Abstract: The present disclosure relates to the generation and uses of an improved set of biomarkers that are aryl hydrocarbon receptor (AHR) target genes, designated as “AHR biomarkers.” The AHR biomarkers described herein allow one to efficiently determine AHR activation groups and sub-groups, in particular for an improved classification of tumors. As used herein, AHR activation groups are called “AHR activation signatures”. The AHR biomarkers comprise markers that are important in diagnosis and therapy, for example for selecting patients for treatment with AHR activation modulating interventions, and monitoring of therapy response.

Abstract: The present invention relates to a newly identified AHR-activating enzyme and uses thereof as marker in the diagnosis and therapy, for example for selecting patients for treatment with IL4I1-modulating interventions, and monitoring of therapy response.

Abstract: A detector and a method for tracking an arrival time of single particles in an ion beam are disclosed, wherein the single particles are provided as a bunch of ions by a synchrotron. Herein, the detector comprises a detector segment comprising a scintillating material, the scintillating material being designated for generating radiation upon passing of a single particle comprised by the bunch of ions through the scintillating material, wherein the scintillating material comprises a plurality of scintillating fibers, the scintillating fibers being provided as a fiber layer, wherein the fiber layer is located perpendicularly with respect to a direction of the incident ion beam; at least one detector element, the detector element being designated for generating a detector signal from the radiation; and at least one evaluation device, the evaluation device being designated for determining information about the single particles from the detector signals provided by the at least one detector element.

Abstract: Described is a parvovirus formulation which comprises (a) at least 1×109 pfu/ml of parvovirus H1 (H-1PV) or a related rodent parvovirus such as LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus or Rat virus (RV) and (b) a pharmaceutically acceptable carrier containing 40-50% Iodixanol (w/v), 0.7-0.9 mmol CaCl2×2 H2O, 50-60 mmol NaCl, 0.9-1.2 mmol KCl, 0.7-0.95 mg/ml Tromethamine and 0.05-0.15 mg/ml Edetate calcium disodium. A preferred use is the therapy of a brain tumour by intratumoral injection.

Abstract: Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.

Abstract: Disclosed is a method for high-throughput detection of genome-wide modifications in a nucleic acid genome obtained from a cell or tissue caused by the activity of a designer nuclease comprising the following steps: a) Extraction of the genomic DNA from cells that were exposed to a designer nuclease under conditions which allow the designer nuclease to introduce a DNA double-strand break (DSB) in the genomic DNA of the cell, b) fragmentation of the nucleic acid to obtain random fragments, c) performing an end repair in order to obtain blunt ends, d) ligation with a linker comprising a sequence complementary to a so called “linker primer”, e) performing a first nucleic acid amplification reaction with a “linker primer” and a so called “ON-target primer”, whereby one primer is located upstream and one primer is located downstream of the on-target site, wherein at least one decoy primer is present in the reaction mixture, f) performing a second nucleic acid amplification reaction whereby so called “nested prim

Abstract: The present invention covers 2-hetarylpyrimidine-4-carboxamide compounds of general formula (I): in which X, Y, Z, R1, R2 and R4 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients.

Abstract: A segmented birefringent chromatic beam shaping device comprises at least three birefringent chromatic segments arranged side by side in a pupil of the beam shaping device. The birefringent chromatic segments are essentially n? waveplates at a first design wavelength. At a second design wavelength, the birefringent chromatic segments are essentially (m+1/2)? waveplates. Each of the birefringent chromatic segments comprises a stack of birefringent elements including at least three chromatic birefringent elements. Orientations of fast axes of each pair of directly consecutive chromatic birefringent elements of each of the birefringent chromatic segments differ by at least 5 deg. The at least three birefringent chromatic segments comprise same sequences of materials, thicknesses and orientations of their birefringent elements so that they only differ is their orientations in the pupil.

Abstract: The present disclosure relates to combinations of at least two components, component A and component B, component A being anti-CEACAM6 antibody TPP-3310 and component B being an anti-TIM-3 antibody, preferentially cobolimab, MBG-453, BMS-986258, Sym-023, LY-3321367 or INCAGN-2390.

Abstract: The present invention relates to nucleic acids encoding the novel parvoviral protein “assembly activating protein” (AAP), the encoded polypeptides, methods of producing the polypeptides, antibodies specific for AAP, the use of the nucleic acids for the preparation of the polypeptides, the use of the nucleic acids or the polypeptides for the preparation of the parvoviral particle and methods of producing parvoviral particles essentially consisting of VP3 by providing in addition to the coding sequence of the parvoviral structural protein VP3 a sequence fragment Z/a nucleic acid encoding AAP in the cell and expressing VP3 and fragment Z under control of a rep-independent promoter. Furthermore, the present invention relates to parvoviral particles essentially consisting of VP3 and/or obtainable by the above method as well as expression cassettes comprising (i) a heterologous promoter and (ii) VP3 coding sequence and/or fragment Z.

Abstract: The present invention relates to protein-inhibitory substituted pyrrolopyridine derivatives of formula (I) in which A, X, R1a, R1b, R2, R3a, R3b, R4a and R4b are as defined herein, to pharmaceutical compositions and combinations comprising the compounds according to the invention, and to the prophylactic and therapeutic use of the inventive compounds, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular for neoplastic disorders, respectively cancer or conditions with dysregulated immune responses or other disorders associated with aberrant MAP4K1 signaling, as a sole agent or in combination with other active ingredients.

Abstract: Disclosed are a method for computer-assisted evaluation of biomarkers in a tissue sample as well as a corresponding system and computer program. The method includes the following steps: providing an image of the tissue sample in which cell nuclei of the tissue as well as biomarkers are represented, automatically determining for a plurality of locations or regions within the image a blood vessel probability that represents a probability that the image at the corresponding location or region represents a blood vessel, automatically determining an assumed blood vessel location within the image based on a distribution of blood vessel probability with respect to the locations or regions within the image, automatically selecting biomarkers represented in the image at locations outside the assumed blood vessel location but within a threshold distance from the assumed blood vessel location, and automatically evaluating the selected biomarkers.

Abstract: Pharmaceutical Combination for the Treatment of Cancer The present invention relates to combinations of at least two components, component A and component B for use in the treatment of cancer, component A being an anti-CEACAM6 antibody and component B being an anti-PD-1 antibody, preferentially nivolumab, or pembrolizumab, or an anti-PD-L1 antibody, preferentially atezolizumab, avelumab, or durvalumab.

Abstract: The present invention relates to a compound of formula (1) (I), wherein Y3 is O or S, wherein s, t, u and w are 0 or 1, wherein i is an integer of from 1 to 3, wherein j is an integer of from 3 to 5, and wherein Z1, Z2 and Z3 are selected from the group consisting of CO2H, —SO2H, —SO3H, —OSO3H, and -0P03H2, R1 is —CH3 or H, X is selected from the group consisting of alkylaryl, aryl, alkylheteroaryl and heteroaryl, Y1 and Y2 are selected from the group consisting of aryl, alkylaryl, cycloalkyl, heterocycloalkyl, heteroaryl and alkylheteroaryl, and wherein A is a chelator residue having a structure selected from the group consisting of (la), (lb) and (lc), wherein R2, R3, R4 and R5 are selected from the group consisting of H, —CH2—COOH and —CH2—C(=0)-NH2 or wherein R2 and R4 form a —(CH2)n— bridge with n being an integer of from 1 to 3, wherein n is preferably 2, and wherein r, v and q are 0 or 1, with the proviso that in case u and w are 0, q and v are 0, and (A) wherein u and w are 1, or (B) wherein u is 0 an

Abstract: The present invention provides a reproducible, effective and scalable process for the purification of (infectious) parvovirus H-1 particles. The purification process allows the separation of empty particles from particles containing a full genome and is compatible with large-scale H-1PV production for clinical applications.

Abstract: The present invention relates to a pharmaceutically compatible iron chelator or a prodrug thereof for use in treating and/or preventing cancer in a subject suspected or known to comprise hypoxic cancer cells, and use in treatment and/or prevention of a human papillomavirus (HPV) related lesion. The present invention further relates to a use of an iron chelator or prodrug thereof for inducing senescence in a cancer cell, preferably a hypoxic cancer cell; and to a method for inducing an irreversible proliferation arrest in cancer cells comprising a) contacting said cancer cells with an iron chelator or prodrug thereof and, thereby, b) inducing an irreversible proliferation arrest in said cancer cells.

Abstract: Disclosed is a method for high-throughput detection of genome-wide modifications in a nucleic acid genome obtained from a cell or tissue caused by the activity of a designer nuclease comprising the following steps: a) Extraction of the genomic DNA from cells that were exposed to a designer nuclease under conditions which allow the designer nuclease to introduce a DNA double-strand break (DSB) in the genomic DNA of the cell, b) fragmentation of the nucleic acid to obtain random fragments, c) performing an end repair in order to obtain blunt ends, d) ligation with a linker comprising a sequence complementary to a so called “linker primer”, e) performing a first nucleic acid amplification reaction with a “linker primer” and a so called “ON-target primer”, whereby one primer is located upstream and one primer is located downstream of the on-target site, wherein at least one decoy primer is present in the reaction mixture, f) performing a second nucleic acid amplification reaction whereby so called “nested prim

Abstract: The present invention relates to a composition comprising Epstein-Barr Virus (EBV) particles for use in vaccination of a subject, wherein said EBV particles comprise a significantly reduced chromosome instability-inducing EBV polypeptide activity. The present invention also relates to a composition comprising EBV particles for use in vaccination of a subject, wherein said vaccination comprises avoiding contacting the cytosol and/or nucleus of cells of said subject with a chromosome instability-inducing EBV polypeptide activity. Moreover, the present invention relates to polynucleotides, host cells, methods, and uses related to the aforesaid compositions.

Abstract: The present invention relates to a nucleic acid molecule which encodes a splice variant of the human P2RX7 receptor, and nucleic acid molecules derived therefrom, a recombinant vector containing said nucleic acid molecules, a host containing said recombinant vector, a polypeptide encoded by said nucleic acid molecules, a host cell expressing said polypeptide, a binding molecule binding to said polypeptide, a pharmaceutical composition comprising said binding molecule, a method for the production of the isolated polypeptide, and other methods and uses in connection therewith.

Abstract: The present invention provides novel compounds that target thrombocyte activity or aggregation capacity through cellular components for the treatment of diseases associated with Non-Alcoholic Fatty Liver Disease (NAFLD). The invention provides these compounds for treating non-alcoholic steatohepatitis (NASH), a progressed stage of NAFL (non-alcoholic fatty liver), in order to avoid the development of liver cirrhosis and Hepatocellular Carcinoma (HCC). Further provided are pharmaceutical compositions, comprising the compounds of the invention, and methods for screening new NASH therapeuticals.