Abstract: The present invention pertains to an improved mesenchymal stromal cell (MSC) preparation and a method for producing the same. The invention provides a new strategy to isolate MSC from bone marrow mononuclear cells (BM-MNCs) by pooling BM-MNCs of multiple unrelated (third-party) bone marrow donors. The MSC preparation manufactured in accordance with the methodology of the invention is characterized by a stable proliferative capability and an increased immunosuppressive potential when compared to individual donor MSC preparations or a pool of individual MSCs generated from multiple donors. The MSCs prepared according to the invention are particularly useful for medical applications such as the treatment of graft-versus-host disease (GvHD) in recipients with hematopoietic stem cell transplants, patients with autoimmune disorders and as a cell-based therapy in regenerative medicine.

Abstract: The invention is based on the modulation of cancer-associated fibroblasts (CAFs) in the treatment of proliferative disorders by radiotherapy. By reducing CAF sensitivity to cellular senescence adverse immune reactions upon radiotherapy of solid tumours and subsequent treatment resistance could be avoided. The invention pertains to senolytics or Interleukin 1 (IL1) signalling inhibitors for use in a method of treating solid tumours and in the treatment or prevention of inflammatory adverse effects upon radiation therapy in context of a cancer treatment. The invention optionally also pertains to senolytics or Interleukin 1 (IL1) signalling inhibitors for use in a method of treating solid tumours and in the treatment or prevention of inflammatory adverse effects upon chemotherapy and/or radiation therapy in context of a cancer treatment.

Abstract: The present invention relates to a combination of inhibitory nucleic acid agents directed at a combination of transcription factors for treatment of heart failure. The combination of inhibited transcription factors comprises one of the groups selected from RARa, TCF7L2, E2F6 and LEF1, or RARa, TCF7L2, E2F7 and NFYb. The combinatorial inhibition of these transcription factors is shown to increase cardiomyocyte proliferation.

Abstract: The present invention relates to a combination of inhibitory nucleic acid agents directed at a combination of miRNAs for treatment of heart failure. The combination of inhibited miRNAs comprises one of the groups selected from miR-1a, and miR-15b, or miR-1a, miR-15b and miR-27b, or miR-1a, miR-27b and miR-34a. The combinatorial inhibition of these miRNAs is shown to increase cardiomyocyte proliferation.

Abstract: The present invention pertains to a novel architecture of non-ribosomal peptide synthases (NRPS). The invention provides artificial NRPS wherein the naturally occurring terminal condensation or thioesterase-domain is replaced by internal condensation or dual condensation/epimerization domains. Moreover, the present invention enables the portability of terminal condensation domains to unrelated NRPS in respect of peptide release of linear peptides. The replacement results in a product independent release of the synthesized product and therefore enables the rational design of NRPS. The invention provides the new NRPS, nucleic acids encoding them, methods for artificial NRPS generation, and methods for producing non-ribosomal peptides.

Abstract: The invention relates to a system for expressing nonribosomal peptide synthetases (NRPSs), polyketide synthases (PKS) or NRPS/PKS hybrid synth(et)ases. NRPS, PKS or hybrids thereof are large multi-domain proteins or multi-domain complexes, the expression of which for the production of peptides often causes difficulties. The invention correspondingly relates to a system for expressing portions of the enzymes which can be assembled post-translationally via protein-protein interactions, introduced in a targeted manner, to form multi-enzyme complexes. The invention discloses protein fragments of such an assembly, and the nucleic acids coding therefor. The invention also relates to a vector system for the protein fragments of the invention and its use for producing functional NRPS/PKS enzyme complexes.

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: The present invention pertains to a novel method for the generation of a vector construct suitable for gene editing applications which comprises a fixed pair of predetermined expressible guide RNA (gRNA) sequences. The method of the invention allows for an easy construction of such vectors and provides in addition thereto vector libraries for the expression of fixed pairs of gRNAs. The vectors of the invention may be advantageously used to cut out larger genomic DNA sequences, or alternatively, to simultaneously introduce mutations in the genome without a loss or larger genomic sequences. Hence, the system of the invention provides for many molecular genetic approaches for genome alteration.

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: The present invention relates to proteins involved in fatty acid synthesis, such as fatty acid synthases (FAS) variants, comprising one or more polypeptide chains, wherein said polypeptide chain(s) comprise one or more subunits comprising a malonyl/palmitoyl transferase domain (MPT domain), acetyl transferase domain (AT domain), and ketoacyl synthase domain (KS domain), and at least one amino acid substitution in the MPT domain at a position corresponding to R130, in the AT domain at a position corresponding to I306, and/or in the KS domain, preferably in the acyl binding channel and/or at KS domain binding site to ACP, to modulate affinities of acyl intermediates, and optionally further amino acid substitution(s). The present invention relates to the respective polypeptide domains. The present invention further relates to nucleic acid molecules encoding the proteins (or the polypeptide domains) and to host cells containing said nucleic acid molecules.

Abstract: N-benzylbenzamides that act as dual soluble 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 catheter assembly includes an elongated catheter shaft, a magnetic sensor, and one or more wires. The elongated catheter shaft has a shaft proximal end and a shaft distal end, and the magnetic sensor includes a coil having a coil proximal end and a coil distal end that is situated toward or at the shaft distal end. The one or more wires extend through the elongated catheter shaft and are situated adjacent the magnetic sensor. Each of the one or more wires is electrically coupled to the coil at the coil distal end.

Abstract: The invention relates to the use of a granulin or a granulin-like compound for producing a pharmaceutical composition for the therapy or prophylaxis of chronic pain, in particular for neuropathic pain.

Abstract: New compounds of the general formula Xm-G-CLn are described as well as methods for their production and use in the analysis, detection and purification of target molecules. These constitute multivalent chelator-compounds with an affinity-tag binding to metal-chelator-complexes which can selectively modify and/or immobilize target molecules by a multitude of probes or functional units.

Abstract: A hyperpolarized liquid contrast agent is for use in a MRT device. The liquid contrast agent passes through a conduit of a MW resonator in the magnetic field of the MRT device. A microwave with a frequency of at least 40 GHz couples into the MW resonator for polarizing the liquid contrast agent upon passage through the conduit in the MW resonator using DNP. The contrast agent is polarized in a continuous passage in the MW resonator and administered immediately. A MW mode is formed in the MW resonator which has an antinode in the magnetic field strength and a node in the electric field strength. The power of the introduced microwave and coupling of the microwave into the resonator are adjusted such that in the area of the line, an amplitude of the MW magnetic field strength B 1 ? 1.5 · 10 - 2 ? Ts ? 1 T 1 , e results, wherein T1,e is the relaxation time of the DNP-active electrons.

Abstract: The invention relates to a device for detecting electromagnetic radiation in the THz frequency range, comprising at least one transistor (FET1, FET2), which has a first electrode, a second electrode, a control electrode, and a channel between the first electrode and the second electrode, and comprising an antenna structure. An electrode is connected to the antenna structure such that an electromagnetic signal which lies in the THz-frequency range and which is received by the antenna structure (1) can be fed into the channel between electrodes and the control electrode is connected to an electrode via a capacitor and/or the control electrode and the first electrode or the control electrode and the second electrode have an intrinsic capacitor such that no AC voltage drop occurs between the control electrode and the first electrode or the second electrode.

Abstract: A sub-harmonic electronic mixer has at least one field effect transistor (FET) having a gate, source, and drain; and a useful signal input at a useful frequency; and a local oscillator input. The input receives the oscillator signal at a frequency being an integral fraction of the useful frequency, plus or minus a mixing frequency to provide a signal output. A gate of the FET and/or the drain and/or the source receives the useful signal to generate a gate-source voltage and/or a drain-source voltage whereby the gate receives the local oscillator signal to generate a gate-source voltage, and the drain or a source receives the local oscillator signal to generate a drain-source voltage. A phase shift is introduced between the signal received at the gate and the signal received at the drain or source of the FET.

Abstract: The present invention relates to antagonists of the expression and/or the function of the micro RNA miRNA-29 for use in the prevention and/or treatment of aortic aneurysms. Further disclosed is a method for the identification of miRNA-29 antagonists, a pharmaceutical composition comprising said miRNA-29 antagonists and a method for preventing and treating age-related aortic aneurysm formation in a subject in need of such a treatment.

Abstract: A double-resonance structure 10 for DNP-NMR and/or ENDOR experiments is described. The double-resonance structure 10 comprises a microwave resonator 30 for generating electromagnetic field suitable for EPR, and an HF resonator 12 for generating electromagnetic fields suitable for NMR. The HF resonator 12 comprises a plurality of electrically conductive strips 14, which are electrically connected so that an HF current can be generated in the plurality of strips 14 such that the HF currents flow in the same direction in the individual strips 14 at the same time. A section of the HF resonator 12 at the same time forms a part of the microwave resonator 30.

Abstract: The invention relates to a device for detecting electromagnetic radiation in the THz frequency range, comprising at least one transistor (FET1, FET2), which has a first electrode, a second electrode, a control electrode, and a channel between the first electrode and the second electrode, and comprising an antenna structure. An electrode is connected to the antenna structure such that an electromagnetic signal which lies in the THz-frequency range and which is received by the antenna structure (1) can be fed into the channel between electrodes and the control electrode is connected to an electrode via a capacitor and/or the control electrode and the first electrode or the control electrode and the second electrode have an intrinsic capacitor such that no AC voltage drop occurs between the control electrode and the first electrode or the second electrode.