Abstract: The invention provides oligonucleotide and/or oligonucleotide analogue molecules that are antagonists of a microRNA, preferably antagonists of human microRNAs hsa-miR-23b-3p and hsa-miR-218-5p, that comprise a mixture of phosphorothioate and phosphodiester linkages, and that are conjugated to at least one oleic acid molecule. Inhibiting these microRNAs allows to increase the endogenous levels of the corresponding proteins MBNL1 and/or MBNL2. The present invention further provides compositions comprising said oligonucleotides and/or oligonucleotide analogue molecules and their uses for the treatment and prevention of DM in a subject in need thereof.

Abstract: The invention relates to nucleic acid products that interfere with or inhibit CNNM4 (Cyclin M4) gene expression. It further relates to therapeutic uses of CNNM4 inhibition for the treatment of diseases, such as liver diseases including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver steatosis, liver fibrosis, liver cirrhosis, liver cancer and other diseases associated with magnesium dysregulation.

Abstract: The present disclosure relates to, inter alia, a weed control method. In one example, a method comprises applying to the locus a weed controlling amount of a pesticide composition comprising a FatA acyl-ACP thioesterase-inhibiting herbicide, wherein the crop plants are modified such that they comprise a FatA acyl-ACP thioesterase which provides the crop plant with tolerance against the FatA acyl-ACP thioesterase-inhibiting herbicide. Recombinant polynucleotides and suitable for use in the methods, and edited FatA acyl-ACP thioesterases are also disclosed.

Abstract: In a first aspect, a multilayer film includes a first outer layer including a first thermoplastic polyimide, a core layer including a polyimide, and a second outer layer including a second thermoplastic polyimide. The polyimide of the core layer includes a first aromatic dianhydride including 3,3?,4,4?-biphenyl tetracarboxylic dianhydride and a first aromatic diamine including p-phenylenediamine. The multilayer film has a total thickness in a range of from 5 to 150 ?m. A thickness of the core layer is in a range of from 35 to 73% of the total thickness of the multilayer film. A minimum peel strength for at least one of the first and second outer layers, when adhered to copper foil and tested following ASTM method IPC-TM-650, method No. 2.4.9B, is greater than 0.9 kgf/cm (0.88 N/mm). In a second aspect, a metal-clad laminate includes the multilayer film of the first aspect and a first metal layer adhered to an outer surface of the first outer layer of the multilayer film.

Abstract: A thermal substrate includes a multilayer film, a first conductive layer adhered to the first outer layer of the multilayer film and a second conductive layer adhered to the second outer layer of the multilayer film. The multilayer film includes a first outer layer including a first thermoplastic polyimide, a core layer including a polyimide and a second outer layer including a second thermoplastic polyimide. The multilayer film has a total thickness in a range of from 5 to 150 ?m, and the first outer layer, the core layer and the second outer layer each include a thermally conductive filler. The first conductive layer and the second conductive layer each have a thickness in a range of from 250 to 3000 ?m.

Abstract: In a first aspect, a multilayer film includes a first outer layer including a first thermoplastic polyimide, a core layer including a polyimide, and a second outer layer including a second thermoplastic polyimide. The polyimide of the core layer includes a first aromatic dianhydride including 3,3?,4,4?-biphenyl tetracarboxylic dianhydride and a first aromatic diamine including p-phenylenediamine. The multilayer film has a total thickness in a range of from 5 to 150 ?m. A thickness of the core layer is in a range of from 35 to 73% of the total thickness of the multilayer film. A minimum peel strength for at least one of the first and second outer layers, when adhered to copper foil and tested following ASTM method IPC-TM-650, method No. 2.4.9B, is greater than 0.9 kgf/cm (0.88 N/mm). In a second aspect, a metal-clad laminate includes the multilayer film of the first aspect and a first metal layer adhered to an outer surface of the first outer layer of the multilayer film.

Abstract: This invention discloses the creation of a novel single ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a group of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery and/or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, antagonize or disrupt, simultaneously and independently, the functional domain of different disease causing proteins.

Abstract: A three-tier employment model provides flexibility when modeling even moderately complex relationships, such as where an employee has multiple job tasks or assignments for an employer. In such an example, a top level can store information for each employee defining the type of relationship that exists between the employee and the employer, such as where the employee works for multiple entities of the employer. A middle level can capture employment terms and conditions that are associated with the relationship(s), as well as one or many work assignments, such as salary information for each assignment. A bottom level can store the actual details of the work to be performed. A three-tier approach thus provides significant flexibility in modeling the employment of a person for an enterprise, and allows companies and enterprises to easily record the reality of their complex work relationships.

Abstract: The present invention relates to a modular parking place for bicycles, formed by one or more compartments (2), each intended for housing a bicycle (1), each compartment (2) being formed by two sets of symmetrical profiles parallel to one another, between which a protective cover (3) is arranged on the upper portion and a door (4) is arranged on the front portion, while the lower portion of each compartment (2) has a longitudinal channel (5) for supporting and guiding bicycles (1), whereas the set of compartments (2) is closed by means of side cover plates (8) at the ends thereof.

Abstract: The present invention relates to a modular parking place for bicycles, formed by one or more compartments (2), each intended for housing a bicycle (1), each compartment (2) being formed by two sets of symmetrical profiles parallel to one another, between which a protective cover (3) is arranged on the upper portion and a door (4) is arranged on the front portion, while the lower portion of each compartment (2) has a longitudinal channel (5) for supporting and guiding bicycles (1), whereas the set of compartments (2) is closed by means of side cover plates (8) at the ends thereof.

Abstract: This invention discloses the creation of a novel single ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a group of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery and/or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, antagonize or disrupt, simultaneously and independently, the functional domain of different disease causing proteins.

Abstract: This invention discloses ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a plurality of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, or disrupt, simultaneously and independently, the functional domain of a different disease causing protein.

Abstract: The invention provides compounds of the formula Poly-([SP-LI]n-PL-L2) including a collection of 152 peptides useful to create the compounds, and their uses thereof for the treatment of a variety of mammalian diseases. The compound, a novel ligand-targeted multi-stereoisomer peptide polymer conjugate, comprises two or more stereoisomer peptides and a peptide-ligand conjugated via linkers to a biocompatible hydrophilic polymer, preferably HPMA. The increased stability and solubility of the compound carrying the stereoisomer peptides and a peptide-ligand provide ideal pharmaceutical properties including the delivery by the polymer of the peptides into the target cells. The compounds of the invention are useful therapeutics for the treatment of a variety of mammalian diseases.

Abstract: This invention discloses a group of 298 peptides from which several peptides are independently selected and synthesized in their stereoisomer and chemically modified forms, and conjugated to a polymer via linkers creating novel anti-HIV-1 multi-peptide-polymer conjugate compounds for the treatment and prevention of HIV-1 infection. The peptides mimic the domains of major HIV-1 proteins, and therefore, they function as inhibitors of the targeted HIV-1 proteins. The polymer is a useful delivery system for the stereoisomer peptides, and certain peptides are peptide-ligands for targeted delivery into the HIV infected cells.

Abstract: This invention discloses ligand-targeted multi-stereoisomer peptide-polymer conjugate compounds comprising a plurality of different synthetic and chemically modified stereoisomer peptides that have been conjugated to a biocompatible polymer carrying a peptide ligand for targeted delivery or encapsulated in ligand targeted polymer nanoparticles. The unique physicochemical properties of the stereoisomer peptides provide therapeutic compounds with ideal biopharmaceutical properties. The stereoisomer peptides carried by the polymer are delivered to cells or tissues to inhibit, suppress, block, or disrupt, simultaneously and independently, the functional domain of a different disease causing protein.

Abstract: The present disclosure relates to a multilayer film for electronic circuitry applications, having advantageous barrier properties against unwanted electron and electromagnetic wave interference, and also protection against dirt or other similar-type unwanted foreign matter interference. The multilayer films of the present disclosure have at least three layers. The first outer layer contains a base polymer, a carbon black filler or pigment and a dielectric filler. The core layer is a polymer with less than 5 weight percent filler. The second outer is similar to the first outer layer and contains a base polymer, a low conductivity carbon black filler or pigment and a dielectric filler. The two outer layers can be the same or different. Optionally, additional layers can also be used between the two outer layers.

Abstract: The present disclosure relates to a multilayer film for electronic circuitry applications, having advantageous barrier properties against unwanted electron and electromagnetic wave interference, and also protection against dirt or other similar-type unwanted foreign matter interference. The multilayer films of the present disclosure have at least three layers. The first outer layer contains a polyimide base polymer, a carbon black filler and a dielectric filler. The core layer is a polyimide with less than 5 weight percent filler. The second outer is similar to the first outer layer and contains a polyimide base polymer, a low conductivity carbon black filler and a dielectric filler. The two outer layers can be the same or different. Optionally, additional layers can also be used between the two outer layers.

Abstract: The invention provides compounds of the formula Poly-([SP-LI]n-PL-L2) including a collection of 152 peptides useful to create the compounds, and their uses thereof for the treatment of a variety of mammalian diseases. The compound, a novel ligand-targeted multi-stereoisomer peptide polymer conjugate, comprises two or more stereoisomer peptides and a peptide-ligand conjugated via linkers to a biocompatible hydrophilic polymer, preferably HPMA. The increased stability and solubility of the compound carrying the stereoisomer peptides and a peptide-ligand provide ideal pharmaceutical properties including the delivery by the polymer of the peptides into the target cells. The compounds of the invention are useful therapeutics for the treatment of a variety of mammalian diseases.

Abstract: The invention relates to a library of 298 peptides useful for formulating a novel therapeutic HIV vaccine. The peptide sequences were selected on the basis of calibration of molecular structure properties of HIV-1 or host cell proteins. A mixture of D- and L-amino acids or all D-amino acids are used to synthesize the stereoisomer peptides for the purpose of increasing their stability. The peptides are expected to have the ability to potently inhibit functioning of proteins important for HIV infection. A plural of the peptides are conjugated together with a biocompatible polymer, preferably HPMA to further increase stability and solubility, decrease drug toxicity, and potentially evade multidrug resistance and exert cooperative effect, since some peptides are the ligands for host proteins such as integrin, trombospondin, VEGFR and LEDGF which can bring the therapeutic peptides to the target cells and therefore help disrupt the interactions between the host proteins and the HIV proteins.

Abstract: A three-tier employment model provides flexibility when modeling even moderately complex relationships, such as where an employee has multiple job tasks or assignments for an employer. In such an example, a top level can store information for each employee defining the type of relationship that exists between the employee and the employer, such as where the employee works for multiple entities of the employer. A middle level can capture employment terms and conditions that are associated with the relationship(s), as well as one or many work assignments, such as salary information for each assignment. A bottom level can store the actual details of the work to be performed. A three-tier approach thus provides significant flexibility in modeling the employment of a person for an enterprise, and allows companies and enterprises to easily record the reality of their complex work relationships.