Abstract: The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Abstract: A method for estimating a stimulated emission depletion microscopy (STED) resolution includes generating a first frame representing a reference image from a field-of-view, the reference image having a predetermined reference resolution, and generating at least one second frame representing a STED image from the same field-of-view, the STED image having the STED resolution to be estimated. The at least one second frame is blurred by applying a convolution kernel with at least one fit parameter to the second frame. An optimal value of the at least one fit parameter of the convolution kernel is determined for which a difference between the first frame and the blurred at least one second frame is minimized. The STED resolution is estimated based on the optimal value of the at least one fit parameter and the predetermined reference resolution.

Abstract: The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Abstract: A method for scanning a sample includes generating at least two illumination points in order to form a point pattern, wherein the point pattern has a settable number of illumination points. At least one freely selectable parameter for defining the point pattern is preset or is set. At least one predefined region of the sample is scanned by moving the point pattern defined by the freely selectable parameter along a first direction such that scan lines assigned to the illumination points of the point pattern are generated, and along a second direction such that further scan lines are generated in each case following the scan lines. The movement of the point pattern in the second direction is carried out in scan steps of identical size or at a constant speed. The illumination points of the point pattern are arranged on a line along the second direction.

Abstract: A digital image processing apparatus for computing a baseline estimate of a digital input image is provided. The digital image processing apparatus is configured to obtain a digital intermediate image by downsampling the digital input image by a predetermined downsampling factor, and compute the baseline estimate based on the digital intermediate image.

Abstract: A fluorescence scanning microscope includes excitation and de-excitation light sources, which are designed to generate an excitation and a de-excitation light distribution, respectively. An illumination unit combines the light distributions to form a light distribution scanning over multiple illumination target points of a sample in such a way that an intensity maximum of the excitation light distribution and an intensity minimum of the de-excitation light distribution are spatially superimposed on one another. A detector detects fluorescence photons emitted from the respective illumination target point as a function of their arrival times. A processor evaluates the fluorescence photons with respect to the arrival times, generates a first pixel and a second pixel based thereon, assembles the first and second pixels to form first and second sample images, respectively, and, by means of the two sample images, determines a spatial offset between the intensity maximum and the intensity minimum.

Abstract: A processor for demixing a fluorescent-light input signal of a fluorescence microscope, the fluorescent-light input signal including at least two fluorescence emission responses that overlap in time, each of the at least two fluorescence emission responses being representative of an individual impulse response of a fluorophore to a fluorescence-triggering light pulse of a clocked time series of fluorescence-triggering light pulses, the processor: receiving a trigger signal comprising a time series of time markers, the trigger signal being representative of a clocking rate, at which the clocked time series of fluorescence-triggering light pulses is generated; and separating at least one fluorescence emission response from the fluorescent-light input signal.

Abstract: A fluorescence scanning microscope includes excitation and de-excitation light sources, which are designed to generate an excitation and a de-excitation light distribution, respectively. An illumination unit combines the light distributions to form a light distribution scanning over multiple illumination target points of a sample in such a way that an intensity maximum of the excitation light distribution and an intensity minimum of the de-excitation light distribution are spatially superimposed on one another. A detector detects fluorescence photons emitted from the respective illumination target point as a function of their arrival times. A processor evaluates the fluorescence photons with respect to the arrival times, generates a first pixel and a second pixel based thereon, assembles the first and second pixels to form first and second sample images, respectively, and, by means of the two sample images, determines a spatial offset between the intensity maximum and the intensity minimum.

Abstract: A fluorescence microscope includes excitation and de-excitation light sources designed to generate excitation and de-excitation light distributions, which excite and de-excite fluorophores present in a sample, respectively. An illumination unit is designed to combine the light distributions such that an intensity maximum of the excitation light distribution and an intensity minimum of the de-excitation light distribution are spatially superimposed on one another in an illumination target point. A detector is designed to detect the fluorescence photons as a function of their arrival times. The processor is designed to evaluate the detected fluorescence photons with respect to their arrival times and, based thereon, to control a delay which a light pulse or a light modulation of the de-excitation light distribution has at a position of the illumination target point in relation to a light pulse or a light modulation of the excitation light distribution.

Abstract: The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Abstract: A method for scanning a sample in microscopy includes generating at least three illumination spots in order to form a spot pattern that contains at least two illumination spots having a first wavelength and an illumination spot having a second wavelength that differs from the first wavelength. At least one specified region of the sample is scanned by moving the spot pattern formed by the illumination spots along a first direction for generating scan lines, which are each associated with the illumination spots of the spot pattern, and by moving the spot pattern formed by the illumination spots along a second direction for generating scan lines respectively after the scan lines.

Abstract: An optical assembly includes a volume grating configured to influence a beam direction of at least one light beam, and a switching device arranged in a beam path upstream of the volume grating. The switching device is configured to switch the beam direction and/or beam position of the at least one light beam from a first beam direction and/or beam position, in which the at least one light beam does not impinge on the volume grating at an acceptance angle of the volume grating, to a second beam direction and/or beam position, in which the at least one light beam impinges on the volume grating at the acceptance angle, and/or vice versa.

Abstract: A method for estimating a stimulated emission depletion microscopy (STED) resolution includes generating a first frame representing a reference image from a field-of-view, the reference image having a predetermined reference resolution, and generating at least one second frame representing a STED image from the same field-of-view, the STED image having the STED resolution to be estimated. The at least one second frame is blurred by applying a convolution kernel with at least one fit parameter to the second frame. An optimal value of the at least one fit parameter of the convolution kernel is determined for which a difference between the first frame and the blurred at least one second frame is minimized. The STED resolution is estimated based on the optimal value of the at least one fit parameter and the predetermined reference resolution.

Abstract: An illumination apparatus for a microscope, for producing a de-excitation or switching light distribution, includes a light source configured to produce a primary illumination light beam and a beam splitter configured to divide the primary illumination light beam into two partial illumination light beams. An illumination objective is configured to focus the partial illumination light beams onto and/or into a sample such that the partial illumination light beams extend, spatially separated from one another, through an entry pupil of the illumination objective and are spatially superposed on and/or in the sample after passing through the illumination objective. A phase influencer is configured to cause a relative phase offset of the partial illumination light beams with respect to one another in such a way that the partial illumination light beams in the entry pupil of the illumination objective have a phase offset of ?.

Abstract: A method for scanning a sample includes generating at least two illumination points in order to form a point pattern, wherein the point pattern has a settable number of illumination points. At least one freely selectable parameter for defining the point pattern is preset or is set. At least one predefined region of the sample is scanned by moving the point pattern defined by the freely selectable parameter along a first direction such that scan lines assigned to the illumination points of the point pattern are generated, and along a second direction such that further scan lines are generated in each case following the scan lines. The movement of the point pattern in the second direction is carried out in scan steps of identical size or at a constant speed. The illumination points of the point pattern are arranged on a line along the second direction.

Abstract: The present invention relates to conjugates of a protein drug and two or more P/A peptides, and pharmaceutical compositions comprising them. The conjugates of the invention exhibit an advantageously reduced immunogenicity as compared to the respective unmasked protein drugs as well as a favorable safety and tolerability profile, which render them particularly suitable for therapeutic use. The conjugates further show an enhanced plasma half-life and, thus, a prolonged duration of action as compared to the respective unmasked protein drugs, which allows for a reduction in the dosing frequency and, thus, side-effect burden. The invention also provides processes of preparing such conjugates as well as activated P/A peptides that are useful as synthetic intermediates in the preparation of the conjugates.

Abstract: An optical assembly includes a volume grating configured to influence a beam direction of at least one light beam, and a switching device arranged in a beam path upstream of the volume grating. The switching device is configured to switch the beam direction and/or beam position of the at least one light beam from a first beam direction and/or beam position, in which the at least one light beam does not impinge on the volume grating at an acceptance angle of the volume grating, to a second beam direction and/or beam position, in which the at least one light beam impinges on the volume grating at the acceptance angle, and/or vice versa.

Abstract: An optical arrangement has an optical beam path for illuminating a sample space with a sequence of laser light pulses generated in a laser cycle, the optical arrangement. At least one laser light source is configured to generate the sequence of laser light pulses along the optical beam path. A wavelength-selective pulse picker is situated in the optical beam path and has, in a predefined illumination clock timing synchronizable with the laser light pulses, an open state in which the pulse picker is light-transparent to at least one laser light pulse towards the sample space. The open state has at least two different transmission states which differ with regard to their respective transmission spectrums, and wherein the two transmission states are switchable on and/or off independently of one another.

Abstract: An illumination apparatus for a microscope, for producing a de-excitation or switching light distribution, includes a light source configured to produce a primary illumination light beam and a beam splitter configured to divide the primary illumination light beam into two partial illumination light beams. An illumination objective is configured to focus the partial illumination light beams onto and/or into a sample such that the partial illumination light beams extend, spatially separated from one another, through an entry pupil of the illumination objective and are spatially superposed on and/or in the sample after passing through the illumination objective. A phase influencer is configured to cause a relative phase offset of the partial illumination light beams with respect to one another in such a way that the partial illumination light beams in the entry pupil of the illumination objective have a phase offset of ?.

Abstract: A method is provided for localizing a physical network fault in a network having a plurality of network participants. The method comprises detecting by a first network participant and a second network participant that communication with a third network participant and the respective further participant of the first and second network participants is disrupted. In response to the detecting, the first network participant and second network participant automatically reduce their baud rate. The method comprises further establishing a connection between the first network participant and second network participant with use of the reduced baud rate, detecting by the first network participant and/or the second network participant that communication with the third network participant is not possible with use of the reduced baud rate, and storing information on the impossibility of communication with the third network participant.