Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Recently, the strongly inhomogeneous current density occuring near a microelectrode was identified as driving a thermocapillary electrolyte flow near gas bubbles growing during electrolysis [Massing et.al. Electrochim. Acta 297, 929 (2019) ]. The present paper is investigating this effect in more detail under various operating conditions. Furthermore, by simplified modeling, the question is answered of whether this effect is also of importance at large planar electrodes. The direction of the thermocapillary force on the bubble is found to change from retarding to advancing the bubble release when the size of the electrode is increased. Conclusions are drawn on how the thermocapillary effect at planar electrodes depends on the electrode coverage and the bubble departure size, also considering industrially relevant values of the current density.

Background: [¹⁸F]PSMA-1007, a positron emission tomography (PET) tracer, specifically targets prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer. PSMA-PET is effective especially for regional detection of biochemical recurrence, which significantly affects patient management. Herein, we established and optimized a one-step radiolabeling protocol to separate and purify [¹⁸F]PSMA-1007 with a CFN-MPS200 synthesizer for clinical application.
Results: A dedicated single use cassette and synthesis program for [¹⁸F]PSMA-1007 was generated using a single-step method for direct precursor radiolabeling. In the cassette, three tube types (fluoro-elastomer, PharMed® BPT, silicone) and two different precursor salts (trifluoroacetic acid or acetic acid) were compared for optimization. Furthermore, three-lot tests were performed under optimized conditions for quality confirmation. Activity yields and mean radiochemical purity of [¹⁸F]PSMA-1007 were > 5000 MBq and 95%, respectively, at the end of synthesis, and the decay-corrected mean radiochemical yield from all three cassettes was approximately 40% using a trifluoroacetic acid salt precursor. Fluoro-elastomer tubings significantly increased the amount of non-radioactive PSMA-1007 (8.5 ± 3.1 μg/mL) compared to those with other tubings (0.3 μg/mL). This reduced the molar activity of [¹⁸F]PSMA-1007 synthesized in the cassette assembled by fluoro-elastomer tubings (46 GBq/μmol) compared to that with PharMed® BPT and silicone tubings (1184 and 1411 GBq/μmol, respectively). Residual tetrabutylammonium, acetonitrile, and dimethyl sulfoxide levels were <  2.6 μg/mL, < 8 ppm, and <  11 ppm, respectively, and ethanol content was 8.0–8.1% in all three cassettes and two different salts. Higher activity yields, radiochemical purities, and decay-corrected radiochemical yields were obtained using an acetic acid salt precursor rather than a trifluoroacetic acid salt precursor (7906 ± 1216 MBq, 97% ± 0%, and 56% ± 4%). In the three-lot tests under conditions optimized with silicone cassettes and acetic acid salt precursor, all quality items passed the specifications required for human use.
Conclusions: We successfully automated the production of [¹⁸F]PSMA-1007 for clinical use and optimized synthesis procedures with a CFN-MPS200 synthesizer using a silicone cassette and acetic acid salt precursor. Cassette availability will facilitate a wide spread use of [¹⁸F]PSMA-1007-PET, leading to an effective prostate cancer management.

In the present study, the martensitic transformation (MT) and magnetic properties exhibited by the Ni-Mn-Sn Heusle-type magnetic shape memory alloys (MSMAs) doped with Zn have been investigated experimentally and theoretically. The inverse magnetocaloric effect (MCE) in Ni₄₇Mn₄₀Sn_13−xZn_x (x = 0, 1) was studied by direct measurements of the adiabatic temperature change, ΔT_ad, in pulsed magnetic fields of 5, 10, and 20 T. The Zn doping of the Ni-Mn-Sn alloy led to a striking enhancement of the value of ΔT_ad, e.g., from –2.5 for undoped to –11 K for Zn-doped alloys under a magnetic field amplitude of 20 T. The first-principles calculations were used to understand the origin of Zn-doping influence on MT, magnetic, and magnetocaloric properties. Particularly, the crystal structure and magnetic ordering influenced by the site occupancy in the undoped and Zn-doped alloys were analyzed. The results show that, whereas the usual transition metal elements with more valence electrons tend to enter the Ni sites, Zn atom prefers to occupy the Sn sublattice. The underlying physics of the drastic enhancement of MCE by Zn doping is discussed in terms of a partial disorder in the occupation sites of Zn atoms.

Spin-pumping in a ferromagnet/non-ferromagnet heterostructure is directly imaged with spatial resolution as well as element selectivity. The time-resolved detection in scanning transmission x-ray microscopy allows to directly probe the spatial extent of the ac spin polarization in Co-doped ZnO which is generated by spin-pumping from an adjacent permalloy microstrip. Comparing the relative phases of the dynamic magnetization component of the two constituents is possible and found to be out of phase. The correlation between the distribution of the magnetic excitation in the permalloy and the Co-doped ZnO reveals that literally there is no one-to-one correlation. The observed distribution is rather complex, but integrating over larger areas clearly demonstrates that the spin polarization in the non-ferromagnet extends laterally beyond the region of the ferromagnetic microstrip. Therefore the observations are better explained by a local spin pumping efficieny and a lateral propagation of the ac spin-polarization in the non-ferromagnet over the range of a few micrometers.

Contrary to a wide-spread belief that alkali metal (AM) atoms intercalated into layered materials form single-layer structures only, recent experiments [Nature 564 (2018) 234] showed that multi-layer configurations of lithium are possible in bi-layer graphene. Using state-of-the-art first-principles calculations, we systematically study the intercalation energetics for various AMs (Li, Na, K, Rb, Cs) in bi-layer graphene and MoS2. We demonstrate that for bilayer graphene as host the formation energy of multilayer structures is negative for K, Rb and Cs and only slightly positive for both Li and Na. In view of the previous experimental data on lithium, a multilayer of Na might, therefore, form, while it is well-known that single-layers of Na in graphitic hosts are energetically very unfavorable. In MoS2, multi-layer structures are considerably higher in energy than the single-layer ones, but the formation of the former can still occur, especially for the AMs with the lowest electronegativity. To rationalize the results, we assess the charge transfer from the intercalants to the host material and analyze the interplay between the ionic and covalent bonding of AM and host atoms. While our theoretical effort primarily focuses on the fundamental aspects of AM intercalation, our findings may stimulate experimental work addressing multilayer intercalation to maximize the capacity of anode materials in AM ion batteries.

In this 2-day webinar we will see the problems arising with the conventional statistical analysis of compositional data, and present a general solution. We will learn how to generate and interpret compositional descriptive statistics; how to explore the inner structure of a data set with tools such as logratio principal component analysis; and we will fit predictive models to explain the variability in compositional data sets. These topics will be covered with a bit of theory, some examples from geochemistry and a few exercises in R, the open source environment for data analysis.

Thorite, ThSiO4 with Zircon structure type, is one of the most abundant natural source of thorium on earth. While actinides are known to form nanoparticles in silicate medium, no direct link between those colloids and crystalline form of thorite was evidenced until now. Here we show that thorite can be produced in experimental conditions close to environmental pH and temperature. Thanks to in-situ Small and Wide Angle X-rays Scattering (SWAXS) measurements, colloids of a few nanometers are first evidenced for low reaction time. These colloids exhibit elongated shapes and finally tend to aggregate after the size has reached 10 nm. Once aggregated, the system goes through a maturation step finishing with the emergence of nanocrystallites presenting thorite zircon structure. This maturation step is longer when the reaction temperature is decreased highlighting kinetic considerations. The conclusions of this article have potential implications in the paragenesis of Th minerals deposits, but also in the behaviour of Th and, by analogy, tetravalent actinides in the environment. The Th-silicate colloids evidenced in this work have, at low temperature and at near neutral pH, a long-term stability and a morphology in favor of a high mobility in groundwaters. If these species are formed in more diluted media, this could be problematic regarding to the spreading of Th and, by analogy of others tetravalent actinides in the environment.

The synthesis of a tetravalent neptunium amidinate [NpCl((S)-PEBA)₃] (1) ((S)-PEBA = (S,S)-N,N’-bis-(1-phenylethyl)-benzamidinate) is reported. This complex represents the first structurally characterized enantiopure transuranic compound. Reactivity studies with halide/pseudohalides yielding [NpX((S)-PEBA)₃] (X = F (2), Br (3), N3 (4)) have shown that the chirality-atmetal is preserved for all compounds in the solid state. Furthermore, they represent an unprecedented example of a structurally characterized metal-organic Np complex featuring a Np–Br (3) bond. In addition, 4 is the only reported tetravalent transuranic azide. All compounds were additionally characterized in solution using paramagnetic NMR spectroscopy showing an expected C₃ symmetry at low temperatures.

As of April 28, 2020, a pandemic called coronavirus disease 2019 (COVID-19) has spread to every continent of the world, infecting around three million people, and taken nearly 200,000 lives [1]. Although such deadly events are not new throughout human history, they often cause fear and uncertainty, mostly because of lacking information about the new strain of the virus. Insight about the virus and its working mechanism is perhaps important yet understanding the human immune response is the key to reducing mortality. Our immune system reacts differently depends on ages, genders, races, and health background. That explains dissimilar disease progression in patients where some develop critical conditions while others only have mild symptoms [2]. Accumulating evidences suggest patient with severe COVID-19 symptoms is due to cytokine - a common name for a broad spectrum of small proteins important in cell signalling, especially in the immune system - dysregulation [3-5]. Therefore, many studies have suggested a screening of cytokine profiles together with other immune cells responses for the determination of correct treatment [3,5]. Meanwhile, nanosensors such as silicon nanowire (SiNW) own advantages of being sensitive to small molecules, rapid and label-free [6]. In this poster, we demonstrate the use of a SiNW sensor in immunotherapy research, more specifically, in a system of switchable T-cell expressing chimeric antigen receptors (CARs). The sensor showed better sensitivity and a lower limit of detection compare to standard ELISA test. Moreover, thanks to its compatibility with CMOS technology which enables mass production, reproducibility is ensured [7]. Since the cytokine release syndrome (CRS) found in COVID-19 patients is also observed in patients receiving CAR-T therapy [4], the knowledge and tools generated by the SiNW sensor developed in this field of study may benefit the community. In the end, a full understanding and control of our immune system might be the key to fight any other pandemic in the future.

Two photoactivatable dicarbonyl ruthenium(II) complexes based on an amide-functionalised bipyridine scaffold (4-position) equipped with an alkyne functionality or a green-fluorescent BODIPY (boron-dipyrromethene) dye have been prepared and used to investigate their light-induced decarbonylation. UV/Vis, FT-IR and 13C NMR spectroscopies as well as gas chromatography and multivariate curve resolution alternating least-squares analysis (MCR-ALS) were used to elucidate the mechanism of the decarbonylation process. Release of the first CO molecule occurs very quickly, while release of the second CO molecule proceeds more slowly. In vitro studies using two cell lines A431 (human squamous carcinoma) and HEK293 (human embryonic kidney cells) have been carried out in order characterise the anti-proliferative and anti-apoptotic activities. The BODIPY-labelled compound allows for monitoring the cellular uptake, showing fast internalisation kinetics and accumulation at the endoplasmic reticulum and mitochondria.

We present Bionic Tracking, a novel method for solving biological cell tracking problems with eye tracking in virtual reality using commodity hardware. Using gaze data, and especially smooth pursuit eye movements, we are able to track cells in time series of 3D volumetric datasets. The problem of tracking cells is ubiquitous in developmental biology, where large volumetric microscopy datasets are acquired on a daily basis, often comprising hundreds or thousands of time points that span hours or days. The image data, however, is only a means to an end, and scientists are often interested in the reconstruction of cell trajectories and cell lineage trees. Reliably tracking cells in crowded three-dimensional space over many timepoints remains an open problem, and many current approaches rely on tedious manual annotation and curation. In our Bionic Tracking approach, we substitute the usual 2D point-and-click annotation to track cells with eye tracking in a virtual reality headset, where users simply have to follow a cell with their eyes in 3D space in order to track it. We detail the interaction design of our approach and explain the graph-based algorithm used to connect different time points, also taking occlusion and user distraction into account. We demonstrate our cell tracking method using the example of two different biological datasets. Finally, we report on a user study with seven cell tracking experts, demonstrating the benefits of our approach over manual point-and-click tracking, with an estimated 2- to 10-fold speedup.

The success of conventional chimeric antigen receptor (CAR) therapy in the treatment of refractory hematologic malignancies has triggered the development of novel exciting experimental CAR technologies. Among them, adaptor CAR platforms have received much attention. They combine the flexibility and controllability of recombinant antibodies with the power of CARs. Due to their modular design, adaptor CAR systems propose answers to central problems of conventional CAR therapy such as safety and antigen escape. This review provides an overview on the different adaptor CAR platforms available, discusses the possibilities and challenges of adaptor CAR therapy and summarizes first clinical experiences.

Metallurgical simulation and evaluation of the resource efficiency of whole production processes are of key importance for a sound environmental impact assessment. An exergy dissipation analysis is suitable for quantifying the theoretical limits for a process and pinpoint hotspots for improvement along the value chain. The production of NdFeB permanent magnets is evaluated through a simulation-based life cycle assessment and exergetic analysis, comprising 107 unit operations, 361 flows and 209 compounds. This methodology highlights areas with the greatest potential for improvements in terms of technology and environmental impact, shedding light on the true resource efficiency and minimum exergy dissipation for the production of permanent magnets, present in several low-carbon technologies. A maximum exergy efficiency of 60.7% shows that there is a limit for sustainability, which can be improved by technological improvements and recovery of waste streams, showing the inconvenient truth that the resource efficiency will never reach 100%.

In this work, we investigate magneto-acoustic attenuation in thin film multiferroic Lamb wave delay lines. By leveraging magneto-acoustic interactions, multiferroics have potential to realize passive chip-scale alternatives to bulky ferrite devices. For the first time, magnetic field dependence of magnetoacoustic interactions in multiferroic Lamb wave devices is characterized. Multiferroic heterostructures of aluminum nitride and cobalt iron boron are fabricated into Lamb wave delay lines operating at 7.492 GHz to study the effect of strain nonuniformity on the multiferroic coupling. The attenuation of the Lamb waves is characterized as a function of the magnitude and angle of an applied in-plane bias magnetic field. It is found that the bias magnitude for peak attenuation is a strong function of angle, indicating that it is due to coupling between the Lamb waves and spin wave modes. This is in contrast with current models of attenuation in multiferroic SAW delay lines, where the uniform surface strains couple to ferromagnetic resonance, which has no angular dependence on the in-plane bias field magnitude. These results are the first steps towards passiv chip-scale alternatives to ferrite devices utilizing Lamb wave devices, which have better coupling and scalability than their SAW counterparts.

Topological spin textures such as skyrmions, merons, and vortices in antiferromagnetic (AFM)/ ferromagnetic (FM) materials are actively explored for utilization in future data storage and signal processing devices. An emergent half-integer spin texture such as a magnetic vortex can be stabilized in a soft magnetic NiFe disk structure. Due to the topological nature, the unwinding of the magnetic vortex phase is mediated by the dynamic creation and subsequent annihilation of magnetic singularities, such as Bloch points. This process enables the formation of intermediate topological phases such as vortex-antivortex (V-AV) pairs and edge states. Interfacial interactions between an AFM and a topologically non-trivial spin structure of a FM can stabilize and extend the lifetime of V-AV phases, which are typically considered intrinsic and dynamic are imaged using high-resolution in-field magnetic force microscopy. Additionally, these interactions are used to protect the emerged chirality in an otherwise degenerate chiral spin system, rather than to introduce a preferred chirality.

Spin orbit torque driven switching is a favourable way to manipulate nanoscale magnetic objects for both memory and wireless communication devices. The critical current required to switch from one stored magnetic state to another depends on the multilayer structure of the device and the intrinsic properties of the materials used, which are difficult to control on a local scale. Here we demonstrate how focused helium ion beam irradiation can be used to modulate the local magnetic anisotropy of a Co thin film at the microscopic scale. In-situ characterisation using the anomalous Hall effect showed up to an order of magnitude reduction of the magnetic anisotropy under irradiation in real-time, and using this, a multi-level storage element is demonstrated. The result is that current-driven spin-switching, with as little as 800 kA cm-2 can be achieved on predetermined areas of the film without the need for physical material patterning.

In order to optimize the catalytic functionality of cerium oxide it is important to understand the structural modifications associated with reduction of the material and the role of the proximity of metals, which are often coupled with the oxide in the applications. For this purpose, the evolution of the short- and long-range structure of cerium oxide ultrathin epitaxial films and nanostructures supported on Pt(111) is investigated using x-ray absorption spectroscopy at the Ce L3 edge and surface x-ray diffraction, during reduction by thermal treatments in vacuum. In epitaxial nanoislands, the reduction is associated with a contraction of the Ce-O distance and with the appearance of Ce-Pt bonds. The formation of a phase with a (2×2) periodicity after a thermal treatment at 1023 K is ascribed to the formation of a Pt5Ce alloy. Films of 3 nm thickness do not show, on average, significant structural modifications with the same thermal treatment, consistent with the hypothesis that the reduction involves only the topmost surface layers and it does not influence significantly the bulk structure of the material. This study demonstrates a strong interaction between cerium oxide and platinum, which has implications for the reactivity and stability of catalysts based on metals combined with reducible oxides.

Ultrasonic investigations of the single-site quadrupolar Kondo effect in diluted Pr system Y_0.966Pr_0.034Ir₂Zn₂₀ are reported. The elastic constant (C₁₁C₁₂)/2 is measured down to ~40 mK using ultrasound for the dilute system Y_0.966Pr_0.034Ir₂Zn₂₀ and the pure compound Yir₂Zn₂₀. We found that the elastic constant (C₁₁C₁₂)/2 of the Pr-dilute system exhibits a logarithmic temperature dependence below T₀ ∼ 0.3 K, where non-Fermi-liquid (NFL) behavior in the specific heat and electrical resistivity is observed. This logarithmic temperature variation manifested in the Γ3-symmetry quadrupolar susceptibility is consistent with the theoretical prediction of the quadrupolar Kondo effect by D. L. Cox [1]. On the other hand, the pure compound Yir₂Zn₂₀ without 4f-electron contributions shows nearly no change in its elastic constants evidencing negligible phonon contributions. In addition, clear acoustic de Haas-van Alphen (dHvA) oscillations in the elastic constant were detected for both compounds on applying magnetic field. This is mainly interpreted as contribution from the Fermi surface of Yir₂Zn₂₀.

Non-symmorphic chiral topological crystals host exotic multifold fermions, and their associated Fermi arcs helically wrap around and expand throughout the Brillouin zone between the high-symmetry center and surface-corner momenta. However, Fermi-arc splitting and realization of the theoretically proposed maximal Chern number rely heavily on the spin-orbit coupling (SOC) strength. In the present work, we investigate the topological states of a new chiral crystal, PtGa, which has the strongest SOC among all chiral crystals reported to date. With a comprehensive investigation using high-resolution angle-resolved photoemission spectroscopy, quantum-oscillation measurements, and state-of-the-art ab initio calculations, we report a giant SOC-induced splitting of both Fermi arcs and bulk states. Consequently, this study experimentally confirms the realization of a maximal Chern number equal to ±4 in multifold fermionic systems, thereby providing a platform to observe large-quantized photogalvanic currents in optical experiments.

In this study, ultrasonic measurements were performed on a single crystal of cubic PrNi₂Cd₂₀, down to a temperature of 0.02 K, to investigate the crystalline electric field ground state and search for possible phase transitions at low temperatures. The elastic constant (C₁₁−C₁₂)/2, which is related to the Γ₃-symmetry quadrupolar response, exhibits the Curie-type softening at temperatures below ∼30 K, which indicates that the present system has a Γ₃ non-Kramers doublet ground state. A leveling-off of the elastic response appears below ∼0.1 K toward the lowest temperatures, which implies the presence of level splitting owing to a long-range order in a finite-volume fraction associated with Γ₃-symmetry multipoles. A magnetic field–temperature phase diagram of the present compound is constructed up to 28 T for H || [110]. A clear acoustic de Haas–van Alphen signal and a possible magnetic-field-induced phase transition at H ∼26 T are also detected by high-magnetic-field measurements.

A novel type of sub-lattice of the Jahn-Teller (JT) centers was arranged in Ti-doped barium hexaferrite BaFe₁₂O₁₉. In the un-doped crystal all iron ions, sitting in five different crystallographic positions, are Fe³⁺ in the high-spin configuration (S = 5/2) and have a non-degenerate ground state. We show that the electron-donor Ti substitution converts the ions to Fe²⁺ predominantly in tetrahedral coordination, resulting in doubly-degenerate states subject to the E ⊗ e problem of the JT effect. The arranged JT complexes, Fe²⁺O₄, their adiabatic potential energy, non-linear and quantum dynamics, have been studied by means of ultrasound and terahertz-infrared spectroscopies. The JT complexes are sensitive to external stress and applied magnetic field. For that reason, the properties of the doped crystal can be controlled by the amount and state of the JT complexes.

Transition metal(II) fluoridometallates(IV) AIIMIVF6∙3H2O (AII = Mn, Zn; MIV = Np, Pu) were synthesized from NpO2 or PuO2 and the respective transition metal chlorides from hydrofluoric acid under mild conditions. The olive-green (Np) or orange (Pu) compounds were obtained as single-crystals and the respective structures were determined by single-crystal X-ray diffraction. In the isotypic compounds, chains of edgesharing tricapped trigonal prismatic polyhedra, [MIVF8/2(H2O)1/1] ∞1, are present and an overall threedimensional network structure is observed in which the AII and MIV atoms are arranged according to the simple NaCl structure type. Within the respective U-Pu series of the Zn and Mn salts the cell volumes and the MIV−F distances decrease due to the actinoid contraction.

Die Kenntnis des Strömungsfeldes einer Zweiphasenströmung (fest/flüssig) in Rührkesseln, insbesondere hinsichtlich der Turbulenz, stellt einen Schwerpunkt für das Verständnis des industriell relevanten Flotationsprozesses sowie dessen numerischen Simulation dar. In dieser Arbeit werden die Strömungsfelder der Fluidphase (deionisiertes Wasser) und Feststoffphase (Polyethylen- bzw. Glaspartikel mit d_P = 63...70 μm; d_P = 150...180 μm; d_P = 425...500 μm) mithilfe von Particle Image Velocimetry und Particle Shadow Velocimetry ermittelt sowie mit Ergebnissen aus der Literatur und numerischen Simulationen verglichen. Es wird der Einfluss der Feststoffpartikel auf das Geschwindigkeitsfeld, die turbulenten Schwankungsgeschwindigkeiten sowie die Verteilung der Partikel im Rührkessel (D_K = 90 mm) betrachtet. Hierfür wird die Volumenkonzentration der Partikel in drei Schritten von 0,025 vol-% auf 0,1 vol-% erhöht und die Partikel werden mittels Scheibenrührer (Re_R = 9,7; 14,9 oder 22,4*10⁴) suspendiert. Entscheidend für den Einfluss der Partikel auf die Flüssigphase sind der Partikeldurchmesser und die Partikeldichte. Bei den betrachteten Volumenkonzentrationen scheint diese vernachlässigbar zu sein. Innerhalb des Rührerstrahls wird in Lauflänge eine zunehmende Dämpfung der radialen Geschwindigkeit sowie teilweise eine leichte Ablenkung des Rührerstrahls Richtung Rührkesselboden festgestellt. Bei den axialen Geschwindigkeiten dominieren Partikel großer Stokes-Zahlen die abwärtsgerichtete Zweiphasenströmung und können dem Fluid nicht folgen. Die turbulenten Schwankungsgeschwindigkeiten werden generell durch die Partikel (Re_P < 170) gedämpft. Es wird bestätigt, dass die konkrete Rührerstellung keinen Einfluss auf das Strömungsfeld im äußeren Bereich des Rührkessels besitzt.

We demonstrate the functionalization of silicon nanowire based field effect transistors (SiNW FETs) FETs with stimuli-responsive polymer brushes of poly(N-isopropylacrylamide) (PNIPAAM) and poly(acrylic acid) (PAA). Surface functionalization was confirmed by atomic force microscopy, contact angle measurements, and verified electrically using a silicon nanowire based field effect transistor sensor device. For thermo-responsive PNIPAAM, the physicochemical properties (i.e., a reversible phase transition, wettability) were induced by crossing the lower critical solution temperature (LCST) of about 32 °C. Taking advantage of this property, osteosarcomic SaoS-2 cells were cultured on PNIPAAM-modified sensors at temperatures above the LCST, and completely detached by simply cooling. Next, the weak polyelectrolyte PAA, that is sensitive towards alteration of pH and ionic strength, was used to cover the silicon nanowire based device. Here, the increase of pH will cause deprotonation of the present carboxylic (COOH) groups along the chains into negatively charged COO− moieties that repel each other and cause swelling of the polymer. Our experimental results suggest that this functionalization enhances the pH sensitivity of the SiNW FETs. Specific receptor (bio-)molecules can be added to the polymer brushes by simple click chemistry so that functionality of the brush layer can be tuned optionally. We demonstrate at the proof-of concept-level that osteosarcomic Saos-2 cells can adhere to PNIPAAM-modified FETs, and cell signals could be recorded electrically. This study presents an applicable route for the modification of highly sensitive, versatile FETs that can be applied for detection of a variety of biological analytes.

Despite the recent progress in the synthesis of crystalline boronate ester covalent organic frameworks (BECOFs) in powder and thin‐film through solvothermal method and on‐solid‐surface synthesis, respectively, their applications in electronics, remain less explored due to the challenges in thin‐film processability and device integration associated with the control of film thickness, layer orientation, stability and crystallinity. Moreover, although the crystalline domain sizes of the powder samples can reach micrometer scale (up to ≈1.5 μm), the reported thin‐film samples have so far rather small crystalline domains up to 100 nm. Here we demonstrate a general and efficient synthesis of crystalline two‐dimensional (2D) BECOF films composed of porphyrin macrocycles and phenyl or naphthyl linkers (named as 2D BECOF‐PP or 2D BECOF‐PN) by employing a surfactant‐monolayer‐assisted interfacial synthesis (SMAIS) on the water surface. The achieved 2D BECOF‐PP is featured as free‐standing thin film with large single‐crystalline domains up to ≈60 μm2 and tunable thickness from 6 to 16 nm. A hybrid memory device composed of 2D BECOF‐PP film on silicon nanowire‐based field‐effect transistor is demonstrated as a bio‐inspired system to mimic neuronal synapses, displaying a learning–erasing–forgetting memory process.

Synthetic nano- and micromotors interact with each other and their surroundings in a complex manner. Here, we report on the anisotropy of active-passive particle interaction in a soft matter system containing an immobile yet photochemical Ag/AgCl-based Janus particle embedded in a dense matrix of passive beads in pure water. The asymmetry in the chemical gradient around the Janus particle, triggered upon visible light illumination, distorts the isotropy of the surrounding electric potential and results in the repulsion of adjacent passive beads to a certain distance away from the Janus particle. This exclusion effect is found to be anisotropic with larger distances to passive beads in front of the Ag/AgCl cap of the Janus particle. We provide insight into this phenomenon by performing the angular analysis of the radii of exclusion and tracking their time evolution at the level of a single bead. Our study provides a novel fundamental insight into the collective behavior of a complex mixture of active and passive particles and is relevant for various application scenarios, e.g., particle transport at micro- and nanoscale and local chemical sensing.

Low-density microplastics are frequently found in sediments of many lakes and reservoirs. The processes leading to sedimentation of initially buoyant polymers are poorly understood for inland waters. This study investigated the impact of biofilm formation and aggregation on the density of buoyant polyethylene microplastics. Biofilm formation on polyethylene films (4 × 4 × 0.15 mm) was studied in a eutrophic reservoir (Bautzen, Saxony, Germany). Additionally, aggregation dynamics of small PE microplastics (∼85 µm) with cyanobacteria were investigated in laboratory experiments. During summer phototrophic sessile cyanobacteria (Chamaesiphon spp. and Leptolyngbya spp.) precipitated calcite while forming biofilms on microplastics incubated in Bautzen reservoir. Subsequently the density of the biofilms led to sinking of roughly 10 % of the polyethylene particles within 29 days of incubation. In the laboratory experiments planktonic cyanobacteria (Microcystis spp.) formed large and dense cell aggregates under the influence of elevated Ca2+ concentrations. These aggregates enclosed microplastic particles and led to sinking of a small portion (∼0.4 %) of polyethylene microplastics. This study showed that both sessile and planktonic phototrophic microorganisms mediate processes influenced by calcium which facilitates densification and sinking of microplastics in freshwater reservoirs. Loss of buoyancy leads to particle sedimentation and could be a prerequisite for the permanent burial of microplastics within reservoir sediments.

Layered α−RuCl3 has been discussed as a proximate Kitaev spin-liquid compound. Raman and terahertz spectroscopy of magnetic excitations confirms that the low-temperature antiferromagnetic ordered phase features a broad Raman continuum, together with two magnonlike excitations at 2.7 and 3.6 meV, respectively. The continuum strength is maximized as long-range order is suppressed by an external magnetic field. The state above the field-induced quantum phase transition around 7.5 T is characterized by a gapped multiparticle continuum out of which a two-particle bound state emerges, together with a well-defined single-particle excitation at lower energy. Exact diagonalization calculations demonstrate that Kitaev and off-diagonal exchange terms in the Fleury-Loudon operator give rise to a pronounced intensity of these features in the Raman spectra. Our Rapid Communication firmly establishes the partially polarized quantum disordered character of the high-field phase.

A novel small signal equivalent circuit model is proposed in the inversion regime of metal/(ZnO, ZnMnO, and ZnCoO) semiconductor/Si3N4 insulator/p-Si semiconductor (MSIS) structures to describe the distinctive nonlinear frequency dependent capacitance (C-F) and conductance (G-F) behaviour in the frequency range from 50 Hz to 1 MHz. We modelled the fully depleted ZnO thin films to extract the static dielectric constant (εr) of ZnO, ZnMnO, and ZnCoO. The extracted enhancement of static dielectric constant in magnetic n-type conducting ZnCoO (εr ≥ 13.0) and ZnMnO (εr ≥ 25.8) in comparison to unmagnetic ZnO (εr = 8.3–9.3) is related to the electrical polarizability of donor-type bound magnetic polarons (BMP) in the several hundred GHz range (120 GHz for CdMnTe). The formation of donor-BMP is enabled in n-type conducting, magnetic ZnO by the s-d exchange interaction between the electron spin of positively charged oxygen vacancies Vo + in the BMP center and the electron spins of substitutional Mn2+ and Co2+ ions in ZnMnO and ZnCoO, respectively. The BMP radius scales with the Bohr radius which is proportional to the static dielectric constant. Here we show how BMP overlap can be realized in magnetic n-ZnO by increasing its static dielectric constant and guide researchers in the field of transparent spintronics towards ferromagnetism in magnetic, n-ZnO.

The lower Guadiana River carves a wide canyon in the Variscan metamorphic rocks of the SW Iberian Peninsula and presents an exceptionally homogeneous and well-preserved case of a strath terrace (ST) some 40 km long and 400 m wide. The rocky surface or strath shows different characteristics and development stages. Upstream, the lateral erosion level forms a flooded riverbed, or submerged strath, that gradually rises above the thalweg and develops into an active floodplain. Downstream, below the 15 m high Pulo do Lobo waterfall, the strath is incised by an inner canyon that forms a terrace on both sides. The inner channel increasingly widens and the ST loses its longitudinal continuity, yet remains prone to flooding during extraordinary magnitude floods. To assess the factors controlling the formation of this ST, we examined the roles of key drivers of ST formation: lithological hardness, tectonic structures and climate change, using cosmogenic data to create a chronologic context. The ST developed favoured by a monotonous succession of phyllites, as shown by Schmidt hammer resistance data, and interbedded more resistant quartz veins do not significantly alter its flat configuration. Variscan structures and measured joints determine the main orientation of the river and control the drainage network pattern. The intersection of the NS and NE-SW fractures promotes a wavy surface due to three-dimensional minor fold trains that act as discontinuities and play an important role in ST erosion through quarrying and plucking. However, we detected no evidence of ST deformation attributable to recent or Late Cenozoic tectonic activity.

The upstream active riverbed progressively changes downstream into an ST. This implies that Be radiometric ages obtained at Pulo do Lobo may not represent the ST's genetic age but rather the time of dismantling of its alluvial or sedimentary cover. This means the strath surface formed prior to its cosmogenic age and was therefore controlled by a higher base level, indicating a higher sea level than the current one, given the downstream area studied. The Quaternary sea level fluctuations show records of only a few meters above the current level. Instead, the sea level low stand maintains an average depth of −60 m, reaching −140 m during the last glacial period. This low base level context could justify the strong incision of the inner channel within the ST, but not the age of strath surface genesis and expansion and thus this surface should have evolved previously. The highest possible sea level stand corresponds to the Pliocene transgression, which reached an elevation of 120 m in the region, covering Miocene paleorelief. The mouth of the Guadiana River at that time resembled a fluvio-deltaic embayment between the Algarve domain and the Guadalquivir depression, which was infilled with fluvial deposits at the end of the transgression. Collectively, these data suggest that cosmogenic dating would define the time of exhumation of this Pliocene sedimentary cover.

Despite great variation of the ST ages, estimated incision rates at the knickpoint area are consistent with the total entrenchment of the Pulo do Lobo fall, especially if we consider that data correspond to an active erosion site. Highest erosion rates were found for the pothole area compared to those obtained for the higher ST surface. Radiometric ages correspond to the period of lowest Quaternary sea level and during which headward erosion would have been very active in the inner channel. The waterfall area shows more resistant lithology in its concentrated quartz veins, but this effect is inconspicuous at the ST surface. The regular gradient of 0.02 m/m and vast extension of this perched strath, linked upstream to the Guadiana riverbed, indicates a relic exhumed surface beneath its sedimentary cover. Notwithstanding the subsiding activity of the Gulf of Cádiz, the continental margin behaves as a tectonically stable block, which allows for the persistence of former morphologies in these ancient landscapes reshaped by bedrock river dissection.

Graphene oxide foils implanted with copper ions at low energy and high dose, have been proposed as hybrid graphene-based materials suitable to be laser irradiated in vacuum to produce hot plasmas. The special lattice structure of the graphene oxide foil can improve the propagation of the laser accelerated electrons inside the foil and to enhance the electron density emerging from the rear foil surface. In such conditions the electric field developed in the non-equilibrium plasma increases and consequently in the forward ion acceleration. The foils have been optimized in thickness and they were irradiated with optimized laser parameters in order to produce high energy and quasi-monoenergetic proton beams by the femtosecond laser at the Institute of Plasma Physics and Laser Microfusion in Warsaw, Poland. Gaf chromic film and silicon carbide detectors were used to monitor the plasma properties and to measure the velocity of the emitted protons and carbon ions from plasma.

A novel multicomponent alloy, V_2.5Cr_1.2WMoCo_0.04, produced from elements expected to favour a BCC crystal structure, and to be suitable for high temperature environments, was fabricated by arc melting and found to exhibit a multiphase dendritic microstructure with W-rich dendrites and V-Cr segregated to the inter-dendritic cores. The as-cast alloy displayed an apparent single-phase XRD pattern. Following heat treatment at 1187 °C for 500 h the alloy transformed into three different distinct phases - BCC, orthorhombic, and tetragonal in crystal structure. This attests to the BCC crystal structure observed in the as-cast state being metastable. The radiation damage response was investigated through room temperature 5 MeV Au⁺ ion irradiation studies. Metastable as-cast V_2.5Cr_1.2WMoCo_0.04 shows good resistance to radiation induced damage up to 40 displacements per atom (dpa). 96 wt% of the as-cast single-phase BCC crystal structure remained intact, as exhibited by grazing incidence X-ray diffraction (GI-XRD) patterns, whilst the remainder of the alloy transformed into an additional BCC crystal structure with a similar lattice parameter. The exceptional phase stability seen here is attributed to a combination of self-healing processes and the BCC structure, rather than a high configurational entropy, as has been suggested for some of these multicomponent "High Entropy Alloy" types. The importance of the stability of metastable high entropy alloy phases for behaviour under irradiation is for the first time highlighted and the findings thus challenge the current understanding of phase stability after irradiation of systems like the HEAs.

Trapezoidal ridge waveguides have been fabricated in YCOB nonlinear optical crystals by carbon ion irradiation and precise diamond-blade dicing. The diced ridges with smooth side-walls allow for near-infrared (1064 nm) light guiding with propagation losses around 1 dB/cm. Refractive index profile of a waveguide has been reconstructed in a reasonable manner. Green second harmonic light have been generated at room temperature via type I birefringent phase matching. Under the pump of continuous and pulsed lasers, conversion efficiencies for guided-wave frequency doubling can be up to ~1.10% Wsup^-1 and ~6.22%, respectively.

In this work the modelling of horizontal two-phase flows within the two-fluid Euler-Euler approach is investigated. A modified formulation of the morphology detection functions within the Algebraic Interfacial Area Density (AIAD) model is presented in combination with different models for the drag force acting on a sheared gas-liquid interface. In case of free surface flows, those closure laws are often based on experimental correlations whose applicability is limited to certain flow regimes. It is investigated here whether the implementation of the modified blending functions in ANSYS CFX avoids this limitation. The influence of the new functions on the prediction of turbulence parameters in free surface flows is also examined quantitatively for the k-ω and k-ε two-equations turbulence models. Transient simulations of the WENKA counter-current stratified two-phase flow experiment were performed for validation. Predict of the correct flow pattern as observed in the experiment improved dramatically when a turbulence damping term was included in the standard two-equation models. Using the k-ω and a modified k-ε turbulence model with damping terms close to the interface, better agreement with the experimental data was achieved. The morphology detection mechanism of the unified blending functions within the AIAD is seen as an improvement with respect to the detection of sharp interfaces. Satisfactory quantitative agreement is achieved for the modified free surface drag. Furthermore, it is demonstrated that turbulence dampening has to be accounted for both turbulence models to qualitatively reproduce the mean flow and turbulence quantities from the experiment.

Since 2005, events have occurred involving increased operational oxidation of M5 fuel rod claddings at several German pressurized water reactors (PWRs). The conspicuous corrosion was observed mainly in the area between the two uppermost spacer grids (SG), i.e. the 8th and the 9th SG. In this area the transition from the active fuel rod area (filled with fuel) to the fuel rod plenum takes place. In some cases, the increased oxide layer was even found in the region of the fuel rod plenum, where no appreciable power is transferred from the fuel rod to the coolant.

One of the hypotheses assumes that an initial oxide layer first arises more or less over the entire length of the fuel rod. Depending on the height position different thermal conditions may occur in the form of temperature fluctuations. According to this hypothesis, it is assumed that the oxide layer ruptures due to the load from alternating temperatures, creating pathways where oxidizing species reach the metallic cladding rod surface. As a result, the oxide layer loses its protective effect and thicker oxide layers can grow up. From earlier experimental investigations at ROCOM (Rossendorf Coolant Mixing Test Facility) it is known that strong, large-scale vortex structures are present in the upper plenum of the RPV.

The aim of the present study was the detection of possible vortices in the upper part of the core. Therefore, a numerical simulation of the flow conditions in a Pre-Konvoi Pressurized Water Reactor (PWR) was carried out based on a complex 3D CFD model. The geometry of the CFD model includes the entire Reactor Pressure Vessel (RPV) plus all relevant internals. The core is modelled as a porous body, the different pressure losses along and transverse to the main flow direction were considered. The spacer-grid levels were taken into account to the extent that in these areas no cross-flow is possible. The calculation was carried out for nominal operating conditions, i.e. for full load operation. Furthermore, a prototypical End of Cycle (EOC) power distribution was assumed. For this, a power distribution was applied as obtained from a stationary full-core calculation with the 3D neutron kinetics code DYN3D. In order to be able to adequately reproduce flow vortexes, the calculation was performed transiently with suitable Detached Eddy Simulations (DES) turbulence models.

The calculation showed fluctuating transverse flow in the upper part of the core, starting at the 8th spacer grid but also revealed that no large dominant vortices exists in this region. It seems that the core acts as a rectifier attenuating large-scale vortices. The analyses included several spacer grid levels in the core and showed that in some areas of the core cross-section an upward increasingly directed transversal flow to the outlet nozzle occurs. In other areas of the core cross-section, on the other hand, there is nearly any cross-flow. However, the following limitations of the model apply: In the model all fuel elements are treated identical and cross flows due to different axial pressure losses for different FA types cannot be displayed. The complex structure of the FAs (eg. flow vanes in spacer grids) could also influence the formation of large-scale vortices. This effect could only be resolved with a very high number of grid elements (several billions). This is currently not possible from a computational point of view. Also, the possible influence of two-phase flows was not considered.

Noble-metal aerogels (NMAs) have drawn increasing attention because of their self-supported conductive networks, high surface areas, and numerous optically/catalytically active sites, enabling their impressive performance in diverse fields. However, the fabrication methods suffer from tedious procedures, long preparation times, unavoidable impurities, and uncontrolled multiscale structures, discouraging their developments. By utilizing the self-healing properties of noble-metal aggregates, the freezing-promoted salting-out behavior, and the ice-templating effect, a freeze-thaw method is crafted that is capable of preparing various hierarchically structured noble-metal gels within one day without extra additives. In light of their cleanliness, the multi-scale structures, and combined catalytic/optical properties, the electrocatalytic and photoelectrocatalytic performance of NMAs are demonstrated, which surpasses that of commercial noble-metal catalysts.

Purpose
To compare the dosimetric results of an in silico study among intensity-modulated photon (IMRT) and robust multi-field optimized intensity-modulated proton (rMFO-IMPT) treatment techniques using a dose-escalated simultaneously integrated boost (SIB) approach in locally recurrent or locally advanced pancreatic cancer patients.

Material and Methods
For each of 15 locally advanced pancreatic cancer patients, a volumetric modulated arc therapy (VMAT), a Tomotherapy (TOMO), and an rMFO-IMPT treatment plan was optimized on free-breathing treatment planning computed tomography (CT) images. For the photon treatment plans, doses of 66Gy and 51Gy, both as SIB in 30 fractions, were prescribed to the gross tumor volume (GTV) and to the planning target volume (PTV), respectively. For the proton plans, a dose prescription of 66Gy(RBE) to the GTV and of 51Gy(RBE) to the clinical target volume (CTV) was planned. For each SIB-treatment plan, doses to the targets and OARs were evaluated and statistically compared.

Results
All treatment techniques reached the prescribed doses to the GTV and CTV or PTV. The stomach and the bowel, of the latter in particular the duodenum and the small bowel, were found to be frequently exposed to doses exceeding 50Gy, irrespective of the treatment technique. For doses below 50Gy, the IMPT technique was statistically significant superior to both IMRT techniques regarding decreasing dose to the OARs, e.g. volume of the bowel receiving 15Gy (V15Gy) was reduced for rMFO compared to VMAT (p=0.003) and TOMO (p<0.001).

Conclusion
With all photon and proton techniques investigated, the radiation dose to gastrointestinal OARs remained critical when treating patients with unresectable locally advanced or locally recurrent pancreatic cancer using a dose-escalated SIB approach.

The distorted kagome lattice antiferromagnet Tb₃Ru₄Al₁₂ with a hexagonal structure has the Néel temperature T_N = 22 K. To clarify the 4 f -electronic state and an influence of electric quadrupoles in Tb₃Ru₄Al₁₂, ultrasonic measurements on a single-crystalline sample at zero magnetic field and under fields were carried. A characteristic elastic softening of the transverse modulus C₆₆ originating from a quadrupole interaction was found. The crystal electric field parameters were determined to reproduce C₆₆, magnetic susceptibilities, and magnetization curves. The obtained level scheme is that the ground and first excited states are singlets, despite the existence of both the magnetic transition and the quadrupole interaction, indicating that Tb₃Ru₄Al₁₂ is a curious compound. The positive sign of the quadrupole-quadrupole coupling constant for C₆₆ indicates a ferroquadrupolar-type interaction of the electric quadrupole O_xy or O² . The anisotropic magnetic field dependencies of T_N in the field along [100] and [001] were also clarified.

The global production of 12,000 metric tonnes of high-level radioactive waste (HLW) every year is a big challenge with respect to its safe long-term storage. In the favored multi-barrier system, bentonite is used as a geo-technical barrier in many disposal programs worldwide. The bentonite seals the space between the canister containing the HLW and the surrounding host rock, thereby fulfilling two major tasks: 1) slow down the process of corrosion when water enters the disposal site, and 2) hinder the discharge of radionuclides into the bio-geosphere in case of a leaking canister. Due to their metabolic activity, microorganisms could influence the properties of the bentonite barrier. In order to investigate the metabolic potential of naturally occurring microorganisms, we conducted anaerobic bentonite-slurry experiments containing uncompact bentonite and a synthetic Opalinus Clay pore water solution. Within one-year incubation at 30 and 60 °C, lactate- or H2-stimulated microcosms at 30 °C showed the dominance and activity of strictly anaerobic, sulfate-reducing and spore-forming microorganisms. Consequently, hydrogen sulfide gas was generated in the respective set ups, leading to the formation of fractures and iron-sulfur precipitations. Experiments that incubated at 60 °C, showed the dominance of thermophilic bacteria, independent of the presence of substrates. The respective set ups showed no significant changes in the analyzed bio-geochemical parameters. The obtained results clearly show that indigenous microorganisms evolve in a temperature- and substrate-dependent manner. The formed metabolites can potentially affect the dissolution behavior of minerals and ions within the bentonite as well as the corrosion process of the canister material and require further investigations.

Stirred tanks are widely used equipment in process engineering. CFD simulations of such equipment on industrial scales are feasible within the Euler-Euler / RANS approach. In this approach, phenomena on particle scale are not resolved and, accordingly, suitable closure models are required. The present work applies a set of closure relations that originates from a comprehensive review of existing results. Focus is on the modeling of interfacial forces which include drag, lift, turbulent dispersion, and virtual mass. Specifically, new models for the drag and lift forces are considered based on the best currently available description. To validate the model a comprehensive set of experimental data including solid velocity and volume fraction as well as liquid velocity and turbulence has been assembled. The currently proposed model compares reasonably well with this dataset and shows generally better prediction compared with other model variants that originate from different combinations of force correlations.

Blood coagulation mechanisms forming a blood clot and preventing hemorrhage have been extensively studied in the last decades. Knowing the mechanisms behind becomes very important particularly in the case of blood vessel diseases. Real‐time and accurate diagnostics accompanied by the therapy are particularly needed for example in diseases related to retinal vasculature. In our study, we employ for the first time fluorescence hyperspectral imaging (fHSI) combined with the spectral analysis algorithm concept to assess physical as well as functional information of blood coagulation in real‐time. By laser‐induced local disruption of retinal vessels to mimic blood leaking and subsequent coagulation and a proper fitting algorithm, we were able to reveal and quantify the extent of local blood coagulation through direct identification of the change of oxyhemoglobin concentration within few minutes. We confirmed and illuminated the spatio‐temporal evolution of the essential role of erythrocytes in the coagulation cascade as the suppliers of oxygenated hemoglobin. By additional optical tweezers force manipulation, we showed immediate aggregation of erythrocytes at the coagulation site. The presented fluorescence‐based imaging concept could become a valuable tool in various blood coagulation diagnostics as well as theranostic systems if coupled with the laser therapy.

This international workshop entitled “How to integrate geochemistry at affordable costs into reac-tive transport for large-scale systems” was organized by the Institute of Resource Ecology of the Helmholtz-Zentrum Dresden Rossendorf in Feb-ruary 2020. A mechanistic understanding and building on that an appropriate modelling of geochemical processes is essential for reliably predicting contaminant transport in groundwater systems, but also in many other cases where migration of hazardous substances is expected and consequently has to be assessed and limited. In case of already present contaminations, such modelling may help to quantify the threads and to support the development and application of suitable remediation measures. Typical application areas are nuclear waste disposal, environmental remediation, mining and milling, carbon capture & storage, or geothermal energy production. Experts from these fields were brought together to discuss large-scale reactive transport modelling (RTM) because the scales covered by such pre-dictions may reach up to one million year and dozens of kilometers. Full-fledged incorporation of geochemical processes, e.g. sorption, precipitation, or redox reactions (to name just a few important basic processes) will thus create inacceptable long computing times. As an effective way to integrate geochemistry at affordable costs into RTM different geochemical concepts (e.g. multidimensional look-up tables, surrogate functions, machine learning, utilization of uncertainty and sensitivity analysis etc.) exist and were extensively discussed throughout the workshop. During the 3-day program of the workshop keynote and regular lectures from experts in the field, a poster session, and a radio lab tour had been offered. In total, 40 scientists from 28 re-search institutes and 8 countries participated. The focus of the workshop was: (1) To provide and discuss existing geochemical concepts in reactive transport modelling to describe sorption and related retardation processes of contaminants on a variety of sedi-ments and rocks. (2) To explicitly set focus on large-scale natural systems as experienced, e.g., in nuclear waste disposal, carbon capture & storage, environmental remediation, or geothermal applications. (3) To explore how the discussed approaches can be integrated at affordable costs into cur-rent paradigms in THMC models and long-term safety assessments in general. (4) To promote the exchange of scientific knowledge and practical experience between the workshop participants in an efficient way. Based on the intensive discussions and very posi-tive feedback on the workshop, a continuation is intended to bundle and strengthen the respective research activities and stipulate the international network that started to form during the conference days.

Introduction: Since epithelial growth factor receptor (EGFR) overexpression is linked to a variety of malignancies, it is an attractive target for immune therapy including with chimeric antigen receptor (CAR)-engineered T cells. Unfortunately, CAR T cell therapy harbors the risk of severe, even life-threatening side effects. Adaptor CAR T cell platforms such as the previously described UniCAR system might be able to overcome these problems. In contrast to conventional CARs, UniCAR T cells are per se inert. Their redirection towards target cells occurs only in the presence of a tumor-specific target molecule (TM). TMs are bifunctional molecules being able to recognize a tumor-associated antigen (TAA) and to cross-link the CAR T cell via a peptide epitope recognized by the UniCAR domain.
Methods: Here, we compare anti-EGFR TMs: a nanobody (nb)-based αEGFR TM derived from the camelid αEGFR antibody 7C12 with a murine and humanized single-chain fragment variable (scFv) based on the clinically used antibody Cetuximab®.
Results: In principle, both the nb- and scFv-based TM formats are able to redirect UniCAR T cells to eliminate EGFR-expressing tumor cells in an antigen-specific and TM-dependent manner. However, the scFv-based αEGFR TM was significantly superior to the nb-based TM especially with respect to lysis of tumor cells.
Discussion: Improved efficiency of the scFv-based TM allowed the redirection of UniCAR T cells towards tumor cells expressing high as well as low EGFR levels in comparison to nb-based αEGFR TMs.

We study the optical properties of thin flakes of InSe encapsulated in hexagonal boron nitride. More specifically, we investigate the photoluminescence (PL) emission and its dependence on sample thickness and temperature. Through the analysis of the PL line shape, we discuss the relative weights of the exciton and electron-hole contributions. Thereafter we investigate the PL dynamics. Two contributions are distinguishable at low temperature: direct band-gap electron-hole and defect-assisted recombination. The two recombination processes have lifetimes ofτ1∼8ns andτ2∼100 ns, respectively. The relative weights of the direct band-gap and defect-assisted contributions show a strong layer dependence due to the direct-to-indirect band-gap crossover. Electron-hole PL lifetime is limited by population transfer to lower-energy states and no dependence on the number of layers was observed. The lifetime of the defect-assisted recombination gets longer for thinner samples. Finally, we show that the PL lifetime decreases at high temperatures as a consequence of more efficient nonradiative recombinations.

Pion induced reactions provide unique opportunities for an unambiguous description of baryonic resonances and their coupling channels by means of a partial wave analysis. Using the secondary pion beam at SIS18, the two pion production in the second resonance region has been investigated to unravel the role of the N(1520)32− resonance in the intermediate ρ production. Results on exclusive channels with one pion (π−p) and two pions (π+π−n, π0π−p) in the final state measured in the π−−p reaction at four different pion beam momenta (0.650, 0.685, 0.733, and 0.786 GeV/c) are presented. The excitation function of the different partial waves and Δπ, Nσ and Nρ isobar configurations is obtained, using the Bonn-Gatchina partial wave analysis. The N(1520)32− resonance is found to dominate the Nρ final state with the branching ratio BR=12.2±1.9%.

In this paper, voxel-based finite element modelling based on spatial geometry and density data is applied to simulate the detailed stress and strain distribution in a large wooden element. As example, a moulded wooden tube with a length of 3 m and a diameter of 0.3 m is examined. Gamma-ray computed tomography is used to obtain the spatial distribution of elastic properties based on the correlation with density. Correlation functions between density and elastic material properties are experimentally determined and serve as link for defining the non-uniform distribution of the material properties in the finite element model. Moreover, also the geometry is obtained by the computed tomography. Due to the consideration of both the geometric imperfections and the spatial variation of the material properties, a detailed analysis of the stress and strain distribution of the wood element is performed. Additionally, a non-destructive axial compression test is performed on the wooden tube to analyse the load-bearing behaviour. By means of digital image correlation, the deformation of the surface is obtained, which also serves for validation of the finite element model.

Undoped ZnO films grown on sapphire by pulsed laser deposition are magnetic at room temperature. A comprehensive study involving x-ray diffraction, positron annihilation spectroscopy, and superconducting quantum Interference device-vibrating sample magnetometer is performed to study the origin of the observed magnetization. Correlations between the saturation magnetization, VZn-2VO concentration and surface to volume ratio of the grain found experimentally show that the magnetization is associated with the vacancy cluster and probably VZn-2VO residing on the grain surface.

Adapter chimeric antigen receptor (CAR) approaches have emerged has promising strategies to increase clinical safety of CAR T-cell therapy. In the UniCAR system, the safety switch is controlled via a target module (TM) which is characterized by a small-size and short half-life. The rapid clearance of these TMs from the blood allows a quick steering and self-limiting safety switch of UniCAR T-cells by TM dosing. This is mainly important during onset of therapy when tumor burden and the risk for severe side effects are high. For long-term UniCAR therapy, the continuous infusion of TMs may not be an optimal setting for the patients. Thus, in later stages of treatment, single infusions of TMs with an increased half-life might play an important role in long-term surveillance and eradication of residual tumor cells. Given this, we aimed to develop and characterize a novel TM with extended half-life targeting the tumor-associated carbohydrate sialyl-Tn (STn).

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies. Due to the lack of specific symptoms and screening methods, this disease is usually diagnosed only at an advanced and metastatic stage. The gold-standard treatment for OC patients consists of debulking surgery followed by taxane combined with platinum-based chemotherapy. Most patients show complete clinical remission after first-line therapy, but the majority of them ultimately relapse, developing radio- and chemoresistant tumors. It is now proposed that the cause of recurrence and reduced therapy efficacy is the presence of small populations of cancer stem cells (CSCs). These cells are usually resistant against conventional cancer therapies and for this reason, effective targeted therapies for the complete eradication of CSCs are urgently needed. In this review article, we highlight the mechanisms of CSC therapy resistance, epithelial-to-mesenchymal transition, stemness, and novel therapeutic strategies for ovarian CSCs.

Designs for nuclear power plants increasingly include passive features. A major focus of the design of modern fast reactors is on inherent and passive safety. Inherent and passive safety features are especially important when active systems such as emergency shutdown systems for reactor shutdown are not functioning properly. This publication discusses the past experience in the development of such systems along with the research that is ongoing. It is a comprehensive publication which provides information on the basic design principles for passive shutdown systems and the related operational experience gathered so far, and also reviews the innovative concepts under development and the needs for research and development and qualification tests.

Carbon-based nanomaterials have attracted a lot of interest lately due to their highly promising applications. Here, we report on the modifications of single-walled carbon nanotubes (SWCNTs) induced by swift (highly energetic) heavy ions. Using scanning force microscopy and Raman spec- troscopy, we observed a dramatic change in the structure of the irradiated SWCNTs, accompanied by an increase of the adhesion force as a function of ion fluence and electronic energy loss. With increasing ion fluence the SWCNTs exhibit a partial transformation from metallic to more semicon- ducting. Moreover, at high fluence they break into segments of 10–20 nm length.

Advancement of optoelectronic and high-power devices is tied to the development of wide band gap materials with excellent transport properties. However, bipolar doping (n-type and p-type doping) and realizing high carrier density while maintaining good mobility have been big challenges in wide band gap materials. Here P-type and n-type conductivity was introduced in β-Ga₂O₃, an ultra-wide band gap oxide, by controlling hydrogen incorporation in the lattice without further doping. Hydrogen induced a 9-order of magnitude increase of n-type conductivity with donor ionization energy of 20 meV and resistivity of 10⁻⁴ Ωcm. The conductivity was switched to p-type with acceptor ionization energy of 42 meV by altering hydrogen incorporation in the lattice. Density functional theory calculations were used to examine hydrogen location in the Ga₂O₃ lattice and identified a new donor type as the source of this remarkable n-type conductivity. Positron annihilation spectroscopy measurements confirm this finding and the interpretation of the experimental results. This work illustrates a new approach that allows a tunable and reversible way of modifying the conductivity of semiconductors and it is expected to have profound implications on semiconductor field. At the same time, it demonstrates for the first time p-type and remarkable n-type conductivity in Ga₂O₃ which should usher in the development of Ga₂O₃ devices and advance optoelectronics and high-power devices.

For the simulation of bubbly flows, knowledge of the lift force as an interaction between gas bubbles and a surrounding shear field is of great importance. The sign of the lift coefficient Cᴸ changes with increasing bubble size, i.e. with more pronounced bubble deformation. Beside this, impurities in terms of surface-active components are well-known to change the complete hydrodynamic behavior of a bubble even if the amount is very small. In the present work, the lift coefficient of single ellipsoidal bubbles is determined with a recently developed method, which is suitable to overcome difficulties connected to low viscous systems. In order to investigate the influence of impurities on the lift force, we conducted experiments with single bubbles of different sizes in purified, deionized and tap water. Overall, the determined lift coefficients show no difference between deionized and tap water but reveal differences to results obtained with purified water. As no significant differences in shape and velocity are found between the different water qualities, it remains unclear how the impurities cause the observed differences. For the deionized and tap water results that are more relevant in practice, a new correlation is proposed to account for the observed differences in comparison to data from the literature. It can be used to calculate Cᴸ of ellipsoidal bubbles in the investigated size range.

Pridopidine is an investigational drug in late stage development for the treatment of Huntington disease and originally postulated to act as dopamine stabilizer by modulating dopamine-dependent motor behavior. However, preclinical studies show pridopidine has highest affinity to sigma-1 receptors. Importantly, mediated by sigma-1 receptors, pridopidine has neuroprotective properties and enhances neuronal plasticity. The aim of our study was to determine the in-vivo the target engagement (receptor occupancy) of pridopidine at clinically relevant doses in healthy volunteers and Huntington disease patients. We used sigma-1 receptor-specific (S)-(-)-[18F]Fluspidine and dopamine D2/D3 receptor-specific [18F]Fallypride PET imaging to quantify the sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine. Eleven male healthy volunteers (pridopidine 0.5 to 90 mg in six dose groups) and three male Huntington disease patients (pridopidine 90 mg) were studied twice before and 2h following single oral doses of pridopidine using S-(-)-[18F]Fluspidine PET (300 MBq, 0-90min p.i.). Distribution volume VT was quantified using kinetic modeling (One-tissue compartment model; metabolite correction). Four male healthy volunteers were studied twice using [18F]Fallpride PET (200 MBq, 0-210min p.i.) before and 2h after a single oral dose of pridopidine (90 mg). Binding potential BPND was assessed by the simplified reference model. Volume-of-interest analyses were performed. For each subject/tracer, the receptor occupancy was calculated by the Lassen plot analysis. In healthy volunteers, there was high sigma-1 receptor occupancy (87 to 91%) across all brain regions at doses ranging from 22.5 to 90 mg. The sigma-1 receptor occupancy was 43% at 1 mg pridopidine. In Huntington disease patients, very similar to healthy volunteers, at 90 mg pridopidine, there was high sigma-1 receptor occupancy (87±7%, n.s.). In contrast, in healthy volunteers, there was only negligible dopamine D2/D3 receptor occupancy (3±2%) at 90 mg pridopidine. We established a sigmoid-shaped dose/sigma-1 receptor occupancy relation (Hill equation) with Hill coefficient larger than 1 in healthy volunteers, suggesting a positive cooperative binding nature of the sigma-1 receptor. Using PET, we report for the first time in the living human brain that after a single dose of 90 mg, pridopidine acts as a selective sigma-1 receptor ligand showing near to complete sigma-1 receptor occupancy (~90%) but only minimal (~3%) dopamine D2/D3 receptor occupancy. Our findings provide significant clarification about pridopidine’s mechanism of action and support further use of the 45 mg bidaily dose to achieve full and selective targeting of the sigma-1 receptor in future clinical trials in Huntington disease and amyotrophic lateral sclerosis.

Sigma receptors are classified into sigma1 and sigma2 subtypes. Sigma1 receptors are widely distributed in the central nervous system (CNS) and in peripheral tissues. Sigma1 receptors play a role in a variety of human CNS diseases, including mood disorders, stroke, neurodegenerative disease, and drug addiction. Therefore, there is a great deal of interest in imaging of sigma1 receptors in the living human brain. In contrast, sigma2 receptors have also been the focus of tumor imaging studies. A number of radioligands have been developed for imaging of sigma1 receptors in the human brain, and a few, including [11C]SA4503 and (-)-S-[18F]fluspidine, have been used in clinical studies. Sigma1 receptors are distributed throughout the grey matter of the human brain. A widespread decrease in [11C]SA4503 binding in patients with Alzheimer’s disease and a significant decrease in binding on the more affected side of the anterior putamen in patients with Parkinson’s disease have been reported. Receptor occupancy studies with [11C]SA4503-PET have shown that some antidepressants and antipsychotics have an affinity for sigma1 receptors in the human brain in addition to their main targets. Recently, it has been reported that the binding of (-)-S-[18F]fluspidine is increased in patients with untreated major depressive disorder (MDD).

Innovations in radiochemistry and pharmacology are opening new vistas for studies of nicotinergic acetylcholine receptors (nAChRs) in human brain by positron emission tomography (PET) and by single-photon emission computed tomography (SPECT). In parallel, instrumentation optimized for molecular imaging in rodents facilitates preclinical studies in models of human diseases with perturbed nAChR signalling, notably Alzheimer’s disease and other neurodegenerative conditions, schizophrenia and other neuropsychiatric disorders, substance abuse, and traumatic brain injury. The nAChRs are ligand-gated ion channels composed of five subunits forming a central pore for cation flux. The most abundant nAChRs in the central nervous system are heteropentamers (designated α4β2), followed by the α7 homopentamer. We present a systematic review of published findings with the various nAChR ligands using imaging techniques in vivo, emphasizing preclinical models and human studies.. Molecular PET imaging of the α4β2 nAChR subtype with the antagonist 2-[18F]fluoro-A-85380 is hampered by the long acquisition times. Newer agents such as (-)-[18F]flubatine, [18F]XTRA or [18F]nifene permit quantitation of α4β2 receptors with PET recordings lasting 90 minutes or less, and without the toxicity risk of earlier epibatidine derivatives. The early PET studies of α7 nAChRs suffered from low pharmacological specificity, further hampered by low natural abundance of the receptor. However, several good α7 nAChR ligands such as [18F]ASEM and [18F]DBT10 have emerged in the past few years. There are still no ligands selective for α6-containing nAChRs, despite their importance for nicotine-induced dopamine release in striatum. Selective α3β4 nAChR radioligands are under development, but remain untested in clinical studies of depression and addiction. Several nAChR ligands find use for pharmacological occupancy studies, and competition from endogenous acetylcholine reduces α4β2 binding site availability, a property that enables monitoring by PET of acetylcholine release in living brain.

The photocatalytic activity of ZnO films, grown by atomic layer deposition on sapphire, was investigated for different amounts of residual hydrogen incorporated unintentionally into the matrix during the crystal growth. A close correlation was found between the level of incorporated hydrogen ; the rate of photocatalytic degradation of methylene blue on ZnO films. The rate of degradation is consistent with predominantly zero-order reaction kinetics. An enhanced photocatalytic activity, observed for films of predominantly (001)-oriented grains ; low concentration of residual hydrogen, is explained by the reduced number of hydrogen-related defects responsible for recombination of charge carriers in combination with the preferential adsorption of water on polar (001) surfaces of ZnO grains.

Diffusive transport and sorption processes of uranium in the Swiss Opalinus Clay were investigated as a function of partial pressure of carbon dioxide pCO2, varying mineralogy in the facies and associated changes in porewater composition. Simulations were conducted in one-dimensional diffusion models on the 100m-scale for a time of one million years using a bottom-up approach based on mechanistic surface complexation models as well as cation exchange to quantify sorption. Speciation calculations have shown, uranium is mainly present as U(VI) and must therefore be considered as mobile for in-situ conditions. Uranium migrated up to 26m in both, the sandy and the carbonate-rich facies, whereas in the shaly facies 16m was the maximum. The main species was the anionic complex CaUO2(CO3)3-2 and hence the effect of anion exclusion was taken into account. This further reduced the migration distances by 30%. The concentrations of calcium and Carbonates reflected by the set pCO2 determine speciation and activity of uranium due to the formation of ternary uranyl complexes and consequently the sorption behaviour. Our simulation results showed, that sorption processes are controlled in descending priority by the carbonate and calcium concentrations, pH, pe and the clay mineral content. Therefore, the variation in porewater composition resulting from the heterogeneity of the facies in the Opalinus Clay formation needs to be considered in the assessment of uranium migration in the far field of a potential repository.

Density Functional Theory and Boltzmann transport equations are used to investigate electronic band structure and thermoelectric (TE) properties of different two-dimensional (2D) materials containing Mo, S, Nb, Se, and Te. In MoS2-based monolayers (MLs) the substitution of S atoms by Te atoms up to the concentrations of 12.5 at % leads to a more significant change of the band structure than in the corresponding case with Se atoms. In particular, the bandgap is reduced. At the high concentration of Se or Te the electronic structure becomes more similar to that of the SeMoS or TeMoS Janus layers, and the MoSe2 or MoTe2 MLs. It is found that local and random introduction of substitutional Se or Te atoms yields not very different results. The substitution of Mo by Nb, at the concentration of 2.1 at% leads to hole levels. The thermoelectric properties of the considered 2D materials are quantified by the Seebeck coefficient and thermoelectric figure of merit. The two characteristics are determined for different levels of p- or n-doping of the MLs and for different temperatures. Compared to the pristine MoS2 ML, Te substitutional atoms cause more changes of the thermoelectric properties than Se atoms. However, MLs with Se substitutional atoms show a high thermoelectric figure of merit in a broader range of possible p- or n-doping levels. In most cases, the maximum thermoelectric figure of merit is about one, both in p- and n-type material, and for temperatures between 300 and 1200 K. This is not only found for MoS2-based MLs with substitutional atoms but also for the Janus layers and for MoSe2 or MoTe2 MLs. Interestingly, for MLs with one Nb as well as two or four Te substitutional atoms highest values of the TE figure of merit of 1.2 and 1.40, respectively, are obtained at a temperature of 1200 K.

Glioblastoma multiforme (GBM) is the most devastating primary brain tumour characterised by infiltrative growth and resistance to therapies. According to recent research, the sigma-1 receptor (sigmaR1), an endoplasmic reticulum chaperone protein, is involved in signaling pathways assumed to control the proliferation of cancer cells and thus could serve as candidate for molecular characterisation of GBM. To test this hypothesis, we used the clinically applied sigmaR1-ligand (S)-(−)-[18F]fluspidine in imaging studies in an orthotopic mouse model of GBM (U87-MG) as well as in human GBM tissue. A tumour-specific overexpression of sigmaR1 in the U87-MG model, revealed in vitro by autoradiography, was confirmed by dynamic PET. The binding parameters demonstrated target-selective binding according to identical KD values in the tumour area and the contralateral side but a higher density of sigmaR1 in the tumour. Different kinetic profiles were observed in both areas, with a slower washout in the tumour tissue compared to the contralateral side. The translational relevance of sigmaR1 imaging in oncology is reflected by the autoradiographic detection of tumour-specific expression of sigmaR1 in samples obtained from patients with glioblastoma. Thus, the herein presented data support further research on sigmaR1 in neuro-oncology.

Production of defects under electron irradiation in a transmission electron microscope (TEM) due to inelastic effects has been reported for various materials, but the microscopic mechanism of damage development in periodic solids through this channel is not fully understood. We employ non-adiabatic Ehrenfest, along with constrained density functional theory molecular dynamics, and simulate defect production in two-dimensional MoS2 under electron beam. We show that when excitations are present in the electronic system, formation of vacancies through ballistic energy transfer is possible at electron energies which are much lower than the knock-on threshold for the ground state. We further carry out TEM experiments on single layers of MoS2 at electron voltages in the range of 20−80 kV and demonstrate that indeed there is an additional channel for defect production. The mechanism involving a combination of the knock-on damage and electronic excitations we propose is relevant to other bulk and nanostructured semiconducting materials.

Dating of ancient relict permafrost is essential for understanding permafrost stability and interpreting past climate and environmental conditions over Pleistocene timescales but presents substantial challenges to geochronology. Here, we date ancient permafrost from the world’s largest thaw slump at Batagay, East Siberia, which potentially provides one of the longest records of Pleistocene environments in western Beringia (East Siberia). We apply four dating methods to the permafrost deposits: (1) optically-stimulated luminescence (OSL) dating of quartz and (2) post-infrared infrared-stimulated luminescence (pIRIR) dating of K-feldspar from sand, (3) ³⁶Cl/Cl dating of ice wedges, and (4) radiocarbon dating of organic material from within wedge ice and its host sediments. Individually, each of the four independent chronometers produces ages consistent with their relative stratigraphic position. Comparability of ages between dating methods is also observed. However, at Batagay quartz OSL appears to date MIS 2/MIS 3 deposits more reliably than K-feldspar pIRIR250, whereas the latter is more consistent with independent chronological controls for older deposits. Collectively, the ages indicate that the lower ice complex developed approximately 650 ka ago during Marine Isotope Stage (MIS) 16, and the upper ice complex approximately 60 to 30 ka ago during late MIS 4 to MIS 3. Sand units below and above the upper ice complex are dated to MIS 6 and 3–2, respectively. Overall, the lower ice complex represents the oldest dated relict permafrost in western Beringia and indicates that thick and cold permafrost at a depth of ~50 m below the ground surface has survived multiple warm interglacials, including the MIS 11c super-interglacial.

Small angle x-ray scattering (SAXS) is a well established technique to detect nanometer scale structure in matter. In typical setup, this diagnostics has an detector directly opened towards the scattering target. However, in a harsh environment of high intensity laser interaction, many high energetic particles and strong radiation are emerging from the laser target interaction. Such setup would therefore suffer a significant increase of noise due to this background which could eventually disable this measurement. In this paper, we present a novel tool consisting of mosaic graphite crystal which works as a mirror for the SAXS signal and allows to hide the detector behind proper shielding. This paper studies the performance of such mirror both by experiment at the European XFEL laboratory and by simulations.

Modelling flow and mass transfer of thermal separation equipment constitutes one of the most challenging tasks in fluids process engineering. The difficulty of this task comes from the multiscale multiphase flow phenomena in rather complex geometries. Both analysis of flow and mass transfer on different scales as well as validation of models and simulation results require advanced experimental and measurement techniques. As a follow-up to intensive discussions during the 2019 Tutzing Symposium “Separation Units 4.0” we present in this article a wide set of available modern experimental technologies, which are used in different research and industry laboratories.

We have investigated the elastic response of a transverse Ising magnet CoNb₂O₆ by means of ultrasound velocity measurement. A huge elastic anomaly in the C₆₆ mode is observed near a quantum critical Point when sweeping a magnetic field perpendicular to the Ising axis. This anomaly appears to become critical only for the Faraday configuration (field parallel to the sound propagation direction) but is much less pronounced for the Voigt geometry (field perpendicular to the sound propagation direction). We propose that the relativistic spin-orbit interaction plays a crucial role in the quantum critical regime resulting in the elastic anomaly, which is enhanced by quantum fluctuations.

Single photon emission computed tomography (SPECT) is the state-of-the-art imaging modality in nuclear medicine despite the fact that only a few new SPECT tracers have become available in the past 20 years.
Critical for the future success of SPECT is the design of new and specific tracers for the detection, localization, and staging of a disease and for monitoring therapy. The utility of SPECT imaging to address oncologic questions is dependent on radiotracers that ideally exhibit excellent tissue penetration, high affinity to the tumor-associated target structure, specific uptake and retention in the malignant lesions, and rapid clearance from non-targeted tissues and organs. In general, a target-specific SPECT radiopharmaceutical can be divided into two main parts: a targeting biomolecule (e.g., peptide, antibody fragment) and a γ-radiation-emitting radionuclide (e.g., 99mTc, 123I). If radiometals are used as the radiation source, a bifunctional chelator is needed to link the radioisotope to the targeting entity. In a rational SPECT tracer design, these single components have to be critically evaluated in order to achieve a balance among the demands for adequate target binding, and a rapid clearance of the radiotracer. The focus of this chapter is to depict recent developments of tumor-targeted SPECT radiotracers for imaging of cancer diseases.
Possibilities for optimization of tracer design and potential causes for design failure are discussed and highlighted with selected examples.

Eine Übersetzung des Artikels "How much ‘normal’ risk does Covid represent?" von David Spiegelhalter, der am 21. März 2020 auf https://medium.com/wintoncentre/how-much-normal-risk-does-covid-represent-4539118e1196 erschien. Sir David John Spiegelhalter ist britischer Statistiker und Winton Professor für das öffentliche Verständnis von Risiko an der the Universität Cambridge. Er ist Fellow am Churchill College, Cambridge.

We probe the electron transport properties in the shell of GaAs/In0.2Ga0.8As core/shell nanowires at high electric fields using optical pump/THz probe spectroscopy with broadband THz pulses and peak electric fields up to 0.6 MV/cm. The plasmon resonance of the photoexcited charge carriers exhibits a systematic redshift and a suppression of its spectral weight for THz driving fields exceeding 0.4 MV/cm. This behavior is attributed to the intervalley electron scattering that results in the doubling of the average electron effective mass. Correspondingly, the electron mobility at the highest fields drops to about half of the original value. We demonstrate that the increase of the effective mass is nonuniform along the nanowires and takes place mainly in their middle part, leading to a spatially inhomogeneous carrier response. Our results quantify the nonlinear transport regime in GaAs-based nanowires and show their high potential for development of nanodevices operating at THz frequencies.

Im Rahmen des Forschungsvorhabens NeoBio wird die Problematik des optimalen Mischprozesses in Biogasanlagen aufgegriffen, um praktikable Lösungsansätze für die optimale Auslegung der Mischprozesse zu finden.
In diesem Zusammenhang steht die Bestimmung instationärer Geschwindigkeitsfelder in Biogasanlagen über in der Fermentersuspension mitschwimmende Funksensoren im Fokus, welche ihre Position über Laufzeitmessungen detektieren. In Kombination mit Inertialsensoren können Bewegungen auch unterhalb des Flüssigkeitsspiegels be-stimmt werden. Die ermittelten Geschwindigkeitsdaten werden für die Auslegung von Rührwerksgeometrien, -korrespondenzen und die Validierung von Modellversuchen genutzt.
In modellmaßstäblichen Untersuchungen an einem Fermenter mit Paddelrührwerk (Maßstab 1:40) konnte bereits gezeigt werden, welchen Einfluss alternative Rührwerk-spositionen auf den Mischprozess haben. Eine Verringerung von Totzonen sowie die Reduzierung der Rühr- bzw. Mischzeit um bis zu 80 % sind erreichbar. Dabei sind die notwendigen Anpassungen überschaubar und somit in der Praxis leicht zu realisieren.
Diese Erkenntnisse werden bereits in aktuellen Anlagen umgesetzt und sind ein Bau-stein bei der Wirkungsgradsteigerung. Um das Optimierungspotential sicher bewerten zu können, müssen die Ergebnisse noch im Originalmaßstab validiert werden. In die-sem Zusammenhang soll die beschriebene Messtechnik eingesetzt werden

This work provides evidence that anisotropic drainage in sheared foam is at the origin of convective instability (CI) in very long foam channels. CI occurs in foam under forced drainage when a critical liquid fraction is exceeded. Liquid spontaneously accumulates at one side of the channel. The weight imbalance induces convection rolls in the foam. Experiments in a very long vertical foam channel demonstrate that the critical liquid fraction is smaller than in previous findings by a factor of five. The critical liquid fraction depends on both the channel length and the inhomogeneity of the liquid feed. Well below the critical liquid fraction, a static, elastic shear deformation of the foam structure occurs. At the critical liquid fraction, initial steady convection rolls are located at the lower region of the channel and expand as the liquid fraction further increases. Combining the drainage equation with both the elastic response of the foam and a model for anisotropic drainage, a critical liquid fraction for the growth of an initial liquid imbalance is derived analytically, which corresponds very well to the experimental findings. Numerical simulations of the drainage equation and the elastic response of the foam reproduce these experimental and analytical findings.

We report the design, synthesis, and evaluation of a series of 1-oxa-8-azaspiro[4.5]decane and 1,5-dioxa-9-azaspiro[5.5]undecane derivatives as selective σ1 receptor ligands. All seven ligands exhibited nanomolar affinity for σ1 receptors (Ki(σ1) = 0.61 – 12.0 nM) and moderate selectivity toward σ2 receptors (Ki(σ2)/ Ki(σ1) = 2 – 44). Compound 8 with the best selectivity among these ligands was selected for radiolabeling and further evaluation. Radioligand [18F]8 was prepared via nucleophilic 18F-substitution of the corresponding tosylate precursor, with an overall isolated radiochemical yield of 12-35%, a radiochemical purity of >99%, and molar activity of 94 – 121 GBq/μmol. Biodistribution studies of [18F]8 in mice demonstrated high initial brain uptake at 2 min. Pretreatment with SA4503 resulted in significantly reduced brain-to-blood ratio (70% - 75% at 30 min). Ex vivo autoradiography in ICR mice demonstrated high accumulation of the radiotracer in σ1 receptor-rich brain areas. These findings suggest that [18F]8 could be a lead compound for further structural modification to develop potential brain imaging agent for σ1 receptors.

Glioblastoma is an aggressive brain tumour with a patient median survival of approximately 14 months. The development of innovative treatment strategies to increase the life span and quality of life of patients is hence essential. This requires the use of appropriate glioblastoma models for preclinical testing, which faithfully reflect human cancers. The aim of this study was to establish glioblastoma patient-derived xenografts (PDXs) by heterotopic transplantation of tumour pieces in the axillae of NMRI nude mice. Ten out of 22 patients’ samples gave rise to tumours in mice. Their human origin was confirmed by microsatellite analyses, though minor changes were observed. The glioblastoma nature of the PDXs was corroborated by pathological evaluation. Latency times spanned from 48.5 to 370.5 days in the first generation. Growth curve analyses revealed an increase in the growth rate with increasing passages. The methylation status of the MGMT promoter in the primary material was maintained in the PDXs. However, a trend towards a more methylated pattern could be found. A correlation was observed between the take in mice and the proportion of Sox2+ cells (r = 0.49, p = 0.016) and nestin+ cells (r = 0.55, p = 0.007). Our results show that many PDXs maintain key features of the patients’ samples they derive from. They could thus be used as preclinical models to test new therapies and biomarkers.

As an emerging class of porous materials, noble metal aerogels (NMAs) have drawn tremendous attention and displayed unprecedented potential in diverse fields. However, the development of NMAs is impeded by the fabrication methods because of their time- and cost-consuming procedures, limited generality, and elusive understanding of the formation mechanisms. Here, by revealing the self-healing behavior of noble metal gels and applying it in the gelation process at a disturbing environment, an unconventional and conceptually new strategy, i.e., a disturbance-promoted gelation method, is developed by introducing an external force field. It overcomes the diffusion limitation in the gelation process, thus producing monolithic gels within 1–10 min at room temperature, 2–4 orders of magnitude faster than for most reported methods. Moreover, versatile NMAs are acquired by using this method, and their superior (photo-)electrocatalytic properties are demonstrated for the first time in light of combined catalytic and optic properties.

In this paper, a novel concept for multi-plane ultrafast electron beam X-ray computed tomography (UFXCT) is presented. The concept is based on multi-plane electron beam scanning on a semi-transparent X-ray target and cuboid-shape scintillation detectors for radiation detection over an extended axial range. The optical part of the scintillation detector acts as both a scintillator and a light guide. With that, we achieve a low detector complexity and number of detector elements, overall power consumption and detector costs. We investigated the performance of this new concept with a prototypical detector module made of cerium doped lutetium yttrium orthosilicate (LYSO:Ce) as scintillator and an avalanche photodiode (APD) array. Thereby, we assessed two design variants: a monolithic LYSO bar detector and a sandwich detector made of multiple LYSO crystals and glass light-guides.

The chemical properties of actinide materials are often predefined and described based on the data available for isostructural species. This is the case for potassium plutonyl (PuVI) carbonate, K4PuVIO2(CO3)3(cr), a complex relevant for nuclear technology and the environment, of which the crystallographic and thermodynamic properties of which are still lacking. We report here the synthesis and characterization of PuVI achieved by single-crystal X-ray diffraction analysis and high-energy-resolution fluorescence-detected X-ray absorption near-edge structure at the Pu M4-edge coupled with electronic structure calculations. The crystallographic properties of PuVI are compared with isostructural uranium (U) and neptunium (Np) compounds. Actinyl (AnVI) axial bond lengths, [O-AnVI-O]2+, are correlated between solid, K4AnVIO2(CO3)3(cr), and aqueous, [AnVIO2(CO3)3]4-(aq) species for the UVI-NpVI-PuVI series. The spectroscopic data are compared to KPuVO2CO3(cr) and PuIVO2(cr) to tackle the trend in the electronic structure of PuVI regarding the oxidation state changes and local structural modifications around the Pu atom.

Lithium-silicon compounds are used as active material in negative electrodes of Li-ion batteries. The knowledge of Li diffusion in these materials is of importance for an optimization of charging/discharging rates and achievable maximum specific capacity as well as for an understanding of the basic lithiation mechanism. We carried out Li tracer self-diffusion experiments on ion-beam sputter-deposited LixSi(O) thin films for x ~ 0.25 and x ~ 4.5 using LixSi/6LixSi hetero-structures in combination with secondary ion mass spectrometry in line scan like mode. Measurements with elastic recoil detection analysis revealed the presence of a considerable amount of oxygen in the films. The diffusivities follow the Arrhenius law in the temperature range between 300 and 500 °C with an activation energy of 0.8 – 0.9 eV. The film containing a higher amount of Li shows faster diffusion by one order of magnitude. The Li diffusivities in the investigated Li-rich materials are several orders of magnitude higher than in Li-poor LixSi films (x = 0.02 to 0.06) as given in literature because of a lower activation energy. This indicates the presence of a direct interstitial-like mechanism. Oxygen present in samples with the same Li concentration of x = 0.06 also enhances diffusion but does not lead to a reduction in the activation energy.

Organosilicate-glass films with a varying ratio of terminal methyl and bridging ethylene groups are synthesized using BTMSE/MTMS mixtures and sol-gel technology. The films have been characterized by Fourier Transform Infrared spectroscopy, Ellipsometric Porosimetry and Positron Annihilation Spectroscopy. The hard bake at 400 ºC generates the final pore structure, which depends on the curing environment. It is shown that ethylene bridge is destructed during the hard bake in air via formation of peroxide radicals that form ΞSiOH during the further transformation. Continuous hard bake leads to condensation of silanol groups and form a structure similar to the ordinary silica.
The pore size of highly porous materials (>30%) is larger in air cured films. Destruction of the ethylene bridge makes the films matrix soft and micropores collapse during the template evaporation due to the capillary forces. It leads to the film shrinkage, increases the size of internal voids. The air cured samples showed better mechanical properties than N 2 cured ones although in the last case ethylene bridging groups were preserved. The reason is that the collapse of micropores increases internal density and creates more favorable condition for condensation of silanol groups.

Cyclic nucleotide phosphodiesterase 2A (PDE2A) is highly expressed in distinct areas of the brain associated with neurodegenerative and neuropsychiatric diseases like Alzheimer's disease, dementia, and schizophrenia. Specific PDE2A radioligands for the imaging of PDE2A via positron emission tomography (PET) would be helpful for the research related to the disease-related changes in the expression of this enzyme in the brain. Therefore, this thesis aims to develop a specific PDE2A radioligand for the imaging of PDE2A in the brain via PET. A series of novel fluorinated PDE2A inhibitors on the basis of a benzoimidazotriazine (BIT) scaffold was prepared by a multistep synthesis route, and their inhibitory potency towards PDE2A and selectivity over other PDEs were evaluated. Based on the in vitro inhibitory activity evaluation, one derivative, 1-(2-chloro-5-methoxy phenyl)-8-(2-fluoropyridin-4-yl)-3-methylbenzo[e]imidazo[5,1-c][1,2,4]triazine turned out to be the prospective compound. Additional in vitro studies of this ligand using mouse liver microsomes (MLM) revealed this ligand has a promising microsomal stability for 18F-labeling.This novel radioligand was prepared by nucleophilic aromatic substitution of the corresponding nitro precursor and evaluated for the potential application for imaging of PDE2A. In vitro autoradiography on pig brain cryosections demonstrated a heterogeneous spatial distribution of this radiotracer corresponding to PDE2A regions. The investigation of the in vivo metabolism of this radiotracer in mice revealed sufficient metabolic stability. PET studies in mice exhibited a moderate brain uptake of the radiotracer. Further, in vivo blocking studies showed a non-target specific binding of the radiotracer. Therefore, further structural modifications are required to improve target selectivity.

Bone defects of critical size after compound fractures, infections, or tumor resections are a challenge in treatment. Particularly, this applies to bone defects in patients with impaired bone healing due to frequently occurring metabolic diseases (above all diabetes mellitus and osteoporosis), chronic inflammation, and cancer. Adjuvant therapeutic agents such as recombinant growth factors, lipid mediators, antibiotics, antiphlogistics, and proangiogenics as well as other promising anti-resorptive and anabolic molecules contribute to improving bone healing in these disorders, especially when they are released in a targeted and controlled manner during crucial bone healing phases. In this regard, the development of smart biocompatible and biostable polymers such as implant coatings, scaffolds, or particle-based materials for drug release is crucial. Innovative chemical, physico- and biochemical approaches for controlled tailor-made degradation or the stimulus-responsive release of substances from these materials, and more, are advantageous. In this review, we discuss current developments, progress, but also pitfalls and setbacks of such approaches in supporting or controlling bone healing. The focus is on the critical evaluation of recent preclinical studies investigating different carrier systems, dual- or co-delivery systems as well as triggered- or targeted delivery systems for release of a panoply of drugs.

Magnetite nanoparticles are a promising cost-effective material for the remediation of polluted wastewaters. Due to their magnetic properties and their high adsorption and reduction potential, they are particularly suitable for the decontamination of oxyanionforming contaminants, including the highly mobile selenium oxyanions selenite and selenate. However, little is known how in field applications the remediation efficiency of magnetite nanoparticles is affected by partial oxidation and the formation of magnetite/maghemite phases. Here we characterize the retention mechanisms and capacity of partially oxidized nanoparticulate magnetite for selenite and selenate in an oxic system at different pH conditions and ionic strengths. Data from adsorption experiments showed that retention of selenate is extremely limited except for acidic conditions and strongly influenced by competing chloride anions, indicating outersphere adsorption. By contrast, although selenite adsorption capacity of oxidized magnetite is also adversely affected by increasing pH, considerable selenite quantities are retained even at alkaline conditions. Using spectroscopic analyses (XPS, XAFS), both mononuclear edge-sharing ( 2 E) and binuclear corner-sharing ( 2 C) innersphere selenite surface complexes were detected, while reduction to Se(0) or Se(-II) species could be excluded. Under favourable adsorption conditions, up to pH ~8, the affinity of selenite to form 2 C surface complexes is higher, whereas at alkaline pH values and less favourable adsorption conditions 2 E complexes become more dominant. Our results demonstrate that magnetite can be used as a suitable reactant for the immobilization of selenite in remedial applications, even under (sub)oxic conditions and without the involvement of reduction processes.

An in-depth analysis of Zn/Al doped nickel ferrite thin films grown by reactive magnetron sputtering was conducted to gain insight into the magnetic properties interesting for applications in spintronics. The material is insulating, ferromagnetic at room temperature and has a low magnetic damping with additional strong magnetoelastic coupling. The sample system is analyzed with regard to crystal structure, chemical composition and static as well as dynamic magnetic properties. Thus a correlation between composition, strain, cation distribution, magnetocrystalline anisotropy and damping is evidenced. X-ray magnetic circular dichroism spectra and field dependent curves at the L3;2 edges of Ni and Fe are performed to complement integral magnetometry measurements and identify their magnetic contributions to the hysteresis. In particular, a strong in uence of the lattice site occupation of Ni2+ Td and cation coordination of Fe2+ Oh on the intrinsic damping is found. Furthermore, the vital role of the incorporation of Zn2+ and Al3+ is evidenced by comparison with a sample of altered composition. A strain-independent reduction of the magnetic anisotropy and damping by adapting the cation distribution is demonstrated.

Attempts to synthesize plutonium (IV) silicate, PuSiO4, have been performed on the basis of the results recently reported in the literature for CeSiO4, ThSiO4 and USiO4 under hydrothermal conditions. Although it was not possible to prepare PuSiO4 by applying the conditions reported for thorium and uranium, an efficient way of PuSiO4 synthesis was established following those optimized for CeSiO4 system. This method was based on the slow oxidation of plutonium (III) silicate reactants under hydrothermal conditions at 150°C in hydrochloric acid (pH = 3 – 4). This result shed a new light on the potential behavior of plutonium in reductive environment, highlighted the representativeness of cerium surrogates to study plutonium in such conditions and brought some important pieces of information on plutonium chemistry in silicate solutions.

We present structure measurements of biaxially orientated polyethylene terephthalate (PET, (C10H8O4)n , also called mylar) shock-compressed to (155+/-20) GPa and (6000+/-1000) K using in situ X-ray diffraction. Comparing to density functional theory molecular dynamics simulations, we find a highly correlated liquid that exhibits a temperature signficantly lower than predicted by some equation-of-state tables, which underlines the influence of complex chemical interactions in this regime. Indeed, at the inferred temperature and pressure, formation of nanodiamonds may be expected as recently observed in polystyrene at similar conditions. While some hints of diamond formation from PET are visible in the diffraction data, the strong liquid correlations prevent a conclusive statement as to whether diamonds are formed inside the sample volume.

Background: The term Pygmy Dipole Resonance (PDR) denotes electric dipole excitations below and around the neutron separation threshold. It may be important, e.g., for the nucleosynthesis of heavy nuclei or the symmetry energy in the Equation of State (EoS). For a deeper understanding of the PDR systematic studies are essential.
Purpose: The tin isotopic chain is a well-suited candidate to investigate the systematics of the PDR and the (g,g') reactions on 112,116,120,124Sn have already been measured in experiments using bremsstrahlung. It was claimed that the extracted electric dipole transition strengths of these isotopes increase with increasing neutron-to-proton ratio with the exception of 120 Sn. Furthermore, previous results from elastic photon scattering experiments on 120Sn are in disagreement with corresponding (p,p') Coulomb excitation data. To examine this discrepancy an additional high-sensitivity bremsstrahlung experiment on 120Sn was performed.
Method: The Nuclear Resonance Fluorescence (NRF) method is used which bases on real photon scattering. The bremsstrahlung experiment presented in this work was performed with a maximum energy of E = 9.5 MeV at the gELBE facility at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR). Besides a state-to-state analysis, the quasi-continuum was investigated as well.
Results: Above Ex = 4 MeV 236 dipole transitions were clearly identified and 168 of those were observed for the first time. Assuming that all analyzed transitions have electric dipole character the summed electric dipole strength equals B(E1) = 374(35) e2 fm2 (0.54(5) % of the TRK sum rule) for transitions from 4 MeV to Sn = 9.1 MeV. This is an enhancement of a factor 2.3 compared to the previously published 120Sn(g,g') results.
Especially, the observation of many weaker transitions in the state-to-state analysis lead to this increase. The photo-absorption cross sections deduced from the quasi-continuum analysis are about two times higher than the results of the (p,p') experiment.
Conclusion: The newly extracted summed B(E1) value of the state-to-state analysis is larger than those of 112,116Sn and smaller than that of 124 Sn. The difference between the present (g,g') data and the results of the inelastic proton scattering experiment above 6.3 MeV is still striking. The deviation may be explained by unobserved decay branchings and unresolved strength. Up to now, there is no explanation for the discrepancy between the extracted photo-absorption cross sections of the analysis of the quasi-continuum and the (p,p')
measurement. Additional experiments may shed light on this deviation.

Amongst various porous materials, noble metal aerogels attract wide attention due to their concurrently featured catalytic properties and large surface areas. However, insufficient understanding and investigation of key factors (e.g. reductants and ligands) in the fabrication process limits on-target design, impeding material diversity and available applications. Herein, unveiling multiple roles of reductants, we develop an efficient method, i.e. the excessive-reductant-directed gelation strategy. It enables to integrate ligand chemistry for creating gold aerogels with a record-high specific surface area (59.8 m² g⁻¹), and to expand the composition to all common noble metals. Moreover, we demonstrate impressive electrocatalytic performance of these aerogels for the ethanol oxidation and oxygen evolution reaction, and discover an unconventional organic-ligand-enhancing effect. The present work not only enriches the composition and structural diversity of noble metal aerogels, but also opens up new dimensions for devising efficient electrocatalysts for broad material systems.

The adenosine A2B receptor has been proposed as a novel therapeutic target in cancer, as for example, its expression is drastically elevated in several tumors and cancer cells. Noninvasive molecular imaging by using positron emission tomography (PET) would allow the in vivo quantification of this receptor in pathological processes and most likely enable the identification and clinical monitoring of respective cancer therapies. On the basis of a bicyclic pyridopyrimidine-2,4-dione core structure, the new adenosine A2B receptor ligand 9 was synthesized containing a 2-fluoropyridine moiety suitable for labeling with the short-lived PET radionuclide fluorine-18. Compound 9 showed a high binding affinity for the human A2B receptor (Ki(A2B) = 2.51 nM) along with high selectivities versus the A1, A2A, and A3 receptor subtypes. Therefore, it was radiofluorinated via nucleophilic aromatic substitution of the corresponding nitro precursor using [18F]F-/K2.2.2./K2CO3 in DMSO at 120 °C. Metabolism studies of [18F]9 in mice revealed about 60 % of intact radiotracer in plasma at 30 minutes p.i. A preliminary PET study in healthy mice showed an overall biodistribution of [18F]9 corresponding to the known ubiquitous but low expression of the A2B receptor. Consequently, [18F]9 represents a novel PET radiotracer with high affinity and selectivity toward the adenosine A2B receptor and a suitable in vivo profile. Subsequent studies are envisaged to investigate the applicability of [18F]9 to detect alterations in the receptor density in certain cancer-related disease models.

In the present work the microstructure of a black Pd film prepared by thermal evaporation and a glossy Pd film deposited by magnetron sputtering was compared. While the glossy Pd film exhibits typical polycrystalline structure with column-like grains, the black Pd film has fractal-like porous structure. Positron annihilation spectroscopy revealed that positronium is formed in nanoscopic cavities of the black Pd film. In conventional metals positronium does not form due to screening by conduction electrons. However, in porous metals containing nanoscopic porosity a thermalized positron may pick an electron on inner surface of a pore and escape into a cavity forming positronium. The average size of nanoscopic pores in the black Pd film was determined from the lifetime of long-lived ortho-positronium component.

High entropy alloys represent a new type of materials with unique combination of physical properties originating due to occurrence of single phase solid solution of numerous elements. Preparation of high entropy alloys films with nanosized grains promises increased effective surface and high intergranular diffusion of elements. In the present work HfNbTaTiZr films were deposited by magnetron sputtering from single phase HfNbTaTiZr target prepared by spark plasma sintering. Chemical composition of high entropy alloys thin films prepared this way was enriched in Ti and depleted in Zr and Nb. Very fine microstructure of the film was documented and defect distribution was found to be non-uniform with depth.

Scandium nitride (ScN) is a semiconductor with a rocksalt-structure that has attracted attention for its potential applications in thermoelectric energy conversion devices, as a semiconducting component in epitaxial metal/semiconductor superlattices. Two ScN films of 118 nm and 950 nm thicknesses were deposited at the same conditions on MgO (001) substrate by reactive magnetron sputtering. Poly-orientation of films was observed with first an epitaxial growth on MgO and then a change in the orientation growth due to the decrease of the adatom mobility during the film growth. Positron lifetime measurements showed a high concentration of nitrogen vacancies in both films with a slightly higher concentration for the thicker ScN film. Presence of nitrogen vacancies explains the values of direct band gaps of 2:53+-0:01 eV, and 2:56+-0:01 eV which has been measured on ScN films of 118 nm and 950 nm thicknesses, respectively.

In metal chalcogenide nanocrystals (NCs), the cations can be partially or fully replaced with other cations through the so-called cation exchange (CE) reactions. Here, we took advantage of these CE reactions to replace the cations on different chalcogenides NCs with 64Cu ions in order to radiolabel them. With respect to other approaches reported in the literature, our CE protocol is easily transferable to the clinic. It requires indeed one single step, in which the water-soluble NCs are mixed with a 64Cu copper(II) chloride solution of high specific activity, in the presence of vitamin C used as a reducing agent for Cu(II) to Cu(I)). Given the quantitative replacement of the cations of the NCs with 64Cu(I), a high radiochemical yield up to 90-95% can be reached. Provided that there is no free 64Cu, no purification step is needed, making the protocol straightforward. At the same time, the amount of NCs required for the exchange is so low (in the range of μg) that the dose of NCs shows no intrinsic cytotoxicity. This protocol works on different types of metal chalcogenide NCs. In ZnSe and ZnS NCs, the Zn(II) ions are exchanged with 64Cu (I) ions, and in CuFeS2 NCs the Fe(III) ions are exchanged with 64Cu(I). To ensure the stability of the NCs during and after the CE reaction, a multi-anchoring coating procedure based on PEG, cysteamine and poly-maleic anhydride was proven to be more efficient than the use of monothiol PEG ligands. With our approach we managed to achieve an unprecedented high specific activity, i.e. the amount of 64Cu radionuclide loaded per NC dose, to dispatch remarkable ionizing effects. Indeed, by exploiting a volumetric cations exchange, our strategy enables to concentrate a large dose of 64Cu (18.5 MBq) in a small NC dose (0.4 μg), reaching a specific activity of about 50 TBq/g. Remarkably, for CuFeS2 NCs even after the CE, the radiolabeled 64Cu:CuFeS2 NCs still show the characteristic dielectric resonance that enables the generation of heat under laser exposure for clinical use (1 W/cm2). The synergic toxicity of photo-ablation and 64Cu radiation exposure is here demonstrated in an in vitro study on glioblastoma and epidermoid carcinoma tumor cells.

Targeting glutamine metabolism has emerged as a potential therapeutic strategy for Myc overexpressing cancer cells. Myc proteins contribute to an aggressive neuroblastoma phenotype. Radiotherapy is one of the treatment modalities for high-risk neuroblastoma patients. Herein, we investigated the effect of glutamine deprivation in combination with irradiation in neuroblastoma cells representative of high-risk disease and studied the role of Myc member interplay in regulating neuroblastoma cell radioresistance. Methods: Cell proliferation and viability assays were used to establish the effect of glutamine deprivation in neuroblastoma cells expressing c-Myc or MycN. Gene silencing and overexpression were used to modulate the expression of Myc genes to determine their role in neuroblastoma radioresistance. qPCR and western blot investigated interplay between expression of Myc members. The impact of glutamine deprivation on cell response following irradiation was explored using a radiobiological 3D colony assay. DNA repair gene pathways as well as CSC-related genes were studied by qPCR array. Reactive Oxygen Species (ROS) and glutathione (GSH) levels were detected by fluorescence and luminescence probes respectively. Cancer-stem cell (CSC) properties were investigated by sphere-forming assay and flow cytometry to quantify CSC markers. Expression of DNA repair genes and CSC-related genes was analysed by mining publicly available patient datasets. Results: Our results showed that glutamine deprivation decreased neuroblastoma cell proliferation and viability and modulated Myc member expression. We then demonstrated for the first time that combined glutamine deprivation with irradiation led to a selective radioresistance of MYCN-amplified neuroblastoma cells. By exploring the underlying mechanism of neuroblastoma radioresistance properties, our results highlight interplay between c-Myc and MycN expression suggesting compensatory mechanisms in Myc proteins leading to radioresistance in MYCN-amplified cells. This result was associated with the ability of MYCN-amplified cells to dysregulate the DNA repair gene pathway, maintain GSH and ROS levels and to increase the CSC-like population and properties. Conversely, glutamine deprivation led to radiosensitization in non-MYCN amplified cell lines through a disruption of the cell redox balance and a trend to decrease in the CSC-like populations. Mining publicly available gene expression dataset obtained from pediatric neuroblastoma patients, we identified a correlation pattern between Myc members and CSC-related genes as well as a specific group of DNA repair gene pathways. Conclusions: This study demonstrated that MycN and c-Myc tightly cooperate in regulation of the neuroblastoma CSC phenotypes and radioresistance upon glutamine deprivation. Pharmacologically, strategies targeting glutamine metabolism may prove beneficial in Myc-driven tumors. Consideration of MycN/c-Myc status in selecting neuroblastoma patients for glutamine metabolism treatment will be important to avoid potential radioresistance.

The introduction of ferromagnetism in MoS2 is important for its applications in semiconductor spintronics. MoS2 powders were synthesized by hydrothermal method, followed by the N plasma treatment at room temperature. Weak ferromagnetism with saturated ferromagnetic magnetization of 0.64 memu/g has been observed in the as-synthesized MoS2 at room temperature, which is significant enhanced to 3.67 memu/g after the N plasma treatment for the proper duration. X-ray photoelectron spectroscopy demonstrates the adsorption of N, and higher valence state of Mo than +4 due to the bonding with N after the N plasma treatment. First principle calculation has been performed to disclose the possible origin of ferromagnetism. One chemical adsorbed N ion on S ion may form conjugated π bonds with adjacent two Mo ions to have a total magnetic moment of 0.75 μB, contributing to the enhanced ferromagnetism.

In this work, a systematic investigation on magnetic critical behavior is performed for the first time on an antiperovskite-type Mn3GaN, which is prepared by intentionally modifying stoichiometry. According to the XRD results, the antiperovskite structure is well preserved, even though all lattice parameters shrink upon reducing Ga and N content down to 60%. The sample exhibits a ferromagneticlike feature with a Curie temperature (T_C) of 394 K rather than frustrated behavior in stoichiometric Mn3GaN. Most importantly, the modified Arrott plots, Kouvel–Fisher plots, as well as critical isotherm method self-consistently co-confirm the critical exponents of β = 0.33, γ = 1.23, and δ = 4.7, unambiguously indicating that the critical behavior follows the 3D-Ising model around T_C.