Abstract: The present invention provides an oligonucleotide which is capable of activating RIG-I and inducing an anti-viral, in particular, an IFN, response in cells expressing RIG-I. The present invention further provides an oligonucleotide which is capable of activating RIG-I and which has target gene-silencing activity. The oligonucleotide of the present invention has a double-stranded section of at least 19, preferably at least 21 bp, at least one 5? triphosphate, and at least one blunt end which bears a 5? triphosphate. The present invention further provides the use said oligonucleotide for inducing an anti-viral, in particular, an IFN, response in vitro and in vivo. The present invention additionally provides the use of said oligonucleotide for preventing and/or treating diseases or conditions such as infections, tumors/cancers, and immune disorders.

Abstract: The present invention provides STING crystals. The present invention also provides STING modulators that interact with sites present in and/or defined by such crystals. The present invention also provides methods of making and using such crystals and modulators. Other aspects and/or features of the present invention will be apparent to those skilled in the art, reading the present specification.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: The invention relates to compositions, methods, kits, and assays related to the use and/or exploitation of isomers of cGAMP as well as the structure of the enzyme cGAS.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: The invention relates to a stop for arrangement on a drilling, milling or countersinking tool for machining a work piece, wherein the work piece has a surface, and wherein the drilling, milling or countersinking tool has a cutting section. The stop comprises a contact surface, wherein the contact surface is arranged such that once a predetermined machining depth in the work piece is reached, the contact surface is seated against the surface, at least in some sections. A connecting element is provided, wherein the connecting element is arranged between the contact surface and the cutting section. The connecting element is suited to prevent a relative movement between the contact surface and the surface.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IL-12-inducing activity to a single-stranded RNA oligonucleotide. The present invention also provides single-stranded RNA oligonucleotides, including antisense RNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: A screw (2) has a head (5) including an underhead bearing surface (12). Lubricant pockets (13) are arranged at least in a part of the underhead bearing surface (12). The lubricant pockets (13) serve to contain lubricant and to release the lubricant when tightening a screw joint (1) to prevent galling effects during multiple tightening processes.

Abstract: The invention relates to a stop for arrangement on a drilling, milling or countersinking tool for machining a work piece, wherein the work piece has a surface, and wherein the drilling, milling or countersinking tool has a cutting section. The stop comprises a contact surface, wherein the contact surface is arranged such that once a predetermined machining depth in the work piece is reached, the contact surface is seated against the surface, at least in some sections. A connecting element is provided, wherein the connecting element is arranged between the contact surface and the cutting section. The connecting element is suited to prevent a relative movement between the contact surface and the surface.

Abstract: Oligonucleotides bearing free, uncapped 5? phosphate group(s) are recognized by RIG-I, leading to the induction of type I IFN, IL-18 and IL-1? production. Bacterial RNA also induces type I IFN production. 5? phosphate oligonucleotides and bacterial RNA can be used for inducing an anti-viral response or an anti-bacterial response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in vitro and in vivo and for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, tumors, allergies, autoimmune diseases, immunodeficiencies and immunosuppression. Single-stranded 5? triphosphate RNA can be used for inducing an anti-viral response, an anti-bacterial response, or an anti-tumor response, in particular, type I IFN and/or IL-18 and/or IL-1? production, in a target cell-specific manner.

Abstract: A fastener assembly (1) includes a screw (2) and a bush (3). The screw (2) includes a head (4), a shank portion (6) and a threaded portion (7) including a thread (8). The shank portion (6) is arranged to face the head (4) and the threaded portion (7) is arranged to face away from the head (4). The shank portion (6) has a diameter and the thread (8) has an outer diameter, the diameter of the shank portion (6) being smaller than the outer diameter of the thread (8). The bush (3) includes a first narrowing location (10) having a diameter being smaller than the outer diameter of the thread (8). The bush (3) is captively connected to the screw (2) by the first narrowing location (10). The bush (3) includes at least one resilient element (15) having an actuation portion (28) and an engagement portion (29).

Abstract: A fastener assembly (1) includes a screw (2) and a bush (3). The screw (2) includes a head (4), a shank portion (6) and a threaded portion (7) including a thread (8). The shank portion (6) is arranged to face the head (4) and the threaded portion (7) is arranged to face away from the head (4). The shank portion (6) has a diameter and the thread (8) has an outer diameter, the diameter of the shank portion (6) being smaller than the outer diameter of the thread (8). The bush (3) includes a first narrowing location (10) having a diameter being smaller than the outer diameter of the thread (8). The bush (3) is captively connected to the screw (2) by the first narrowing location (10). The bush (3) includes a second narrowing location (11) including at least one resilient element (15) being designed and arranged to elastically engage the thread (8). The bush (3) includes a slot (17) or a gap (19) being designed and arranged to continuously extend over the bush (3) in an axial direction.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IFN-?-inducing activity to a RNA oligonucleotide. The present invention also provides RNA oligonucleotides, including siRNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: Tis invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.

Abstract: The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IFN-?-inducing activity to a RNA oligonucleotide. The present invention also provides RNA oligonucleotides, including siRNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

Abstract: The present invention provides a TLR7 ligand and its use in therapeutic applications. Specifically, the present application provides a RNA oligonucleotide comprising a G:U wobble base pair in the context of a fully double-stranded structure and its use in treating disease such as viral infections, immune disorders and cancer.

Abstract: The invention relates to an advancement guide unit (5) for ensuring the straight-line motion of a manually guided machine tool (I), particularly a portable drill, in the direction of advancement thereof and is substantially composed of a support element (12) for support on a work-piece to be treated and a carriage (30) guided displaceably on the support element (12) relative thereto in the direction of advancement for supporting and guiding the machine tool (1). According to the Invention, a damper (33) acting 48 in the direction of advancement is disposed between the support element (12) and the carriage (30), said damper damping the initial stroke of the carriage (30) toward the support element (12) over a predefined initial stroke distance (y). In a refinement, the damper (33) is disposed between the support element (12) and carriage (30) such that the damping of the initial stroke of the carriage (30) only commences after a primary, undamped initial stroke of the carriage (30).

Abstract: This invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.

Abstract: The invention describes a method of determining whether a double stranded RNA (dsRNA) silences gene expression in a cell in vivo by an RNA interference (RNAi) mechanism by performing 5?-rapid amplification of cDNA ends (5?RACE) to detect the cleavage site of the mRNA in the RNA sample.

Abstract: The present invention provides an oligonucleotide which is capable of activating RIG-I and inducing an anti-viral, in particular, an IFN, response in cells expressing RIG-I. The present invention further provides an oligonucleotide which is capable of activating RIG-I and which has target gene-silencing activity. The oligonucleotide of the present invention has a double-stranded section of at least 19, preferably at least 21 bp, at least one 5? triphosphate, and at least one blunt end which bears a 5? triphosphate. The present invention further provides the use said oligonucleotide for inducing an anti-viral, in particular, an IFN, response in vitro and in vivo. The present invention additionally provides the use of said oligonucleotide for preventing and/or treating diseases or conditions such as infections, tumors/cancers, and immune disorders.