customer segment based on the predicted outcome. The processor re-associates the customer to a second customer segment, where the second customer segment is associated with a second objective of the contact center different from the first business objective. The processor handles the pending interaction according to the second objective instead of the first objective.

Abstract: The present application discloses an acid labile lipophilic molecular conjugate of cancer chemotherapeutic agents and methods for reducing or substantially eliminating the side effects of chemotherapy associated with the administration of a cancer chemotherapeutic agent to a patient in need thereof.

Abstract: A method for transferring a macromolecular complex to muscle cells by exsanguinating a region of the subject's microvasculature and delivering the complex to this region under high hydrostatic pressure. A balloon catheter having a balloon that extends substantially the full length of the cannula that is inserted into the subject is provided for use in the systemic delivery of macromolecular complex.

Abstract: The present invention relates to a power converter (1, 1?) comprising an input terminal (+IN, ?IN) connected to an input power source, at least an input switch arrangement (T1, T2; T10, T12), and an output terminal (+OUT, ?OUT). The input switch arrangement (T1, T2; T10, T12) is arranged to convert the input power, where the power converter (1) further comprises a control unit (P1, N1) that is arranged to control at least the input switch arrangement (T1, T2; T10, T12). The control unit (P1, N1) is arranged to perform said control of the input switch arrangement (T1, T2; T10, T12) in dependence of the efficiency of at least a part of the power converter, the control unit (P1, N1) having information regarding the power at the input terminal (+IN, ?IN) and the power at the output terminal (+OUT, ?OUT). The present invention also relates to a corresponding method.

Abstract: As discussed in detail herein, isolated epitope peptides derived from SEMA5B bind to an HLA antigen and induce cytotoxic T lymphocytes (CTL) and thus are suitable for use in the context of cancer immunotherapy, more particularly cancer vaccines. The inventive peptides encompass both the above mentioned amino acid sequences and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted or added, provided such modified versions retain the requisite HLA binding and/or CTL inducibility of the original sequences. Further provided are polynucleotides encoding any of the aforementioned peptides as well pharmaceutical agents or compositions that include any of the aforementioned peptides or polynucleotides. The peptides, polynucleotides, pharmaceutical agents or compositions of this invention find particular utility in the treatment and/or prevention of cancers and tumors, including, for example, esophageal cancer, NSCLC, RCC and SCLC.

Abstract: Methods for treating muscular wasting diseases such as Duchenne muscular dystrophy are disclosed. Specifically, the methods include administering to a subject in need of treatment for a muscular wasting disease, an NF-?B activation inhibitor capable of blocking the activation of NF-?B.

Abstract: The invention relates to a modular transport platform (MTP) configured to penetrate a target cell, deliver the MTP into the target cell, provide a pH dependent membrane disruption activity, direct intracellular transport into a target subcellular compartment of the target cell, and couple the active agent within the modular platform. The modular transport platform includes: (1) a ligand module to target a specific receptor on the surface of the target cell; (2) an endosomolytic module that provides pH-dependent membrane disruption activity within the target cell; (3) an intracellular transport module to cause delivery of the MTP to a particular subcellular compartment; (4) a module for intracellular retention; (5) a module for subcellular recognition; (6) a substance to be transported by the MTP; and (7) a carrier module for unifying the modules and coupling the modules with the transported substance.

Abstract: The present invention relates to the intrathecal (IT) administration of recombinant enzyme to treat lysosomal storage disorders. In an exemplary embodiment, intrathecal administration of human ?-L-iduronidase (rhIDU) injections in MPS I affected animals resulted in significant enzyme uptake, significant rh-iduronidase activity in brain and meninges and a decrease of glycosaminoglycan (GAG) storage in cells of MPS I subjects to that of normal subjects. Intrathecal administration proved more effective than intravenous treatment at alleviating MPS I symptoms, indicating it is a useful method of treating lysosomal storage disorders.

Abstract: The present invention discloses novel macromolecule transduction domain (MTD) peptides which facilitate the traverse of a biologically active molecule across the cell membrane. Also disclosed are polynucleotides encoding the MTD peptides, methods of identifying the MTD peptides; methods of genetically engineering a biologically active molecule to have cell permeability by using the MTD peptides, methods of importing a biologically active molecule into a cell by using the MTD peptides, and uses thereof.

Abstract: Provided are 9-base morpholino antisense compounds targeted to polyCUG repeats in the 3?UTR region of dystrophia myotonica protein kinase (DMPK) mRNA, and related methods for treating myotonic dystrophy DM1.

Abstract: Aspects of the invention provide methods for selecting a candidate oligonucleotide for activating expression of a target gene. Further aspects of the invention provide methods of selecting a set of oligonucleotides that is enriched in oligonucleotides that activate expression of a target gene. Further aspects provide single stranded oligonucleotides that modulate gene expression and compositions and kits comprising the same. Methods for modulating gene expression using the single stranded oligonucleotides are also provided.

Abstract: The present application relates to polypeptides derived from the soluble part of the glycoprotein of the enveloped virus of Primate T-cell leukemia virus (PTLV), or fragments or variants thereof named receptor binding domain ligands (RBD) selected for their ability to bind specifically to the nutrient transporter GLUT1.

Abstract: The present invention provides compositions and methods for providing factor replacement therapy. In particular, the present invention provides replacement therapy for subjects suffering from cystinosis.