Abstract: Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

Abstract: Soluble versions of heterodimeric receptors, e.g., CD94/NKG2 receptors, and methods of producing and using such constructs, are described. The constructs comprise soluble fragments of, each receptor monomer, and some constructs further comprise at least one immunoglobulin Fc domain. Exemplary constructs are those wherein (1) each soluble fragment is linked to an immunoglobulin Fc domain, which are then allowed to dimerize, (2) each soluble fragment is linked to an immunoglobulin Fc domain mutated to promote forced dimerization with the correct counterpart, and (3) single-chain constructs where the monomeric receptor fragments are linked, and the C-terminal fragment is linked to an Fc domain.

Abstract: The present invention relates to agents that are non-competitive antagonists of the CD94/NKG2A receptor such as certain anti-NKG2A antibodies, in particular humanized versions of murine anti-NKG2A antibody Z199, as well as methods of producing and using such agents and antibodies.

Abstract: The present invention relates to novel compositions and methods for regulating an immune response in a subject. More particularly, the invention relates to specific antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects. The invention also relates to fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly in therapy, to increase NK cell activity or cytotoxicity in subjects.

Abstract: Described herein are anti-NKG2A antibodies suitable for human therapy, including humanized versions of murine anti-NKG2A antibody Z270, as well as related methods and materials for producing and using such antibodies. Exemplary complementarity-determining regions (CDRs) sequences and sites for optional amino acid back-substitutions in framework region (FR) and/or CDRs of such antibodies are also described.

Abstract: Soluble versions of heterodimeric receptors, e.g., CD94/NKG2 receptors, and methods of producing and using such constructs, are described. The constructs comprise soluble fragments of, each receptor monomer, and some constructs further comprise at least one immunoglobulin Fc domain. Exemplary constructs are those wherein (1) each soluble fragment is linked to an immunoglobulin Fc domain, which are then allowed to dimerize, (2) each soluble fragment is linked to an immunoglobulin Fc domain mutated to promote forced dimerization with the correct counterpart, and (3) single-chain constructs where the monomeric receptor fragments are linked, and the C-terminal fragment is linked to an Fc domain.

Abstract: Bispecific antibodies comprising (a) a first light-heavy chain pair having specificity for a first target and a sufficient number of substitutions in its heavy chain constant domain with respect to a corresponding wild-type antibody of the same isotype to significantly reduce the formation of first heavy chain-first heavy chain dimers and (b) a second light-heavy chain pair comprising a heavy chain having a sequence that is complementary to the sequence of the first pair heavy chain sequence with respect to the formation of intramolecular ionic interactions, wherein the first pair or second pair comprises a substitution in the light chain and complementary substitution in the heavy chain that reduces the ability of the light chain to interact with the heavy chain of the other light chain-heavy chain pair are provided. Methods of producing such antibodies in one or more cells also are provided.

Abstract: A hybrid wafer comprises a single-crystal SixGe1-x layer (15), where 0?x?1, a high thermal conductivity layer (10), and between the single-crystal SixGe1-x layer (15) and the high thermal conductivity layer (10), an intermediate layer (21) having a thickness of between 1 nanometer and 1 micrometer and comprising at least one amorphous or polycrystalline SixGe1-x layer (21a), where 0?x?1.

Abstract: Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

Abstract: The present invention relates to agents and methods that are capable of augmenting NK-mediated killing of target cells by reducing inhibitory KIR signalling without reducing the binding of KIR to HLA-C. As described herein, transduction of negative signaling via KIR, upon binding of KIR to its HLA class I ligand, can involve a ligand-binding induced, conformational reorientation of the KIR molecules allowing interactions to form between adjacent KIRs in specific domains, leading to accelerated clustering. Methods and agents such as monoclonal antibodies for reducing KIR-mediated inhibition of NK cell cytotoxicity without reducing or blocking HLA-binding by, e.g., reducing or blocking dimerization of KIR, are provided.

Abstract: The invention is a method for obtaining a reactive sputtering process with a reduced or eliminated hysteresis behavior. This is achieved by focusing the ion current onto a small area, a reduced erosion area (14), which is in constant motion along the target (10) to avoid melting of target material. This means that the current density is very high at the reduced erosion area (14) while the average overall current density is significantly lower. The problem with arcing during reactive sputtering will be suppressed since the compound layer is effectively removed if the current density is sufficiently high. Moreover, the high current density results in a substantial increase of the fraction of ionized sputtered species.

Abstract: The present invention relates to agents and methods that are capable of augmenting NK-mediated killing of target cells by reducing inhibitory KIR signalling without reducing the binding of KIR to HLA-C. As described herein, transduction of negative signaling via KIR, 5 upon binding of KIR to its HLA class I ligand, can involve a ligand-binding induced, conformational reorientation of the KIR molecules allowing interactions to form between adjacent KIRs in specific domains, leading to accelerated clustering. Methods and agents such as mono-clonal antibodies for reducing KIR-mediated inhibition of NK cell cytotoxicity without reducing or blocking HLA-binding by, e.g., reducing or blocking dimerization of KIR, are provided.

Abstract: The invention is a method for obtaining a reactive sputtering process with a reduced or eliminated hysteresis behavior. This is achieved by employing a target made from a mixture of metal and compound materials. In the method according to the present invention, the fraction of compound material is large enough to eliminate or significantly reduce the hysteresis behavior of the reactive sputtering process and enable a stable deposition of compound films at a rate significantly higher than what is possible from a target completely made from compound material.

Abstract: The invention is a method for obtaining a reactive sputtering process with a reduced or eliminated hysteresis behaviour. This is achieved by focusing the ion current onto a small area, a reduced erosion area (14), which is in constant motion along the target (10) to avoid melting of target material. This means that the current density is very high at the reduced erosion area (14) while the average overall current density is significantly lower. The problem with arcing during reactive sputtering will be suppressed since the compound layer is effectively removed if the current density is sufficiently high.

Abstract: A method and apparatus for generation of a discharge in own vapors of a radio frequency electrode for sustained self-sputtering and evaporation comprising the steps of: (a) generation of a radio frequency discharge by a radio frequency electrode of a hollow geometry in an auxiliary gas introduced into the discharge area at a pressure necessary for an initiation of a hollow cathode discharge inside the hollow electrode causing sputtering and/or evaporation of the electrode surface; (b) increasing the radio frequency power to said hollow electrode to enhance density of vapors containing particles released from the electrode by the sputtering and/or evaporation in the radio frequency generated hollow cathode discharge up to a density at which a self-sustained discharge remains after the inflow of said auxiliary gas is closed and the pumping of gas is adjusted to a value necessary for the maintenance of the discharge. The hollow radio frequency electrode may serve as an inlet of said auxiliary gas.