Abstract: Disclosed herein are bispecific aptamers having affinity for multiple ligands and in particular, VEGF, IL8 and Ang2, as well as pharmaceutical compositions comprising the same. Methods of using some bispecific aptamers for the treatment of retinal diseases and disorders are also disclosed, as well as methods of making such bispecific aptamers and compositions.

Abstract: The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease. In some cases, stem-loop aptamers are provided for the inhibition of Factor D.

Abstract: The application discloses methods and compositions for inhibiting functions associated with vascular endothelial growth factor-A (VEGF-A). The methods and compositions may involve the use of pan-variant specific aptamers for binding to VEGF-A, and preventing or reducing association of VEGF-A with Flt-1, KDR, or Nrp-1. The methods and compositions may include one or more aptamers that bind to receptor binding face of VEGF-A. The methods and compositions may include one or more aptamers that bind to a receptor binding domain of VEGF-A. The application further provides anti-VEGF-A aptamers for the treatment of ocular diseases or disorders. In some cases, the anti-VEGF-A aptamers may have a stem-loop secondary structure.

Abstract: The application discloses methods and compositions for inhibiting functions associated with Interleukin-8 (IL8). The methods and compositions may involve the use of aptamers for binding to IL8 and preventing or reducing association of IL8 with CXCR1, CXCR2, or both. The methods and compositions may include one or more aptamers that bind to an N-terminal domain of IL8. The methods and compositions may include one or more aptamers that bind to a hydrophobic pocket of IL8. The methods and compositions may include one or more aptamers that bind to an N-loop of IL8. The methods and compositions may include one or more aptamers that bind to a GAG binding site of IL8. The application further provides anti-IL8 aptamers for the treatment of ocular diseases or disorders. In some cases, the anti-IL8 aptamers may have a stem-loop secondary structure.

Abstract: Provided are chemically modified ribonucleic acid (RNA) aptamers comprising one or more of 2?F guanylate, 2?OMe cytidylate, 2?OMe adenylate, and a deoxy pyrimidine nucleotide with a moiety on the 5 position of the pyrimidine; and methods of making the aptamers.

Abstract: Methods and compositions for serum-stabilizing micelles for drug delivery or imaging agent delivery are provided, as well as methods and compositions to enhance micelle-mediated drug delivery. This invention provides a process for synthesizing a lipid micelle comprising one or more lipid-oligonucleotide conjugate molecules, the process comprising contacting an amount of lipid molecules with an amount of lipid-oligonucleotide conjugate molecules sufficient to create a lipid micelle comprising lipid-oligonucleotide conjugate molecules.

Abstract: The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease. In some cases, stem-loop aptamers are provided for the inhibition of Factor D.

Abstract: Provided are chemically modified ribonucleic acid (RNA) aptamers comprising one or more of 2?F guanylate, 2?OMe cytidylate, 2?OMe adenylate, and a deoxy pyrimidine nucleotide with a moiety on the 5 position of the pyrimidine; and methods of making the aptamers.

Abstract: A transaction card product comprising a transaction card, an account identifier, a security panel, and an activation code. The account identifier uniquely links the transaction card to a remote account having a balance value available for redemption toward one or more of goods or services. The security panel is coupled to the transaction card and substantially entirely covers the account identifier. The security panel is configured to be at least partially removed from a remainder of the transaction card product to permit access to the account identifier. The activation code has data therein to prompt a point-of-sale terminal to begin a transaction card activation process, the activation code having a first portion directly secured to and extending over the security panel, wherein the activation code is characterized by an absence of any data directly identifying the remote account.

Abstract: The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease. In some cases, stem-loop aptamers are provided for the inhibition of Factor D.

Abstract: The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease. In some cases, stem-loop aptamers are provided for the inhibition of Factor D.

Abstract: Methods and compositions are provided for rapidly identifying novel structure-switching aptamers.

Abstract: Methods and compositions for serum-stabilizing micelles for drug delivery or imaging agent delivery are provided, as well as methods and compositions to enhance micelle-mediated drug delivery. This invention provides a process for synthesizing a lipid micelle comprising one or more lipid-oligonucleotide conjugate molecules, the process comprising contacting an amount of lipid molecules with an amount of lipid-oligonucleotide conjugate molecules sufficient to create a lipid micelle comprising lipid-oligonucleotide conjugate molecules.

Abstract: A composition is provided comprising an oligonucleotide aptamer conjugated to an antigen, wherein the aptamer is directed against a cell-surface target of an antigen-presenting cell. Also provided are methods of delivering an antigen to a dendritic cell and of eliciting an immune response in a subject.

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: An article treatment method is disclosed including removing an affected area from an article, the article including the affected area and a substrate composed of a substrate material, forming an unaffected surface. A structural material is applied to the unaffected surface by cold spraying a plurality of particles of the structural material from a cold spray apparatus. The structural material and the article are finished, forming a treated article including an unused article conformation. A turbine component treatment method is disclosed for a turbine component including a hard-to-weld (HTW) alloy, wherein applying the structural material includes impacting the plurality of particles, and plastically deforming the plurality of particles to form a mechanical bond between the structural material and the HTW alloy. An airfoil treatment method is disclosed further including the cold spraying forming a near net shape of an unused airfoil composition.

Abstract: The present application provides a turbine component for use in a hot gas path of a gas turbine. The turbine component may include an outer surface, an internal cooling circuit, a number of cooling pathways in communication with the internal cooling circuit and extending through the outer surface, and a number of adaptive cooling pathways in communication with the internal cooling circuit and extending through the outer surface. The adaptive cooling pathways may include a high temperature compound therein.

Abstract: A system for checking calibration of a multi-axis machine includes a robotic arm and a mount configured to receive a removable machine tool and a controller electronically connected to the multi-axis machine. The removable machine tool includes a removable spray nozzle and a laser housing that is coupled to the machine tool. The laser housing includes a laser affixed inside the housing for emitting a laser beam and a calibration workpiece coupled to a mounting table. The calibration workpiece comprises a plurality of laser sensors disposed along an outer surface of the calibration workpiece. The controller is programmed to point the laser beam at each laser sensor. The laser sensors generate signals that are communicated back to the controller if the laser beam is detected by the laser sensor.

Abstract: The present invention provides methods of preparing an oligonucleotide, nucleoside or nucleoside analog for selective introduction into a subject's cells, the method comprising (1) selecting a targeted aptamer, internalizing nucleic acid or tumor-homing nucleic acid via iterative rounds of selection, and (i) hybridizing it to an oligonucleotide, (ii) replacing one or more nucleotide with a nucleoside or nucleoside analog, or (iii) synthesizing the it with one or more nucleoside or nucleoside analogs; or (2) preparing a naive combinatorial aptamer, internalizing nucleic acid or tumor-homing nucleic acid prodrug library, and running iterative rounds of selection for the cells. The present invention also provides the agent, the pharmaceutical composition, and methods of treating or preventing cancer and/or viral infection, the method comprising administration of the oligonucleotide, nucleoside or nucleoside analog for selective introduction into a subject's cells.

Abstract: A method for coating a component and forming at least one cooling hole in a component is provided. The method includes providing the component having a surface and including a plurality of apertures formed therein. The method includes masking at least one of the plurality of apertures with a plug comprising a removable material. The method includes applying at least one coating to the surface of the component. The method includes eliminating the plug including removable material leaving open apertures in the surface of the coated component. Also provided is a water-soluble aperture plug including water soluble high temperature resistant filler materials including aluminum oxide, zirconium oxide, magnesium oxide, silicon dioxide, zircon, graphite, tungsten carbide, silicon carbide, silicon nitride, boron nitride, aluminum nitrides and binding agents and dispersants including phosphates, silicates, sugar, salt, gum, resin, polyvinyl alcohol (PVA), polyethylene glycol, and combinations thereof.