Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: Efforts to use RNA-cleaving DIMA enzymes (DNAzymes) as gene silencing agents in therapeutic applications have stalled due to their low efficacy in clinical trials. Here the present invention reports a xeno-nucleic acid (XNA) modified version of the classic DNAzyme 10-23 that achieves multiple turnover activity under cellular conditions and resists nuclease digestion. The new reagent overcomes the problem of product inhibition limiting previous 10-23 designs using molecular chemotypes with DNA. FANA, and TNA backbone architectures that balance the effects of enhanced biological stability with RNA hybridization and divalent metal ion coordination. In cultured mammalian cells. X 10-23 facilitates persistent gene silencing by efficiently degrading exogenous and endogenous mRNA transcripts. Together, these results demonstrate that new molecular chemotypes can improve the activity and stability of DNAzymes, and may provide a new route for nucleic acid enzymes to reach the clinic.

Abstract: The present invention relates to the development of and use of genetically modified human differentiated cells coupled with xenotransplantation into animal models to identify injury and disease-specific RNA and/or protein biomarkers. Specifically, the present invention encompasses two complementary methods for biomarker discovery that enable the direct and selective labelling, isolation, and analysis of human-specific RNA and/or proteins from xenotransplantation (or chimeric) animal models. Both methods involve the treatment of animal models with an RNA analog and/or amino acid analog that enables the specific isolation and quantification of human RNAs and/or proteins for the identification of novel human biomarkers for a large array of human injuries and diseases.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: Microglia/monocytes exist within a ‘niche’ which limits the total number of microglia/monocytes/macrophages that reside within a mammalian central nervous system (CNS). Therefore, methods are needed that can help therapeutically modify microglia, monocytes, and macrophages or the cells that give rise to them to compete with endogenous microglia and partially or completely occupy the CNS niche. The present disclosure features therapeutic microglia, monocytes, or macrophages that have a selective advantage in comparison to endogenous brain resident microglia in their response to CSF1R inhibitors. Specifically, therapeutic cells developed in the present disclosure do not die at a given dose of CSF1R inhibitor that is sufficient to kill endogenous microglia. The therapeutic cells described herein can be used to treat neurological diseases.

Abstract: The invention relates to a spur gear wheel with a gear body (4, 5) made from a sintered material, which has a circumference around which teeth (6, 7) are distributed projecting in the radial direction, and which is delimited by two end faces (8, 9, 10, 11) in the axial direction. At least one shaped element (12) in the form of a recess (13) and/or an elevation (14) and/or a compacted area is provided on at least one end face (8, 9, 10, 11) in the region of the teeth (6, 7) and/or in the radial direction underneath the teeth (6, 7).

Abstract: The invention relates to a rolling tool (2) for producing crowned teeth on a gear (5) using a transverse rolling process, in particular for compressing the teeth of the gear (5) at least in some areas, comprising a tool body (6) which has tool teeth (7) projecting radially outward for meshing with the teeth of the gear (5) to be rolled, wherein at least some areas of the tool teeth (7) are concave in the axial direction in the area of the tooth flanks.

Abstract: The invention relates to a tool for compacting the surface of a component (2) produced by powder metallurgy, comprising a mold (1) and a stamp (20), wherein in the mold (1) a recess (5) is provided which extends from a first mold opening (6) to a second mold opening (8), and which has a wall surface (10) for supporting the component (2), and the stamp (20) has a stamp length (23) and a stamp surface (21), wherein the inner diameter (12) of the recess (5) of the mold (1) becomes smaller from the first mold opening (6) in the direction of the second mold opening (8) or an external diameter (22) of the stamp (20) becomes greater over the stamp length (23), and wherein a compaction element (17) is arranged on the wall surface (10) of the mold (1) or on the stamp surface (21). The compaction element (17) is configured to have a thread-like progression.

Abstract: The invention relates to a tool for compacting the surface of a component (2) produced by powder metallurgy, comprising a mold (1) and a stamp (20), wherein in the mold (1) a recess (5) is provided which extends from a first mold opening (6) to a second mold opening (8), and which has a wall surface (10) for supporting the component (2), and the stamp (20) has a stamp length (23) and a stamp surface (21), wherein the inner diameter (12) of the recess (5) of the mold (1) becomes smaller from the first mold opening (6) in the direction of the second mold opening (8) or an external diameter (22) of the stamp (20) becomes greater over the stamp length (23), and wherein a compaction element (17) is arranged on the wall surface (10) of the mold (1) or on the stamp surface (21). The compaction element (17) is configured to have a thread-like progression.

Abstract: The invention relates to a rolling tool (2) for producing crowned teeth on a gear (5) using a transverse rolling process, in particular for compressing the teeth of the gear (5) at least in some areas, comprising a tool body (6) which has tool teeth (7) projecting radially outward for meshing with the teeth of the gear (5) to be rolled, wherein at least some areas of the tool teeth (7) are concave in the axial direction in the area of the tooth flanks.

Abstract: The invention relates to a spur gear wheel with a gear body (4, 5) made from a sintered material, which has a circumference around which teeth (6, 7) are distributed projecting in the radial direction, and which is delimited by two end faces (8, 9, 10, 11) in the axial direction. At least one shaped element (12) in the form of a recess (13) and/or an elevation (14) and/or a compacted area is provided on at least one end face (8, 9, 10, 11) in the region of the teeth (6, 7) and/or in the radial direction underneath the teeth (6, 7).