Abstract: The present invention relates to a method for the synthesis of compounds useful in the preparation of antibody drug conjugates (ADC), namely, monoprotected dimeric bifunctional prodrugs based on duocarmycin analogs. In a further aspect, compounds obtained by the method according to the present invention are provided. The monoprotected bifunctional prodrug is used for preparing antibody drug conjugates composed of an antibody moiety and the monoprotected bifunctional prodrug. The antibody compound conjugates thus obtained are provided. Further, a method of preparing an antibody drug conjugate composed of two identical or two different antibody moieties is provided as well as the antibody compound conjugate containing two different antibody moieties accordingly. These conjugates can be used in pharmaceutical compositions, in particular, for use in treatment of tumors, e.g. for use in ADC therapy.

Abstract: The present invention relates to a nanoelectronic device, comprising a substrate layer (10), a first electrode layer (12) disposed on the substrate layer (10), a dielectric layer (16) disposed on the first electrode layer (12), a second electrode layer (18) disposed on the dielectric layer (16), wherein the dielectric layer (16) and the second electrode layer (18) are dimensioned such that at least one protruding portion (18a, 18b) of the second electrode layer (18) is formed in which the second electrode layer (18) extends beyond the dielectric layer such that opposing faces of the first and second electrode are formed (16), at least one semiconductor layer (20) disposed between the first electrode layer (12), one of the protruding portions (18a, 18b) of the second electrode layer (18) and the dielectric layer (16); and a gating arrangement (22) in contact with at least the semiconductor layer (20) as well as the first (12) and second (18) electrode layers.

Abstract: The invention relates to shaped parts produced from popcorn which has previously been hydrophobised with a polymer. This allows very light and flexible shaped parts to be produced.

Abstract: The present disclosure concerns agents for use in a new therapeutic application for the prevention or treatment of cardiac arrhythmia and sudden cardiac death. More specifically, the present disclosure concerns an expression construct capable of enhancing expression of TBX5 in a subject to be treated, for use in the prevention or monotherapeutic treatment of a ventricular heart disease and associated complications selected from cardiac arrhythmia and sudden cardiac death.

Abstract: The present invention relates to humanised antibodies that bind amyloid peptides, which antibodies comprise mutations in the heavy chain and/or light chain variable domains, which mutations improve the binding activity. The antibodies may be useful in the treatment of Alzheimer's disease (AD).

Abstract: The present invention relates to methods, pharmaceutical compositions and uses thereof for treating and alleviating Alport syndrome, various aspects and symptoms associated with Alport syndrome in a patient in need thereof comprising administering empagliflozin to the patient.

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: A device for generating negative ions comprises: a) an ionizer (14) including a heatable ionizer surface; b) a heater (60) for heating said ionizer whereby positive ions (30) are generated at said ionizer surface (14e); c) a target (34) including a material for generating negative ions when said positive ions impigne on said material; wherein d) said ionizer is arranged opposite the target; e) said target is electrically negatively biased in respect to said ionizer; f) said ionizer comprises an aperture (22) through which said generated negative ions are extracted from said target to generate a beam (50) of negative ions; and wherein g) said ionizer surface (14e) is planar.

Abstract: The present disclosure is directed to novel therapeutic approaches for the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of an organ. Specifically disclosed are agents for use in increasing homodimer-formation of ARNT in an organ in the prevention, treatment and/or delaying progression of chronic injury, progressive loss of functional parenchymal cells, or fibrosis of said organ, as further defined in the claims. In embodiments, said agent may be (i) an inhibitor of protein phosphatase 2A (PP2A) activity, (ii) an inhibitor of the transcriptional repressor complex FKBP12/YY1, or (iii) an expression construct, which is capable of over-expressing ARNT in said organ, as well as combinations of (i), (ii), and/or (iii).

Abstract: The present invention provides a new method for producing Engineered Heart Muscle (EHM) under chemically fully defined conditions all compatible with GMP regulations. The resulting human myocardium generates force and shows typical heart muscle properties.

Abstract: The present invention provides contrast agents of the formula [N(A1,A2,A3) M](counter ion(s)) for use in a diagnostic method practiced on the human or animal body. It also refers to the contrast agents, as well as pharmaceutical compositions containing same. Further, it relates to a method of in vitro medical imaging, especially of diagnostic imaging, comprising administering said compound to a sample.

Abstract: The present invention provides a new method for producing Engineered Heart Muscle (EHM) under chemically fully defined conditions and compounds all compatible with GMP regulations. The resulting human myocardium generates force and shows typical heart muscle properties.

Abstract: The present invention relates to a pouch-like structure useful for mechanically preventing distension and/or resisting dilation of the heart and for supporting the hearts function by controllable and paracrine support of a failing heart in a mammal. The pouch-like structure is composed at least partly of engineered tissue comprising genetically engineered cells, such as genetically engineered cells other than cardiac myocytes whereby said genetically engineered cells contain a gene encoding a paracrine factor, said gene encoding the paracrine factor being under control of an inducible promoter system or a heterologous promoter system. Further, the present invention relates to a method for the preparation of the pouch-like structure for therapeutic, disease modelling, and drug development applications. In addition, the present invention relates to cells other than cardiac myocytes for use in the preparation of the pouch-like structure as described herein.

Abstract: A method for creating a microscope image of an object includes emitting excitation light, illuminating points on the object in a rastering manner, and detecting a raster partial image of a predetermined magnification for each illuminated point. An optical sensor detects emission light from the object excited by the excitation light. Distances between pairs of raster partial images correspond to distances of the illumination points multiplied by a correction factor. A microscopy device includes a light source, a rastering device, an optical sensor, and a deflecting device for deflecting the emission light. The deflecting device feeds excitation light passing through an inlet to the rastering device, light deflected at the rastering device to a first outlet, and emission light passing through the first outlet to the rastering device such that the emission light is deflected from the optical axis in the same direction as the excitation light.

Abstract: A method of operating a multi-functional limb movement auxiliary device comprising a plurality of actuators configured to move, upon activation, limb movement auxiliary device members in at least two independent degrees of freedom, a bio-signal sensing unit that is configured to acquire bio-signals indicative of motor activity, a control unit configured to receive and evaluate the acquired bio-signals, the method comprising steps of acquiring bio-signals from the user of the limb movement auxiliary device, applying a novelty detection method (ND) for comparing digitally converted, acquired bio-signals with calibration bio-signals, and, based on a result of the comparison, for assigning a similarity measure to the acquired, digitally converted bio-signals, applying at least one sequential estimator (SEQ-E) to the acquired, digitally converted bio-signals, if the assigned similarity measure is equal to or larger than a pre-determined threshold value, applying at least one simultaneous estimator (SIM-E) to th

Abstract: The present invention is directed to a method for producing bioengineered heart muscle (BHM) from pluripotent stem cells, generally comprising the steps of inducing mesoderm differentiation, cardiac differentiation, and cardiac maturation by directed tissue formation. The method is a robust, serum-free and reproducible way to produce BHM for multiple applications, and is applicable to multiple pluripotent stem cell lines. The present invention is also directed to the BHM produced by the method disclosed herein, as well as to uses of said BHM in pharmacologic and toxicity screenings, and its use in medicine.

Abstract: The present invention is directed to a method for producing bioengineered heart muscle (BHM) from pluripotent stem cells, generally comprising the steps of inducing mesoderm differentiation, cardiac differentiation, and cardiac maturation by directed tissue formation. The method is a robust, serum-free and reproducible way to produce BHM for multiple applications, and is applicable to multiple pluripotent stem cell lines. The present invention is also directed to the BHM produced by the method disclosed herein, as well as to uses of said BHM in pharmacologic and toxicity screenings, and its use in medicine.

Abstract: The present invention is directed to a method for producing bioengineered heart muscle (BHM) from pluripotent stem cells, generally comprising the steps of inducing mesoderm differentiation, cardiac differentiation, and cardiac maturation by directed tissue formation. The method is a robust, serum-free and reproducible way to produce BHM for multiple applications, and closed herein, as well as to uses of said BHM in pharmacologic and toxicity screenings, and its use in medicine.

Abstract: A method for specifically detecting and optionally for quantifying Mycobacterium avium ssp. paratuberculosis (MAP) in a sample of an individual is provided. For this purpose, the detection of the presence of the IS900 region in a sample is performed by nucleic acid amplification using specific oligonucleotides. In a further aspect, a test kit for specifically detecting MAP in a sample by amplification methods is also provided. Finally, specific oligonucleotides that are suitable for specifically detecting MAP are described.

Abstract: The present invention relates in a first aspect to compounds for use in the treatment of leukodystrophy whereby these compounds are quinoline derivatives, e.g. laquinimod. In a further aspect, the present invention relates to methods for the treatment of Leukodystrophy, in particular, peroxisomal disorders including Zellweger syndrome.