Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Abstract: The disclosure relates to medical devices and methods of manufacturing medical devices. An orthopedic screw includes an inner core member having a head having a first outer diameter, a tip having a second outer diameter, and a body extending between the head and the tip and having a third outer diameter that is less than the first outer diameter and the second outer diameter. An outer body member is disposed circumferentially around the body of the inner core member and defines an outer body member external thread. The tip of the inner core member can define an inner core member external thread that forms an interrupted thread with the outer body member external thread.

Abstract: The invention relates to methods for synthesizing amanitin derivatives having an amino group attached to position 6? of the central tryptophan moiety. The invention furthermore relates to an amanitin derivative having an amino group attached to position 6? of the central tryptophan moiety, conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

Abstract: The invention relates to an electric axial flux machine comprising a stator, a rotor having a rotor shaft and at least a first disk-shaped rotor body that is rotationally and linearly fixedly arranged on the rotor shaft, and comprising a cooling device for cooling the axial flux machine. According to the invention, the cooling device comprises a first cooling channel module for holding a coolant, said cooling channel module being designed such that is can be placed as a separate component axially directly adjacent to the rotor body, on the side remote from the stator.

Abstract: The disclosure relates to medical devices and methods of manufacturing medical devices. An intramedullary rod includes a head member, a shaft member partially disposed within a distal recess of the head member, and an outer body member disposed circumferentially around the shaft member and a portion of the head member. Medical device systems and methods of manufacturing medical devices are also described.

Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4?, 5? or 7? of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.

Abstract: The present invention relates to a method of formation of a sulphur bridge between tryptophan and cysteine in solid phase peptide synthesis under iodine treatment. The invention also relates to the resulting compounds of the method and their respective use.

Abstract: A universal clamp apparatus for orthopedic exterior fixators is disclosed. Preferably, the universal clamp apparatus has two pin/rod clamps, each having seating grooves for attaching to a frame rod associated with a frame of the fixator and/or a bone pin for implantation in a bone fragment. A clamp screw extends through and connects the first and second pin/rod clamps. An ergonomically designed knob having at least one collapsible or non-collapsible turn lever acts as a torque amplifier when rotated by hand without tools to tighten and untighten the pin/rod clamps to the frame rod and/or bone pin by movement along the clamp screw. The pin/rod clamps have planar sides that are contiguous and have radial ratchet grooves that are in mating engagement and provide a ratcheting mechanism so that the rotation of the pin/rod clamps relative to each other occurs in incremental rotational steps.

Abstract: A universal clamp apparatus for orthopedic external fixators is disclosed. Preferably, the universal clamp apparatus has two pin/rod clamps, each having seating grooves for attaching to a frame rod associated with a frame of the fixator and/or a bone pin for implantation in a bone fragment. A clamp screw extends through and connects the first and second pin/rod clamps. An ergonomically designed knob having at least one collapsible or non-collapsible turn lever acts as a torque amplifier when rotated by hand without tools to tighten and untighten the pin/rod clamps to the frame rod and/or bone pin by movement along the clamp screw. The pin/rod clamps have planar sides that are contiguous and have radial ratchet grooves that are in mating engagement and provide a ratcheting mechanism so that the rotation of the pin/rod clamps relative to each other occurs in incremental rotational steps.

Abstract: Amatoxins, as well as antibody-drug conjugates (ADCs) comprising an amatoxin are provided, as well as compositions and methods of using the same. The compositions and methods provided herein can be used for cancer therapy. They can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, as well as prevention of graft-versus-host-disease (GVHD), are provided.

Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Abstract: The invention relates to a PSMA-targeting conjugate comprising (a) an amatoxin; (b) a small molecule PSMA-targeting moiety; and (c) optionally a linker linking said amatoxin and said small molecule PSMA-targeting moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Abstract: A device cleans a core engine of a jet engine. The device has: a nozzle installation which is configured for introducing a cleaning medium into the core engine; a connector configured to connect the device in a rotationally fixed manner to a shaft of a fan of the jet engine; and a line connection configured to supply the cleaning medium, which is connected to the nozzle installation by a rotary coupling. The nozzle installation comprises nozzles, comprising at least one flat jet nozzle, and at least one full cone nozzle or hollow cone nozzle.

Abstract: A device cleans a core engine of a jet engine. The device has: a nozzle installation configured to introduce a cleaning medium into the core engine; a connector configured to connect the device in a rotationally fixed manner to a shaft of a fan of the jet engine; and a line connection configured to supply the cleaning medium, the line connection being connected to the nozzle installation by a rotary coupling. The nozzle installation has first contact faces configured to bear axially on fan blades of the fan, the first contact faces being configured for defined positioning of the nozzle installation relative to the jet engine.

Abstract: Embodiments of a universal clamp apparatus for an orthopedic exterior fixator are disclosed. The universal clamp apparatus can be operated without the need for tools, with extraordinary tightening precision, and with low risk of losing stability. The universal clamp apparatus has at least one pin/rod clamp, but preferably two pin/rod clamps. Each clamp has seating grooves for snapping in and attaching to at least one of the following: a frame rod associated with a frame of the fixator and/or a bone pin for implantation in a bone fragment. A screw mechanism, such as a clamp screw, extends through and connects the first and second pin/rod clamps. An ergonomically designed knob having at least one collapsible or non-collapsible turn lever acts as a torque amplifier when rotated to tighten and untighten the pin/rod clamps to the frame rod and/or bone pin by movement along the clamp screw.

Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a BCMA-binding moiety comprising (i) the variable domains of humanized antibody J22.9-ISY, and (ii) a heavy chain constant region comprising a D265C mutation; and (c) a protease-cleavable linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of multiple myeloma.

Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6? of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6? of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

Abstract: The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6? of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6? of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

Abstract: An assembly for assisting with positioning of an intervertebral implant, including an implant holder having an elongate body extending along a longitudinal axis between first and second ends, the first end being adapted to be attached to the stabilising wedge of an intervertebral implant, the first end of the implant holder having a deflection device including an opening having a central axis substantially perpendicular to the longitudinal axis of the implant holder but not converging with the longitudinal axis, the opening allowing the braid of an implant to pass therethrough in such a way that, when in use, the braid may have a first portion extending substantially perpendicularly to the longitudinal axis from the implant to the opening, and a second portion extending from the opening to the free end in a plane substantially parallel to the longitudinal axis of the implant holder to allow the tensioning of the braid.