Abstract: The present invention relates to a method for single-cell imaging mass spectrometry (MS) by correlating an optical image of a cell sample with an MS image. The method of the invention is in particular useful in research to test concomitantly optical and molecular phenotypes at a single-cell resolution.

Abstract: The present invention relates to compounds of formula: and methods for linking tetrazines with dienophiles to establish at least two linkages by sequentially performing at least two cycloaddition reactions. The methods in particular allow establishing multi-labeling strategies. In particular, the invention relates to methods for forming linkages by cycloaddition reactions, wherein the method comprises reacting a first alkyl-substituted tetrazine with a first dienophile comprising a trans-cyclooctenyl group followed by reacting a second tetrazine with a second dienophile comprising a cyclooctynyl group, wherein the reaction of the first tetrazine with the first dienophile proceeds in the presence of the second dienophile.

Abstract: A method for storage of an item of information (210) is disclosed. The method comprises encoding bytes (720) in the item of information (210), and representing using a schema the encoded bytes by a DNA nucleotide to produce a DNA sequence (230). The DNA sequence (230) is broken into a plurality of overlapping DNA segments (240) and indexing information (250) added to the plurality of DNA segments. Finally, the plurality of DNA segments (240) is synthesized (790) and stored (795).

Abstract: A method for scanning a sample using an electrically or electronically controllable microscope includes performing a continuous scanning of the sample so as to repeatedly generate a plurality of images of the sample, each of the plurality of images corresponding to a different time, the microscope being controlled via a control computer during the scanning. The plurality of images are analyzed using at least one second computer connected via a network, wherein the at least one second computer is configured to classify each of the plurality of images as one of interesting and non-interesting while the continuous scanning of the sample with the microscope continues. The continuous scanning of the sample is automatically influenced based on the classifying of the images performed by the at least one second computer.

Abstract: An optical arrangement for imaging a sample is disclosed. The optical arrangement comprises at least one first objective lens and at least one second objective lens, at least one illumination source for producing an illumination beam, detector for imaging radiation from the sample, and at least one mirror for reflecting the radiation from one of the first objective lens or the second objective lens into the detector. The at least one mirror is double-sided and dependent on the illumination beam at the other one of the first objective lens and the second objective lens.

Abstract: A method for storage of an item of information (210) is disclosed. The method comprises encoding bytes (720) in the item of information (210), and representing using a schema the encoded bytes by a DNA nucleotide to produce a DNA sequence (230). The DNA sequence (230) is broken into a plurality of overlapping DNA segments (240) and indexing information (250) added to the plurality of DNA segments. Finally, the plurality of DNA segments (240) is synthesized (790) and stored (795).

Abstract: The present invention relates to the finding that vault RNAs (vtRNA) associate with p62, an important factor of cellular autophagy. The invention provides the modulation of the binding of vtRNA to p62 as a novel strategy to influence autophagic flux in cells. Thus, the present invention provides inhibitors of vtRNA for use in the treatment of diseases associated with a pathological reduced or insufficient autophagy in cells, such as cancer and neurodegenerative disorders. Further provided are methods for screening novel therapeutic compounds modulating autophagy via the p62/vtRNA axis.

Abstract: In a manipulation container (1) for cryomicroscopy, having at least one holder (9) for a sample carrier mount (7) and at least one manipulation opening (2) for manipulating sample carriers or sample carrier mounts (7), the holder (9) for a sample carrier mount (7) is movable into a displacement path (11), passing completely through the manipulation container (1), of a displacement apparatus (3) for the sample carrier mount (7).

Abstract: The present invention relates to a pump (15) for pumping a coolant (9) within a Dewar vessel (1) and to a corresponding Dewar vessel (1) for storing samples in a coolant (9). The Dewar vessel (1) comprises a thermally insulated reservoir (3) for the coolant (9) and a sample vessel (11) provided separately and arranged in the thermally insulated reservoir (3). The reservoir (3) is connected to the sample vessel (11) in such a way that the level of coolant (9) is constant in the sample vessel (11). Pump (15) may help in keeping the level of coolant (9) in the sample vessel (11) constant. For this purpose the pump (15) comprises a chamber (17) with an inlet (19) and an outlet (21), a closing element (23) and a pressure increasing device (25). Therein, the inlet (19) is connectable to the reservoir (3) and the outlet (21) is connectable to a sample vessel (11) of the Dewar vessel (1).

Abstract: The present invention relates to the field of microfluidics and in particular to methods for detecting microfluidic droplets and particles within droplets, as well as sorting the droplets. These methods allow for quantifying properties and activities of the particles within the droplets. For this purpose, the invention provides microfluidic droplets comprising suitably labelled particles. The invention also provides microfluidic devices and systems having properties which make them particularly suitable for use in the methods of the invention.

Abstract: A microscope module (300) for imaging a sample (270) is disclosed. The microscope module (300) includes at least one illumination objective (210) for producing an illumination beam along an illumination beam path (215) arranged to illuminate lower surface of the sample (270) and at least one detection objective (220) having a detection path (225). The detection path (225) is at an angle to the illumination beam path (215).

Abstract: The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting.

Abstract: A microscope and imaging method in which a layer of the sample is illuminated by a thin strip of light and the sample is viewed perpendicular to the plane of the strip of light. The depth of the strip of light thus essentially determines the depth of focus of the system. To record the image, the object is displaced through the strip of light, which remains fixed in relation to the detector, and fluorescent and/or diffused light is captured by a planar detector. Objects that absorb or diffuse a large amount of light are viewed from several spatial directions. The three-dimensional images, which are captured from each direction can be combined retrospectively to form one image, in which the data is weighted according to its resolution. The resolution of the combined image is then dominated by the lateral resolution of the individual images.

Abstract: The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Abstract: The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity, wherein the PA subunit is from Influenza A 2009 pandemic H1N1 virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of the polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of the polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods of identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit the endonucleolytic activity, as well as the compounds themselves.

Abstract: The present invention relates to the automation of incubation, processing, harvesting and analysis of samples in a multi-cell plate. In particular, a multi-cell plate including a body with a plurality of cells is presented. Furthermore, an automated crystal harvesting and processing system with a cutting unit, a fluid unit and a removing device is presented. The multi-cell plate further includes a sealing film for sealing the cells on a first side of the body and a sample film for sealing the cells on a second side of the body. The sample film is adapted for accommodating a biological material for crystallization. Furthermore, the sample film is of a thickness and composition that makes it compatible with x-rays and also with laser ablation. The design of the multi-cell plate and the automated crystal harvesting and processing system allows for several steps of incubation, processing, harvesting and analysis of the samples to be automated.

Abstract: In a light microscope (1) for cryomicroscopy, encompassing at least an objective (2) and a sample stage (3) having a cutout (7) for a coolable holder (8) for a sample carrier mount, the cutout (7) being covered by a cover (6), the sample stage (3) is displaceable in two horizontal directions (4). The cover (6) rests floatingly on the sample stage (3), and the objective (2) passes through a cutout (12), corresponding to the objective (2), in the cover (6). The method for cooling a holder (8) for a sample carrier mount in a light microscope (1) for cryomicroscopes, by means of a flow of liquid nitrogen through a cooling conduit (15), open at at least one end, in the holder (8), is notable for the fact that the quantity of liquid nitrogen is dimensioned so that all of the nitrogen is present in gaseous form at at least one open end (16) of the cooling conduit (15).

Abstract: A method for scanning a sample using an electrically or electronically controllable microscope, includes scanning the sample so as to generate a plurality of images of the sample, each of the plurality of images corresponding to at least one of a different region of the sample and a different time. The microscope is controlled via a control computer during the scanning. The plurality of images are analyzed using at least one second computer connected via a network. The plurality of images are classified and/or the scanning is influenced based on the analyzing.

Abstract: A compound of formula (I), a stereoisomeric form thereof, or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined herein, is provided. The compounds of formula (I) are valuable pharmacologically active compounds and are suitable for the treatment of osteoarthritis. The preparation of the compounds of formula (I), their use as pharmaceuticals, and pharmaceutical compositions including them are also provided.

Abstract: The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameliorating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.