摘要:
The present invention concerns novel Gram-negative bacteria efflux pump inhibitors. It further relates to the use of Gram-negative bacteria efflux pump inhibitors to prevent and/or treat antibiotic resistance by potentiating the activity of antibiotics. Infections by multidrug resistant (MDR) Gram-negative bacteria are a major threat to global healthcare. The inventors have discovered a novel class of Resistance Nodulation cell Division-efflux pump inhibitors. The inventors tested the effects of these inhibitors on growth inhibition of different bacteria as well as their impact on the boosting of antibiotic activity in different bacteria. Particularly, the inventors tested the effects of these inhibitors on E. coli, A. baumannii, K. pneumoniae and P. aeruginosa.
摘要:
Disclosed herein is an optical system comprising a microscope objective lens (10), a sample holder (12), and an optical pad (20) to be provided in a gap between said microscope objective lens (10) and said sample holder (12). The optical pad (20) is attached or attachable to one of the microscope objective lens (10) and the sample holder (12) and has a dry, free surface (22) configured to be in contact with an abutment surface (24) provided on the other of the microscope objective lens (10) and the sample holder (12) during microscopy, but free to move with respect to it to allow for carrying out microscopy at different relative positions between said free surface (22) and said abutment surface (24). The pad (20) is deformable such that the relative distance between said microscope objective lens (10) and said sample holder (12) can be varied by a working distance while continuously filling the gap between said microscope objective lens (10) and said sample holder (12).
摘要:
The invention is based on the finding that a subjects suffering from a viral infection and which is distinguished by a systemic inflammatory complication such as systemic endotheliitis are in particular indicated for a treatment with mesenchymal stromal cell (MSC) compositions. The invention provides treatments in the context of SARS Cov2 infections, in severely affected subjects receiving mechanical ventilation. Provided are MSC compositions for use in treatments, diagnostic stratification methods, and diagnostic kits for such purposes.
摘要:
The invention pertains to a novel structure (I) that provides an activity as a dual inhibitor of the enzymes soluble epoxide hydrolase (sEH) and 5-lipoxygenase (5-LOX). The invention pertains to multiple derivatives of the new class of dual inhibitors, their application in medicine, pharmaceutical compositions comprising them as well as to methods for synthesizing the new compounds.
摘要:
The invention is based on the surprising finding of the ability of gene editing nucleases to be automatically packaged into viral particles. The invention provides viral particles, such as viral capsids, containing a high amount of the gene editing nuclease that efficiently transduce target cells with either components for gene editing or alternatively any other cargo attached to the gene editing nuclease. Since the viral particles of the invention do not need to contain any components of the viral genome, they can both efficiently and safely transduce mammalian cells for editing genome sequences or other purposes. The invention provides the viral particles, compositions comprising them, methods for their generation, and medical and laboratory applications of the new transduction methods and tools.
摘要:
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.
摘要:
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. The present invention further relates to a method for the production of short fatty acids, CoA esters of short fatty acids, ethyl esters of short fatty acids, esters of short fatty acids with other metabolites, and/or enzyme bound short fatty acids (C 6 to C 12 ), comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention further relates to a method for the production of biofuels, flavoring compounds and/or fine chemicals, comprising the expression of said nucleic acid molecules, preferably in said host cells. The present invention also relates to the use of the proteins, nucleic acids molecule or host cells for the bulk production of short fatty acids (C 6 to C 12 ), the specific production of C 6 fatty acids and/or C8 fatty acids, the bulk production of CoA esters of short fatty acids (C 6 to C 12 ), the specific production of C 6 -CoA esters and/or C 8 -CoA esters, the bulk production of ethyl esters of short fatty acids (C 6 to C 12 ), the specific production of C 6 fatty acid ethyl esters and/or C 8 fatty acid ethyl esters, the bulk production of esters of short fatty acids (C 6 to C 12 ) with other metabolites, the specific production of C 6 fatty acid esters with other metabolites and/or C 8 fatty acid esters with other metabolites, the bulk production of enzyme bound short fatty acids (C 6 to C 12 ), the specific production of enzyme bound C 6 fatty acids and/or enzyme bound C 8 fatty acids, the production of biofuels, fine chemicals and/or flavoring substances.
摘要:
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 ac- cording to the invention are particularly useful for medical applications such as the treatment of graft-versus-host disesase (GvHD) in recipients with hematopoietic stem cell transplants, patients with autoimmune disorders and as a cell-based therapy in regenerative medicine.
摘要:
Bei einer Dialysezelle für eine In-vitro-Freisetzungstestapparatur zum Ermitteln eines Freisetzungsverhaltens, wie einer Freisetzungsrate, einer Substanz einer Stoffzusammensetzung, wie eines Arzneimittels, welche Substanz an Molekularträger, wie Liposome, Mizellen oder Nanopartikel, gebunden ist, gegenüber einem Substanzaufnahmefluid mit einem Zelleninnenraum und einer den Zelleninnenraum zumindest teilweise begrenzende Dialysemembran, die die gebundene Substanz zurückhält, für in das Substanzaufnahmefluid freigesetzte Substanz durchlässig ist und für das Substanzaufnahmefluid zumindest teilweise durchlässig ist, ist vorgesehen, dass die Dialysemembran an einer Tragstruktur befestigt ist, die zur festen Montage der Dialysezelle an einer gegenüber der In-vitro-Freisetzungstestapparatur ortsfesten Montageposition ausgelegt ist.
摘要:
Die vorliegende Erfindung betrifft ein Verfahren zur Diagnose, Früherkennung und/oder Risikostratifizierung einer pulmonalen Hypertonie bei einem Subjekt und/oder Überwachung einer Therapie einer solchen Erkrankung bei einem Subjekt, umfassend das Quantifizieren mindestens einer Komponente des vaskulären endothelialen Wachstumsfaktor (VEGF) - Signalwegs als Biomarker, insbesondere das Quantifizieren der Biomarker soluble Fms-like tyrosine kinase-1 (sFlt) und/oder placental growth factor (PIGF). Weiterhin betrifft die Erfindung einen diagnostischen Kit zur Durchführung des erfindungsgemäßen Verfahrens, und seine Verwendung.