Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Background
Although T-cells genetically modified to express chimeric antigen receptors (CARs) are successfully used to treat hematological malignancies, patients still suffer from several drawbacks of conventional CAR (cCAR) therapy. CAR-T-cells can cause severe to life-threatening adverse reactions like on-target, off-tumor toxicities which cannot be controlled in patients. Moreover, cCAR therapy often fails to successfully affect solid tumors and bears the risk to encourage tumor escape variants upon targeting of only one single tumor-associated antigen (TAA). In order to overcome these problems, we have established a novel on/off-switchable RevCAR system facilitating combinatorial targeting strategies.
Methods
For combinatorial targeting one T-cell has to be modified with two separate CARs recognizing different TAAs. The first CAR mediates the activation and the second CAR the costimulatory signal. In case of ‘AND’ gate targeting, dual-CAR-T-cells have to recognize both TAAs on the surface of the target cells to get activated. However, such combinatorial targeting strategies are struggling with several challenges including the adjustment of signal strength and affinity of both split CARs as well as the CAR size limiting the number of transduced specificities. In order to overcome these obstacles, our idea was to construct small RevCARs comprising only a small peptide epitope as extracellular domain. By removing the extracellular single-chain variable fragment (scFv) of cCARs, RevCARs avoid tonic signaling induced by scFv dimerization. As RevCARs do not have an extracellular antigen binding moiety, they cannot bind to any antigen per se. Thus, actually they are switched off. Only in the presence of a bispecific target module (RevTM), RevCAR-T-cells can be redirected to tumor cells and switched on. Finally, short-living RevTMs allow a repeatedly on/off-switch and controllability of RevCAR-T-cells and furthermore a flexible redirection of RevCAR-T-cells to any target.
Results
For proof of concept two small peptide epitopes were selected to construct the respective RevCARs. Additionally, a series of different RevTMs was generated recognizing one of the two peptide epitopes and simultaneously any potential TAA. RevTMs were able to efficiently redirect RevCAR-T-cells specifically against different tumor targets. Moreover, we show that combinatorial targeting can be achieved using our RevCAR system. Here, dual-RevCAR-T-cells were efficiently activated only after engagement by two RevTMs targeting the activating or costimulatory RevCAR and different TAAs.
Conclusions
Taken together, we developed a switchable RevCAR platform showing high effectiveness, increased specificity, improved safety, easy controllability, and small size facilitating combinatorial tumor targeting.

The scientific drilling campaign PALEOVAN was conducted in the summer of 2010 and was part of the international continental drilling programme (ICDP). The main goal of the campaign was the recovery of a sensitive climate archive in the East of Anatolia. Lacustrine deposits underneath the lake floor of ‘Lake Van’ constitute this archive. The drilled core material was recovered from two locations: the Ahlat Ridge and the Northern Basin. A composite core was constructed from cored material of seven parallel boreholes at the Ahlat Ridge and covers an almost complete lacustrine history of Lake Van. The composite record offered sensitive climate proxies such as variations of total organic carbon, K/Ca ratios, or a relative abundance of arboreal pollen. These proxies revealed patterns that are similar to climate proxy variations from Greenland ice cores. Climate variations in Greenland ice cores have been dated by modelling the timing of orbital forces to affect the climate. Volatiles from melted ice aliquots are often taken as high-resolution proxies and provide a base for fitting the according temporal models. Colleagues from the PALEOVAN scientific team fitted proxy data from Lake Van to the ice core data and constructed an age model that based on the fitting. Embedded volcaniclastic layers had to be dated radiometrically in order to provide independent age constraints to this climate-stratigraphic age model. Solving this task by an application of the 40Ar/39Ar method was the main objective of this thesis. Earlier efforts to apply the 40Ar/39Ar dating resulted in inaccuracies that could not be explained satisfactorily. Two stratovolcanos are located at the western and the northern shore of Lake Van: Nemrut and Süphan. Both volcanoes have deposited volcaniclastic materials into the lake’s basin throughout the entire lacustrine history of Lake Van. Feldspars and volcanic glasses from rhyolitic and trachytic tephra were analysed for their chemical composition in order to evaluate their suitability as target materials for the 40Ar/39Ar method. The absence of K-rich feldspars in suitable tephra layers implied that crystals needed to be 500 micrometer in size minimum, in order to apply single-crystal 40Ar/39Ar dating. Some of the samples did not contain any of these grain sizes or only very few crystals of that size. In order to overcome this problem this study applied a combined single-crystal and multi-crystal approach with different crystal fractions from the same sample. The preferred method of a stepwise heating analysis of an aliqoute of feldspar crystals has been applied to three samples. The Na-rich crystals and their young geological age required 20 mg of inclusion-free, non-corroded feldspars. Small sample volumes (usually 25 % aliquots of 5 cm3 of sample material – a spoon full of tephra) and the widespread presence of melt-inclusion led to the application of combined single- and multigrain total fusion analyses. 40Ar/39Ar analyses on single crystals have the advantage of being able to monitor the presence of excess 40Ar and detrital or xenocrystic contamination in the samples. Multigrain analyses may hide the effects from these obstacles. The results from the multigrain analyses are therefore discussed with respect to the findings from the respective cogenetic single crystal ages. Some of the samples in this study were dated by 40Ar/39Ar on feldspars on multigrain separates and (if available) in combination with only a few single crystals. 40Ar/39Ar ages from two of the samples deviated statistically from the age model. All other samples resulted in identical ages. The deviations displayed older ages than those obtained from the age model. t-Tests compared radiometric ages with available age control points from various proxies and from the relative paleointensity of the earth magnetic field within a stratigraphic range of 10 m. Concordant age control points from different relative chronometers indicated that deviations are a result of erroneous 40Ar/39Ar ages. The thesis argues two potential reasons for these ages: (1) the irregular appearance of 40Ar from rare melt- and fluid- inclusions and (2) the contamination of the samples with older crystals due to a rapid combination of assimilation and ejection. The contamination with older crystals by detrital processes cannot be excluded due to the analysis of multigrain fractions. However, this process appears unlikely because apparent ages are normally distributed. Another aliquot of feldspar crystals that underwent separation for the application of 40Ar/39Ar dating was investigated for geochemical inhomogeneities. Magmatic zoning is ubiquitous in the volcaniclastic feldspar crystals. Four different types of magmatic zoning were detected. The zoning types are compositional zoning (C-type zoning), pseudo-oscillatory zoning of trace element concentrations (PO-type zoning), chaotic and patchy zoning of major and trace element concentrations (R-type zoning) and concentric zoning of trace elements (CC-type zoning). Samples that deviated in 40Ar/39Ar ages showed C-type zoning, R-type zoning or a mix of different types of zoning (C-type and PO-type). Feldspars showing PO-type zoning typically represent the smallest grain size fractions in the samples. The constant major element compositions of these crystals are interpreted to represent the latest stages in the compositional evolution of feldspars in a peralkaline melt. PO-type crystals contain less melt- inclusions than other zoning types and are rarely corroded. This thesis concludes that feldspars that show PO-type zoning are most promising chronometers for the 40Ar/39Ar method, if samples provide mixed zoning types of Quarternary anorthoclase feldspars. Five samples were dated by applying the 40Ar/39Ar method to volcanic glass. High fractions of atmospheric Ar (typically > 98%) significantly hampered the precision of the 40Ar/39Ar ages and resulted in rough age estimates that widely overlap the age model. Ar isotopes indicated that the glasses bore a chorine-rich Ar-end member. The chlorine-derived 38Ar indicated chlorine-rich fluid-inclusions or the hydration of the volcanic glass shards. This indication strengthened the evidence that irregularly distributed melt-inclusions and thus irregular distributed excess 40Ar influenced the problematic feldspar 40Ar/39Ar ages. Whether a connection between a corrected initial 40Ar/36Ar ratio from glasses to the 40Ar/36Ar ratios from pore waters exists remains unclear. This thesis offers another age model, which is similarly based on the interpolation of the temporal tie points from geophysical and climate-stratigraphic data. The model used a PCHIPinterpolation (piecewise cubic hermite interpolating polynomial) whereas the older age model used a spline-interpolation. Samples that match in ages from 40Ar/39Ar dating of feldspars with the earlier published age model were additionally assigned with an age from the PCHIPinterpolation. These modelled ages allowed a recalculation of the Alder Creek sanidine mineral standard. The climate-stratigraphic calibration of an 40Ar/39Ar mineral standard proved that the age versus depth interpolations from PAELOVAN drilling cores were accurate, and that the applied chronometers recorded the temporal evolution of Lake Van synchronously. Petrochemical discrimination of the sampled volcaniclastic material is also given in this thesis. 41 from 57 sampled volcaniclastic layers indicate Nemrut as their provenance. Criteria that served for the provenance assignment are provided and reviewed critically. Detailed correlations of selected PALEOVAN volcaniclastics to onshore samples that were described in detail by earlier studies are also discussed. The sampled volcaniclastics dominantly have a thickness of < 40 cm and have been ejected by small to medium sized eruptions. Onshore deposits from these types of eruptions are potentially eroded due to predominant strong winds on Nemrut and Süphan slopes. An exact correlation with the data presented here is therefore equivocal or not possible at all. Deviating feldspar 40Ar/39Ar ages can possibly also be explained by inherited 40Ar from feldspar xenocrysts contaminating the samples. In order to test this hypothesis diffusion couples of Ba were investigated in compositionally zoned feldspar crystals. The diffusive behaviour of Ba in feldspar is known, and gradients in the changing concentrations allowed for the calculation of the duration of the crystal’s magmatic development since the formation of the zoning interface. Durations were compared with degassing scenarios that model the Ar loss during assimilation and subsequent ejection of the xenocrystals. Diffusive equilibration of the contrasting Ba concentrations is assumed to generate maximum durations as the gradient could have been developed in several growth and heating stages. The modelling does not show any indication of an involvement of inherited 40Ar in any of the deviating samples. However, the analytical set-up represents the lower limit of the required spatial resolution. Therefore, it cannot be excluded that the degassing modelling relies on a significant overestimation of the maximum duration of the magmatic history. Nevertheless, the modelling of xenocrystal degassing evidences that the irregular incorporation of excess 40Ar by melt- and fluid inclusions represents the most critical problem that needs to be overcome in dating volcaniclastic feldspars from the PALEOVAN drill cores.
This thesis provides the complete background in generating and presenting 40Ar/39Ar ages that are compared to age data from a climate-stratigraphic model. Deviations are identified statistically and then discussed in order to find explanations from the age model and/or from 40Ar/39Ar geochronology. Most of the PALEOVAN stratigraphy provides several chronometers that have been proven for their synchronicity. Lacustrine deposits from Lake Van represent a key archive for reconstructing climate evolution in the eastern Mediterranean and in the Near East. The PALEOVAN record offers a climate-stratigraphic age model with a remarkable accuracy and resolution.

Background
The development of chimeric antigen receptors (CARs) has rapidly emerged as a promising approach in cancer immunotherapy. Nonetheless, drawbacks associated with CAR T cell therapies include on-target/off-tumor effects and cytokine release syndrome. Aiming an increased clinical safety while preserving the efficacy of such therapy, we developed a novel modular universal CAR platform termed UniCAR. UniCAR T-cells are exclusively activated in the presence of a target module (TM), which establishes the cross-link between antigen-specific cancer cells and UniCAR T-cells in an individualized time- and target-dependent manner. The carbohydrate antigen sialyl-Tn (STn) is a particularly interesting target due to its expression in several types of cancer and absence in normal healthy tissues. Given the small size of such TMs, they are rapidly eliminated and thus, possible side effects and activation of UniCAR T-cells can be easily controlled by TM dosing. In late phases of treatment, TMs with extended half-life may play an important role by improving the eradication of residual tumor cells.
Methods
In this work, a novel longer-lasting TM against STn was developed, characterized and compared to the previously developed short-lived anti-STn TM. Short-lived TMs are composed of a tumor-specific binding moiety fused to the La peptide epitope (E5B9) which is recognized by UniCAR T-cells. In extended half-life TMs, these two components are fused via an Fc domain derived from the human IgG4 molecule. Functional and pharmacokinetic properties were assessed using in vitro and in vivo assays.
Results
The developed anti-STn IgG4-based TM efficiently activates and redirects UniCAR T-cells to STn-expressing tumors in a highly efficient target-specific and target-dependent manner, promoting the secretion of pro-inflammatory cytokines, tumor cell lysis of breast and bladder cancer cells in vitro and of breast cancer cells in experimental mice. A comparable or increased killing efficiency was obtained at a lower concentration range in comparison to the results obtained for the anti-STn scFv-based TM. Additionally, PET studies demonstrate the specific enrichment of the anti-STn IgG4-based TM at the tumor site presenting a prolonged serum half-life compared to the scFv short-lived TM.
Conclusions
Taken together, these data demonstrate the effective and potential application of this CAR T cell-derived modular system to target STn in different types of cancer using different TM formats. The use and combination of such molecules with different formats and half-lives provides highly promising and customized tools for retargeting of UniCAR T-cells in a flexible, individualized and safe manner at different stages of treatment.

Clinical translation of chimeric antigen receptor (CAR) T cell therapy in myeloid malignancies is progressing slowly compared to its success in treatment of B cell malignancies. Clinical experiences with CAR T cell therapies against the currently investigated tumor-associated antigens (TAA) (e.g. CD33, CD123 and FMS-like tyrosine kinase 3 (FLT3)) were discouraging and severe side effects occurred (cytokine release syndrome, neurotoxicity and myeloid aplasia) (Hoffmann et al. Journal of Clinical Medicine 2019). Probably targeting a single TAA is insufficient to treat high risk myeloid malignancies with CAR T cell therapies. Therefore, combined targeting of two or even more TAAs seems to be a promising approach. In order to implement such a multiple tumor targeting strategy, we developed a modular CAR T cell system termed UniCAR. The system consists of a universal CAR (UniCAR) directed against the La peptide epitope E5B9 combined with single-chain variable fragment (scFv) -based target modules (TM). In contrast to conventional CARs, anti-tumor activity of UniCAR T cells is only turned on in the presence of the TMs. Thus, this approach will allow UniCAR T cell control due to the short half-life of the TM and therefore has a favorable safety profile. Furthermore, different TMs against several TAAs can be administered both sequentially or in parallel to increase the anti-tumor efficacy or face disease relapse due to antigen escape mechanisms. In the field of myeloid malignancies our group developed retargeting strategies against the TAAs CD33 and CD123 (Cartellieri et al. Blood Cancer Journal 2016). In addition, we have developed a new TM for the UniCAR system that is directed against the TAA FLT3. FLT3 is highly expressed on acute myeloid leukemia (AML) cells and also present on CD123low AML samples (Riccioni et al. British Journal of Haematology 2011).

The novel FLT3 TM was constructed by fusion of the variable domain of the heavy and the light chain of the murine anti-FLT3 monoclonal antibody (4G8) to the E5B9 UniCAR epitope. In light of a potential clinical application, we in parallel generated a humanized FLT3 TM to further decrease its immunogenicity. Both FLT3 TMs were tested in vitro against different AML cell lines, by using flow cytometry based killing assays as described elsewhere (Fasslrinner et al. British Journal of Haematology 2019). The functionality of the FLT3 TMs in vitro was highly effective. Both FLT3 TMs were able to redirect UniCAR T cells for AML cell lysis already in the picomolar range and were moreover comparable effective than the previously developed CD123 TM. Thus, humanization of the FLT3 TM did not lead to a decrease in anti-tumor efficacy.

In summary, we could show that both the novel murine FLT3 TM and the humanized counterpart redirected UniCAR T cells and induced highly effective elimination of AML cells in vitro. Thus, the flexible application of the FLT3-based UniCAR system seems to be a promising tool for cell-based AML therapy alone or even in combination with other AML-specific TMs (e.g. CD33, CD123).

Hematological malignancies are successfully treated with chimeric antigen receptor (CAR) armed T cells. Despite the clinical success, CAR T cell therapy struggles still with some problems including the selection of tumor escape variants and on-target, off-tumor side reactions as well as massive cytokine release and uncontrollability of CAR T cell activity in the patients. In order to enable controllability of CAR T cells and to avoid unspecific side effects, we established a novel switchable, split and adaptable CAR platform technology, termed RevCAR system.

The novel RevCARs lack the single chain variable fragment (scFv) commonly used as extracellular domain in conventional CARs. Instead of the scFv, RevCARs contain only a small peptide epitope as extracellular portion. This design reduces the CAR size, avoids unspecific antigen binding and prevents antigen independent tonic signaling caused by scFv dimerization. As RevCAR T cells do not recognize anything, they are per se inert. Only in the presence of a corresponding bispecific antibody based target module (RevTM) they can be specifically redirected to tumor cells. Therefor RevTMs consist of two scFvs. One recognizes the RevCAR peptide epitope and the other one simultaneously binds to a tumor associated antigen (TAA). By dosing of the RevTM, which has a very short half-life, the reactivity of RevCAR T cells can be switched on and off reversibly. Another advantage is that the RevCAR system can be flexibly adapted to any tumor antigen simply by exchanging the RevTM. Furthermore, the small RevCAR size is favorable for inserting more than one RevCAR in the same T cell thus facilitating the mode of gated targeting which is a highly attractive approach to minimize the risk for on-target, off-tumor toxicities against healthy tissues and to increase tumor specificity of conventional CAR T cells. For 'AND' gate targeting via the RevCAR system, two different RevCARs were constructed and expressed simultaneously in the same T cell. The two RevCARs differed with respect to the extracellular peptide epitope and the intracellular signaling domain. Moreover, the respective transmembrane domain was selected to isolate the respective RevCAR signal. The first RevCAR is designed to transmit the activation signal, the second RevCAR to deliver a costimulatory signal. For efficient RevCAR T cell activation, both RevCARs must be engaged via their respective RevTM which on the one hand binds to one of the two RevCAR epitopes and on the other hand to one of two TAAs expressed on the same target cell. Here, we present two RevCAR/RevTM systems for retargeting of AML cells as well as solid tumor cells including via gated targeting.

In summary, we show proof of concept for a novel switchable RevCAR system that can be used for retargeting of AML cells as well as solid tumors. The novel modular RevCAR platform is characterized by small size, lacks unwanted tonic signaling effects, allows the control of RevCAR T cell activity, enables gated targeting strategies, and can be adapted to any tumor antigen and tumor type.

In Zusammenarbeit mit dem Landkreis Nordsachsen, dem Beruflichen Schulzentrum Torgau sowie Unternehmen und Verbänden beteiligt sich die TU Bergakademie Freiberg am GlasCampus Torgau. Ziel der gemeinsamen Initiative sind die Gewinnung und Qualifizierung von Fachkräften sowie die Förderung des Fachkräftenachwuchses für die mitteldeutsche Glas-, Keramik- und Baustoffwirtschaft. Daneben soll die Innovationskraft der Unternehmen durch die Förderung des Wissens- und Technologietransfers sowie kooperativer Forschungs- und Entwicklungsaktivitäten gestärkt werden.

The clinical efficacy of CAR T cell therapies has been widely recognized, particularly in the treatment of hematologic malignancies. Nevertheless, CAR T cells also have the capability to elicit undesired effects such as on-target/off-tumor recognition and cytokine release syndrome. To increase clinical safety of CAR T cell therapy, a novel modular universal CAR platform termed UniCAR was developed by our group. In the UniCAR system, antigen-binding specificity and signaling features are two distinct moieties, in which the antigen specificity is provided by targeting modules (TMs) to redirect UniCAR T cells in an individualized time- and target-dependent manner. In this way, UniCAR T-cells acquire killing potential only in the presence of a tumour-specific TM. Given the reduced size of such molecules, they are rapidly eliminated and therefore, need to be continuously infused. Thus, possible side effects and activation of UniCAR T cells can be easily monitored and controlled by TM dosing. During the onset of therapy, tumor burden and the risk for severe side effects are high and regulation of CAR T cell activity is particularly important at this stage. For this reason, TMs with extended half-life may play an important role by improving eradication of residual tumor cells in late phases of treatment and further expedite clinical application. In this line of thought, a set of novel short-lived and longer-lasting TMs directed against several tumor-associated antigens was developed. Short-lived TMs are composed of a tumor-specific binding moiety fused to the La peptide epitope (E5B9) which is recognized by UniCAR T cells. In order to generate extended half-life TMs, these two components are fused via an Fc domain derived from the human IgG4 molecule. In vitro and in vivo assays have shown that both short-lived and longer-lasting TMs efficiently redirect UniCAR T cells to cancer cells in a highly target-specific manner, thereby promoting the secretion of pro-inflammatory cytokines and tumor cell lysis. Further assays using PET-imaging, demonstrated that all TM formats specifically enriched at the tumor site presenting either short or prolonged serum half-lives. From a clinical point of view, after the initial reduction of tumor burden promoted by the small TMs, IgG4-based TMs could be subsequently administrated allowing a more convenient and personalized treatment of the patients avoiding the continuous infusion of the short-lived TMs. Furthermore, the specific accumulation of such IgG4-based TMs at the tumor site sets these molecules as attractive candidates for in vivo imaging and endoradiotherapy. Taken together, combination of switchable UniCAR T cells and TMs with different sizes, specificities and half-lives represent a flexible and individualized approach at different stages of cancer treatment.

In aerobic wastewater treatment, aeration is the most critical element of the treatment system. It supplies microorganisms with the required amount of dissolved oxygen, maintains solids in suspension and controls membrane fouling, where needed. However, conventional activated sludge, where air is used, is limited to low-strength wastewaters as higher loadings or more intense feeds require both higher biomass and dissolved oxygen concentrations. In membrane bioreactors, despite being able to operate at higher biomass concentrations, their operation at high biomass concentrations and high organic loadings has not been tested. By replacing air with pure oxygen, oxygen transfer rates increase at lower flowrates. In this work, the potential and limitations of pure oxygen systems over conventional ones are reviewed. Also, the effect of the operational parameters or the mixed liquor characteristics on oxygen transfer is determined. Pure oxygen affects bacterial structure, controls foam formation, improves bacterial enzymatic activity and, in membrane bioreactors, leads to a better recovery of permeability after cleanings. It treats much higher loadings without compromising final effluent quality. Fine bubbles are more efficient in oxygen transfer due to their increased contact area. Nevertheless, pure oxygen aeration at times is not essential or it may generate effluent organic matter of a higher refractory character. We then recommend that it be used to applications where conventional aeration is not adequate.

The common acute lymphoblastic leukemia antigen CD10 is a marker for several hematological malignancies, including acute lymphoblastic leukemia as well as T and B cell lymphomas, Burkitt lymphomas, and some solid tumors like renal cell carcinomas, pancreatic tumors and melanomas. Because of its tumor related expression pattern, CD10 is an attractive target for adoptively transferred T cells that are genetically modified to express chimeric antigen receptors (CARs). Recently, conventional CAR T cell therapy targeting CD19-positive hematological malignancies was clinically approved because of its impressive effectiveness in patients. However, CAR T cells can also cause severe side effects like on-target, off-tumor reactions, tumor lysis syndrome and cytokine release syndrome. Most critically, activity of conventional CAR T cells cannot be controlled, once they are applied in patients. As CD10 is also widely expressed on normal tissues, CAR T cell reactivity has to be controllable in order to stop CAR T cell therapy in case of on-target, off-tumor toxicities occur. Especially for this purpose, we have recently established a switchable, modular and universal CAR platform technology, named UniCAR system, which can be repeatedly turned on and off. In contrast to conventional CARs, that directly recognize a tumor-associated antigen (TAA) on the tumor cell surface via their extracellular single-chain variable fragment (scFv), the UniCAR system is structured in a modular manner of two components. The first component are T cells genetically engineered to express UniCARs and the second component are target modules (TMs). Most importantly, UniCARs cannot directly bind to a TAA because their extracellular scFv is directed against the peptide epitope E5B9 which is not present on the surface of living cells. Consequently, UniCAR armed T cells are per se inert. They can be redirected towards tumor cells only via a TM. TMs consist of a scFv targeting a TAA and the epitope E5B9 recognized by UniCARs allowing a cross-linkage of UniCAR T cells with tumor cells which results in T cell activation. As TMs have a very short half-life, UniCAR T cell activity can be controlled by dosing of the TM. Once the TM is administered, UniCAR T cells can be switched on, but once the TM injection is stopped and the TM is eliminated, UniCAR T cells are switched off immediately. Here, we show proof of concept for functionality of the UniCAR system targeting CD10-positive malignancies. Therefor, a novel anti-CD10 TM was constructed which is able to redirect UniCAR T cells to eliminate CD10-expressing tumor cells. In summary, we have established a universal, switchable, modular UniCAR platform technology that can be used to target CD10-positive malignancies.

The focus of this presentation will be nanopatterning by different self-assembly mechanisms and how it can be applied for influencing the magnetic properties, mainly magnetic shape anisotropy, of materials.
We would like to show that well-established macroscopic material processing techniques – broad-beam ion irradiation, high-temperature annealing, and physical vapor deposition – can be used to fabricate nanopatterned materials in a bottom-up fashion and to give them tuneable magnetic properties.

Metal-organic frameworks (MOFs) are emerging as an appealing class of highly tailorable electrically-conducting materials with potential applications in opto-electronics. Yet, the realization of their proof-of-concept devices remains a daunting challenge, attributed to their poor electrical properties. Following our recent report on a semiconducting Fe3(THT)2(NH4)3 (THT, 2,3,6,7,10,11-triphenylenehexathiol) two-dimensional MOF with record-high mobility and band-like charge transport, here, we demonstrate Fe3(THT)2(NH4)3 MOF-based photodetector operating in photoconductive mode capable of detecting a broad wavelength excitation of charge carriers. The narrow IR bandgap of the active layer (~0.45 eV) constrains the performance of the photodetector at room temperature by band-to-band thermal. At 77 K, the device performance is significantly improved; two orders of magnitude higher voltage responsivity, lower noise equivalent power, and higher specific detectivity of 7×108 cm Hz1/2 W–1 are achieved under 785 nm excitation. These figures of merit are retained over the analyzed spectral region (400–1575 nm) and are commensurate to those obtained with the first demonstrations of graphene and black phosphorus based photodetectors. This work demonstrates the feasibility of integrating conjugated MOFs as an active element into broadband photodetectors, thus bridging the gap between materials’ synthesis and technological applications.

The adjustment of fine grain morphologies has been approved to be a crucial issue for improving characteristics and properties of cast and wrought aluminium alloys. Several methods are known to achieve grain refinement in solidification processes: add-on of grain refiners, rapid cooling conditions, mechanical or electromagnetic stirring or ultrasonic treatment.
AC magnetic fields provide a contactless method to control the flow inside a liquid metal and the grain size of the solidified ingot. Many studies have shown that beneficial effects like a distinct grain refinement or the promotion of a transition from a columnar to an equiaxed dendritic growth (CET) can be obtained. However, electromagnetically-driven melt convection may also produce segregation freckles on the macroscale. The achievement of superior casting structures needs a well-aimed control of melt convection during solidification.
Previous investigations considered the use of time-modulated AC magnetic fields to control the heat and mass transfer at the solidification front. It has been shown recently under laboratory conditions that an accurate tuning of the magnetic field parameters can avoid segregation effects and homogenize the mechanical properties.
This present study examines the directional solidification of commercial wrought aluminium alloys EN AW 6082 from a water-cooled copper chill. Rotating time-modulated magnetic fields were used to agitate the melt. The impact of flow on the resulting macro and micro structure are investigated. The solidified structure was reviewed in comparison to an unaffected solidified ingot and ingot prepared with chemical grain refiner Ti3B. In addition results from extrusion process experiments and the achieved mechanical properties are introduced. Our results demonstrate the potential of time–modulated magnetic fields to control the grain size and to open the possibility to reduce the amount of grain refiner and to reduce the press capacity.

Several open issues remain concerning the quantitative understanding of irradiation hardening in high-Cr steels. One of these issues is addressed here by correlating yield points that are observed in stress-strain curves with dislocation decoration observed by TEM for neutron-irradiated Fe-Cr alloys. It is found that both higher neutron exposure and higher Cr content promote irradiation-induced loops to arrange preferentially along dislocation lines. Consequently, the activation of dislocation sources requires unlocking from the decorating loops, thus resulting in a yield drop. This process is considered within the source hardening model as opposed to the dispersed barrier hardening model, the latter aimed to describe dislocation slip through a random array of obstacles. Microstructure-informed estimates of the unlocking stress are compared with measured values of the upper yield stress. As functions of neutron exposure, a cross-over from the dominance of dispersed-barrier hardening accompanied by smooth elastic-plastic transitions to the dominance of source hardening accompanied by yield drops is observed for Fe-9% Cr and Fe-12% Cr.

n-type doped Ge quantum wells with SiGe barriers represent a promising heterostructure system for the development of radiation emitters in the terahertz range such as electrically pumped quantum cascade lasers and optically pumped quantum fountain lasers. The non-polar lattice of Ge and SiGe provides electron-phonon scattering rates that are one order of magnitude lower than polar GaAs. We have developed a self-consistent numerical energy-balance model based on a rate equation approach which includes inelastic and elastic inter- and intra-subband scattering events and takes into account a realistic 2DEG distribution in all the subband states of the Ge/SiGe quantum wells by considering subband-dependent electronic temperatures and chemical potentials. This full-subband model is here compared to the standard discrete-energy-level model, in which the material parameters are limited to few input values (scattering rates and radiative cross-sections). To provide an experimental case study, we have epitaxially grown samples consisting of two asymmetric coupled quantum wells forming a three-level system, which we optically pump with a free electron laser. The benchmark quantity selected for model testing purposes is the saturation intensity at the 1-3 intersubband transition. The numerical quantum model prediction is in reasonable agreement with the experiments and therefore outperforms the discrete-energy-level analytical model, whose prediction of the saturation intensity is off by a factor 3.

Liquid metal batteries (LMBs) are fascinating electrochemical cells. Built as a stable density stratification of two liquid metals separated by a molten salt electrolyte, such cells offer cheap stationary energy storage and a long life time. Due to the totally liquid interior of the cells, fluid flow is of paramount importance for the safe operation of LMBs. As highly resistive electrolyte needs to be as thin as possible, a strong fluid flow might easily wipe it away and short circuit the cell. Aside from that, a slight flow might be highly beneficial. When discharing a Li-Bi LMB, Li will cross the electrolyte layer and alloy into Bi. As this process is diffusion-controlled, a Li-rich layer will build up on top of the positive electrode. A mild flow might equalize the alloy, thus reducing concentration polarization and improving the cell's efficiency.

The talk will first explain the set-up and operation of liquid metal batteries. Afterwards, different possible flow mechanisms in LMBs will be presented and discussed. These will include thermally driven Rayleigh-Benard convection, solutal convection, pinch effects, interface instabilities, the Tayler instability and electro-vortex flow. Besides of flow simulation, the modelling of the electric potential distribution, the current density and magnetic fields will be presented. Special attention will be paied to the implementation of the solvers in OpenFOAM, as well as the description of specialized discretisation schemes, which are necessary e.g. for computing the current density. Finally, it will be shown how different flows in the battery effect the cell voltage, and the integrity of the three layers.

Objectives: Proton therapy (PT) reduces the integral dose in healthy tissue compared to X-ray therapy (XT). At the same time PT is more sensitive to anatomical changes and organ motion than XT, making MRI guidance especially relevant for PT. Recently, we have integrated for the first time a 0.22 T in-beam MRI scanner with a proton therapy research beamline. As a next step, absolute and relative dosimetry in the presence of magnetic fields of the MRI scanner has to be established. This work investigates the influence of the static magnetic (B0) field of the MRI scanner on ionisation chamber (IC) readings for proton beams and the feasibility to correct the readings for the B0 field.

Materials & methods: Either a Semiflex 0.3 or a PinPoint3D IC was positioned in an MR-compatible water phantom to measure the absolute dose at five proton energies (70, 110, 150, 190, 226.7 MeV) in the entrance plateau area of the Bragg curve for a 10 x 10 cm2 pencil beam scanned irradiation field. The entrance window of the phantom was placed at the imaging isocentre of the MRI scanner. Dose measurements were repeated at the same position and under the same conditions without the B0 field. The IC signal was corrected to standard environmental conditions and for the beam quality.

Results & Conclusion: Systematic energy-dependent differences between dose readings with and without the B0 field were observed. For the Semiflex 0.3, the measured dose in the presence of the B0 field increased by 0.75%, 0.58%, 0.59% and 0.41% for 70 MeV, 110 MeV, 150 MeV and 190 MeV, respectively, and decreased by 0.36% for 226.7 MeV. For the same energies, the dose measured by the PinPoint3D increased by 0.81%, 0.69%, 0.63%, 0.47% and 0.31%. For all energies, the standard deviations were smaller than 0.10% and 0.19% for the Semiflex 0.3 and PinPoint3D IC, respectively.
Beam energy-dependent correction of IC readings is mandatory and appears feasible for accurate proton beam dosimetry in magnetic fields.

The separation of fine particles is a challenging task where a proper understanding of the interfacial properties is crucial. In our research, we focus on flotation, which is a powerful and widely used separation technique, where valuable mineral particles are selectively separated from unwanted gangue, with particles in the size range of about 10 µm to 200 µm. For this process, particle properties such as wettability, size or morphology are fundamental separation features.
Although, it is a well-established processing technique that is used all over the world in industry, there are still some challenges with regard to the processing of ultrafine particles with sizes below 10 µm. The aim of this project, which is part of the German research foundation priority programme DFG-SPP 2045 “MehrDimPart”, is to gain a deeper understanding of the microprocesses that occur during flotation and to have a closer look on the influence of particle properties, like wettability and morphology.
For this research glass particles are used as their surface chemistry can be modified in different ways. Here, the functionalisation was carried out by esterification with alcohols, where the wettability of the product can be controlled by the length of the alkyl chain. In order to investigate the effect of particle morphology on flotation three differently shaped glass particles were used and esterified, including fibres, spheres and fragments with differing shapes. Inverse gas chromatography is used to characterise the particles surface energy distributions, which provide information about the particles wettability as well as the heterogeneity of the surface.

Froth flotation is a well-established and efficient particle processing technique especially for the selective separation of mineral particles from unwanted material within sizes ranging from 10 µm to 200 µm. However, there are still some challenges and unexplored opportunities when it comes to the separation of ultrafine particles (< 10 µm). Within the German research foundation priority programme DFG-SPP 2045 “MehrDimPart” we aim to develop a novel multidimensional separation device for such ultrafine particles based on the particle parameters of wettability, morphology (shape or roughness) and size.
One important aspect of our investigations in this new flotation device lies in the modification of the materials surface, which is achieved via esterification with alcohols. To study the effect of the particle morphology/shape on the hydrophobization of glass microparticles, three differently shaped but same sieve sized fractions are used for applying esterification, among them spherical particles, elongated particles and particle fragments with varying shapes. The characterisation of the particle wettability is realised using the inverse gas chromatography method with additional information on the surface energy components distributions. The wettability is varied using alcohols with different chain length and the resulting surface energy components distributions are put in context with flotabilities of the particles in two flotability characterisation set-ups, i.e. tube microflotation and particle adhesion to hydrocarbons.

A reliable solution-phase synthesis of the water-soluble dipeptidic fluorogenic transglutaminase substrate Z-Glu(HMC)-Gly-OH is presented. The route started from Z-Glu-OH, which was converted into the corresponding cyclic anhydride. This building block was transformed into the regioisomeric - and -dipeptides. Key step was the esterification of Z-Glu-Gly-OtBu with 4-methylumbelliferone. The final substrate compound was obtained in an acceptable yield and excellent purity without the need of purification by RP-HPLC. The advantage of this acyl donor substrate for the kinetic characterisation of inhibitors and amine-type acyl acceptor substrates is demonstrated by evaluating commercially available or literature-known irreversible inhibitors and the biogenic amines serotonin, histamine and dopamine, respectively.

The waiting times in case of failure of the cooling system of the spent fuel storage pool were determined with the three-dimensional numerical calculation tool ANSYS CFX. With the calculated variant, it is assumed that the swivel gate is opened when required. For the decay heat of 1.5 MW, waiting times until the spent fuel storage pool has been heated to 60 °C or 80 °C were calculated and the temperature offset between the spent fuel storage pool and the storage chamber pool was determined.

The calculations showed that the coolant from the flood chamber and the storage chamber, which is located above the lower edge of the open swivel gate, mixes ideally with the water from the spent fuel pool. The results of the CFD analysis can be used for the cross-code verification of models in integral codes.

The Helium ion microscope is well known for its high-resolution imaging and nanofabrication performance. We have recently developed and presented a time-of-flight based secondary ion mass spectrometer that can be retrofitted to existing microscopes [1, 2].

Depth profiling in SIMS in general is usually done by sputtering into deeper layers and plotting the signal intensity over time. The actual milling depth can only be estimated and the common approach is to measure the crater depth with atomic force microscopy every time a compositional change is observed.

Direct imaging and chemical analysis of a cross-section with high spatial resolution can avoid this challenge. The cross sections will be prepared ex-situ by milling, grinding and low energy argon ion polishing.

[1] Klingner, N.; Heller, R.; Hlawacek, G.; von Borany, J.; Notte, J. A.; Huang, J. and
Facsko, S.; Ultramicroscopy 162(2016), 91-97
[2] Klingner, N.; Heller, R.; Hlawacek, G.; Facsko, S. and von Borany, J.; Ultramicroscopy 198(2019), 10-17

In industry there is need for predicting the morphology of two-phase liquid-gas flows that are part of e.g. distillation processes, pipeline transport units, chemical reactors or heat transfer units. Knowledge of the behavior of the flow and its regime facilitate for the engineers to have proper design of downstream processes and the pipeline in order to achieve the best reliable and economic outcome. One topic that is not studied sufficiently is the characterization of not fully developed flow due originated from insufficient developing or calming length as it can be found downstream of elbow bends and in short straight pipes, which are frequently encountered in industrial applications. In order to study this topic and characterize the flows, an experimental instrumentation was set up using Wire-mesh Sensors. This work is a numerical work using ANSYS CFX 19.1 in order to set up simulations of the experimentally investigated pipe geometries and flow regimes, followed by validation with the WMS data. Therefore, this work is concerned with gas-liquid flow in a horizontal straight pipe of DN50 and DN200 and horizontal elbow bends with the same diameters and curvature ratio of R/D=1. Each of the geometries is studied for annular and stratified wavy flow.

Die vorliegende Arbeit beschäftigt sich mit der Charakterisierung einer Zweiphasenströmung durch eine komplexe Rohrgeometrie in Form eines horizontalen 90°-Rohrbogens mit einem Innendurchmesser D = 50mm und einem relativen Radius R=1 . Basierend auf experi-mentellen Gittersensordaten wird der Bereich stromauf- und stromabwärts der Bogengeometrie untersucht. Die experimentellen Untersuchungen erfolgten an einer horizontalen, nicht vollständig eingelaufenen Zweiphasenströmung. Schwerpunkt der Untersuchungen war da-bei die Beurteilung des Einflusses der Rohrleitungslänge. Ein bleibender Einfluss des Rohrbogens auf die Strömungsmorphologie konnte nicht festgestellt werden. Für die Bestimmung des Gasanteils und des Zweiphasendruckverlustes wurden existierende Modellansätze systematisiert und bezüglich der Anwendung auf nicht eingelaufende Zweiphasenströmungen, bzw. den Bereich des Rohrbogens überprüft. Basierend auf der Abweichung der Korrelationen wurden kombinierte Berechnungsansätze für den Gasanteil und den Zweiphasendruck-verlust ausgewählt, welche die experimentellen Daten mit bester Näherung korrelierten.

Introduction
The A2AR has emerged as a potential therapeutic target due to its involvement in basic functions of the neuronal, cardiovascular and immune systems. Blockade of A2AR is regarded as potential tool related to CAR T-cell immunotherapy of cancer. Furthermore, A2AR are believed to regulate myocardial oxygen demand and to increase coronary circulation by vasodilation. With regard to Parkinson’s disease A2AR antagonists, such as the FDA approved Nourianz®, are used as an adjunctive treatment to levopoda®. Therefore noninvasive imaging to monitor changes of receptor density and/or occupancy during the A2aR-tailored therapy is of utmost importance. We recently developed the A2AR PET radiotracer [18F]FLUDA which demonstrated superior pharmacokinetic properties among the radiotracers available. Towards its clinical translation, an automated radiosynthesis was developed and the radiotracer was fully characterized in vitro and in vivo including toxicity and dosimetry1 studies.
Methods
The binding affinity (Ki) of FLUDA towards the human A2AR and A1R subtypes was estimated in vitro by competitive radioligand binding assays. In addition, selectivity studies were performed. An automated two-step one-pot radiosynthesis of [18F]FLUDA was developed. In vitro autoradiography was performed on cryosections of mice brain. Dynamic PET/MR studies under baseline and blocking conditions were assessed. The time-activity curves of the SUV ratio (SUVR) of striatum over cerebellum were used as measure for specific uptake. Metabolism was investigated in CD-1 mice via radio-HPLC analysis of extracted plasma and brain samples. Single-dose acute toxicity of FLUDA was assessed in male and female Wistar rats.
Results
A high A2aR binding affinity and high A1R selectivity were recorded for FLUDA (KiA2aR= 0.60 nM and KiA1R= XX nM). The two-step one-pot automated radiosynthesis of [18F]FLUDA was successfully established (radiochemical yield: 9±1%; radiochemical purity: ≥98%; molar activity= 69 333 GBq/µmol). In vitro autoradiography with [18F]FLUDA revealed a specific accumulation in the striatum, which is characterized by the binding parameters KD = 4.3 ± 0.7 nM and Bmax = 556 ± 143 fmol/mg wet weight (Fig.1A). In vivo evaluation in mice revealed that only the parent radiotracer was found in plasma and brain samples at 15 min p.i.. PET scans (n=3) showed a selective binding of [18F]FLUDA in striatum (SUVR15 30 min p.i.>8), which was significantly reduced by pre-treatment with 2.5 mg/kg i.p. tozadenant (30%, n=3, p<0.05, Fig.1B/C). The single dose toxicity study of FLUDA did not reveal any adverse effects for ~ 1000-fold of expected human dose.
Conclusion
The fully automated radiosynthesis of [18F]FLUDA allows its translation to clinical radiopharmacy. [18F]FLUDA exhibited a A2AR-specific accumulation in the striatum in vitro and in vivo. No safety concerns are expected upon administration of [18F]FLUDA according to toxicity and dosimetry studies. Altogether, these results encourage the performance of clinical trials to validate the potential of [18F]FLUDA for imaging of neuronal, cardiovascular and cancer-related diseases.
Acknowledgments
The authors thank the European Regional Development Fund and Sächsische Aufbaubank (SAB) for financial support (project no. 100226753).
[1] Kranz, M. et al. (2020) this volume.
 

Evaluating the economic viability as well as the sustainability of the Circular Economy (CE) system requires a deep understanding of the distribution of all elements, compounds, alloys, materials etc. in flows. In this paper, the circularity of the copper value chain, including primary and secondary processing, is rigorously evaluated. The studied system comprises the metallic copper production from primary sources (from mineral to metal), copper-containing commodity production (copper is mixed with other metals) and copper recycling through secondary smelting to close the loop. This is linked to photovoltaic (PV) panels and battery storage. A simulation model of this system is created using HSC Sim, considering more than 30 elements (and its various compounds), 180 unit operations and 800 flows. From the mass and energy balances obtained through the simulation, an exergy analysis is conducted to evaluate the resource consumption from a second law (entropy) perspective. Additionally, these results are complemented through a Life Cycle Assessment (LCA), the recovery of technology elements and by-products is discussed, while quantifying the losses through the value chain. Through the digitalization of the complete system, a better CAPEX and OPEX understanding of the metal recovery and losses can be obtained, as well as the associated resource consumption and environmental impacts. New flowsheets and technologies can be evaluated. Several scenarios show how the resource consumption and the environmental impacts are affected by the recovery of different materials to produce different products.

The extensive efforts on reducing the carbon footprint of cement production have motivated the investigations on the use of supplementary cementitious materials (SCM) as additive and/or substitute in cement blends. However, previous studies were focused on limited types of SCM including natural pozzolans, ground granulated blast furnace slag (GGBFS) and fly ash – which could readily exhibit reactivity in cementitious systems. In this article, a review on the advances in the valorisation of novel industrial by-products (non-ferrous slag, municipal incinerator bottom ash, and jarosite waste) are presented to provide solution in reducing the volume of industrial landfills while creating greener materials for building applications. The second part of this paper demonstrates a case study applying exergy to compare the footprint of the flowsheets derived from the valorisation of industrial by-products as SCM.

Für die Veranstaltung ist kein Abstract erforderlich.

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Laser wakefield accelerators (LWFA) feature unique electron bunch characteristics, namely micrometer beam size with duration ranging from a few fs to tens of fs. Precise knowledge of the longitudinal profile of such ultra-short electron bunches is essential for the design of future table-top x-ray light-sources.
Spectral measurements of broadband transition radiation from LWFA electron bunches passing through a metal foil are especially promising for non-destructively analyzing ultrashort longitudinal bunch characteristics with single-shot capability.

Our broadband, single-shot spectrometer combines the TR spectrum in UV/VIS (200-1000nm), NIR (0.9-1.7μm) and mid-IR (1.6-12μm). A complete characterization and calibration of the spectrometer have been done with regard to wavelengths, relative spectral sensitivities, and absolute photometric sensitivity. Our spectrometer is able to characterize electron bunches with charges as low as 1 pC and resolve time-scales from 0.4 to 40 fs. In addition, complementary data on the transverse bunch profile is provided by simultaneously imaging the CTR in the far- and near-field.

We present recent experimental results of different LWFA injection mechanisms, such as self-truncated ionization-injection and self-injection. By analyzing the transition radiation spectra and reconstructing electron bunch profiles including error analysis, we determine electron bunch profiles and peak currents of the respective injection regimes. In addition to bunch durations and peak currents, we discuss sub-fs beam micro-structures and systematic experimental scans of the nitrogen doping concentration for ionization-induced injection.

Introduction
Systemic administration of rotenone is able to reproduce the main pathological and behavioral hallmarks of Parkinson’s Disease (PD) in mice. Therefore, those mice are potentially useful for the development of therapies targeting the nicotinic acetylcholine receptor (α4β2nAChR) or the adenosine A2A receptor (A2AR).
Thus, we evaluated the ability of the rotenone model to resemble the decreased availability of α4β2nAChR and the increased availability of A2AR found in the brain of PD patients [1,2,3]. PET/MR imaging was performed to quantify these changes at early and later stages of the disease.
Methods
Two groups of 12-14-months-old male C57BL/6JRj mice (27-36 g) treated for 2 months (n=6) or 4 months (n=7) with rotenone, 5 days/week, 5 mg/kg p.o., and their corresponding control groups (n=7 and n=5, respectively) were investigated. (-)-[18F]Flubatine (6.4±1.9 MBq; Am: 1185±713GBq/μmol) for α4β2nAChR investigation and [18F]FESCH (5.0±1.8 MBq; Am: 116±19 GBq/μmol, EOS) [4] or [18F]FLUDA (5.7±1.2 MBq; Am: 96±10 GBq/μmol, EOS) for A2AR investigation were injected intravenously followed by 60 min dynamic PET scans[4]. The cerebellum was used as a reference tissue. The time-activity curves (TACs) of the SUV ratio (SUVR) of thalamus or striatum over cerebellum were used as measure for specific uptake.
Results/discussion
Specific uptake of (-)-[18F]Flubatine was observed in the thalamus of control and rotenone mice (SUVR60min p.i. ~3.5, all groups included). However, for none of the two treatment groups changes in α4β2nAChR availability compared to the control group were detected (figure 1).
Specific uptake of [18F]FESCH and [18F]FLUDA was observed in the striatum of control and rotenone mice (SUVR10-20 min p.i. ~4.8, all groups included) (figure 2).
PET scans revealed no significant differences in A2AR availability between control group and 2 months rotenone treatment group. However, the SUVR of the 4 months rotenone treatment group were higher compared to the control group (SUVR20-40 min p.i. 3.4 vs. 2.9, respectively), although statistically not significant due to the rather small and highly variable data set.
Altogether, the trend of these results indicates no accordance with clinical findings although a slightly increased availability of A2AR during the course of the disease can be mentioned.
Conclusion
Taking into account the high variability of the dataset, the investigation by PET/MR of the rotenone mouse model after 2 mo. and 4 mo. treatment shows no concordance with the clinical findings regarding α4β2nAChR and A2AR availabilities.
We assume that the rotenone mouse model might not be suitable to assess PD-related changes in the availability of the two targets and thus perhaps not suitable for the investigation of the related targeting-drug.
Acknowledgments
The European Regional Development Fund and Sächsische Aufbaubank are acknowledged for financial support (Project No. 100226753).
References
[1] Vuorimaa et al. Contrast Media Mol Imaging 2017; 6975841. [2] Meyer et al., Arch Gen Psych 2009, 66 : 866-877. [3] Cannon et al., Neurobiol Dis 2009 ; 34 : 279-90. [4] Khanapur et al., J Nucl Med 2017; 58: 466–472.

L-[11C]Methionin ([11C]Met) ist ein oft verwendetes PET-Radiopharmakon zur Diagnose Hirn-, Kopf-, Hals- sowie vom multiplen Myelom indizierten Tumoren. Die Radiosynthese von [11C]Met ausgehend von [11C]CO2 mit dem TRACERlab FXC-pro System liefert mitunter schwankende Ausbeuten, deren Ursache unklar ist.

Introduction
The sigma-1 receptor (S1R) is a chaperone protein of the mitochondrion-associated endoplasmic reticulum membrane and regarded as potential therapeutic target for a variety of malignant tumors including glioblastoma. Noninvasive assessment of changes in the availability of S1R could help to better understand the pathophysiology of glioblastoma and to improve diagnosis or treatment follow-up. We aim to evaluate the potential of (S)-(−)-[18F]fluspidine, a highly specific S1R radioligand, to characterize the expression of S1R in an orthotopic glioblastoma model in mouse with small-animal PET/MRI.

Methods
U87 human glioblastoma cells were stereotactically implanted into the striatum of three female nude mice (8 weeks old). At a median tumor size of 27 mm3 (determined with MR) 60 min dynamic PET scans were performed after i.v. injection of (S)-(-)-[18F]fluspidine (9.1 ± 2.1 MBq; Am: 140 ± 50 GBq/µmol, EOS). Time-activity curves (TACs) from the tumor and the contralateral regions were analyzed (PMOD v3.9). Peak-to-end ratios (P/E; Peak: SUV mean from 2-9 min, end: SUV mean from 45-60 min) were used to compare regions. Statistics: unpaired two-tailed Student’s T-test (P < 0.05).
To determine the S1R affinity (KD) and density (Bmax) in the tumor and the contralateral region, in vitro autoradiography was performed with (S)-(-)-[18F]fluspidine using cryosections of tumor bearing mice.

Results & discussion
Autoradiography showed an equal affinity of [18F]fluspidine for S1R in the contralateral and tumor region (KD: 17.5 ± 1.3 vs. 18.0 ± 4.9 nM), but a higher Bmax in the tumor (490 ± 43 vs. 1756 ± 40 fmol/mg prot). PET TACs reflected significantly different kinetic profiles in the tumor and the contralateral side (P/E: 3.10 ± 0.48 vs. 1.81 ± 0.16, p < 0.05) (Figure 1). Interestingly, the tumor regions were characterized not only by a lower initial uptake compared to the contralateral side (SUV2-9 min p.i.: 0.89 vs. 1.17, p < 0.05) but also by a slower washout resulting in equivalent SUVs in both regions at 45 min p.i. (SUV45-60 min p.i.: 0.38 vs. 0.34 respectively). This slower radiotracer washout from the tumor compared to the contralateral side is assumed to be caused by the higher S1R site density found in the tumor, along with the specific pathophysiology of the tumor itself (neovascularization, oncotic pressure).

Conclusions
The PET investigation revealed a significant difference in the pharmacokinetics of (S)-(-)-[18F]fluspidine between the brain tumor and the contralateral region, probably related to different S1R availabilities. These results show the suitability of (S)-(-)-[18F]fluspidine for the non-invasive determination of the S1R status in an orthotopic glioblastoma model.

Objectives: The development of CB2R PET radioligands has been intensively explored due to the pronounced CB2R upregulation in various pathological conditions. Herein we report on the development of a series of highly affine fluorinated indole-carbamate ligands targeting the CB2R. Starting from a pinacol-ester precursor, cooper-mediated automated radiofluorination and preliminary biological evaluation were also performed for the most promising ligand.
Methods: A series of fifteen indole-carbamate derivatives was synthesized and their binding affinities (Ki) towards CB2R were determined. Compound RM365 was further selected for PET development due to its high CB2R affinity (KiCB2 = 2.1 nM) and pronounced selectivity over CB1R (factor >300). A fully automated copper-mediated radiofluorination of [18F]RM365 was established starting with the corresponding arylboronic ester precursor. The metabolic stability of [18F]RM365 was investigated in plasma and brain samples (30 min p.i) by radio HPLC. PET studies with [18F]RM365 were performed under baseline and blocking conditions (60 min scan).

Results: [18F]RM365 was obtained with moderate radiochemical yield (5%), high radiochemical purity (>98%) and molar activities of about 35 GBq/µmol. PET studies revealed that [18F]RM365 readily crossed the blood-brain barrier and accumulated in the spleen, a CB2R-rich organ. Metabolite studies at 30 min p.i. showed that 55% and 90% of the total extracted activity accounted for the percentage of parent tracer, in plasma and brain samples, respectively.

Conclusion: A fully automated cooper-mediated radiosynthesis was established for [18F]RM365. Further blocking experiments will demonstrate the CB2R specificity of [18F]RM365 in vivo and will be use as pass-fail criterion for further application of the radiotracer in CB2R-related animal models.

In thin amorphous carbon (a-C) films being in contact with a thin nickel layer, metal-induced crystallization and layer exchange (LE) occur at temperatures lower than 700 °C. Analysis of thin film stacks with different architectures (a-C/Ni, Ni/a-C and Ni/a-C/Ni) by means of ion beam analysis, Raman spectroscopy, X-ray diffraction and transmission electron microscopy revealed that the degree of LE and the structural quality of the crystallized carbon layers depend on the initial layer sequence. A LE degree of approx. 93 % was found for Ni/a-C bilayers, where graphenic layers formed on the Ni surface, whereas in a-C/Ni bilayers only 83 % of carbon was transferred from the surface towards the fused silica substrate. The diffusion of carbon in the outward direction produces turbostratic carbon with basal planes oriented parallel to the Ni surface, while for the inward direction planar and curved turbostratic structures coexist. The crystallization and the LE are driven by the crystallization energy of a-C. The LE is mediated by the wetting of the Ni grain boundaries by carbon. The directionality of the LE was explained primarily by the difference in the surface and interface energies in the a-C/Ni and Ni/a-C stacks that were obtained from thermodynamic considerations.

The administration of antibodies blocking the immune checkpoint molecules programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) has evolved as a very promising treatment option for cancer patients. PD-1/PD-L1 inhibition has significantly enhanced expansion, cytokine secretion, and cytotoxic activity of CD4(+) and CD8(+) T lymphocytes, resulting in enhanced antitumor responses. Anti-PD-1 or anti-PD-L1 therapy has induced tumor regression and improved clinical outcome in patients with different tumor entities, including melanoma, non-small-cell lung cancer, and renal cell carcinoma. These findings led to the approval of various anti-PD-1 or anti-PD-L1 antibodies for the treatment of tumor patients. However, the majority of patients have failed to respond to this treatment modality. Comprehensive immune monitoring of clinical trials led to the identification of potential biomarkers distinguishing between responders and non-responders, the discovery of modes of treatment resistance, and the design of improved immunotherapeutic strategies. In this review article, we summarize the evolving landscape of biomarkers for anti-PD-1 or anti-PD-L1 therapy.

Aim/Introduction: The Al18F-labeling method is as modern technique an alternative to conventional 18F-labeling procedures that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure in aqueous solution [1]. In search for versatile applicable chelators, which allow stable binding of both 18F and radiometals such as 68Ga or 111In, a cyclohexanediamine-triazole-chelator was designed. This chelator was conjugated via copper-catalyzed azide-alkyne cycloaddition (CuAAC) to the well-known binding motif (glutamate-urea-lysine) of the prostate-specific membrane antigen (PSMA) [2-5] complemented by 2-azidoacetyl moiety as linker unit (ligand L1). Furthermore, ligand L2 was synthesized bearing a 6-azidohexanoyl moiety as linker to investigate the influence of the linker on the stability of final 18F or radiometal complex.
The aim of this study was to investigate the radiopharmacological potential of L1 and L2 after radiolabeling regarding binding properties, cell internalization, and in vivo behavior in a murine prostate cancer model.
Methods: For the in vitro assays PSMA-positive LNCaP cells were used. The incubation with the respective radiolabeled ligand (RCY>95%) was terminated via a cell harvester. Internalization experiments were carried out by the “acid wash” method. In vivo studies (biodistribution and small animal PET) were performed with mice bearing a prostate tumor.
Results: In competition assays versus [177Lu]Lu-PSMA-617 (“gold standard”), the affinity of non-labeled L1 and L2 was slightly lower than that of PSMA-617. Saturation analysis of [68Ga]Ga-L1, [111In]In-L1, and [18F]F-L1 binding on LNCaP homogenate was comparable to [18F]F-L2 binding. The obtained Kd values were in a range of 20 to 30 nM. Internalization experiments with LNCaP cells revealed a lower uptake of the differently labeled L1 and L2 conjugates compared to [64Cu]Cu-PSMA-617.
Furthermore, in vivo behavior of both [18F]F-L1 and [18F]F-L2 was investigated in prostate carcinoma bearing mice by biodistribution experiments and small animal PET imaging. Thereby, PSMA dependent tumor uptake could be observed.
Conclusion: After successful radiolabeling, the conjugates L1 and L2 showed promising binding properties towards PSMA. The chelator presented here offers a flexible platform for radiolabeling of peptides or proteins for various PET and SPECT applications.
References: [1] F. Cleeren, Bioconjugate Chem. 2016, 27, 790. [2] K. Kopka, J. Nucl. Med. 2017, 58,17S. [3] H.R. Kulkarni, Br. J. Radiol. 2018, 91, 20180308. [4] Y. Tolkach, Breast Cancer Res.Treat. 2018, 169, 447. [5] M.C. Haffner, Hum.Pathol. 2009, 40, 1754.

We have investigated the influence of the position of the dopants and the number of Bragg mirrors in the confinement of localized states in the continuum of a InGaAs/InAlAs superlattice with a structural defect. The potential profile of the conduction band of the superlattice was determined by self-consistently solving the Schrödinger-Poisson equations. The influence of these parameters was analyzed by the oscillator strength of the optical transition between the ground state and the first localized state in the continuum. The best location for the dopants is in the structural defect quantum well, for which an oscillator strength of 0.25 was obtained. It is found that two Bragg mirrors are enough to confine the first localized state in the continuum without decreasing the oscillator strength of the optical transition from the ground state.

A series of tetradentate N₂O₂-type Schiff base complexes with tetravalent 4f-and 5f-block metals, [M(salpn)₂] (H₂salpn = N,N’-disalicylidene-1,3-diaminopropane; M = Ce, Th, U, Np, and Pu), were prepared to systematically investigate their solid state structure, and their complexation behaviour in solution with the goal to investigate the subtle differences between 4f and 5f-elements. X-ray diffraction revealed that all investigated metal cations form [M(salpn)₂] complexes. All the complexes show the same ligand arrangement with meridional conformation, amongst which only Ce(IV) exhibits unique behaviour upon crystallisation. [Ce(salpn)₂] crystallises in two less symmetric systems (P-1 or P2₁/n), whilst all the other [M(salpn)₂]
crystallise in a more symmetric orthorhombic system (Pban). Quantum chemical calculations suggest that the observed structural peculiarity of Ce(IV) stems from the geometrical flexibility due to the more "ionic" nature of bonds to the 4f element. ¹H NMR measurements revealed that [M(salpn)₂] forms two different species in solution with and without an additional solvent molecule, where the relative distribution of the two species depends mainly on the ionic radius of the metal centre. Again, Ce(IV) behaves differently from the tetravalent actinides with a higher ratio of the solvent-moleculecoordinated species than the ratio expected from its ionic radius. Hence, this study is successful in observing subtle differences between 4f- (i.e. Ce) and 5f-elements (actinides; Th, U, Np, and Pu) both in the solid state and in solution on an analytically distinguishable level, and in relating the observed subtle differences to their electronic structure.

A new caesium sputter negative ion source with planar ionizer for Accelerator Mass Spectrometry (AMS) is being built, regarding quantifying the ratios of long-lived cosmogenic radionuclides in micrometeorites.
The focus of the ion source is on an optimal ion-optics design, together with a realization of new concepts for the construction and function of the ionizer, with the possibility of the precise in-situ adjustment of the ion-optical components, and optimization of the caesium ion beam and ion transport. In addition, the source is designed for operation with higher cathode voltage (up to 20 kV), which aims to increase the sputter rate of the sample, and in turn to increase the extracted negative current. Higher ion currents and better ion yields mean shorter measuring times, higher precision due to higher counting statistics and/or higher throughput of samples in an AMS runs.
The authors would like to thank the Federal Ministry of Education and Research of Germany for its financial support (project 05K2016), and the HZDR’s Ion Beam Center for its essential contribution to the realization of this project.

The rapid development of extreme ultraviolet (EUV) and x-ray ultrafast coherent light sources such as free electron lasers (FELs) has triggered the extension of wave-mixing techniques to short wavelengths. This class of experiments, based on the interaction of matter with multiple light pulses through the Nth order susceptibility, holds the promise of combining intrinsic ultrafast time resolution and background-free signal detection with nanometer spatial resolution and chemical specificity. A successful approach in this direction has been the combination of the unique characteristics of the seeded FEL FERMI with dedicated four-wave-mixing (FWM) setups, which leads to the demonstration of EUV-based transient grating (TG) spectroscopy. In this perspective paper, we discuss how the TG approach can be extended toward more general FWM spectroscopies by exploring the intrinsic multiparameter nature of nonlinear processes, which derives from the ability of controlling the properties of each field independently.

The superimposed rotation and inclination of a catalytic fixed bed reactor is a promising process intensification strategy for gas-limited multiphase reactions. The reactor inclination forces flow stratification and the rotation leads to a binary and intermittent catalyst wetting. This way, the accessibility of the gas-phase to the catalyst is enhanced and a twofold increase of the conversion for the α-methylstyrene hydrogenation was shown experimentally. In this contribution, a hybrid model approach is introduced to predict the space-time-yield for the hydrogenation of α-methylstyrene and to identify beneficial operating conditions to enhance the process performance.

The inclined rotating fixed-bed reactor with inner tube is a promising process intensification concept for gas-limited reactions. In order to take full advantage of the reactor concept the installation of an inner concentric displacement tube is proposed to support the wetting intermittency of the whole fixed-bed at different liquid filling levels. The effects of operating conditions and design parameters on flow stratification, liquid filling level and specific pressure drop are analysed to identify the process window. In particular, the influence of superficial phase velocities, inclination angle, rotational velocity, particle diameter and inner tube diameter are studied. The liquid phase distribution is characterized with a capacitance-based wire-mesh sensor, which is adapted to cope with organic liquid, porous alumina catalyst packings and reactor rotation. Furthermore, the radial porosity distribution in the annular fixed-beds is determined using gamma-ray computed tomography.

Objectives: For about 10 years, numerous ligands have been developed and tested for their suitability for 18F-labeling in the form of [18F]aluminum monofluoride. Initially, the well-known macrocyclic ligands NOTA and NODA [1,2] with high temperature reactions were used. Under current approaches, open chain ligands, derived from ethylene diamine, provide a much faster complex formation at lower temperatures (<40°C) [3]. The use of a terminal alkyne linker, as one of these new approaches, also enables the conjugation to target molecules via copper catalyzed azide-alkyne cycloaddition (CuAAC) as the final step in ligand synthesis. Furthermore, these triazole-containing ligands offer interesting additional applications, besides kit-like 18F-labeling, they also can be used for the stable fixation of other radiometal ions preferring a six-fold coordination. Radionuclides like 68Ga, 111In or 64Cu show promising results with these ligands and are under current investigation.
Methods: Ligand L1-L3 synthesis was carried out via CuAAC with subsequent product characterization. Radiolabeling reactions with the ligands L1-L3 were carried out under comparable conditions for different radionuclides: 0.1 M sodium acetate buffer pH 4-5, 10 µg ligand, 20 min mixing at room temperature with [68Ga]GaCl3, [111In]InCl3, [64Cu]CuCl2 or freshly prepared [18F]AlFCl2-solution. Examples for the ligand synthesis, radiolabeling experiments with different radionuclides, stability studies and initial in vitro and in vivo studies will be presented in this work.
Results: The [68Ga]Ga-L1, [64Cu]Cu-L1, and [18F]AlF-L1 complexes show comparable in vivo behavior 5 min after single intravenous injection in NMRI nu/nu mice. The gallium and fluorine labeled species show faster renal elimination than the copper compound. The [68Ga]Ga-L1 complex also shows higher stability in serum than the corresponding copper complex [64Cu]Cu-L1. The 18F-labeled species show very low defluorination in vivo and therefore high stability.
Conclusion: The incorporation of the ligand via CuAAC opens up many new possibilities for the radiolabeling of peptides and small antibody-derived proteins by 18F as coordinated [18F]aluminum monofluoride. Additional options are given due to the flexibility of the triazole-containing conjugates for further radionuclides like 68Ga, 64Cu and 111In.

We investigate the ultrafast magnetization dynamics of FePt in the L10phase after an optical heating pulse, asused in heat-assisted magnetic recording. We compare continuous and nano-granular thin films and emphasizethe impact of the finite size on the remagnetization dynamics. The remagnetization speeds up significantlywith increasing external magnetic field only for the continuous film, where domain-wall motion governs thedynamics. The ultrafast remagnetization dynamics in the continuous film are only dominated by heat transportin the regime of high magnetic fields, whereas the timescale required for cooling is prevalent in the granular filmfor all magnetic field strengths. These findings highlight the necessary conditions for studying the intrinsic heattransport properties in magnetic materials.

Intro
Reactor‐produced Hg‐197 saw previous medical use in radiolabelled chlormerodrin for SPECT imaging[1] in the 1960s and 70s but was discontinued because of the up-and‐coming Tc‐99m generator system's widespread use, the uncertain in vivo stability of Hg‐197 labelled compounds and the low molar activity of the Hg‐197 itself (<2 GBq/μmol).[2] Cyclotron produced Hg‐197(m) is able to overcome the chemical toxicity issue, due to the much higher molar activity achieved (>500 GBq/μmol),[3] allowing access, at innocuous mercury concentrations, to the theranostically useful decay modes and half‐life of the radiometal's metastable nuclear isomer (γ for SPECT imaging and conversion and auger electrons for tumour therapy. Hg‐197g T1/2 = 64.1 h, Hg‐197m T1/2 = 23.8 h).
Objective
The development of an in vivo stable mercury compound able to conjugate to a cancer‐targeting carrier. Radiopharmaceutical applications obviously require high in vivo stability but the fast metabolism of most mercury compounds in solution is a prevalent issue.[4] However, Hg‐C organometallics show good water‐stability and bypass the issue of Hg‐S bonds suffering from competition by common thiol‐containing biomolecules, e.g., cysteine. Therefore, this project is specifically focussed on the strongest of this kind: the mercury‐phenyl bond.[5] Previous study has shown that the syntheses of monodentate ligands for κ1‐L2Hg species suffer from significant cleavage. [6] For this reason, our research is centred on the synthesis of a bidentate chelator design, due to the entropic advantage, the improved formation kinetics and the stability imparted by steric shielding.
Current Results
Separation from the gold target leaves the produced Hg‐197(m) in an acidic aqueous solution as the chloride salt. Consequently, transmetallation, via boronic acid or stannyl derivatives, was chosen as a feasible route for forming the mercury‐carbon bonds. Following several chelator attempts, all showing low selectivity for the 1:1‐compound, a better fitting structure was found using the bispidine backbone (being known in co‐ordination chemistry for a variety of metals, good bio‐stability and its bridge linking‐functionalisation).[7] After improvement of the reaction conditions, radiolabelling experiments showed good evidence of specific binding with the bispidine derivative 9‐butyl‐1,5‐diphenyl‐3,7‐bis(2‐(trimethylstannyl)benzyl)‐3,7‐diazabicyclo[3.3.1]nonan‐9‐ol “L1(SnMe3)2,” as analysed by thiol‐impregnated radio‐TLC and supported by radio‐HPLC, whilst ESI‐MS of the stable mercury compound provided evidence that the desired 1:1 product had been formed. The in vitro stability tests conducted on the radiolabelled compound showed exciting results, with negligible degradation after 5 days (thereafter the activity was below analytical levels) in solutions with excess glutathione and 2,2′,2″‐nitrilotris (ethane‐1‐thiol). The only noticeable (ca. 5% degradation after 48 h), but expected reaction, was with sodium sulphide. Biodistribution experiments in healthy male Wistar rats showed no build‐up in the kidneys, with excretion occurring through the liver, indicating no de‐metallation.
Summary
The bisarylmercury bispidine (L1Hg) shows good stability in vitro as well as in vivo and is a promising candidate as a biocompatible mercury binding compound. Further
research is continuing into full characterisation, conjugation to peptides and proteins, subsequent in vivo studies and for derivatives based on the structural design.

ACKNOWLEDGEMENTS
Regina Herrlich, Ulrike Gesche, Thomas Wünsche. Hg‐197(m) measurements were carried out at the CANAM infrastructure of the NPI CAS Rez supported through MEYS project no. LM2011019.

REFERENCES
1. Sodee DB. Comparison of 99mTc‐pertechnetate and 197Hgchlormerodrin for brain scanning. J Nucl Med 1968;9(12):645.
2. Ribeiro Guevara S, Zizek S, Repinc U, Perez CS, Jacimovic R, Horvat M. Anal Bioanal Chem 2007;387:2185–2197.
3. Walther M, Preusche S, Bartel S, Wunderlich G, Freudenberg R, Steinbach J, Pietzsch H‐J. Appl Radiat Isot 2015;97:177‐181.
4. Henke KR, Robertson D, Krepps MK, Atwood DA. Wat Res 2000;34:3005‐3013.
5. Dean JA. Lange's Handbook of Chemistry, 15th ed. McGraw‐Hill, Inc: 1998.606 p.
6. Wilhelm M, Saak W, Strasdeit H. Z Naturforsch 2000;55b:35‐38.
7. Comba P, Haaf C, Wadepohl H. Inorg Chem 2009;48:6604‐6614.

Carbon monoxide has been demonstrated to exhibit several beneficial effects on biological targets (anti-inflammatory, anti-proliferative, anti-apoptotic effects, causes vasodilation, etc.).1 Consequently, the development of CO releasing molecules (CORMs), that allows for controlled release of CO under physiological conditions, has therefore become a major field of scientific and medical interest.2,3 Considerable research interest has been drawn on light-activated CORMs (photoCORMs) which only release CO upon radiation with a certain energy. However, despite a large number of photoCORMs reported, relatively little information is available on the precise mechanism of CO release from most photoCORMs and even less compounds have been tested as anti-cancer agents in cells so far.
Herein, we report about the synthesis of ruthenium(II) dicarbonyl complexes functionalized with bidentate or tridentate (pyridyl, phenanthroline or diquinolyl) ligands and appending dyes for tuning the release properties as well as tracking the compound in cells. The mechanism of CO release in aqueous media (before and after light-activation) has been investigated. The photo-induced CO release kinetics of the Ru(II) photoCORMs, as well as in vitro studies in cancerous and healthy cell lines will be presented.4,5

References

[1] R. Motterlini, L. E. Otterbein, Nat. Rev. Drug Discov. 9 (2010) 728-743.
[2] U. Schatzschneider, Br. J. Pharmacol. 172 (2015) 1638-1650.
[3] F. Zobi, Future Med. Chem. (2013) 5, 175-188.
[4] M. Kubeil, R. R. Vernooij, C. Kubeil, B. R. Wood, B. Graham, H. Stephan, L. Spiccia, Inorg. Chem. 56 (2017) 5941-5952.
[5] M. Kubeil, T. Joshi, B. R. Wood, H. Stephan, ChemistryOpen (2019) 8, 637-642.

Acknowledgements

MK was supported by a Marie Curie International Outgoing Fellowship from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 627113.

Ammonia is one of the most highly produced chemicals in the world, being the source of all nitrogen-based fertilizers. Its conventional production relies on fossil fuels reforming as its source of hydrogen, cryogenic air separation for nitrogen, and the Haber-Bosch process for the ammonia synthesis itself. This route has made ammonia production responsible for the consumption of 1% of all energy worldwide, and for the emissions of 298 Mt CO2 eq./year. In a future where most energy comes from fluctuating sources, such as the one envisioned in the Energiewende, energy intensive industries like ammonia production would need to adapt its operation to mimic that of energy generation. A potential alternative for ammonia production is to obtain hydrogen and nitrogen from water electrolysis, and pressure swing adsorption (PSA) respectively. In our effort for the flexibilization of the chemical industry, we have designed a small ammonia production plant using these technologies. With it we intend to cover the fertilizing needs of a large German farm (1,000 ha), requiring a minimum production of 100 t NH3/year. As a first step, we purchased the electricity used for the water electrolyzer in the day-ahead market. The rest of the plant relied on a steady industrial supply. Our first results indicated the plant was not profitable. The main reason behind this are the capital investment in the intermediate hydrogen storage unit

Clear understanding of molecular events followed by lung epithelial cells/tissue response to inhaled nanoparticles is still lacking. As these interaction events in lungs eventually lead to diseases and potentially persistent inflammation [1,2], one urgently needs new and relevant investigation methods which could provide new insights into the key mechanisms of interaction. In our latest research we have thus focused on this toxicology problem first by developing an appropriate in vitro lung epithelial model and second by developing and implementing relevant advanced correlative imaging techniques capable of gathering more insight of interaction properties on scales well below optical resolution limit. In order to understand the mechanisms of molecular initiative events we have first performed live cell imaging using STED super-resolution microscopy by which few tens to hundred nm resolution was achieved locally. As the technique is incapable of providing resolution further down to nm and lacks the visualization of non-labeled surrounding structures and morphology, we thus introduced suitable complementary correlative microscopy techniques with high surface contrast, SEM and Helium Ion Microscopy (HIM). Main focus, besides sample and sample holder preparation for these high vacuum techniques, was dedicated to HIM measurements which in general are capable of providing better resolution and sensitivity compared to SEM [3]. From this ongoing study we briefly present the first interesting results of correlative microscopy combining optical, electron and ion based techniques on the epithelial cells exposed to TiO2 nanoparticles from micro to nano scale.
References:
1. Li, X., Jin, L. & Kan, H. Air pollution: a global problem needs local fixes. Nature 570, 437–439 (2019).
2. Underwood, E. The polluted brain. Science 355, 342–345 (2017).
3. Hlawacek, G. et Al. Helium Ion Microscopy. J. Vac. Sci. Technol. 32, (2014)

Clear understanding of molecular phenomena of cells/tissue response after interacting with dangerous metal nanoparticles is still lacking. In our research we thus focus on highly relevant scientific/toxicology problem, which is understanding of the mechanisms of molecular initiative events between nanoparticles (typically smaller than 100 nm) and lung tissue cells during inhalation [1]. It is strongly believed that nanoparticles can trigger toxic effects with increasing risk for further cardiovascular diseases [2]. However, limited spatial resolution of optical microscopy, even in super-resolution mode, prevents visualization of interaction phenomena at smaller, nanometer scales which could reveal some of still unclear molecular events. In order to get better insight on the phenomena at such small scales one needs to introduce proper correlative microscopy techniques which in our case are electron (eSEM) and ion based (PIXE, HIM). Since these techniques are commonly employed in high vacuum and detection principles differ reasonably in comparison to optical imaging techniques, special sample holders have to be developed in order to perform efficient correlative microscopy on different submicron scales.
In this pilot study we first tested the performance of correlative microscopy on epithelial cells nebulized with TiO2 nanoparticles using optical, eSEM and RISE techniques, while in the second pilot study we developed the concept for robust special holder preparation in order to enable super-resolution optical imaging (STED) as well as ion based imaging on the same sample site. Despite integrating few to few tens micron sized layers consisting of Mylar foil, water and glass which introduce refractive index mismatches, we were able to improve confocal resolution by at least factor 2-3 using STED imaging. This was a proof-of-concept that we can perform high resolution optical imaging on these holders which can successfully be implemented as well in correlative electron/ion based imaging, thus giving the opportunity to gain better insight of the measured complex samples from nano to micro scale.

[1] Iztok Urbančič et al., “Nanoparticles Can Wrap Epithelial Cell Membranes and Relocate Them Across the Epithelial Cell Layer,” Nano Letters 18, 5294–5305.
[2] Robert D. Brook et al., “Air Pollution and Cardiovascular Disease: A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association,” Circulation 109, 2655–2671

Deep learning models, especially deep convolutional neural networks (CNNs), have been intensively investigated for hyperspectral image (HSI) classification due to their powerful feature extraction ability. In the same manner, ensemble-based learning systems have demonstrated high potential to effectively perform supervised classification. In order to boost the performance of deep learning-based HSI classification, the idea of deep learning ensemble framework is proposed here, which is loosely based on the integration of deep learning model and random subspace-based ensemble learning. Specifically, two deep learning ensemble-based classification methods (i.e., CNN ensemble and deep residual network ensemble) are proposed. CNNs or deep residual networks are used as individual classifiers and random subspaces contribute to diversify the ensemble system in a simple yet effective manner. Moreover, to further improve the classification accuracy, transfer learning is investigated in this study to transfer the learnt weights from one individual classifier to another (i.e., CNNs). This mechanism speeds up the learning stage. Experimental results with widely used hyperspectral datasets indicate that the proposed deep learning ensemble system provides competitive results compared with state-of-the-art methods in terms of classification accuracy. The combination of deep learning and ensemble learning provides a significant potential for reliable HSI classification.

Hyperspectral image (HSI) classification is a core task in the remote sensing community, and recently, deep learning-based methods have shown their capability of accurate classification of HSIs. Among the deep learning-based methods, deep convolutional neural networks (CNNs) have been widely used for the HSI classification. In order to obtain a good classification performance, substantial efforts are required to design a proper deep learning architecture. Furthermore, the manually designed architecture may not fit a specific data set very well. In this paper, the idea of automatic CNN for the HSI classification is proposed for the first time. First, a number of operations, including convolution, pooling, identity, and batch normalization, are selected. Then, a gradient descent-based search algorithm is used to effectively find the optimal deep architecture that is evaluated on the validation data set. After that, the best CNN architecture is selected as the model for the HSI classification. Specifically, the automatic 1-D Auto-CNN and 3-D Auto-CNN are used as spectral and spectral-spatial HSI classifiers, respectively. Furthermore, the cutout is introduced as a regularization technique for the HSI spectral-spatial classification to further improve the classification accuracy. The experiments on four widely used hyperspectral data sets (i.e., Salinas, Pavia University, Kennedy Space Center, and Indiana Pines) show that the automatically designed data-dependent CNNs obtain competitive classification accuracy compared with the state-of-the-art methods. In addition, the automatic design of the deep learning architecture opens a new window for future research, showing the huge potential of using neural architectures' optimization capabilities for the accurate HSI classification.

There is a growing demand for mineral resources worldwide, and yet industry is facing increasing obstacles in obtaining public acceptance for new exploration and mining projects. Numerous recent citizen protests highlight the public perception of ‘dirty’ mining projects and increase the reluctance of investors to finance explorations. Non-invasive exploration techniques can be defined as energy efficient, low-impact technologies. They assist in the detection and mapping of mineral deposits and improve exploration targeting with minimal environmental impact, while demonstrating that industry cares about reducing disturbance to the communities and environment in which they operate. However, it is increasingly understood that non-invasive technologies can help to maintain the social licence to operate and consequently lower the investment risk of exploration. To demonstrate this premise, we established an EU-funded research initiative called INFACT (Innovative, Non-Invasive and Fully Acceptable Exploration Technologies), which supports the development of innovative exploration and stakeholder engagement approaches. Our project will establish a set of permanent, accessible reference sites to trial and assess the technological and social performance of existing and emerging innovative, non-invasive exploration techniques like UAVs infrared hyperspectral imaging, magnetics, EM and radiometry.

Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9 and 29%. An in vitro competitive binding assay using L-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of L-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.

The fusion of remote sensing datasets for combined classifications has recently received great attention. Separate data acquisition and subsequent fusion allow for sensor-specific adjustments of experimental parameters and flexible sensor combinations. In mineral exploration, multi-sensor approaches are particularly promising to extend the range and accuracy of mineral phase detection. However, the time-efficient and accurate integration of data with differing resolution, field of view or acquisition modi remains challenging. This motivates us to promote a multi-source data integration based on efficient feature extraction strategies. An important pre-requisite for a successful integration is data co-registration. A workflow combining automated keypoint detection and matching provides an accurate and fast method to align multi-sensor datasets of different spatial sampling distances for a joint processing. For feature extraction, we employ innovative methods that consider both spatial and spectral aspects such as Orthogonal Total Variation Component Analysis (OTVCA). Besides the reduction of dimensionality and consequently processing time, the method allows the integration of textural and spectral information, such as short wave and long wave hyperspectral imagery or reflectance and luminescence data that are not directly interpretable with a single method. Application-relevant mineral assemblage classes such as alteration zones, ore zones or mineralized veins, become then discriminable as the spatio-spectral patterns are evident by extracting relevant features from all datasets. We use a Support Vector Machine with Radial Basis Function Kernel (SVM-RBF) to demonstrate the classification of mineralogical domains from such multi-source feature fused sets. We choose SVM as it is particularly robust when handling high-dimensional data with low number of training samples and against the heterogeneity of classes that is typical for mineralogical datasets. The optimal classification parameters are determined by five-fold cross- validation to ensure the best possible classification result with the given data. Training data required for the classification can be defined according to user knowledge, high resolution mineralogical analyses or spectral point measurements. The proposed multi-source data integration workflow shows to exceed the classification accuracy of single-source data and could be beneficial for many potential application fields in mineral exploration, mineral processing, recycling or food industry.

The root cause of “Light and Elevated Temperature Induced Degradation” (LeTID) of the carrier lifetime in multicrystalline silicon (mc-Si) wafers is investigated by depositing hydrogen-rich silicon nitride (SiN x :H) films of different compositions on boron-doped mc-Si wafers. The extent of LeTID observed in mc-Si after rapid thermal annealing (RTA) shows a positive correlation with the amount of hydrogen introduced from the SiN x :H layers into the bulk. The concentration of in-diffused hydrogen is quantified via measuring the resistivity change due to the formation of boron–hydrogen pairs in boron-doped float-zone silicon wafers processed in parallel to the mc-Si wafers. The measurements clearly show that the in-diffusion of hydrogen into the silicon bulk during RTA depends on both the atomic density of the SiN x :H film as well as the film thickness. Importantly, the impact of SiN x :H film properties on LeTID shows the same qualitative dependence as the hydrogen content in the silicon bulk, providing evidence that hydrogen is involved in the LeTID defect activation process.

Current Euler-Euler modeling based on phase-averages shows inconsistencies since the finite size of the bubbles is not properly accounted for. As a result, nonphysical gas concentration can appear in the center or the near wall region of a pipe if the bubble diameter is larger than the mesh size (Tomiyama, Shimada et al. 2003). In addition, mesh independent solutions may not exist in these cases.
By employing particle-center-averages (Prosperetti 1998), these inconsistencies can be remedied and mesh independent solutions are obtained. In this approach, the number density of bubble centers is the primary variable. This requires an additional wall-contact force to ensure that bubble centers cannot come arbitrarily close to walls (Lucas, Krepper et al. 2007). The gas volume fraction can be calculated from the number density by a convolution (Kitagawa, Murai et al. 2001) with a kernel that has a support corresponding to the extent of a bubble. In addition, the derivation shows explicitly that bubbles respond to pressure and stress of the continuous liquid phase such that no additional closure models for the gas phase pressure or stress are required.
In the present contribution, the convolution method is replaced by a diffusion-based method (Sun and Xiao 2015), which is much easier to implement in CFD codes using unstructured meshes like OpenFOAM. A physically motivated model for the wall-contact force is introduced. The remedy of the issues with the conventional phase-averaged two-fluid model is demonstrated using a simplified two-dimensional test case. Furthermore, comparison is made for real pipe flow cases where experimental data are available.

References
Kitagawa, A., Y. Murai and F. Yamamoto (2001). "Two-way coupling of Eulerian–Lagrangian model for dispersed multiphase flows using filtering functions." International journal of multiphase flow 27(12): 2129-2153.
Lucas, D., E. Krepper and H.-M. Prasser (2007). "Use of models for lift, wall and turbulent dispersion forces acting on bubbles for poly-disperse flows." Chemical Engineering Science 62(15): 4146-4157.
Prosperetti, A. (1998). Ensemble averaging techniques for disperse flows. Particulate Flows, Springer: 99-136.
Sun, R. and H. Xiao (2015). "Diffusion-based coarse graining in hybrid continuum–discrete solvers: Theoretical formulation and a priori tests." International Journal of Multiphase Flow 77: 142-157.
Tomiyama, A., N. Shimada and H. Asano (2003). Application of Number Density Transport Equation for the Recovery of Consistency in Multi-Field Model. ASME/JSME 2003 4th Joint Fluids Summer Engineering Conference, American Society of Mechanical Engineers.

Objectives:

An MRI- and particle therapy compatible patient-individualized abdominal corset was developed and its efficacy to reduce respiratory-induced pancreas motion was evaluated by orthogonal 2D-cine and 4D-MRI.

Patients & Methods:

Nine patients (6 female; average age 72.9±9.6 years) with tumors of the pancreas (7), gallbladder (1), or liver (1) provided written informed consent to be scanned on a 3T MRI scanner (Philips Healthcare) by means of orthogonal 2D-cine and 4D-MRI, without and with a patient-individualized abdominal corset, respectively. A polyethylene (PE) abdominal corset (ORD Dresden GmbH) was customized based on an optical 3D-surface scan (Artec Eva®). For MR imaging the patients were positioned supine on a flat tabletop using an anterior coil holder to avoid compression of the chest wall. For 2D-cine MRI, coronal and sagittal slices were selected to image the pancreatic head. The 4D-MRI dataset was reconstructed by retrospectively resorting a multi-slice 2D acquisition into 10 respiratory phases. Pancreas motion was determined as center-of-mass displacement in three orthogonal directions (inferior-superior (IS), anterior-posterior (AP), left-right (LR)).

Results and Conclusion:

MRI revealed predominant motion in IS direction, which was reduced by 42% (p<0.05) in both 2D-cine (5.0±3.7 mm without corset; 3.8±1.1 mm with corset) and 4D-MRI (8.6±3.7 mm without corset; 5.0±2.4 mm with corset) through the corset which furthermore reduced the motion variability by 40% (p<0.01). The corset had no effect on motion in AP and LR direction. This confirms earlier results obtained with a custom-made polyurethane corset [1]. However, the homogeneous material properties of PE allow the corset to be integrated in PT without increasing range uncertainties. Pancreas motion in IS direction can be significantly reduced in patients scheduled for PT by an individualized abdominal corset.

[1] Heerkens et al, Phys Imaging Radiat Oncol 2017; 2:7–10.

Mass transfer is of paramount importance for an efficient operation of liquid metal batteries. We show for the first time that electrodynamically driven flow can indeed improve mixing of liquid electrodes, and reduces concen tration polarisation substantially. Simulating the discharge of a realistic Li||Bi cell at 1 A/cm², the corresponding overpotential reduces by up to 62%. Moreover, the formation of intermetallic phases is delayed, which improves
capacity usage. Finally, we demonstrate that vertical magnetic fields – which are originating from external sources – change the flow structure entirely, and will homogenise the positive electrode even better.

Liquid metal batteries (LMBs) consist of a stable density stratification of two liquid metal electrodes, separated by a molten salt electrolyte. Discharing the cell, the anode metal dissolves in the cathode metal. Due to slow diffusion, concentration layers develop especially at high current densities, and lead to considerable concentration polarisation. As the density difference between the anode and cathode metal is usually large, the formed density stratification is often very stable. The talk will describe how to simulate the electric potential, current density and Lorentz force in a liquid metal battery. Finally, it will be shown that electrodynamically driven flow is able to mix the cathode alloy of an LMB, thus reducing concentration polarisation. A 10 cm Li||Bi cell, studied experimentally by Ning et al., will be used as reference case.

Inherent boron dilution in PWRs constitutes one of the key issues in nuclear safety research. This issue has been therefore widely investigated analytically and experimentally through several test facilities in Germany. Besides the knowledge gained on the matter, the experimental research has contributed to the creation of large databases for the validation of computational tools used in accident analyses such as system and computational fluid dynamic (CFD) codes. In Part I of a series of two papers, the multidimensional features of the thermal-hydraulic system code ATHLET are assessed based on the experimental results from the boron dilution experiment E2.3 carried out at the ROCOM test facility. In Part II, a code to code evaluation is performed against the CFD code ANSYS CFX. The aim of the present paper is twofold: first to validate the 3D-Module of ATHLET as well as the “Profile Model I” boron transport model concerning the transport and thermal mixing in the developed multidimensional vessel during the progression of a complex boron dilution event. The obtained results with ATHLET 3.1A are satisfactory and meet the validation exercise goals, especially concerning the calculation of the average boron concentration. However, the limitations of the code to simulate thermal mixing in the cold legs lead to few deviations concerning the calculation of the minimum boron concentration.

Modelling of fluid mixing in reactor circuits with the thermal-hydraulic system code ATHLET

The present paper gathers the main insights obtained during the numerical simulation of a 10 % main steam line break (MSLB) in a generic German PWR KONVOI reactor with the thermal-hydraulic system code ATHLET 3.1 A. The contents of this paper are focused first on the transient thermal-hydraulic calculation during affected steam generator (SG) 1 boil-off and subsequently on the multidimensional fluid mixing study of the overcooled water stream and the coolant in the reactor pressure vessel. With this aim, the boundary conditions from the test PKL G3.1, carried out at the PKL test facility in the framework of the OECD/PKL-II project, are implemented in the simulation over the plant nominal parameters from the KONVOI reactor. The thermal-hydraulic and fluid mixing results obtained in the simulations are qualitatively assessed against suitable experimental data from the PKL and ROCOM test facilities, showing a good agreement between simulation and test behaviour.

Annular-dispersed two-phase flow in pipes consists of a thin wavy liquid film covering the pipe wall and a gas core with entrained liquid droplets. Knowledge of the film thickness and entrained liquid fraction is of importance in numerous industrial applications, such as the thermal design of heat exchangers.
The application of X-ray microtomography to obtain these parameters in case of small diameter pipes is presented here. The three-dimensional, time-averaged liquid fraction distribution has been measured in air-water annular flow in a horizontal pipe. In combination with pressure drop measurements, the film and entrained liquid mass flow rates are derived using a simple annular flow model. The portrayed method may also serve as a basis for the validation of computational fluid dynamics simulations of annular flow.

The long‐term availability of minerals and metals from primary (i.e. geogenic) and secondary (i.e. recycling) resources is not only the key to most economic activity, but also to the realization of important societal developments, such as the transition to a renewables‐based energy system and the rollout of e‐mobility. Due to several factors, the utilization of raw materials from geogenic sources will continue to form an essential part of the raw materials supply for a growing global population. In order to develop a highly skilled work force, to develop novel approaches for raw materials utilization, approaches that deploy resource‐ and energy‐efficient technologies for the delineation, extraction and beneficiation of mineral resources, while at the same time minimizing environmental risks, the Helmholtz International Research School for Predictive Geometallurgy (PREDICT) provides the first‐ever training programme dedicated to predictive geometallurgy and adaptive processing. PREDICT has pooled the interdisciplinary and intersectoral expertise of leading German and South African research institutes, world‐leading mining and metallurgical companies, covering all the links in the raw materials chain from exploration to mineral beneficiation and mine planning. PREDICT not only develops cuttingedge methodologies to take geometallurgical resource potential models to an entire new level but also implements and tests an optimal adaptive processing approach for a beneficiation plant model. In addition, we will combine both models by establishing feedback loops for model reconciliation.
Furthermore, PREDICT will close the loop by implementation of the model results in a simulation‐based mine‐planning block model.

This part of a series of two papers compares CFD simulation results of a boron dilution scenario with experimental results. The simulation was carried out with ANSYS CFX using the SST turbulence scheme, experimental data were produced in the ROCOM test facility, experiment E2.3. The main features of the scenario are asymmetric, transient mass flow conditions in the affected loops 1 and 2 of a KONVOI-type reactor vessel and reduced density of the underborated coolant slugs fed into the reactor trough the cold legs of both loops. The CFD simulation was able to capture the density stratification in the loops affected by underboration and the mixing in the downcomer and in the lower plenum. Good agreement with the experiment was obtained for the temporal evolution of average boron concentration in several measuring sections of the reactor vessel and of the boron distribution in the core inlet. In general, minimal values of boron concentration were found to be lower in the simulation than in the experiment.

The modern mining industry faces a number of important technical challenges, such as declining ore grades, complex mineral associations, fine-grain size and increasing geological variability. To meet these challenges geometallurgical models are constructed to quantita-tively predict how ores will behave during extraction and beneficiation. Current geometal-lurgical programs carried out by industry, focus on the definition of larger spatial domains that have similar characteristics. However, a consequent application and further develop-ment of geometallurgical programs should lead to an implementation of spatially more highly resolved geometallurgical resource models that are truly predictive for each mined block (including uncertainty), in order to improve raw material quality control and the process efficiency of mining operations. Such an approach would also enable the targeted recovery of by-products, which may generate significant additional revenue and improve overall efficiency. In order to construct relevant resource models, detailed quantitative information on the spatial distribution and geometallurgical behaviour of the by-products within the deposit is crucial.
The aim of this thesis is the development and creation of a predictive geometallurgical model by means of a case study and the presentation of the resulting advantages for the extraction of ores. Based on this, a general structure for the development of predictive geo-metallurgical models is developed, which can be applied to different types of commodities, as well as by-products, is cost-efficient, able to adapt to future data, and predicts metallurgi-cal parameters. As the case study serves the Thaba Chromium Mine in the western Bushveld Complex (South Africa), which is operated by Cronimet Chrome Mining SA (Pty) Ltd. In par-ticular, this thesis focusses on four distinct chromitite seams of the Lower and Middle Groups (LG and MG) at Thaba Mine, namely the LG-6, LG-6A, MG-1 and MG-2, which are considered as target seams for an open-cast and future underground mining scenario.
In order to understand the geological and geochemical architecture of the Thaba Mine deposit and as a foundation of the predictive geometallurgical model, an extensive geo-chemical dataset as well as logging and drill core data provided by Cronimet was evaluated and a 3D geological model was developed. A statistical assessment was performed to evalu-ate the variability within and between the chromitite seams and to separate the mine lease area into distinct geochemical clusters. The distribution of the samples belonging to the dif-ferent geochemical clusters was then transposed onto the geology of the mine lease area. This allowed the definition of spatial domains. These spatial domains, recognized by the as-sessment of assay data only, are then validated by mineralogical attributes; implications for mineral beneficiation are tested and verified.
According to this assessment, the chromitites of the Thaba Mine area can be subdivided into three distinct geochemical domains, domains that constitute the suitable foundation for a geometallurgical model. An extensive supergene altered domain or weathered domain is distinguished from a domain affected by hydrothermal alteration. The latter domain occurs below the depth of modern weathering, but in obvious proximity to faults and around a prominent dunite pipe. The third domain is represented by ores least affected by post-magmatic alteration processes. This domain occupies the centre of fault blocks below the extent of modern weathering.
Furthermore, the geochemical data is used to develop a tailored and easy-to-use multi-variate classification scheme for the chromitite layers in the Thaba Mine, based on a com-prehensive classification routine for the LG and MG chromitites. This routine allows a clear attribution with known uncertainty of all relevant chromitite layers. It comprises of a hierar-chical discrimination approach relying on linear discriminant analysis and involves five dis-tinct steps. Overall classification results for unknown samples belonging to one of the layers are 81 %. The approach may, however, be extended across the entire Bushveld, provided that an appropriate geochemical data set is available.
For detailed characterization of the mineral assemblages in the chromitite ores, selected core samples of the target layers were analysed in detail by various analytical methods, such as Mineral Liberation Analysis and Electron Probe Microanalysis. Therefore, we extended the common measurement protocols for electron probe microanalysis to ensure applicability to a wider range of PGM compositions and its overall accuracy as well as consistency. Based on the results two distinct major mineral assemblages are defined: The first assemblage is rich in platinum group element-sulphides, along with variable proportions of malanite/ cu-prorhodsite and alloys of Fe and Sn. The associated base metal sulphides are dominated by chalcopyrite and pentlandite, along with pyrite and subordinate millerite/ violarite. Associ-ated silicates are mainly primary magmatic orthopyroxene and plagioclase. The second as-semblage is rich in platinum group element-sulpharsenides and -arsenides as well as -antimonides and -bismuthides, which are associated with a base metal sulphide assemblage dominated by pentlandite and Co-rich pentlandite. The assemblage is also marked by an abundance of alteration minerals, such as talc, serpentine and/or carbonates, which are closely associated with the platinum group minerals. Statistical evaluation reveals that these two mineral assemblages cannot be attributed to their derivation from different chromitite layers, but document the effects of pervasive hydrothermal alteration.
The knowledge of the detailed mineralogical investigation was transferred to a large da-taset comprising similar mineralogical data for unweathered ore of the deposit. Hence, it was possible to identify seven distinct ore types via statistical assessment, subsequently val-idated through beneficiation tests of drill core material. In addition, metallurgical test work for large batch samples of the weathered domain was carried out. Furthermore, beneficia-tion tests were aligned with process chemistry and mineralogy to monitor the results.
The predictive geometallurgical model aims to express the recoverability of PGE as by-product from the chromite processing stream. Within this context, the weathered ores were regarded as a single domain, as chromite ores from this oxidized zone were consistently found to have very low PGE recoveries. Any attempt to recover PGE by flotation from this zone appears to be challenging. For unweathered ores, the approach towards a predictive geometallurgical model needs to be somewhat more complex. The following steps were performed:
(i) Building a predictive model of the recoverability of PGE as a function of chemical composition, i.e. establish a chemical proxy for PGE recoverability;
(ii) Performing a geostatistical modelling of the geochemical dataset, i.e. interpolation through cokriging, and
(iii) Combining step (i) and (ii) to generate a spatially-resolved geometallurgical model able to predict the potential to recover PGE by flotation in terms of probabilities.
The resultant predictive, spatially-resolved geometallurgical model displays the PGE pro-cessing potential in terms of probabilities and therefore incorporates uncertainty.
Based on the work flow applied in this study, a more generic framework towards a predictive geometallurgical model can be proposed that can be applied to different commodities, is able to adapt to future data, and predicts metallurgical parameters, e.g. the recoverability of an ore as probabilities (and therefore including uncertainty). Furthermore, the model can be applied to main as well as by-product and therefore represents a holistic modelling approach. Most of the modelled parameters are derived from primary ore properties (e.g. rock or particle stream), e.g. modal mineralogy, mineral association, densities, etc., combined with a minimum of empirical test work.

In the effort to become more sustainable the mining industry currently faces a number of important challenges. One important direction of change would be to achieve a more holistic use of mineral resources, i.e., by considering the efficient extraction and beneficiation of all possible valuable constituents – rather than only focusing on the major commodity. Thus, geometallurgical models need to be adapted accordingly. Instead of only centring on the efficient extraction and beneficiation of a single (economically most relevant) commodity, future geometallurgical models should be expanded to consider all potential products.
In the present contribution, a generic framework is proposed that can be applied to a large variety of different commodities; it is able to adapt to future data, predicts metallurgical parameters, e.g. the recoverability of an ore as probabilities, and can be extended to include environmental footprint calculations. Most of the parameters are derived from primary ore properties (e.g. rock or particle streams), e.g. modal mineralogy, mineral association, densities, etc., combined with a minimum of conventional test work. The work flow is demonstrated with a case study, in which the beneficiation potential of PGE as a by-product in an existing chromite mine in the Bushveld Complex of South Africa is considered. All available data were incorporated in a geological block model and interpreted to form geometallurgical domains of sufficient size to be considered during mine planning. The resultant predictive, spatially-resolved geometallurgical model displays the PGE processing potential in terms of probabilities and therefore incorporates uncertainty. The viability of the geometallurgical model relates well to the original geological architecture, is cost- and time-effective and highly versatile to form a foundation for further use and development during exploitation.

Non-collinear antiferromagnets are revealing many unexpected phenomena and they became crucial for the field of antiferromagnetic spintronics. To visualize and prepare a well-defined domain structure is of key importance. The spatial magnetic contrast, however, remains extraordinary difficult to be observed experimentally. Here, we demonstrate a magnetic imaging technique based on a laser induced local thermal gradient combined with detection of the anomalous Nernst effect. We employ this method in one the most actively studied representative of this class of materials - Mn₃Sn. We undoubtedly proof that the observed contrast is of magnetic origin. We further show an algorithm to prepare a well defined domain pattern at room temperature based on heat assisted recording principle. Our study opens a prospect to study spintronics phenomena in non-collinear antiferromagnets with spatial resolution.

We investigate magnetization dynamics in asymmetric interlayer exchange coupled Py/Ru/Py trilayers using both vector network analyzer-based and electrically-detected ferromagnetic resonance techniques. Two different ferromagnetic resonance modes, in-phase and out-of-phase, are observed across all three regimes of the static magnetization configurations, through antiparallel alignment at low fields, the spin-flop transition at intermediate fields and the parallel alignment at high fields. The non-monotonic behavior of the modes as a function of the external field is explained in detail by analyzing the interlayer exchange and Zeeman energies, and is found to be solely governed by the interplay of their dynamical components. In addition, the linewidths of both modes were determined across the three regimes and the different behaviors of the linewidths versus external magnetic field are attributed to mutual spin pumping induced in the samples. Interestingly, the difference between the linewidths of the out-of-phase and in-phase modes decreases at the spin-flop transition and is reversed between the antiparallel and parallel aligned magnetization states.

Zur Untersuchung der ablaufenden Prozesse in großen Behältern, wie z. B. Biogasfermentern, Bioreaktoren und Belebtschlammbecken, wurde am HZDR das Konzept instrumentierter, strömungsfolgender Sensorpartikel entwickelt [1],[2]. Bisher wurden damit die Strömungsverhältnisse mit probabilistischen Auswertemethoden ausschließlich basierend auf der Messung der vertikalen Position als Funktion des hydrostatischen Drucks charakterisiert und Parameter einfacher Prozessmodelle für Anlagen im Labor- und Pilotmaßstab bestimmt.
Derzeit wird das Konzept des Sensorsystems mit dem Ziel weiterentwickelt, eine räumliche Lage- und Bewegungsverfolgung für Bioreaktoren basierend auf Inertialsensoren zu realisieren. Dies umfasst sowohl die dafür zu qualifizierenden Sensoren für Beschleunigung, Drehrate, Magnetfeld sowie Umgebungsdruck als auch die Softsensor-Algorithmen zur Bestimmung der Lage und der Bewegung. Damit sollen zukünftig Auftriebsmanöver der Sensorpartikel autonom ablaufen und die räumliche Strömungscharakterisierung erfolgen.
Im Beitrag werden drei Softsensor-Algorithmen zur Bewegungsverfolgung vorgestellt und verglichen. Diese sind ein linearisiertes Kalman-Filter (Error State Kalman Filter ESKF) und zwei nichtlineare Komplementärfilter (Direct und Passive Complementary Filter DCF, PCF) nach [3]. Diese Algorithmen wurden mit praxisrelevanten simulierten Strömungsbewegungen (siehe Abb. 1) unter Berücksichtigung von Unsicherheiten der Sensoren und realen Sensordaten analysiert. Die Simulationsergebnisse zeigen, dass durch die genaue Lagebestimmung, die Beschleunigung permanent im Koordinatensystem des Behälters nahezu driftfrei bestimmt wird (Abb. 1 und 2). Der Beitrag führt einen umfassenden Vergleich anhand simulierter und gemessener Referenztrajektorien von drei qualifizierten, kommerziellen Inertialsensoreinheiten und diskutiert die relevanten Implikationen für die Auslegung des Sensorsystems.

The gas and ice giants in our solar system can be seen as a natural laboratory for the physics of highly compressed matter at temperatures of a few thousand kelvins. In turn, our understanding of their structure and evolution depends critically on our ability to model such matter. One key aspect is the miscibility of the elements in their interiors. Here, we demonstrate the feasibility of X-ray Thomson scattering to quantify the degree of species separation in a 1:1 carbon-hydrogen mixture at a pressure of ~150GPa and a temperature of ~5,000 K. Our measurements provide absolute values of the structure factor that encodes the microscopic arrangement of the particles. From these data, we find a lower limit of 24+6-7 % of the carbon atoms forming isolated carbon clusters. In principle, this procedure can be employed for investigating the miscibility behaviour of any binary mixture at the high-pressure environment of planetary interiors, in particular, for non-crystalline samples where it is difficult to obtain conclusive results from X-ray diffraction. Moreover, this method will enable unprecedented measurements of mixing/demixing kinetics in dense plasma environments, e.g., induced by chemistry or hydrodynamic instabilities.

We apply density functional theory molecular dynamics (DFT-MD) simulations to calculate the ionization degree of plasmas in the warm dense matter regime. Standard descriptions of the ionization potential depression (IPD) have been challenged recently by experiments approaching unprecedentedly high densities indicating that improved IPD models are required to describe warm dense matter. We propose a novel ab initio method to calculate the ionization degree directly from the dynamic electrical conductivity using the Thomas-Reiche-Kuhn (TRK) sum rule. This approach is demonstrated for carbon at a temperature of 100 eV and pressures in the Gbar range. We find substantial deviations from widely applied IPD models like Stewart-Pyatt and Ecker-Kröll implying that condensed matter and quantum effects like band structure and Pauli blocking need to be included explicitly in ionization models. Our results will help to precisely model matter under conditions occurring, e.g., during inertial confined fusion implosions or inside astrophysical objects such as brown dwarfs and low-mass stars.

The TELBE Terahertz (THz) facility at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) offers narrowband high-field high-repetition rate THz radiation for driving low-energy excitations in matter in the spectral region between 0.1 THz and 1.5 THz [1]. In combination with our pulse-resolved data acquisition and the numerous available probing techniques based on table-top laser systems, we can resolve THz-driven dynamics with few 10 fs time resolution and high dynamic range of up to 120 dB [2]. This makes TELBE a unique facility for exploring low-energy THz excitations offering (resonant) access to a multitude of fundamental modes, e.g., lattice vibrations, molecular rotations, spin precession and the motion of free electrons [3]. Recently, we demonstrated THz high harmonic generation (HHG) in the model 2D material graphene [4]. Here, the ultrafast collective thermal response of free background electrons near the Dirac point [5] enables very efficient generation of harmonics in the technologically relevant THz frequency range. We further show that the underlying principle of the collective response can be generalized to other 2D and 3D Dirac materials, such as CdAs. The crucial role of doping in graphene can be exploited by, e.g. electrochemical gating, which allows tuning of the HHG efficiency by almost two orders of magnitude. The corresponding setup for phase-resolved nonlinear THz spectroscopy further enables a novel technique: Higgs spectroscopy, which offers new ways for understanding unconventional superconductivity. Using this technique, we recently discovered a new collective mode distinct from the heavily damped Higgs mode in different families of cuprates [6]. Our results establish Higgs spectroscopy as a new approach to uncover interactions directly relevant to superconductivity.
In this contribution, I will also discuss experiments on the selective THz control of magnetic properties in a number of different materials [7], which is enabled by probing techniques, such as Faraday Rotation or MOKE, using the NIR and UV output from our table-top sources.
[1] B. Green et al., Sci. Rep. 6, 22256 (2016)
[2] S. Kovalev et al., Struct. Dyn. 4, 024301 (2017)
[3] T. Kampfrath et al. Nat. Photonics 7, 680–690 (2013)
[4] H. Hafez et al., Nature 561, 507 (2018)
[5] Z. Mics et al., Nature Communications 6, 7655 (2015)
[6] H. Chu et al., arXiv preprint, arXiv:1901.06675 (2019)
[7] S. Kovalev et al., J. Phys. D: Appl. Phys. 51, 114007 (2018)

How does functionality in quantum devices emerge? The answer lies in the numerous elementary processes, the interactions and correlations of (quasi-)particles that happen on timescales of femtoseconds. Thorough understanding of these processes can eventually lead to more efficient OLEDs, faster microprocessors, and other functional materials. A complex, but highly insightful method to access the required spectral and dynamic information in solid state systems is time- and angle-resolved photoemission spectroscopy. This lecture attempts to give an overview on this powerful technique for exploring non-equilibrium properties of matter. This includes discussions of elementary scattering processes, experimental techniques, and latest results on optoelectronic systems and correlated materials.

The exploration of nonlinear optical phenomena has not only deepened the understanding of light-matter interaction, but it also enabled novel technologies that make use of the resulting synthesis of electromagnetic radiation at new frequencies. Whereas the nonlinear responses of matter in the microwave and optical regimes are well explored, research addressing the intermediate Terahertz (THz) regime is still largely in its infancy, despite its high technological relevance, e.g. for novel high-speed (opto-)electronics.
For these future applications in the THz range, graphene is a highly promising material, because of the unique optical properties originating from its prototypical Dirac-type electronic structure. Soon after its discovery, there have multiple predictions of efficient harmonic generation in the THz range [1, 2], but experimental evidence has remained incomplete. Recently, we experimentally demonstrated the highly efficient THz harmonics generation (HG) in a single layer graphene sample (up to 7th order) at ambient conditions upon excitation with a moderate THz field of only 85 kV/cm (see Fig. 1) [3]. Our observations have been successfully described by a thermodynamic model, which clearly explains the experimentally observed crucial role of the graphene doping level for THz HG [3, 4]. By using gated graphene samples and multilayer structures, we are able to predictably modify the HG efficiency and thereby corroborate the thermodynamic model.

In addition, we employed the same experimental scheme to other Dirac materials, such as topological insulators and Dirac/Weyl semimetals, showing that THz HG is a rather universal phenomenon based on the linear band dispersion in the vicinity of the Dirac point.

[1] S. Mikhailov et al., Microelectron. J. 40 (2009) 712.
[2] I. Al-Naib, Phys. Rev. B, 90 (2014) 245423
[3] H. Hafez, S. Kovalev et al., Nature, 561 (2018) 507
[4] Z. Mics et al., Nat. Commun., 6 (2015) 7655

Activations with neutrons in the keV energy range were routinely performed at the Karlsruhe Institute of Technology (KIT) in Germany in order to simulate stellar conditions for neutron-capture cross sections. A quasi-Maxwell-Boltzmann neutron spectrum of kT = 25 keV, being of interest for the astrophysical s-process, was produced by the ⁷Li(p,n) reaction utilizing a 1912 keV proton beam at the Karlsruhe Van de Graaff accelerator. Activated samples resulting in long-lived nuclear reaction products with half-lives in the order of yr - 100 Myr were analyzed by Accelerator Mass Spectrometry (AMS). Comparison of this data to cross sections from Time-of-Flight (ToF) measurements showed that the selected AMS data is systematically lower than the ToF data. To investigate this discrepancy, ⁵⁴Fe(n,gamma)⁵⁵Fe and ³⁵Cl(n,gamma)³⁶Cl reaction cross sections were newly measured at the Frankfurt Neutron Source (FRANZ) in Germany. To complement the existing data, an additional neutron activation of ⁵⁴Fe and ³⁵Cl at a proton energy of 2 MeV was performed. The results will give implications for the stellar environment at kT = 90 keV, reaching the yet not experimentally explored high-energy s-process range. AMS measurements of the activated samples are scheduled.

The Lower and Middle Group chromitites of the Bushveld Complex are the source of a very large portion of the global chrome supply. Yet, the effectiveness of chromite beneficiation circuits is highly sensitive to mineralogical and textural variations in feed composition. The use of geochemical proxies, based on data acquired routinely during the exploration and mining process may provide a cost- and time-efficient alternative to more time-consuming and expensive mineralogical analyses. Such an approach is presented in this study, which focuses on the LG-6, LG-6A, MG-1 and MG-2 chromitite seams at the Thaba mine located on the western limb of the Bushveld Complex. According to a sound statistical assessment, the chromitites of the Thaba mine area can be subdivided into three distinct domains, domains that constitute the suitable fundament for a geometallurgical model. Accordingly, a least altered (orthomagmatic) domain is distinguished from a supergene altered domain and a domain affected by widespread hydrothermal alteration. The latter domain occurs below the depth of modern weathering, but in obvious proximity to faults and around a prominent dunite pipe. The orthomagmatic domain is represented by ores least affected by post-magmatic alteration processes. This domain occupies the centre of fault blocks below the extent of modern weathering.

The Bushveld Complex in South African contains vast resources of Cr, PGE and V. Currently, the Merensky Reef, the Platreef and the UG-2 chromitite seam are the major mining targets for PGE, although chromitites of the Lower Group (LG) and Middle Group (MG) may also contain concentrations up to several ppm PGE.
In a suite of chromitite samples from the Thaba Mine in the western Bushveld Complex it was shown that Pt concentrations in weathered chromitite seams (LG-6 to MG-4) generally exceed those of Pd. However, differences are observed by comparing individual chromitite seams as total PGE concentrations of weathered chromitites from the LG-6 to MG-4 range between 760 and 1300 ppb. Elevated concentrations of Pt and Pd are also present in hanging and footwalls of chromitite seams (median 333 ppb Pt). The PPGE (Rh, Pt, Pd) contents of weathered ores are generally lower than those of the pristine ores. The IPGE (Os, Ir, Ru) are very similar in both pristine and weathered ores. Particularly, Ru concentration are in the same range as the pristine ores.
Platinum concentrations increase from LG-6 to MG-4, whereas Pd remains at near-constant levels, resulting in a strong increase of the Pt/Pd ratio from 2.2 to 15.3. Platinum, largely remains within the chromitite seams and is only locally mobilized within the chromitites and their surrounding hanging and footwalls, whereas a large proportion of the Pd is leached out. Weathering causes mobilization of Pt and Pd out of the chromitites, locally into the hanging and footwall. The general decrease (in particular of Pd) can also be observed by comparing the average Pt/Pd ratio of pristine chromitites from the Thaba Mine. The IPGE are generally less affected by weathering processes which may be explained by the fact that laurite [(Ru,Os,Ir)S2] commonly occurs as inclusions in chromite, and PGM incorporated in chromite are largely unaffected by weathering processes.

All major sources of economically important platinum-group elements (PGE) are associated with sulfides and chromite in mafic-ultramafic rocks. The Bushveld Complex in South Africa is the largest PGE deposit worldwide. Chromitites of the Lower Group (LG) and Middle Group (MG) of the Bushveld Complex hold PGE contents of a few ppm. However, these chromitites are mainly mined for chromium only and extraction of PGE as a by-product is limited. Surface weathering in the area of the Bushveld Complex is up to 50 m down from surface. Attempts to recover Pt and Pd from these weathered ores lead to recoveries of <30 %, despite that Pt and Pd concentrations are similar in pristine and weathered ores. The recovery of PGE from near-surface chromitites of the LG and MG would increase the resource efficiency of current mining operations.. Therefore, an efficient utilization of these ores requires geochemical and mineralogical characterization of the PGE within these ores and the development of novel approaches of mineral beneficiation.

The tailings of industrial mineral production are a major environmental and financial burden for mining operations. Because most historic and current beneficiation plants extract only one – or few – commodities contained in the ore, tailings dams should be regarded as anthropogenic ore deposits, i.e., potential sources of raw materials. Their recovery would have a number of associated benefits: effectively reducing the waste volume as well as the environmental burden whilst simultaneously increasing the efficiency of metal / mineral production from a non-renewable resource. In some cases, this may be achieved at minimal cost, since raw materials in tailings dams are already mined, milled and deposited at surface.
Yet, most tailings are low-grade resources; technologies applied in beneficiating tailings need to be well-selected and highly efficient. For this purpose, a sound understanding of the beneficiation characteristics of such tailings needs to be developed. With the latest advances of mineral characterization and data mining techniques, the Helmholtz Institute Freiberg for Resource Technology has been developing a framework that enables predictive geometallurgical studies of tailings materials. This presentation will illustrate three particular parts of this framework, namely (i) resource models that account for mineral processing properties, (ii) economic evaluation of by-product recovery in early stages of projects, and (iii) the use of single particles’ information for modelling mineral processing units. By combining these techniques, we are able to quantify the potential of transforming tailings into valuable resources.

A new analytical tool for mineral analysis will be introduced: Laboratory-based Spectral 3D X-ray Computed Tomography (Sp-CT). Results from a spectral imaging detector, prototype installed inside a TESCAN CoreTOM micro-CT system, will be presented and discussed in the context of mineralogical and chemical analysis of geological materials. The technique will be demonstrated to allow:

a) 3D mineral classification from the transmitted energy spectrum characteristic of a mineral phase.
b) Quick bulk chemical quantification of heavy elements with K-edge > 20 keV at high concentrations that are difficult to analyse by other methods.
c) Reducing common CT artefacts such as scattering and beam hardening, as well as improved contrast by selectively choose the most convenient energy range.
The advantages of Sp-CT will open new possibilities in geometallurgy and minerals processing research to move from the predominant 2D based image characterization towards more representative 3D characterization. These are fundamental steps to enable automated and routine 3D characterization that ultimately has the potential to provide faster and lower cost analysis to, for example, the mining industry, as well as more comprehensive rock characterization technique for Earth sciences research.

This contribution presents and validates a new method to correct for the main limitations of volume quantification using X-ray computed tomography: limited spatial resolution and lack of mineralogical classification. The volume of a phase of interest (cassiterite, SnO2) is calculated using the intensity of voxels at interphases, which are typically the regions of main uncertainty in 3D imaging. Instead of traditional segmentation methods that define boundaries between phases, our method considers interphases as regions that can be several voxels across. The method is validated using a feedback loop between 2D scanning electron microscopy-based image analysis and bulk chemical analysis where the advantages of each technique are used to correct for the limitations of another. The percent of cassiterite derived from our method are within 10% deviation from those measured by scanning electron microscopy-based image analysis and bulk chemical analysis, when the P50 of the particle size distribution is at least 5 times the voxel size of the scan, which is a better agreement than results derived from other segmentation methods. Therefore, our method reduces the uncertainty of volume quantification and lowers the limit of grain sizes for which volumes can be reliably measured using computed tomography. The reduced uncertainty and bias can contribute to broadening the application of 3D imaging to mineral engineering as complementary to well established techniques.

Fluid flows in liquid metal batteries can be generated by a number of effects. We start with a short overview of different driving mechanisms and then address questions specific to the metal pad role instabilities in three-layer systems. We focus on the role of the conductivity distribution in the cell, noting at the same time that interfacial tension should be considered as well for smaller cells. Following this discussion, numerical results on the excitation of interfacial waves in two-layer liquid metal systems with miscibility gaps bearing an interface normal electric current are presented. Confirming recent results from the literature, we find that magnetic damping plays a decisive role for strong vertical magnetic fields. In addition, boundary conditions for the electric field strongly influence critical currents and growth rates.

The aim of this work is to compare and improve optical and structural properties of GaN layers prepared using TMGa or TEGa precursors. MOVPE grown GaN buffer layers on sapphire substrates are usually grown from TMGa precursor at the temperatures above 1000 °C. These layers contain deep and shallow acceptor levels which are responsible for blue and yellow defect bands in luminescent spectra. Both defect bands are detrimental for all major nitride device applications. Especially n-doped GaN layers suffer from strong yellow defect bands. In this work, it is shown that yellow band photoluminescence intensity can be suppressed by using TEGa precursor during the growth of n–doped GaN layers. Different kinds of growth parameters, such as growth temperature or growth rate, have been studied. It is also shown that the change of carrier gas (H2 or N2) has very strong influence on the layer quality. H2 carrier gas increased intensity of yellow band in sample grown from TEGa precursor while N2 carrier gas had the same effect for sample grown from TMGa precursor. Variable energy positron annihilation spectroscopy showed creation of single VGa in H2 atmosphere and clustering of VGa to big complexes ((VGa)3(VN)n) in N2 atmosphere.

Striving to improve the critical current density Jc of superconducting YBa 2 Cu 3 o 6+x (YBCO) thin films via enhanced vortex pinning, the interplay between film growth mechanisms and the formation of nanosized defects, both natural and artificial, is systematically studied in undoped and BaZrO 3 (BZO)-doped YBCO thin films. The films were grown via pulsed laser deposition (PLD), varying the crystal grain size of the targets in addition to the dopant content. The microstructure of the PLD target has been observed to have a great impact on that of the deposited thin films, including the formation of vortex pinning centers, which has direct implications on the superconducting performance, especially on the isotropy of flux pinning properties. Based on experimentally measured angular dependencies of Jc, coupled with a molecular dynamics (MD) simulation of flux pinning in the YBCO films, we present a quantitative model of how the splay and fragmentation of BZO nanorods artifically introduced into the YBCO film matrix explain the majority of the observed critical current anisotropy. To obtain the freedom to engineer future high-temperature superconductor (HTS) applications for desired operating magnetic field and temperature ranges, it is necessary to optimize the vortex pinning landscape for an enhanced, isotropic flux pinning performance 1-6. In addition to naturally formed crystalline defects, which typically have spatial dimensions distinctly below the superconducting coherence length, defect-engineering with artificially produced pinning centers (APCs) with dimensionalities of 1D-3D have been observed to be extremely effective 7-10. However, the complex nucleation process of YBCO during PLD process, that leads to growth island size variation, and the manner in which this could affect the size and distribution of the nanoscale structural defects is chiefly neglected. Especially, a clear gap exists in the current literature regarding how ordered arrays of nanoscale defects can also influence and regulate the distribution and growth of more effective APCs and thus decrease the anisotropy by allowing vortices to be trapped in a wider angular range 11. Partly, the clear lack of information on the subject is arguably be due to the rather general assumption that during PLD process, the film growth method of our choice, the target material is largely decomposed on the atomic level, and thus its properties should not have an effect on the formation and nucleation of particles on the substrate surface. This assumption, which our studies have led us to challenge, would precariously force one to downplay the potential importance of target microstructure on the functional properties of derived films. The angular dependence of the J c has an excellent physical importance providing an approach to the problem of flux pinning and vortex dynamics anisotropy in HTSs, both from the experimental and theoretical point of view. For instance, in the angular dependent critical current plots, one can easily observe how the various types of pinning centers such as correlated linear, columnar or planar defects and, on the other hand, defects based on growth mechanisms together with YBCO's intrinsic pinning can dramatically alter the angular dependence of J c (B) 4. For understanding the origin of angular dependent flux pinning J c (θ), experimental tools like transmission electron microscopy (TEM) are often exploited to probe the structural properties and features, such as the defects naturally formed during the film growth, as well as the size, shape, orientation and distribution of the artificially produced and self-assembled pinning centers 5,12,13. However, methods like positron annihilation spectroscopy,

We present an innovative multi-sensor system, based on non-invasive optical spectroscopy for the characterization of material streams. The novel hardware and software set-ups are explained in detail and first results from RGB stereoscopy and object detection are shown.

A systematic study of the influence of interstitial hydrogen on the structure, morphology of surface, magnetic and magnetothermal properties in multicomponent (Nd_0.5Pr_0.5)₂Fe₁₄BH_x (x = 0; 2.7; 4.3) are reported. Partial substitution of Pr for Nd allows a decrease of the spin-reorientation transition temperature from 135 K for Nd₂Fe₁₄B to 73 K for (Nd_0.5Pr_0.5)₂Fe₁₄B. Hydrides (Nd_0.5Pr_0.5)₂Fe₁₄BH_x crystallize in a tetragonal crystal structure (space group P42/mnm) of the Nd₂Fe₁₄B-type. Both lattice constants and unit cell volume increase upon hydrogen absorption. It was also found that the surface of the hydrogenated sample was very severely damaged by the introduction of hydrogen. Magnetic studies of both initial compound and the hydrides were performed on bulk and powder samples in static and pulsed magnetic fields up to 14 and 58 T, respectively. Hydrogenation has a significant effect on magnetic properties of a multicomponent alloy (Nd_0.5Pr_0.5)₂Fe₁₄B: Curie temperature and saturation magnetization increase, while temperature of SRT decreases (T_SRT = 63 K for (Nd_0.5Pr_0.5)₂Fe₁₄BH_x with x = 2.7 and 4.3). The magnetocaloric effect (MCE) in the range of spin-reorientation transition also decreases significantly. We analyzed magnetic properties of (Nd_0.5Pr_0.5)₂Fe₁₄BH_x and compare them with that of Nd₂Fe₁₄BH_x. Magnetic phase diagrams are constructed.

We report on low-temperature heat-transport properties of the spin-1/2 triangular-lattice antiferromagnet Cs₂CuCl₄. Broad maxima in the thermal conductivity along the three principal axes, observed at about 5 K, are interpreted in terms of the Debye model, including the phonon umklapp scattering. For thermal transport along the b axis, we found a pronounced field-dependent anomaly, close to the transition into the three-dimensional long-range-ordered state. No such anomalies were found for the transport along the a and c directions.We argue that this anisotropic behavior is related to an additional heat-transport channel through magnetic excitations, that can best propagate along the direction of the largest exchange interaction. In addition, peculiarities of the heat transport of Cs₂CuCl₄ in magnetic fields up to the saturation field and above are discussed.

Liquid metal electrodes are one of the key components of different electrical energy storage technologies. The understanding of transport phenomena in liquid electrodes is mandatory in order to ensure efficient operation. In the present study we focus our attention on the positive electrode of the Li||Bi liquid metal battery. Starting from a real experimental setup, we numerically investigate the charge transfer in a molten salt electrolyte and the mass transport in the positive electrode. The two phenomena are tightly coupled, because the current distribution influences the concentration field in the positive electrode. The cell is studied during charging when compositional convection becomes apparent. First results of compositional convection from a non-uniform current distribution are presented, highlighting its capability to affect the flow in the positive electrode and the cell performance.

The present work initially studies the impact of a laboratory microwave (MW)’s location (before and after a jaw crusher) on grindability of a copper ore. Additionally, the role of MW’s radiation time (15–150 sec) and grinding time (13, 15 and 17 min) on the produced particle size distribution (PSD), mineral liberation degree (LD) and energy consumption are investigated. relative work index (RWI), standard Bond work index (Wi), and grindability index (GI) together with the breakage and selection functions were utilized to assess the grinding efficiency and its kinetics of the untreated and MW-pretreated (at a constant power of 0.9 kW) samples. Bond work indices were obtained 13.70, 13.04 and 10.86 kWh/t for the untreated, MW-treated uncrushed and MW-treated crushed samples, respectively. Besides, the results confirmed that the microwave pretreatment was comparatively effective at the shortest grinding time (13 min). Furthermore, locating the microwave after the crushing stage indicated substantial improvements in the sample’s grindability and its kinetics rate. The product size (P80) of the MW-treated crushed sample (13 min, 0.9 kW, 150 sec) showed enhancements of 27% and 17% in comparison with the un-microwaved and MW-treated uncrushed samples. Finally, the comparative GIs acquired in the entire spectrum of the particle range were reasonably higher if the microwave was located after the jaw crusher, particularly for the coarse fraction sizes.

The present work aims at investigating the effect of microwave local positions (i.e. before crushing (BC), after crushing (AC) and after milling (AM)) on microwave-assisted flotation of chalcopyrite and pyrite in a porphyry copper complex deposit. Individual given samples for each state were pre-treated with a variable power microwave at a power level of 90 to 900W for 15, 30, and 60s. Furthermore, froth floatation experiments were carried out using a laboratory mechanical Denver flotation cell on both microwave-treated and untreated samples. Particle surface properties were characterized by a scanning electron microscopy (SEM) and an energy-dispersive X-ray spectroscopy (EDX) analysis. The results showed that the chalcopyrite and pyrite floatabilities increased monotonically by rising the exposure time and power level for the uncrushed preconditioned samples (BC) due to the enhancement of mineral liberation degrees together with the formation of sulphide species and polysulphides on the mineral surfaces. However, flotation results of treated samples for the crushed one (AC) revealed an optimum range. Formation of intensive oxide layers on the mineral surfaces of milled samples (AM) led to a substantial reduction in their recoveries by increasing the microwave’s power level and the sample’s exposure time. The results obtained from mineral’s floatabilities in recleaner stage showed that the microwave-assisted sample at 900W for 30s at BC state favourably provided 5% higher S.E.’s than that of the untreated sample. Finally, it was concluded that the microwave pretreatment of samples induced the best floatability responses if it located before the crusher.

By means of Rutherford backscattering spectrometry, electron microscopy, and energy-dispersive X-ray spectroscopy, the distribution and interaction of In and As atoms implanted into thermally grown SiO2 films to concentrations of about 1.5 at % are studied in relation to the temperature of subsequent annealing in nitrogen vapors in the range of T = 800–1100°C. It is found that annealing at T = 800–900°C results in the segregation of As atoms at a depth corresponding to the As+-ion range and in the formation of As nanoclusters that serve as sinks for In atoms. An increase in the annealing temperature to 1100°C yields the segregation of In atoms at the surface of SiO2 with the simultaneous enhanced diffusion of As atoms. The corresponding diffusion coefficient is DAs = 3.2 × 10–14 cm2 s–1.

Hyperspectral image (HSI) classification has become a hot topic in the field of remote sensing. In general, the complex characteristics of hyperspectral data make the accurate classification of such data challenging for traditional machine learning methods. In addition, hyperspectral imaging often deals with an inherently nonlinear relation between the captured spectral information and the corresponding materials. In recent years, deep learning has been recognized as a powerful feature-extraction tool to effectively address nonlinear problems and widely used in a number of image processing tasks. Motivated by those successful applications, deep learning has also been introduced to classify HSIs and demonstrated good performance. This survey paper presents a systematic review of deep learning-based HSI classification literature and compares several strategies for this topic. Specifically, we first summarize the main challenges of HSI classification which cannot be effectively overcome by traditional machine learning methods, and also introduce the advantages of deep learning to handle these problems. Then, we build a framework that divides the corresponding works into spectral-feature networks, spatial-feature networks, and spectral-spatial-feature networks to systematically review the recent achievements in deep learning-based HSI classification. In addition, considering the fact that available training samples in the remote sensing field are usually very limited and training deep networks require a large number of samples, we include some strategies to improve classification performance, which can provide some guidelines for future studies on this topic. Finally, several representative deep learning-based classification methods are conducted on real HSIs in our experiments.

By considering the spectral signature as a sequence, recurrent neural networks (RNNs) have been successfully used to learn discriminative features from hyperspectral images (HSIs) recently. However, most of these models only input the whole spectral bands into RNNs directly, which may not fully explore the specific properties of HSIs. In this paper, we propose a cascaded RNN model using gated recurrent units to explore the redundant and complementary information of HSIs. It mainly consists of two RNN layers. The first RNN layer is used to eliminate redundant information between adjacent spectral bands, while the second RNN layer aims to learn the complementary information from nonadjacent spectral bands. To improve the discriminative ability of the learned features, we design two strategies for the proposed model. Besides, considering the rich spatial information contained in HSIs, we further extend the proposed model to its spectral-spatial counterpart by incorporating some convolutional layers. To test the effectiveness of our proposed models, we conduct experiments on two widely used HSIs. The experimental results show that our proposed models can achieve better results than the compared models.

Spectral features cannot effectively reflect the differences among the ground objects and distinguish their boundaries in hyperspectral image (HSI) classification. Multi-scale feature extraction can solve this problem and improve the accuracy of HSI classification. The Gaussian pyramid can effectively decompose HSI into multi-scale structures, and efficiently extract features of different scales by stepwise filtering and downsampling. Therefore, this paper proposed a Gaussian pyramid based multi-scale feature extraction (MSFE) classification method for HSI. First, the HSI is decomposed into several Gaussian pyramids to extract multi-scale features. Second, we construct probability maps in each layer of the Gaussian pyramid and employ edge-preserving filtering (EPF) algorithms to further optimize the details. Finally, the final classification map is acquired by a majority voting method. Compared with other spectral-spatial classification methods, the proposed method can not only extract the characteristics of different scales, but also can better preserve detailed structures and the edge regions of the image. Experiments performed on three real hyperspectral datasets show that the proposed method can achieve competitive classification accuracy.

Colourless crystalline compounds of centrosymmetric [Np(NO3)6]2− were yielded from 3 M HNO3 aq under presence of double-headed 2-pyrrolidone derivatives (L). In the obtained crystal structures, H+ was also involved as a countercation to compensate the negative charge of [Np(NO3)6]2−, where initial hydration around H+ was fully removed during crystallization despite its strongest hydration enthalpy. Instead, such an anhydrous H+ was captured by L to form a [H+···L]n hydrogen bond polymer. In [Np(NO3)6]2−, Np4+ centre is twelve-coordinated with 6 bidentate NO3−, and therefore, present in an icosahedral geometry bearing inversion centre. In such a centrosymmetric system, any f-f transitions stemming from 5f3 electronic configuration of Np4+ are electric-dipole forbidden. This is the reason why the compounds currently obtained were colourless unlike ordinary Np(IV) species with olive-green.

We report the optical and magneto-optical properties of amorphous and crystalline Co60Fe20B20 films with thicknesses in the range of 10 nm to 20 nm characterized using spectroscopy ellipsometry (SE) and magneto-optical Kerr effect (MOKE) spectroscopy. We derived the spectral dependence of the dielectric tensor from experimental data for samples prior and after annealing in vacuum. The features of the dielectric function can be directly related to the transitions between electronic states and the observed changes upon annealing can be ascribed to an increase of the crystalline ordering of CoFeB.