Single strontium Rydberg ion confined in a Paul trap

Trapped Rydberg ions are a promising new system for quantum information processing. They have the potential to join the precise quantum operations of trapped ions and the strong, long-range interactions between Rydberg atoms. Combining the two systems is not at all straightforward. Rydberg atoms are severely affected by electric fields which may cause Stark shifts and field ionization, while electric fields are used to trap ions. Thus, a thorough understanding of the physical properties of Rydberg ions due to the trapping electric fields is essential for future applications. Here we report the observation of two fundamental trap effects. First, we investigate the interaction of the Rydberg electron with the trapping electric quadrupole fields which leads to Floquet sidebands in the excitation spectra. Second, we report on the modified trapping potential in the Rydberg state compared to the ground state which results from the strong polarizability of the Rydberg ion. By controlling both effects we observe resonance lines close to their natural linewidth demonstrating an unprecedented level of control of this novel quantum platform

Characterization of an Ex Vivo Skin Model for the Assessment of Dexamethasone-Loaded Core Multishell-Nanocarriers

Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine protease (SP) activity directly affects the biochemical environment in the superficial compartments, which interact with topically applied formulations. It further impacts the skin barrier structure and is a key regulator of inflammatory mediators. Herein, we used short-term cultures of ex vivo human skin treated with trypsin and plasmin as inflammatory stimuli to assess the penetration and biological effects of the anti-inflammatory drug dexamethasone (DXM), encapsulated in core multishell-nanocarriers (CMS-NC), when compared to a standard cream formulation. Despite a high interindividual variability, the combined pretreatment of the skin resulted in an average 2.5-fold increase of the transepidermal water loss and swelling of the epidermis, as assessed by optical coherence tomography, as well as in a moderate increase of a broad spectrum of proinflammatory mediators of clinical relevance. The topical application of DXM-loaded CMS-NC or DXM standard cream revealed an increased penetration into SP-treated skin when compared to untreated control skin with an intact barrier. Both formulations, however, delivered sufficient amounts of DXM to effectively suppress the production of interleukin-6 (IL-6), interleukin-8 (IL-8) and Thymic Stromal Lymphopoietin (TSLP). In conclusion, we suggest that the herein presented ex vivo inflammatory skin model is functional and could improve the selection of promising drug delivery strategies for anti-inflammatory compounds at early stages of development. View Full-Tex

Single strontium Rydberg ion confined in a Paul trap

Trapped Rydberg ions are a promising new system for quantum information processing. They have the potential to join the precise quantum operations of trapped ions and the strong, long-range interactions between Rydberg atoms. Combining the two systems is not at all straightforward. Rydberg atoms are severely affected by electric fields which may cause Stark shifts and field ionization, while electric fields are used to trap ions. Thus, a thorough understanding of the physical properties of Rydberg ions due to the trapping electric fields is essential for future applications. Here we report the observation of two fundamental trap effects. First, we investigate the interaction of the Rydberg electron with the trapping electric quadrupole fields which leads to Floquet sidebands in the excitation spectra. Second, we report on the modified trapping potential in the Rydberg state compared to the ground state which results from the strong polarizability of the Rydberg ion. By controlling both effects we observe resonance lines close to their natural linewidth demonstrating an unprecedented level of control of this novel quantum platform

High-speed infrared monitoring and simulations of bulk metallic glass casting

Bulk metallic glasses (BMGs) are exceptional candidates for small, highly precise, load-bearing parts in the mm- to cm-range. Their high strength and elasticity make them superior to their crystalline counterparts. In order to obtain the amorphous atomic structure of this special group of alloys, the molten material must be quenched sufficiently quickly to below their glass transition. Die casting into permanent molds made of copper has frequently been applied to vitrify glass-forming melts at the laboratory scale. However, a transition into industrially available, economical casting techniques has not yet been realized. The comparably high cooling rates which occur during BMG casting hamper the applicability of existing casting techniques. Systematic studies dedicated to BMG casting are scarce, and therefore improvements via casting technology are limited due to the absence of applicable knowledge. In this thesis, (BMG) die-casting experiments were monitored using a high-speed infrared camera for the first time. To successfully deploy this technique, the main requirements were identified and intrinsic phenomena reported. A casting apparatus was tailored which included means for shielding unwanted emission, anti-reflection coating, alignment, and a new cold-crucible induction melter. A suitable mold was designed using the commercial casting simulation software ProCAST. The infrared (IR) emission properties were thoroughly investigated, revealing distinct behavior for each individual alloy studied (a Au-based BMG, a Zr-based BMG, and AlSi7Mg0.3 as a crystalline reference). The data were applied to (re)calibrate the IR camera. Die-casting experiments using Cu molds covered with an IR-transparent sapphire wafer at the front, i.e. the side facing the camera, allowed observation of the melt during mold filling and subsequent cooling. Immediate insights were obtained concerning how the flow patterns depend on the flow direction with respect to gravity. The mold-filling dynamics for horizontally flowing melt was assessed by comparing the volumetric flow rate determined from experiments and state-of-the-art casting simulations. These casting simulations seem to overestimate the mold-filling capabilities compared with results from high-speed thermography. The mode of visualization also helped to identify a high degree of turbulence which spreads from the sprue through the gating, disturbs the melt front, and obscures the initial casting conditions during horizontal casting. In contrast, counter-gravity casting generated particularly reproducible casting quality with reduced turbulence. The mold geometry designed may be deployed for future studies on heat transfer, on the importance of skin formation during casting, and on local cooling. The latter was described thoroughly using a low-melting Au-based alloy. Because of its weak interaction with the sapphire wafer, IR calibration generated good agreement with complementary fast differential scanning calorimetry (FDSC) experiments, which produced a detailed picture of the crystallization kinetics of the alloy. It was obvious that the cooling rates in these experiments vary greatly. It is not just the cooling rates that count: the actual thermal history, especially directly in front of the “crystallization nose”, played a bigger role in crystallization (or successful vitrification). Combining the two techniques – high-speed IR monitoring and FDSC – offers great potential for studying processes with high cooling or heating rates. The knowledge about casting modeling and heat transfer gained through the high-speed IR monitoring technique was applied to investigate a continuous casting process for precious BMGs on the site of the industrial partner PX Holding SA. Bulk glassy rods with diameters of 10 mm and lengths > 500 mm were processed. Comparing temperature data recorded during continuous casting and setting up a computational model revealed that precise knowledge of the heat transfer coefficient is indispensable for sound casting simulations. Again, the results from experiments and simulation were complemented by data of the crystallization kinetics determined by FDSC

Influences of residual stresses on the serrated flow in bulk metallic glass under elastostatic four-point bending – A nanoindentation and atomic force microscopy study

The effects of residual stress on the deformation behavior of a Zr-based bulk metallic glass (BMG) during nanoindentation were studied by atomic force microscopy. The residual stress was introduced by elastostatically preloading a beam-shaped BMG sample by four-point bending up to tensile and compressive stress levels of +/- 2.0 GPa for up to 14 days. Strain-rate-controlled nanoindentations were performed on the four-point bent samples at various times during loading and after unloading to analyze the serrated flow during indentation. The hardness of the alloy, the pile-up behavior as well as the serrations strongly depend on the magnitude and sign of the applied residual stresses. Tensile stresses suppress pile-up formation, decrease the hardness but increase the jump width of the serrated flow during nanoindentation. In contrast, increased pile-up formation with increased hardness occurs along with a successive serrated flow behavior on the compression side. The discrepancy of pile-up and serrated flow is explained by a difference in the shear banding mechanism. The results suggest that for compressive stress individual shear planes are successively activated, leading to localized shear steps on the surface. For tensile residual stresses, the plastic volume is more widely spread, leading to vanishing pile-up together with an intermittent activation of a big number of shear events, causing big serrations. Due to the widely varying pile-up behavior, a hardness correction was performed. This strongly reduced the apparent hardness variations across the beam. For this specific testing arrangement, only reversible mechanical property variations with time due to long-time prestraining at high elastostatic stresses were observed

Results on patient-reported outcomes are underreported in summaries of product characteristics for new drugs

Background!#!Summaries of product characteristics (SmPCs) are regulatory documents published upon drug approval. They should report all relevant study data and advise how to use drugs safely and effectively. Patient-reported outcomes (PROs) are increasingly used in clinical trials to incorporate the patient perspective-SmPCs should thus adequately report PROs. In Germany, new drugs undergo mandatory early benefit assessment. Pharmaceutical companies submit dossiers containing all evidence; the subsequent dossier assessments focus on patient-relevant outcomes and comprehensively report PROs.!##!Objective!#!The primary aim was to investigate to what extent PROs recorded as outcomes in clinical trials of new drugs are reported in SmPCs.!##!Methods!#!We analysed dossier assessments with randomized controlled trials (RCTs) of new drugs entering the market between 01/2014 and 07/2018 and the corresponding SmPCs, and compared PRO reporting in both document types. For this purpose, we evaluated dossier assessment characteristics (e.g. drug name, indication, disease category) and study characteristics (e.g. evaluable PROs available?). PROs were divided into symptoms and health-related quality of life (HRQoL). SmPCs were screened to identify RCTs. We conducted 3 main evaluation steps: (1) Did the RCT included in the dossier assessment contain evaluable PROs? (2) If yes, was the RCT included in the SmPC? (3) If yes, were the PROs reported in the SmPC? Results are presented descriptively.!##!Results!#!88 dossier assessments including 143 RCTs on 72 drugs were considered: 109 (76.2%) RCTs included evaluable PROs, of which 89 were included in SmPCs. 38 RCTs (42.7%) investigated oncologics, 18 (20.2%) anti-infectives, and 33 (37.1%) other drugs. The RCTs considered symptoms more often than HRQoL (82 vs. 66 RCTs). In SmPCs, PROs were reported for 41 RCTs (46.1%), with a slightly higher reporting rate for RCTs considering HRQoL (43.9%) than for RCTs considering symptoms (41.5%). In oncologic indications, PROs were reported for 36.7% of RCTs considering HRQoL and 33.3% of RCTs considering symptoms. In infectious diseases, the rates were 21.4% (symptoms) and 0% (HRQoL), and for other diseases about 60% (symptoms) to 70% (HRQoL).!##!Conclusion!#!Even though a large amount of PRO data on new drugs is available from clinical trials included in SmPCs, the corresponding results are underreported

Förderung der Methodenkompetenz von Studierenden des Praxissemesters durch ICM

Mertens C, Schumacher F, Basten M. Förderung der Methodenkompetenz von Studierenden des Praxissemesters durch ICM. In: Buchner J, Freisleben-Teutscher C, Haag J, Rauscher E, eds. Inverted Classroom. Vielfältiges Lernen. Brunn am Gebirge: ikon VerlagsGesmbH ; 2018: 177-181

Signalling strength determines proapoptotic functions of STING

The cGAS/STING signalling pathway is responsible for sensing intracellular DNA and activating downstream inflammatory genes. Here the authors show mouse primary T cells and T leukaemia are hyperresponsive to STING agonist, and this strong STING signalling is associated with apoptosis induction