Abstract: The present invention pertains to a novel method for the generation of highly diverse RNA expressing vectors and vector libraries for use in targeted gene knock out, knock down and genome modification approaches. The invention pertains to a method for generating such higher order libraries without the need of classical cloning technologies. This is particularly useful for libraries based on large vectors wherein a sequence cannot be easily mutated with classical mutagenesis methods. The vectors and libraries generated according to the methods of the invention are in particular for RNA assisted silencing technologies such as RNA interference, and for targeted genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system or similar RNA/DNA-encoded gene perturbation systems which use small guide RNAs to target the CRISPR complex to a specific genomic sequence. The invention provides also kits comprising the materials for performing the methods of the invention.

Abstract: The present invention pertains to a novel method for the generation of highly diverse RNA expressing vectors and vector libraries for use in targeted gene knock out, knock down and genome modification approaches. The invention pertains to a method for generating such higher order libraries without the need of classical cloning technologies. This is particularly useful for libraries based on large vectors wherein a sequence cannot be easily mutated with classical mutagenesis methods. The vectors and libraries generated according to the methods of the invention are in particular for RNA assisted silencing technologies such as RNA interference, and for targeted genome editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system or similar RNA/DNA-encoded gene perturbation systems which use small guide RNAs to target the CRISPR complex to a specific genomic sequence. The invention provides also kits comprising the materials for performing the methods of the invention.

Abstract: The present invention relates to a compound of formula (I) wherein E1 to E6 are independently Si or Ge; X1 to X4 are independently selected from the group consisting of H, SiH3, halogen and Si(Y)3; Y is independently selected from C1 to C20 alkyl and halogen; R1 to R12 are independently selected from the group consisting of C1 to C20 alkyl, C2 to C20 alkenyl, C2 to C20 alkynyl, C3 to C20 cycloalkyl, C6 to C20 aryl, C7 to C20 arylalkyl, C7 to C20 alkylaryl and Z; and Z is independently selected from the group consisting of H, halogen and C1 to C20 alkyl; a process for their preparation; and the use of the compound for preparing the Si- and Ge-containing solid.

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: Ephrin type receptor tyrosine kinase inhibitors, also known as Eph tyrosine kinase receptor inhibitors, for treating cancer, an inflammatory disease, an autoimmune disease, or a degenerative disease characterized at least in part by the abnormal activity or expression of the Eph receptor tyrosine kinase. The inhibitors are particularly useful for treating certain cancers.

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: The present invention relates to a method for storing gaseous hydrogen, comprising the steps of producing methanoate (formate) through contacting gaseous hydrogen with carbon dioxide in the presence of a hydrogen dependent carbon dioxide reductase (HDCR), and thereby storing of said gaseous hydrogen. The HDCR and/or its complex is preferably derived from Acetobacterium woodii.

Abstract: The present invention provides a cellular system for the detection of the presence of one or more antibody species in sample, preferably a serum or plasma sample. The method is in particular useful for the analysis of patients who have been sensitized against blood group antigens expressed on erythrocytes, platelets or granulocytes. The system uses fluorescence labeled cells specific for each antigen and hence, for each antibody species. Provided are the methods, system and diagnostic kits for performing the methods of the invention. In addition, the present invention discloses a method for removing antibodies from a sample such as a serum sample. Such a method is useful for absorbing antibodies from poly-agglutinating sera.

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 present invention relates to a method for storing gaseous hydrogen, comprising the steps of producing methanoate (formate) through contacting gaseous hydrogen with carbon dioxide in the presence of a hydrogen dependent carbondioxide reductase (HDCR), and thereby storing of said gaseous hydrogen. The HDCR and/or its complex is preferably derived from Acetobacterium woodii.

Abstract: A capillary cell is described along with an arrangement and a method for receiving, positioning and examining a microscopic specimen, in particular a cleared fluorescent specimen with the help of a single-plane fluorescence microscope. The capillary cell is suitable for being positioned in a chamber volume and contains a capillary section, which comprises a wall. The wall encloses a specimen volume and is planar and transparent in at least some sections. In addition, the capillary cell includes an upper and a lower closure section, which are connected to the capillary section and which seal the capillary section. The specimen volume is separated from the chamber volume by the capillary section, the upper closure section and the lower closure section.

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 present invention relates to a method for storing gaseous hydrogen, comprising the steps of producing methanoate (formate) through contacting gaseous hydrogen with carbon dioxide in the presence of a hydrogen dependent carbondioxide reductase (HDCR), and thereby storing of said gaseous hydrogen. The HDCR and/or its complex is preferably derived from Acetobacterium woodii.