Abstract: The present invention pertains to a novel treatment of pathologies caused by an increased synthesis or accumulation of sulfolipids such as sulfatide. The invention provides mutated arylsulfatase A (ARSA or ASA, EC 3.1.6.8) enzymes with increased activity towards sulfatide metabolization. The invention provides nucleic acids encoding the mutant ARSA, the use of the proteins and nucleic acids, as well as pharmaceutical compositions comprising them, in the treatment of lysosomal storage disorders (LSDs) such as metachromatic leukodystrophy (MLD).

Abstract: A process for polymerizing ?-butyrolactone that includes contacting racemic ?-butyrolactone or an enantiomer thereof with a catalyst/initiator system which includes a rare earth metal, a chiral ligand, at least one nucleophilic ligand, optionally at least one solvent ligand, and optionally an alkali based co-catalyst. The chiral ligand is an enantiomer of a unit of formula I Each Rz independently is substituted or unsubstituted linear C1-C20 alkyl, or substituted or unsubstituted branched, or cyclic C3-C20 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C5-C20 heteroaryl, or halogen. Each Ra independently is H, Me+, (MeZ)+, wherein Z is a charge equalizing anion, or wherein two Ra together are alkaline earth metal, wherein Me+ is alkali metal or alkaline earth metal.

Abstract: The present invention is in the field of the cultivation of biological cells and tissues with organ-like function on a microphysiological scale and provides a method for the microphysiological co-cultivation of 3D organoid tissue and at least one 2D cell layer.

Abstract: A surgical simulator having at least two holding elements on a support surface, wherein a bore for receiving a bearing pin is present laterally on the holding elements at least one location, and at least one bow is arranged coaxially with respect to the bearing pin which extends on a circular or rectangular line about the support surface, wherein, by a coaxial movement of the bow about the circular or rectangular line, a work field of variable size can be adjusted, and, by the movement of the bow as frame element on the holding elements, the support surface can be spanned in an arc shape, and the use of such a surgical simulator for medical and veterinary training purposes.

Abstract: The present invention relates to means and methods for conjugating/attaching target molecules such as proteins to a label and/or carrier. Specifically, the present invention provides a complex comprising a metal cation coordinating (i) a metal cation ligand being a carbonate selected from CO32? and HCO3— and (ii) a metal cation chelating domain comprising a chelating ligand and a label and/or carrier. This complex can be used for attaching a label and/or a carrier to a target molecule, preferably a protein. The attachment of the label or carrier via the complex of the invention involves the replacement of the metal cation ligand with a coordinating group of the target molecule so that a product complex with the target molecule as primary ligand in the coordination sphere of the metal cation is formed. Accordingly, the present invention also provides for uses and methods involving the attachment of a label and/or carrier to a target molecule.

Abstract: Provided is a method for determining, in a sample, enrichments of a first and a second stable-labeled tracer of a target substance including glucose, the first tracer and the second tracer having the same or similar chemical structure as the target substance, the method including: ionizing the first tracer, the second tracer and the target substance of the sample; measuring intensities of ions deriving from the target substance, the first tracer and the second tracer using a mass analyzer; calculating an enrichment of the first tracer from a first ratio of intensity of the ions deriving from the first tracer to the intensity of the ions deriving from the target substance employing a first calibration curve independent of enrichments of each of the second tracer; wherein the mass analyzer is operated so as to resolve an ion peak deriving from a tracer and having a width ?(m/z) at half maximum peak height equal to or smaller than 1×10?2.

Abstract: Device and method for comminution or inactivation of circulating tumor cells (CTC) or tumor cell clusters (CTCC) from a tumor-affected organ or organ part, wherein it is proposed that in the venous drain of the tumor-affected organ or organ part a pump (2) with a pressure-increasing section and a pressure-reducing throttle (13) is arranged and is operated at the output side in its design point given by volumetric flow (Q) and pumping pressure (p) according to the volumetric flow and the blood pressure of the venous drain of the tumor-affected organ or organ part. Circulating tumor cells (CTC) and tumor cell clusters (CTCC) are thus comminuted and inactivated to thus reduce the risk of metastasis formation in cancerous diseases.

Abstract: The invention relates to a method for the tamper-proof storing of data in a bidirectionally linked blockchain structure. The method comprises the steps of creating an additional block Bi to extend the blockchain structure which comprises the data to be stored as payload data creating a bidirectional linking of the additional block Bi to a predefined number of preceding blocks, wherein creating the bidirectional linking comprises performing a backward linking of the additional block to the predefined number of preceding blocks and performing a forward linking of the predefined number of preceding blocks to the additional block.

Abstract: The present invention relates to excipients for stabilizing active agents, in particular peptides, polypeptides, nucleic acids, viruses, virus-like particles, proton pump inhibitors and antibiotics. The excipient reduces aggregate and/or particle formation in preparations comprising said agents. The excipient is a diamide of a dicarboxylic acid comprising at least one N—H amido group, at least one unsubstituted or substituted N-hydroxyethylamido group and/or at least one unsubstituted N-hydroxymethylamido group. In particular, the excipient is N,N,N?,N?-tetrakis-(2-hydroxyethyl) adipinic acid amide.

Abstract: The invention relates to a method for producing dry pet food articles, dry pet food articles produced by the method, and the use of the resulting dry pet food articles. The dry pet food articles are produced by a method that includes the steps of providing a moulding material by contacting popcorn with a binder composition, the binder composition including a protein, a sugar alcohol, and water; and forming an article from the moulding material by administering heat and/or pressure to the moulding material in a mould. The dry pet food articles can be produced easily and provide very low caloric value per weight and particularly per volume, while also being well received by pets in terms of taste and texture.

Abstract: For exploiting novel use-cases, in particular sophisticated human-machine interaction, with an intraoral electronic tongue monitoring system designed to be worn by a user on the upper or lower jaw and featuring a support sheet bearing a number of intraoral sensors arranged in an array for recording tongue movement and/or tongue pressure, it is proposed that the system comprises at least one extraoral sensor located outside of the oral cavity delimited by the teeth when the system is in place, in particular such that extraoral and/or intraoral and/or interlabial movements of the tongue and/or lip pressure can be recorded with the system and/or such that the system may be used as an input device controlled through tongue movement using a human-machine-interface provided by the system.

Abstract: The present invention relates to an enzymatic process for the modification of free fatty acids (FFAs) derived from renewable feedstocks of bio-based oils. Specifically, the invention describes the hydrolysis of any bio-based oil, such as high oleic sunflower oil (HOSO), to FFAs, containing high amounts of oleic acid (OA), which is further hydrated to 10-hydroxystearic acid (10-HSA).

Abstract: N-benzylbenzamides that act as dual soluble epoxide hydrolase (sEH)/peroxisome proliferator-activated receptor ? (PPAR?) modulators and are useful as medications in the treatment of Metabolic Syndrome (MetS) cluster diseases, including diabetes. Methods of making and using the same are further provided.

Abstract: A device and a method for training a model are disclosed, wherein the method of training the model includes: first classifying a plurality of data packets using the model, wherein a first class is assigned to each data packet of a plurality of data packets, wherein the first class is associated with a receiver of a plurality of receivers; second classifying the plurality of data packets, wherein a second class is assigned to each data packet of the plurality of data packets, wherein the second class is associated with a receiver of the plurality of receivers; and training the model using the plurality of first classes and the plurality of second classes assigned to the plurality of data packets.

Abstract: The invention relates to a device for the detection of gamma rays coming from a source without image truncation and without image overlapping, comprising, at least, two detection cells and each of said cells comprising a detection space adapted to receive the gamma rays that penetrate through an opening, wherein said detection space comprises one or more detection assemblies, with some of said assemblies being positioned such that they stand in the way of the gamma rays coming into the overlap volume thereof.

Abstract: A method for the detection of impaired responsiveness of CD4+ T-cells to regulatory T-cells (Treg), Treg resistance, by measuring the expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PPARGC1A (PGC-1?) in activated CD4+ T-cells, in particular in patients suffering from relapsing remitting multiple sclerosis. The invention relates to an in vitro screening method for the detection of an autoimmune disease or a condition, comprising the steps of generating a functional gene expression profile by measuring the expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PPARGC1A (PGC-1?) in Treg-resistant CD4+ T-cells from patients suffering of an autoimmune disease or condition, and comparing the obtained gene expression profile with the expression profile from Treg-sensitive CD4+ T-cells from healthy controls.

Abstract: The present invention describes a new alkynylation and cyanation agent, as well as its preparation and use to introduce nitrile (cyano) or alkyne groups into chemical target molecules by means of an electrophilic reaction. To enable an electrophilic reaction, the chemical backbone of dibenzothiophene was used.

Abstract: The invention relates to an actuator (1; 1a; 1b) which can be moved from an initial position into a working position having at least one actuator element (2; 2a; 2b) whose dimensions can changed by an electrical signal, Appropriately, at least two restoring means (20, 30; 20a, 30a; 20b, 30b) acting on the actuator element (2; 2a; 2b) are provided for movement into the working position. With the at least two restoring means, a total restoring means characteristic curve, which is composed of portions of the individual, preferably preloaded restoring means as well as a portion of a variable stiffness of the actuator element, can be advantageously tailored.

Abstract: Provided are methods in a system of at least a second and a third artificial intelligence unit, comprising: inputting first input values to at least one second artificial intelligence unit, and obtaining output values based on the input values from the at least one second artificial intelligence unit; at least temporarily storing situation data, the situation data comprising first input values and/or second output values of the at least one second unit; using the situation data as input values of the third artificial intelligence unit, the third artificial intelligence unit generating third output values in response to the input values; and checking whether the second output values of the at least one second unit satisfy one or more predetermined conditions based on the third output values. Also provided is a system for carrying out such a method.

Abstract: The present invention relates to novel inhibitors of adipose triglyceride lipase (ATGL) having an improved inhibitory activity against human ATGL (hATGL) as well as pharmaceutical compositions comprising these inhibitors, and their therapeutic use, particularly in the treatment or prevention of a lipid metabolism disorder, including, e.g., obesity, non-alcoholic fatty liver disease, type 2 diabetes, insulin resistance, glucose intolerance, hypertriglyceridemia, metabolic syndrome, cardiac and skeletal muscle steatosis, congenital generalized lipodystrophy, familial partial lipodystrophy, acquired lipodystrophy syndrome, atherosclerosis, or heart failure.