Abstract: Site-specific modification of proteins with microbial transglutaminase (MTG) is a powerful and versatile strategy for a controlled modification of proteins under physiological conditions. Solid-phase microbead-immobilization is used to site-specifically and efficiently attach different functional molecules important for further downstream applications to proteins of therapeutic relevance including scFV, Fab-fragment and antibodies. MTG remained firmly immobilized with no detectable column bleeding and enzyme activity was sustained during continuous operation. Immobilized MTG shows enhanced selectivity towards a certain residue in the presence of several reactive residues which are all targeted when the conjugation was carried out in solution. The generation of dual site-specifically conjugated IgG1 with immobilized and MTG in solution is reported, i.e. site-specific conjugation to glutamine and lysine residues of IgG1 antibody.

Abstract: An exemplary mounting structure can be provided for interferometric imaging and an interferometric imaging apparatus comprising same. The mounting structure comprises at least one curved surface for receiving an interferometric grating to rest thereon. The surface can be provided having a plurality of apertures, whereas that the grating when so received, covers at least one of the apertures.

Abstract: A particle beam therapy system delivers a particle beam for particle radiation therapy to a target volume in a patient from different treatment angles. The particle beam enters an active static magnetic field region perpendicularly to a magnetic field. Magnets and/or coils generate a cylindrically shaped magnetic field system with magnetic fields oriented axially in the magnetic field system. The active magnetic field region has an outer radial guiding field region and an inner radial bending field region, with an arc scan magnet system at an outer edge, a first number of coils generating a static magnetic guiding field that is predominantly effective in the outer radial guiding field region, and a second number of coils predominantly effective in an inner radial bending field region. A treatment control system controls the magnets and/or coils to guide the particle beam according to a treatment plan for the target volume of the patient.

Abstract: A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH2, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine.

Abstract: A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH2, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine.

Abstract: The present application discloses in detail mutant ligands of the human G protein alpha-subunit -G?i1-, wherein at least one amino acid residue has been replaced with alanine if the at least one amino acid residue is a non-alanine residue, or at least one amino acid residue has been replace with glycine if the at least one amino acid residue is alanine and wherein the at least one amino acid residue is comprised in a first group containing of the amino acid residues with position R32A, K54A, I55A, I56A, H57A, R176A, E245A, Y296A, T327A, N331A, V332A and D350A or is comprised in a second group containing G42A, A59G, T177A, D200A, A226G, E297A, A300G and F334A or is comprised in a third group containing V50A, A59G, R178A 30 and K180A.

Abstract: A laser ablation cell (1) comprises a flow channel (11) having an essentially constant cross-sectional area so as to ensure a strictly laminar flow in the flow channel. A sample chamber (21) is provided adjacent to a lateral opening (14) of the flow channel. A laser beam (41) enters the sample chamber (21) through a lateral window (16) and impinges on a surface (24) of a sample (23) to ablate material from the sample. The sample may be positioned in such a distance from the flow channel that the laser-generated aerosol mass distribution has its center within the flow channel. This leads to short aerosol washout times. The laser ablation cell is particularly well suited for aerosol generation in inductively coupled plasma mass spectrometry (ICPMS), including imaging applications.

Abstract: A method and a system for resolving a crystal structure of a crystal at atomic resolution by collecting X-ray diffraction images. The method includes the steps: a) ejecting a droplet of fluid comprising single or multiple of crystal into an ultrasonic acoustic levitator; b) levitating the droplet of fluid with the crystal in the ultrasonic acoustic levitator; b) monitoring the position and the spinning of the droplet with a visualization apparatus; c) applying X-ray to the crystal, the X-ray stemming from an X-ray source; and d) detecting the X-ray diffraction images from the crystal irradiated by the X-ray source by an X-ray detector being capable to capture two dimensional diffraction patterns.

Abstract: A system for particle beam therapy has an adjustable gantry for beam delivery to a patient site. The gantry has a beam coupling section, a first beam bending section with beam deflection and/or focusing magnets. A beam transport section receiving the particle beam from the first beam bending section and guiding the particle beam to a second beam bending section. The beam exits at a window of a beam nozzle. A patient table/chair is rotatable in the horizontal plane or in a plane being parallel to the horizontal plane and optionally being adjustable vertically. The gantry is supported by a tilting mechanism allowing the gantry to be tilted vertically by an angle ?1?[?90°; +90°]. A rotation mechanism is disposed in a way that the second beam bending section and the beam nozzle are rotatable by an angle ?2?[?180°; +180°] around a direction given by the angle ?1.

Abstract: The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Abstract: A compact, small foot print, light source based on electron beam acceleration for insertion devices in EUV range metrology and actinic mask inspection using coherent scattering methods includes spiral storage rings providing plane straight sections. A magnet structure generates emittance for brilliance and coherent light content. A booster feeds the storage ring by top-up injection and keeps electron beam intensity stable. A booster level below the storage ring receives the electron beam from a linear accelerator in a central booster area. The source fits into laboratories or maintenance areas. Injection, RF-acceleration, beam manipulating devices and large diagnostics systems are required once. Higher average currents stored in the spiral enhance central cone power. Bunches are limited by ion trapping and a gap clears ions. The current is increased in the spiral. Gain in central cone power increases 5 fold, assuming a gap size of half single storage ring circumference.

Abstract: X-ray scattering imaging can provide complementary information about the unresolved microstructures of a sample. The scattering signal can be accessed with various methods based on coherent illumination, which span from self-imaging to speckle scanning. The directional sensitivity of the existing methods is limited to a few directions on the imaging plane and it requires the scanning of the optical components, or the rotation of either the sample or the imaging setup, if the full range of possible scattering directions is desired. A new arrangement is provided that allows the simultaneous acquisition of the scattering images in all possible directions in a single shot. This is achieved by a specialized phase grating and a device for recording the generated interference fringe with sufficient spatial resolution. The technique decouples the sample dark-field signal with the sample orientation, which can be crucial for medical and industrial applications.

Abstract: A salt separator separates salts and/or solid materials from a pumpable aqueous fluid mixture under process conditions, which lie in the range of the critical point for the fluid mixture. The salt separator contains a reaction zone in a cavity for transforming the pumpable aqueous fluid mixture into a raw mixture, e.g. a methanation reaction, and a feed opening for the pumpable aqueous fluid mixture to the cavity. The feed opening is realized in a rising pipe that protrudes into the cavity. A first extraction opening is provided for the raw mixture freed of salts and/or solid materials. The first extraction opening is arranged in the upper region of the cavity and a second extraction opening is provided for a brine containing the salt and/or the solid materials. The second extraction opening is arranged in the lower region of the cavity and is located lower down than the feed opening.

Abstract: A movable gantry for delivery of a particle beam using beam scanning technique contains an inlet section for an accelerated particle beam having quadrupole magnets, first and second bending sections having dipole and quadrupole magnets for beam correction, a transfer section having quadrupole magnets for beam correction and a degrader and a last beam bending section having separate and/or combined dipole/quadrupole/higher order multipole magnets forming an achromatic section. All the magnets of the achromatic last bending section are located downstream of the degrader. Any dispersion in this achromatic last bending section is suppressed. A scanning section having two separate or one combined fast deflection magnets that deflect the beam at the iso-center in a direction perpendicular to the beam direction to perform lateral scanning is provided. A beam nozzle section is provided and has a beam nozzle.

Abstract: Methods and a system for scanning scattering contrast inspection for the identification of defects in an actual pattern block on a sample as compared to a desired pattern block. Most of the information in the reciprocal space (spatial frequency domain) is omitted in order to increase the throughput. That information in the reciprocal space is captured which gives the highest defect information, namely contrast signal between the defective and defect-free structure. Deviations from the expected diffraction pattern allow rapid identification of defects on the actual pattern. The first method learns the correct reconstructed diffraction image by comparing the repetitive pattern blocks. The second method focuses on the appearance of predictable defects in the spatial frequency domain of the reconstructed diffraction image thereby defining regions of interest where the defects materialize.

Abstract: The present application relates to methods for the enzymatic functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Abstract: Among the existent X-ray phase-contrast modalities, grating interferometry appears as a promising technique for commercial applications, since it is compatible with conventional X-ray tubes. However, since applications such as medical imaging and homeland security demand covering a considerable field of view, the fabrication of challenging and expensive large-area gratings would be needed. A scanning setup is a good solution, because it uses cheaper line detectors instead of large-area 2D detectors and would require smaller gratings. In this setup, the phase-retrieval using the conventional phase-stepping approach would be slow, so having a faster method to record the signals becomes fundamental. To tackle this problem, a scanning-mode grating interferometer configuration is used, in which a grating is tilted to form Moire fringes perpendicular to the grating lines. The sample is then translated along the fringes, so each line detector records a different phase step for each slice of the sample.

Abstract: A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH2, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine.

Abstract: The radionuclide 43Sc is produced at commercially significant yields and at specific activities and radionuclidic purities which are suitable for use in radiodiagnostic agents including imaging agents. In a method, a solid target having an isotopically enriched target layer prepared on an inert substrate is positioned in a specially configured target holder and irradiated with a charged-particle beam of protons or deuterons. The beam is generated using an accelerator such as a biomedical cyclotron at energies ranging from 3 to about 22 MeV. The method includes the use of three different nuclear reactions: a) irradiation of enriched 43Ca targets with protons to generate the radionuclide 43Scin the nuclear reaction 43Ca (p,n)43Sc, b) irradiation of enriched 42Ca targets with deuterons to generate the radionuclide 43Sc in the nuclear reaction 42Ca(d,n)43Sc, and c) irradiation of enriched 46Ti targets with protons to generate the radionuclide 43Sc in the nuclear reaction 46Ti (p,a)43Sc.

Abstract: An X ray detector with single photon measurement capabilities includes a layer of photosensitive material and an N×M array of photo-detector diodes in the layer of photosensitive material. The photo-detector diodes have a bias potential interface and a diode output interface. An N×M array of high gain, low noise readout unit cells are assigned to the photo-detector diodes. Each readout unit cell has an input interface connecting the diode output interface to a high-gain charge-to-voltage amplifier with integration capacitors. The high-gain charge-to-voltage amplifier can switch between different gains. A comparator and a digital block monitors the charge of the integration capacitance and switches the gain depending from the monitored charge of the integration capacitance. The pixel detector provides the possibility of in pixel intermediate evaluation of an automatic gain switching circuit state to increase the dynamic range of the detector in case of quasi continuous incoming particle flux.