We present the first prototype of a novel thermal neutron detector using the time projection method. The system consists of 8 TimePix ASICS with postprocessed InGrid meshes. Each ASIC has 256 × 256 pixels of 55 µm×55 µm in size with the capability to measure charge or time. This allows to visualize entire conversion particle tracks with their spatial and time information and, by using event reconstruction algorithms, discriminate against the background of others. By using the Scalable Readout System the detector as presented here could also be upscaled to much larger active areas. In the current configuration we could achieve a spatial resolution of σ = (115 ± 8) µm.
Cancer stem cells (CSCs) are a major cause of tumor therapy failure. This is mainly attributed to increased DNA repair capacity and immune escape. Recent studies have shown that functional DNA repair via homologous recombination (HR) prevents radiation-induced accumulation of DNA in the cytoplasm, thereby inhibiting the intracellular immune response. However, it is unclear whether CSCs can suppress radiation-induced cytoplasmic dsDNA formation. Here, we show that the increased radioresistance of ALDH1-positive breast cancer stem cells (BCSCs) in S phase is mediated by both enhanced DNA double-strand break repair and improved replication fork protection due to HR. Both HR-mediated processes lead to suppression of radiation-induced replication stress and consequently reduction of cytoplasmic dsDNA. The amount of cytoplasmic dsDNA correlated significantly with BCSC content (p=0.0002). This clearly indicates that HR-dependent avoidance of radiation-induced replication stress mediates radioresistance and contributes to its immune evasion. Consistent with this, enhancement of replication stress by inhibition of ataxia telangiectasia and RAD3 related (ATR) resulted in significant radiosensitization (SER37 increase 1.7-2.8 Gy, p<0.0001). Therefore, disruption of HR-mediated processes, particularly in replication, opens a CSC-specific radiosensitization option by enhancing their intracellular immune response.
Wasp venom allergy is the most common insect venom allergy in Europe. It is manifested by large local reaction or anaphylactic shock occurring after a wasp sting. The allergy can be treated by specific immunotherapy with whole venom extracts. Wasp venom is difficult and costly to obtain and is a subject to composition variation, therefore it can be advantageous to substitute it with a cocktail of recombinant allergens. One of the major venom allergens is phospholipase A1, which so far has been expressed in Escherichia coli and in insect cells. Our aim was to produce the protein in secreted form in yeast Pichia pastoris, which can give high yields of correctly folded protein on defined minimal medium and secretes relatively few native proteins simplifying purification.Residual amounts of enzymatically active phospholipase A1 could be expressed, but the venom protein had a deleterious effect on growth of the yeast cells. To overcome the problem we introduced three different point mutations at the critical points of the active site, where serine137, aspartate165 or histidine229 were replaced by alanine (S137A, D165A and H229A). All the three mutated forms could be expressed in P. pastoris. The H229A mutant did not have any detectable phospholipase A1 activity and was secreted at the level of several mg/L in shake flask culture. The protein was purified by nickel-affinity chromatography and its identity was confirmed by MALDI-TOF mass spectrometry. The protein could bind IgE antibodies from wasp venom allergic patients and could inhibit the binding of wasp venom to IgE antibodies specific for phospholipase A1 as shown by Enzyme Allergo-Sorbent Test (EAST). Moreover, the recombinant protein was allergenic in a biological assay as demonstrated by its capability to induce histamine release of wasp venom-sensitive basophils.The recombinant phospholipase A1 presents a good candidate for wasp venom immunotherapy.
An advanced ray‐tracing numerical method is coupled to an ionospheric plasma transport code to model the self‐consistent propagation of an obliquely incident high‐frequency (HF) beam in the ionosphere. An HF radar propagation scenario is presented as an application. During the daytime, a density increase in the lower ionosphere is predicted causing the defocusing of the incident HF beam.
We report on cross-coupled composite-cavity microresonators consisting of a vertical cavity and a second-order distributed feedback structure which employ the same organic active medium and support surface-normal and in-plane emission at the same time. The optical coupling is due to a first-order light diffraction on a second-order Bragg grating and, in the degenerate case, can be as efficient as the coupling observed in more classical cascade coupled cavities. When the system is non-degenerate, the diffraction efficiency is suppressed because of sub-coherence-length dimensions of the composite-cavity and both resonators tend to operate as independent structures without experiencing substantial losses due to diffraction on the distributed-feedback grating.
The Jülich Electric Dipole moment Investigation (JEDI) collaboration aims at a direct measurement of the Electric Dipole Moment (EDM) of protons and deuterons using a storage ring. The measurement is based on a polarization measurement. In order to reach highest accuracy, one has to know the exact trajectory through the magnets, especially the quadrupoles, to avoid the influence of magnetic fields on the polarization vector. In this paper, the development of a beam-based alignment technique is described that was developed and implemented at the COoler SYnchrotron (COSY) at Forschungszentrum Jülich. Well aligned quadrupoles permit one to absolutely calibrate the Beam Position Monitors (BPMs). The method is based on the fact that a particle beam, which does not pass through the center of a quadrupole, experiences a deflection. The precision reached by the method is approximately 40μm. Some consequences for the design of a new high precision storage ring for EDM mesasurements are discussed.
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