Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

By employing large-scale molecular dynamics simulations of atomistically resolved oligoelectrolytes in aqueous solutions, we study in detail the first four layer-by-layer deposition cycles of an oligoelectrolyte multilayer made of poly(diallyl dimethyl ammonium chloride)/poly(styrene sulfonate sodium salt) (PDADMAC/PSS). The multilayers are grown on a silica substrate in 0.1 M NaCl electrolyte solutions and the swollen structures are then subsequently exposed to varying added salt concentration. We investigated the microscopic properties of the films, analyzing in detail the differences between three- and four-layer systems. Our simulations provide insights into the early stages of growth of a multilayer, which are particularly challenging for experimental observations. We found rather strong complexation of the oligoelectrolytes, with fuzzy layering of the film structure. The main charge compensation mechanism is for all cases intrinsic, whereas extrinsic compensation is relatively enhanced for the layer of the last deposition cycle. In addition, we quantified other fundamental observables of these systems, such as the film thickness, water uptake, and overcharge fractions for each deposition layer.

Three different Spark Plasma Sintering (SPS) treatments were applied to highly sinteractive, near-stoichiometric UO2.04 nanocrystalline (5 nm) powders produced by U(IV) oxalate hydrothermal decomposition at 170 °C. The sintering conditions for reaching 95 % Theoretical Density (TD) in regular SPS, high pressure SPS (HP-SPS), and, for the first time, two-step SPS (2S-SPS), were found. Densification to 95 % TD was achieved at 1000 °C in regular SPS (70 MPa applied pressure), 660 °C in HP-SPS (500 MPa), and 650-550 °C in 2S-SPS (70 MPa). With the goal of minimising the grain growth during densification, the sintering treatments were optimised to favour densification over coarsening, and the final microstructures thus obtained are compared. Otherwise identical, stochiometric UO2 samples of different grain sizes, ranging from 3.08 μm to 163 nm, were produced. Room-temperature oxidation of the powders could not be avoided due to their nanometric dimensions, and a final annealing treatment was designed to reduce hyper stoichiometric samples to UO2.00.

LuCo₃ is an itinerant ferromagnet whose magnetic properties strongly depend on the position of the 3d electronic states relative to the Fermi level. Here, we report on the magnetization of a LuCo₃ single crystal in pulsed magnetic fields up to 58 T. We find a field-induced phase transition just below 50 T from a low-spin to a high-spin state. The transition shows a pronounced anisotropy of the magnetization jump and hysteresis. A series of ab initio calculations based on the density functional theory show that the transition is due to a significant change in the occupancies of the Co 3d electronic states. At the same time, some features in the majority spin density of the Co 3d states are slightly modified and pass through the Fermi level when the spin state is changed, which leads to the instability of the 3d-electron subsystem. Thereby, the applied magnetic field causes a significant redistribution in the majority and minority spin states in the Co 3d subsystem, which results in the sharp change in the magnetization.

We report the magneto-structural and magnetocaloric properties study of Tb purified by distillation and further processed by severe plastic deformation (SPD). Both parent and the SPD-processed Tb contain nanosized structural elements and have a very pronounced (00 l ) texture. We observe an improved magnetocaloric effect (MCE) in the distilled nanocrystalline Tb while novel properties emerge in the sample after severe plastic deformation. The latter demonstrates zero thermal expansion over a wide temperature range while its MCE vanishes. We show that the absolutely new physical properties in Tb result from the structural transformation and modification of magnetic interactions.

On September 12, 2019 at 12:49:48 (UT) a bolide was observed by hundreds of eye-witnesses from the Netherlands, Germany, Belgium, Denmark and the UK. One day later a small meteorite stone was found by accident in Flensburg. The presence of short-lived cosmogenic radionuclides with half-lives as short as 16 days proves the recent exposure of the found object to cosmic rays in space linking it clearly to the bolide event. An exceptionally short exposure time of ~5000 years was determined. The 24.5 g stone has a fresh black fusion crust, a low density of <2 g/cm³, and a magnetic susceptibility (MS) of logχ= 4.35 (χ in 10^-9 m³/kg). The rock consists of relict chondrules and clusters of sulfide and magnetite grains set in a fine-grained matrix. The most abundant phases are phyllosilicates. Carbonates (~3.9 vol.%) occur as calcites, dolomites, and a Na-rich phase. The relict chondrules (often surrounded by sulfide laths) are free of anhydrous silicates and contain abundant serpentine. Lithic clasts are also surrounded by similar sulfide laths partly intergrown with carbonates. ⁵³Mn-⁵³Cr ages of carbonates in Flensburg indicate that brecciation and contemporaneous formation of the pyrrhotite-carbonate intergrowths by hydrothermal activities happened no later than 4564.6±1.0 Ma (using D'Orbigny as Mn-Cr anchor). This corresponds to 2.6±1.0 or 3.4±1.0 Ma after CAIs, depending on the exact age CAI age. This is the oldest dated evidence for brecciation and carbonate formation, which likely occurred during parent body growth and incipient heating due to ²⁶Al.
The O isotope composition of Flensburg reveals that it plots at the ¹⁶O-rich end of the CM chondrite field and in the transition field to the CV-CK-CR chondrites. This is unexpected since the O-isotope compositions of strongly aqueously-altered chondrites are generally found to be at the ¹⁶O-poor end of the CM range. The mass-dependent Te isotopic compositionof Flensburg is slightly different from mean CM chondrites and is most similar to those of the ungrouped C2 chondrite Tagish Lake. On the other hand, the 50Ti and 54Cr isotope nomalies indicate that Flensburg is similar to CM chondrites, as do the ~10 wt.% H₂O. Yet, the bulk Zn, Cu, and Pb concentrations are about 30% lower than those of mean CM chondrites. The He, Ne and, Ar isotopes of Flensburg show no solar wind contribution; its trapped noble gas signature is similar to that of CMs with a slightly lower concentration of ²⁰Ne_tr.
Based on the bulk H, C and N elemental abundances and isotopic compositions, Flensburg is clearly unique among the analyzed chondrites as it has the lightest bulk H and N isotopic compositions of any type 1 or 2 chondrite. The number of soluble organic compounds in Flensburg is even lower than that of the brecciated CI chondrite Orgueil.
The extraordinary significance of Flensburg is given by the observation that it represents the oldest chondrite sample, in which the contemporaneous episodes of aqueous alteration and brecciation are 81 perfectly visible. The characterization of a large variety of carbonaceous chondrites with different alteration histories is important for interpreting returned samples from the OSIRIS-REx and Hayabusa 2 missions.

A benchmarking databank based on different spectral, multiscale, multisensor exploration technologies was created. The benchmarking is composed of 63 rock samples from drill cores from a polymetallic (Cu-Zn-Pb) massive sulphide deposit in the Iberian Pyrite Belt. The samples had been analyzed by portable XRF, point hyperspectral spectrometer, portable FTIR, VNIR-SWIR imaging hyperspectral sensor and a LWIR imaging thermal hyperspectral sensor.

The mineralogical information from the boreholes will be complemented with mineral chemistry extracted from the spectral features of the alteration minerals that display chemical variations. The chemical variations in minerals generate shifts on the position of the metal-OH vibrational absorptions. This systematic variation can be recorded using the SWIR wavelength region of hyperspectral data. The shifts sometimes occur systematically with respect to ore deposits and hence mineral chemical information extracted from hyperspectral surveys can be used for mineral exploration. The mineral chemistry of the samples will be validated using scanning electron microscopy data integrated with the mineral liberation analysis (SEM-MLA).

In order to apply this type of research techniques aiming at a 3D model of the alteration areas of the entire deposit based on the hyperspectral data, it is essential to have the availability of drill cores along the whole extension of the mineral deposit. Consequently, the research was focused in a study area in the Southern Spain, the Elvira deposit of the MATSA–VALORIZA mining company, where 7 km of drill core were scanned with the hyperspectral sensors.

New exploration technologies (NEXT) is a project that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement nº 776804.

Chimeric antigen receptor T cells (CAR-T) targeting CD19 or B cell maturation antigen (BCMA) are highly effective against B cell malignancies. However, application of CAR-T to less differentially expressed targets remains a challenge due to lack of tumor-specific antigens and CAR-T controllability. CD123, a highly promising leukemia target, is expressed not only by leukemic and leukemia-initiating cells, but also by myeloid, hematopoietic progenitor, and certain endothelial cells. Thus, CAR-T lacking fine-tuned control mechanisms pose a high toxicity risk. To extend the CAR-T target landscape and widen the therapeutic window, we adapted our rapidly switchable universal CAR-T platform (UniCAR) to target CD123. UniCAR-T efficiently eradicated CD123+ leukemia in vitro and in vivo. Activation, cytolytic response, and cytokine release were strictly dependent on the presence of the CD123-specific targeting module (TM123) with comparable efficacy to CD123-specific CAR-T in vitro. We further demonstrated a pre-clinical proof of concept for the safety-switch mechanism using a hematotoxicity mouse model wherein TM123-redirected UniCAR-T showed reversible toxicity toward hematopoietic cells compared to CD123 CAR-T. In conclusion, UniCAR-T maintain full anti-leukemic efficacy, while ensuring rapid controllability to improve safety and versatility of CD123-directed immunotherapy. The safety and efficacy of UniCAR-T in combination with TM123 will now be assessed in a phase I clinical trial (ClinicalTrials.gov: NCT04230265).

Liposomes containing copper and the copper ionophore neocuproine were prepared and characterized for in vitro and in vivo anticancer activity. Thermosensitive PEGylated liposomes were prepared with di_erent molar ratios of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and hydrogenated soybean phosphatidylcholine (HSPC) in the presence of copper(II) ions. Optimal, temperature dependent drug release was obtained at 70:30 DPPC to HSPC weight ratio. Neocuproine (applied at 0.2 mol to 1 mol phospholipid) was encapsulated through a pH gradient while using unbuffered solution at pH 4.5 inside the liposomes, and 100 mM HEPES bu_er pH 7.8 outside the liposomes. Copper ions were present in excess, yielding 0.5 mM copper-(neocuproine)2 complex and 0.5 mM free copper. Pre-heating to 45 °C increased the toxicity of the heat-sensitive liposomes in short-term in vitro experiments, whereas at 72 h all investigated liposomes exhibited similar in vitro toxicity to the copper(II)-neocuproine complex (1:1 ratio). Thermosensitive liposomes were found to be more effective in reducing tumor growth in BALB/c mice engrafted with C26 cancer cells, regardless of the mild hyperthermic treatment. Copper uptake of the tumor was verified by PET/CT imaging following treatment with [64Cu]Cu-neocuproine liposomes. Taken together, our results demonstrate the feasibility of targeting a copper nanotoxin that was encapsulated in thermosensitive liposomes containing an excess of copper.

Quantum electrodynamics predicts the vacuum to behave as a nonlinear medium, including effects such as birefringence. However, for experimentally available field strengths, this vacuum polarizability is extremely small and thus very hard to measure. In analogy to the Heisenberg limit in quantum metrology, we study the minimum requirements for such a detection in a given strong field (the pump field). Using a laser pulse as the probe field, we find that its energy must exceed a certain threshold depending on the interaction time. However, a detection at that threshold, i.e., the Heisenberg limit, requires highly nonlinear measurement schemes--while for ordinary linear-optics schemes, the required energy (Poisson or shot noise limit) is much larger. Finally, we discuss several currently considered experimental scenarios from this point of view.

Modelling electrochemical devices, such as fuel cells, batteries or electrolysers asks typically for coupling electrochemistry with flow simulation and mass transfer. While solvers for mass transfer and fluid dynamics are well established in the open-source CFD library OpenFOAM, electrochemistry simulations are a rather young field of application. The presentation shall give therefore an overview on different approaches on how to simulate potential and current distributions as well as the cell voltage of electrochemical devices using OpenFOAM.

Brief overview and status of the STM-FPGA-DAQ HLS-Cores for LaBr peak detection, moving window deconvolution and zero suppression

Ziel/Aim: Um neue PET-Tracer in die Patientenversorgung überführen zu können, werden in der nuklearmedizinischen Forschung zunehmend prospektiv-klinische Studien mit den vielversprechendsten Radioliganden initiiert. Damit diese Studien möglichst effizient und effektiv durchgeführt werden können, bedarf es der möglichst engen Kooperation und Kommunikation von Expert*innen aus verschiedenen Berufsgruppen.

Methodik/Methods: Wir beleuchten am Beispiel der Multicenter-Studie „Ga-68-PSMA-11 in Hochrisiko-Prostatakrebs“ der Phasen-I/-II, welche wesentlichen Professionen aus forschender Klinik, Wirkstoffherstellung und Verwaltung bei der Planung, Vorbereitung und Durchführung prospektiv-nuklearmedizinischer Studien involviert sein können und welche Aufgaben diese zur Studienverwirklichung wahrnehmen. Darauf aufbauend leiten wir organisatorische Maßnahmen ab, durch die die interprofessionelle Kooperation bei prospektiven Bildgebungsstudien (auch über mehrere Prüfzentren) gefördert werden kann.

Ergebnisse/Results: In die Beispielstudie sind im engeren fachlichen Kreis Mediziner aus Nuklearmedizin/Urologie/Pathologie, MTA-Rs, Studienassistenten, Radiochemiker/-pharmazeuten, BTA/CTA, MTA und Gesundheits-/Krankenpfleger involviert. Im weiteren fachlichen Kreis sind ferner Strahlenschutzbeauftragte, Qualitätsmanager, klinische Monitore, Juristen, Datenschutzbeauftragte, Projektmanager und Studienkoordinatoren eingebunden, und dies jeweils an bis zu elf Prüfzentren in Deutschland, Österreich und der Schweiz.

Schlussfolgerungen/Conclusions: Interprofessionelle Kooperation ist für die Durchführung prospektiv-nuklearmedizinischer Studien essentiell. Hierzu bedarf es u. a. der grundlegenden Bereitschaft, sich in andere (Tätigkeits-)Rollen hineinzuversetzen und über Professionsgrenzen hinaus kooperieren zu wollen, ausreichend Zeit zum gegenseitigen Austausch, Fähigkeit/Fertigkeiten zum berufsübergreifenden Projektmanagement und eine integrale Betrachtung benötigter Expertisen mit Stärkung professionsübergreifender Kommunikation insbesondere über die Leitungsebene.

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Aim: For the imaging of PSMA-positive prostate cancer, several fluorine-18 (¹⁸F)-labelled compounds have been developed and translated into the clinics. Next to a clinical study comparing the tracer-specific characteristics of [¹⁸F]DCFPyL and [¹⁸F]PSMA-1007 intra-individually(1), a direct comparison of their preclinical characteristics has only recently been published(2). In this work, the importance of glutamic acids in the structure of [¹⁸F]PSMA-1007 is further elucidated using derivatives with none to three glutamic acids (Glu), respectively. Furthermore, [¹⁸F]DCFPyL and [¹⁸F]PSMA-1007 are evaluated regarding their preclinical characteristics using the in vitro and in vivo methods established at DKFZ Heidelberg, Germany. Materials and Methods: The precursors for radiofluorination containing different amino acid linkers (0-3 Glu) were synthesized by means of solid phase chemistry. The radiolabeling of [¹⁸F]PSMA-1007, its derivatives, and [¹⁸F]DCFPyL were performed prior to each experiment as described(3,4). The binding affinities of non-radioactive reference compounds were determined by competitive binding assays against [⁶⁸Ga]Ga-PSMA-10 in LNCaP cells. The internalization of the respective radioligands in LNCaP cells was compared. Biodistribution and pharmacokinetics were evaluated in vivo in LNCaP-tumor bearing BALB/c Nude mice using μPET. Results: The Glu variation in the linker structure resulted in similar binding affinities (Ki 3-14 nM) whereby the insertion of three Glu showed the highest Ki values. Internalization assays revealed that the insertion of Glu influences the internalization rate, whereby the insertion of two Glu ([¹⁸F]PSMA-1007) leads to the highest internalization rate (54.04±13.7%) in a total range between 27.3±3% to 54±13.7%. In comparison to [¹⁸F]PSMA-1007, a higher proportion of [¹⁸F]DCFPyL remains cell surface bound; only 27.83 ± 4.31% of the radiotracer is internalized. [¹⁸F]DCFPyL also has a slightly lower binding affinity (18.02±9.63 nM). μPET imaging showed outstanding imaging properties, especially of [¹⁸F]DCFPyL and [¹⁸F]PSMA-1007. In mice, the liver uptake is reduced by introduction of Glu linkers. The data will be analysed more detailed soon. Conclusion: Comparative cell experiments revealed a high binding affinity for all tracers and the highest internalization rate for [¹⁸F]PSMA-1007. The insertion of Glu in the linker structure plays an important role in pharmacokinetics due to the decreased lipophilicity of the respective radiotracer. Especially [¹⁸F]DCFPyL and [¹⁸F]PSMA-1007 are of excellent imaging quality. Their apparent non-inferiority is currently under further assessment in clinical trials. References: (1) Giesel F et al (2017): JNM, doi: 10.2967/jnumed.117.204669. (2) Robu S et al (2018): EJNMMI Res., 8(1):30. (3) Cardinale J et al. (2017): JNM, 58(3):425-431. (4) Chen Y et al. (2011): Clin Cancer Res., 17(24):7645-53.

Aim/Introduction: The development of innovative radiotracers targeting PSMA for non-invasive imaging of prostate cancer and successive treatment results in an increasing number of multicentre clinical trials using the most promising PSMA ligand candidates. For prospective studies with short-lived radiopharmaceuticals like [⁶⁸Ga]Ga-PSMA-11, a regulatory and country-specific structure has to be established before recruitment of patients is possible. This structure allows the decentralized manufacturing of the investigational medicinal product (IMP) according to Good Manufacturing (GMP) and subsequent implementation of the respective tracer compliant with Good Clinical Practice (GCP). Materials and Methods: For the multicenter clinical trial (phases-I/-II) ,,Ga-68-PSMA-11 in high-risk prostate cancer“ (NCT03362359) within DKTK a harmonized decentralized radiotracer production in multiple radiopharmacies has been set up for the very first time in the German speaking Radiopharmacy/Nuclear Medicine Community. In this prospective clinical study Nuclear Medicine physicians, radiopharmacists, urologists, pathologists and study related experts like lawyers and study nurses out of eleven study sites within the so-called D-A-CH region (Germany-Austria-Switzerland) have been involved. The basis for the accurately specified radioactive IMP manufacturing procedure was defined by EU-GMP requirements plus national standards (e.g. Medicinal Products Act and Radiation Protection Law). Results: For the recruiting study sites the required allowances, e.g. manufacturing authorization from local authorities as well as approval from ethics committees and national regulatory bodies such as BfS and BfArM in Germany, BASG in Austria as well as BAG and Swissmedic in Switzerland, have been obtained. The challenge of manufacturing a short-lived radiopharmaceutical at each of the participating geographically different sites with identical specification by adaption of production and quality control processes and parameters according to the IMP dossier (IMPD) during the starting phase of the clinical trial under a centralized quality assurance management has been achieved. Conclusion: The initiation and establishment of a multicentre clinical trial including the manufacturing of a short-lived radiopharmaceutical IMP across local study sites is very complex, but manageable. In view of the high European and national regulatory and legal burdens and the number of involved partners it is feasible in a defined time frame. Based on the achieved structures, the decentralized manufacture of novel short-lived radiopharmaceuticals can be established in the D-A-CH region and even on a European level for further investigator initiated multicentre clinical trials. We estimate our experiences important for the development of the field Nuclear Medicine at the national and international level taking into account the new EU regulation No 536/2014. References: None.

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Crystals melt when thermal excitations or the concentration of defects in the lattice is sufficiently high. Upon melting, the crystalline long-range order vanishes, turning the solid to a fluid. In contrast to this classical scenario of solid melting, here we demonstrate a counter-intuitive behavior of the occurrence of crystalline long-range order in an initially disordered matrix. This unusual solidification is demonstrated in a system of passive colloidal particles accommodating chemically active defects - photocatalytic Janus particles. The observed crystallization occurs when the amount of active-defect-induced fluctuations (which is the measure of the effective temperature) reaches critical value. The driving mechanism behind this unusual behavior is purely internal and resembles a blast-induced solidification. Here the role of "internal micro-blasts" is played by the photochemical activity of defects residing in the colloidal matrix. The defect-induced solidification occurs under non-equilibrium conditions: the resulting solid exists as long as a constant supply of energy in the form of ion flow is provided by the catalytic photochemical reaction at the surface of active Janus particle defects. Our findings could be useful for understanding of the phase transitions of matter under extreme conditions far from thermodynamic equilibrium.

Neuromorphic architectures merge learning and memory functions within a single unit cell and in a neuron-like fashion. Research in the field has been mainly focused on the plasticity of artificial synapses. However, the intrinsic plasticity of the neuronal membrane is also important in the implementation of neuromorphic information processing. Here we report a neurotransistor made from a silicon nanowire transistor coated by an ion-doped sol–gel silicate film that can emulate the intrinsic plasticity of the neuronal membrane. The neurotransistors are manufactured using a conventional complementary metal–oxide–semiconductor process on an 8-inch (200 mm) silicon-on-insulator wafer. Mobile ions allow the film to act as a pseudo-gate that generates memory and allows the neurotransistor to display plasticity. We show that multiple pulsed input signals of the neurotransistor are non-linearly processed by sigmoidal transformation into the output current, which resembles the functioning of a neuronal membrane. The output response is governed by the input signal history, which is stored as ionic states within the silicate film, and thereby provides the neurotransistor with learning capabilities.

Here, we present a miniaturized lab-on-a-chip detecting system for an all-electric and label-free analysis of the emulsion droplets incorporating the nanoscopic silicon nanowires-based field-effect transistors (FETs). We specifically focus on the analysis of β-galactosidase activity, which is an important enzyme in the glycolysis metabolic pathway. Furthermore, the efficiency of the synthesis and action of β-galactosidase can be one of the markers for several diseases, eg., cancer, hyper/hypoglycemia, cell senescence, or other disruptions in cell functioning. We measure the reaction and reaction kinetics-associated shift of the source-to-drain current I sd in the system, which is caused by the change of the ionic strength of the microenvironment. With these results, we demonstrate that the ion-sensitive FETs are able to sense the interior of the aqueous reactors; thus, the conjunction of miniature nanosensors and droplet-based microfluidic systems conceptually opens a new route toward a sensitive, optics-less analysis of biochemical processes.

We report on the ongoing plasma accelerator development at the HZDR, moving from plasma-acceleration studies towards real plasma-accelerators that can be controlled and applied in the lab.
We show experimental investigations of proton acceleration from laser-irradiated solid foils with the DRACO PW laser, where highest proton cut-off energies were achieved for temporal pulse shape parameters well different from that of a Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal laser pulse shape and to study the effect on proton acceleration from thin foil targets. The results show that short and asymmetric pulses generated by positive third order dispersion values are favourable for proton acceleration and can lead to maximum energies of 60 MeV for thin plastic foils. Assuming appropriate control of the spectral phase of the laser and comparable temporal contrast conditions, we believe that the presented method can be universally applied to improve the proton acceleration performance using any other laser system operated in the PW regime.

Tyrosine kinase (TK) receptors including epidermal growth factor receptors (EGFRs) are known to be overexpressed in a wide variety of solid tumors associated with poor prognosis. The HBED-CC chelator N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid 1 was coupled via one or both its propionic acid moieties with the quinazoline EGFR-TK inhibiting pharmacophore 4-amino-N-(4-((3-bromophenyl)amino)quinazolin-6-yl)butanamide 3 resulting in either a monomeric 4 or a dimeric 5 species. Ligands 4 and 5 reacted with Ga3+ generating the corresponding complexes Ga4 and Ga5. Both ligands and complexes were characterized with mass spectrometry and NMR spectroscopy and evaluated in vitro with MTT assays in A431 cells, where they showed IC50 values in the range 51.6 to 68.8 μM. Labeling of ligands 4 and 5 with the PET radionuclide 68Ga was quantitative and resulted in tracers [68Ga]Ga4 and [68Ga]Ga5 with radiochemical purities greater than 98%, which were also characterised by comparative RP-HPLC studies with Ga4 and Ga5 respectively. Radiotracers [68Ga]Ga4 and [68Ga]Ga5 were stable (in tact tracer over 98%) in the reaction mixture (120 min) and in human serum (30 min). Both tracers were evaluated in vivo with biodistribution experiments in SCID mice bearing A431 tumors presenting tumor uptake of 1.34 for [68Ga]Ga4 and 1.01 %ID/g for [68Ga]Ga5 at 5 min, which was slightly decreased at 60 min p.i. and then remained stable until 120 min p.i. To the best of our knowledge, this is the first report of monomeric and dimeric quinazoline conjugates with the chelator HBED-CC, which can serve as a basis for further development of EGFR-TKI targeting tracers.

Extremely defect graphene oxide (dGO) is proposed as an advanced sorbent for treatment of radioactive waste and con-taminated natural waters. dGO prepared using a modified Hummers oxidation procedure, starting from reduced graphene oxide (rGO) as a precursor, shows significantly higher sorption of U(VI), Am(III) and Eu(III) compared to standard gra-phene oxides (GO). Earlier studies revealed the mechanism of radionuclide sorption related to defects in GO sheets. There-fore, explosive thermal exfoliation of graphite oxide was used to prepare rGO with large number of defects and holes. De-fects and holes are additionally introduced by Hummers oxidation of rGO thus providing extremely defect-rich material. Analysis of characterization by XPS, TGA, FTIR shows that dGO oxygen functionalization is predominantly related to de-fects, such as flake edges and edge atoms of holes, whereas standard GO exhibits oxygen functional groups mostly on the planar surface. The high abundance of defects in dGO results in a 15-fold increase in sorption capacity of U(VI) compared to standard Hummers GO. The improved sorption capacity of dGO is related to abundant carboxylic groups attached hole edge atoms of GO flakes as revealed by synchrotron-based extended X-ray absorption fine structure (EXAFS) and high-energy resolution fluorescence detected X-Ray absorption near edge structure (HERFD-XANES) spectroscopy.

The oxidation state and local atomic environment of admixtures of In, Cu, and Ag in synthetic sphalerite crystals were determined by X-ray absorption spectroscopy (XAS). The sphalerite crystals doped with In, Cu, Ag, In–Cu, and In–Ag were synthesized utilizing gas transport, salt flux, and dry synthesis techniques. Oxidation states of dopants were determined using X-ray absorption near edge structure (XANES) technique. The local atomic structure was studied by X-ray absorption fine structure spectroscopy (EXAFS). The spectra were recorded at Zn, In, Ag, and Cu K-edges. In all studied samples, In was in the 3+ oxidation state and replaced Zn in the structure of sphalerite, which occurs with the expansion of the nearest coordination shells due to the large In ionic radius. In the presence of In, the oxidation state of Cu and Ag is 1+, and both metals can form an isomorphous solid solution where they substitute for Zn according to the coupled substitution scheme 2Zn2+ ↔ Me+ + In3+. Moreover, Ag K-edges EXAFS spectra fitting, combined with the results obtained for In-and Au-bearing sphalerite shows that the Me-S distances in the first coordination shell in the solid solution state are correlated with the ionic radii and increase in the order of Cu < Ag < Au. The distortion of the atomic structure increases in the same order. The distant (second and third) coordination shells of Cu and Ag in sphalerite are split into two subshells, and the splitting is more pronounced for Ag. Analysis of the EXAFS spectra, coupled with the results of DFT (Density Function Theory) simulations, showed that the In–In and Me+–In3+ clustering is absent when the metals are present in the sphalerite solid solution. Therefore, all studied admixtures (In, Cu, Ag), as well as Au, are randomly distributed in the matrix of sphalerite, where the concentration of the elements in the “invisible” form can reach a few tens wt.%.

In a lithium/sulfur (Li/S) battery, the reduction of sulfur during discharge involves a particular mechanism, where the active material successively dissolves into the electrolyte to form lithium polysulfide intermediate species (Li2Sx), with x being a function of the state of charge. In this work, sulfur K-edge Resonant Inelastic X-ray Scattering measurements were performed for the characterization of different Li2Sx polysulfide standard solutions. High Energy Resolution Fluorescence Detected X-ray Absorption Spectroscopy allowed clear separation the pre-edge absorption peak corresponding to terminal sulfur atoms from the main absorption peak due to internal atoms, and to evaluate quantitatively the evolution of the peak area ratio as a function of the polysulfide chain length. Results of this experimental work demonstrate that the normalized area of the pre-edge is a reliable fingerprint of Li2Sx mean chain length in agreement with recent theoretical predictions. As a perspective, this work confirms that operando HERFD XAS can be used to differentiate mean polysulfide composition, which is key issue in the characterization of Li/S cells.

Black and smooth Al films were characterized by the variable energy positron annihilation spectroscopy (VEPAS). It was found that in smooth films positronium (Ps) is formed on the surface only while in black metal films, it is formed also in nanoscopic pores inside the film. The mean pore size increases from the substrate to the surface due to increasing film roughness.

This work suggests new alternative explanation why a single InGaN quantum well (QW) or the deepest QWs in the multiple quantum well (MQW) structures suffer with a high non-radiative recombination rate. According to SIMS results, positron annihilation spectroscopy and photoluminescence measurements we suggest that vacancy of Ga in complex with hydrogen atoms can play a dominant role in non-radiative Shockley-Read-Hall recombination of the deepest QWs in InGaN/GaN MQW structures. Vacancy of gallium originate dominantly in GaN buffer layers grown at higher temperatures in H2 atmosphere and are transported to the InGaN/GaN MQW region by diffusion, where they are very effectively trapped in InGaN layers and form complex defects with hydrogen atoms during epitaxy of InGaN layers. Trapping of gallium vacancies is another suggested mechanism explaining why the widely used In containing prelayers help to increase the luminescence efficiency of the InGaN/GaN MQW active region grown above them. Understanding the mechanism why the luminescence efficiency is suppressed in deeper QWs may be very important for LED community and can help to develop new improved technologies for the growth of InGaN/GaN MQW active region.

Die Erfindung betrifft ein Verfahren zur Herstellung eines keramischen Materials mit lokal einstellbarem Permeabilitätsgradienten, dessen Anwendung in einem Beschichtungsverfahren- Materialbearbeitungsverfahren sowie dessen Verwendung. Die Aufgabe ein Material zur Verfügung zu stellen, welches zum Leiten und Isolieren von Magnetfeldern geeignet ist sowie in magnetischen Kopplungselementen verwendet werden kann, wird durch ein Verfahren zur Herstellung eines keramischen Materials mit lokal einstellbarem Permeabilitätsgradienten gelöst, wobei das Verfahren folgende Schritte umfasst: - Erzeugen eines keramischen Materials mittels Erhitzen einer Ausgangsmaterialkomposition bis zu einer Temperatur unterhalb der Schmelztemperatur der Ausgangsmaterialkomposition, - Abkühlen des erzeugten keramischen Materials auf Raumtemperatur nach einer definierten Abkühlrate zur Einstellung einer Vortex-Dichte in dem erzeugten keramischen Material, und - nachfolgende lokale Temperaturbehandlung zum Erhitzen des keramischen Materials über dessen ferroelektrische Ordnungstemperatur und zum Einstellen des lokalen Permeabilitätsgradienten.

Voltage control of magnetism through electric field-induced oxygen motion (magneto-ionics) could represent a significant breakthrough in the pursuit for new strategies to enhance energy efficiency in magnetically actuated devices. Boosting the induced changes in magnetization, magneto-ionic rates and cyclability continue to be key challenges to turn magneto-ionics into real applications. Here, it is demonstrated that room-temperature magneto-ionic effects in electrolyte-gated paramagnetic Co3O4 films can be largely increased both in terms of generated magnetization (6 times larger) and speed (35 times faster) if the electric field is applied using an electrochemical capacitor configuration (utilizing an underlying conducting buffer layer) instead of placing the electric contacts at the side of the semiconductor (electricdouble-layer transistor-like configuration). This is due to a greater uniformity and strength of the electric field in the capacitor design. These results are appealing to widen the use of ion migration in technological applications such as neuromorphic computing or iontronics in general.

The non-destructive investigation of single vacancies and vacancy clusters in ion irradiated samples requires a depth-resolved probe with atomic sensitivity to defects. The recent development of short-pulsed positron beams provides such a probe. Here, we combine depth-resolved Doppler broadening and positron annihilation lifetime spectroscopies to identify vacancy clusters in ion irradiated Fe and measure their density as a function of depth. Despite large concentrations of dislocations and voids in the pristine samples, positron annihilation measurements uncovered the structure of vacancy-clusters and the change in their size and density with irradiation dose. When combined with TEM measurements, the study demonstrates that the increase in the density of small vacancy clusters with irradiation is associated with a remarkable reduction in the size of large voids, revealing a novel mechanism for the interaction of cascade damage with voids in ion irradiated materials, a consequence of the high porosity of the initial microstructure.

The effect of average incorporated ion energy and impinging atomic oxygen flux on the structure and permeability of SiOx thin films by a microwave driven low-pressure discharge with additional RF bias is studied by means of positron annihilation lifetime spectroscopy (PALS) and complementary analytical approaches. The film growth and structure were controlled by the particle fluxes. Acorrelation between the pore sizes and pore size distribution as measured by positron annihilation lifetime spectroscopy (PALS) and the adjusted plasma parameters was established. The corresponding barrier performance was measured by oxygen transmission rate (OTR) and could be explained by the pore size distribution. The dominant pore size characteristic for dangling bonds within the SiOx-network was found to be in the range of 0.8 nm. The chemical composition and morphology were analysed by means of X-ray photoelectron spectroscopy (XPS), FTIR diffuse reflectance measurements (DRIFT) and atomic force microscopy (AFM). It was observed that a combination of both an increase in incorporated energy per deposited Si atom and low oxygen to silicon ratio resulted in an enhanced cross-linking of the SiOx network and thereby lead to a decrease in micropore density and to a shift of the pore size distribution function to lower values.

Radiolabeled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection, we recently developed the fluorine-18-labelled PSMA-ligand [¹⁸F]PSMA-1007 as the next generation radiofluorinated Glu-ureido PSMA inhibitor after [¹⁸F]DCFPyL and [¹⁸F]DCFBC. Since radiosynthesis so far has been suffering from rather poor yields, novel procedures for the automated radiosyntheses of [¹⁸F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly-used radiosynthesisers. Using the novel one-step procedure, the [¹⁸F]PSMA-1007 was produced in good radiochemical yields ranging from 25 to 80% and synthesis times of less than 55 min. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and, at the same time, high yielding production pathway for the next generation PSMA radioligand [¹⁸F]PSMA-1007. Actually, it turned out that the radiosynthesis is as easily realised as the well-known [¹⁸F]FDG synthesis and, thus, transferable to all currently-available radiosynthesisers. Using the new procedures, the clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

Effects of steel alloying agents on the formation of the surface oxide layer of galvanized press hardened steel after austenitization annealing were examined with various advanced microscopy and spectroscopy techniques. The main oxides on top of the original thin Al2O3 layer, originating from the primary galvanizing process, are identified as ZnO and (Mn,Zn)Mn2O4 spinel. For some of the investigated steel alloys, a non-uniform, several nanometer thick Cr-enriched additional film was found at the Al2O3 layer. At a sufficiently high concentration, Cr can act as a substitute for Al during annealing, strengthening and regenerating the original Al2O3 layer with Cr2O3. Further analysis with secondary ion mass spectrometry allowed a reliable distinction between ZnO and Zn(OH)2.

Background: To summarize the research activities of the “clinical research group heavy ion therapy”, funded by the German Research Foundation (DFG, KFO 214), on the impact of intrinsic tumor characteristics (grading, hypoxia) on local tumor control after carbon (¹²C-) ion- and photon irradiations. Methods: Three sublines of syngeneic rat prostate tumors (R3327) with various differentiation levels (highly (-H), moderately (-HI) or anaplastic (-AT1), (diameter 10 mm) were irradiated with 1, 2 and 6 fractions of either ¹²C-ions or 6 MV photons using increasing dose levels. Primary endpoint was local tumor control at 300 days. The relative biological effectiveness (RBE) of ¹²C-ions was calculated from TCD50-values (dose at 50% tumor control probability) of photons and ¹²C-ions and correlated with intrinsic tumor parameters. For the HI-subline, larger tumors (diameter 18 mm) were irradiated with either carbon ions, oxygen ions or photons under ambient as well as hypoxic conditions to determine the variability of the RBE under different oxygenation levels. In addition, imaging, histology and molecular analyses were performed to decipher the underlying mechanisms. Results: Experimental results revealed (i) a smaller variation of the TCD50-values between the three tumor sublines for 12C-ions (23.6 - 32.9 Gy) than for photons (38.2 - 75.7 Gy), (ii) steeper dose-response curves for ¹²C-ions, and (iii) an RBE that increased with tumor grading (1.62 ± 0.11 (H) vs 2.08 ± 0.13 (HI) vs 2.30 ± 0.08 (AT1)). Large HI-tumors resulted in a marked increase of TCD₅₀, which was increased further by 15% under hypoxic relative to oxic conditions. Noninvasive imaging, histology and molecular analyses identified hypoxia as an important radioresistance factor in photon therapy. Conclusions: The dose-response studies revealed a higher efficacy of ¹²C-ions relative to photon therapy in the investigated syngeneic tumor model. Hypoxia turned out to be at least one important radioresistance factor, which can be partly overridden by high-LET ion beams. This might be used to increase treatment effectiveness also in patients. The results of this project served as a starting point for several ongoing research projects.

Purpose Since the clinical introduction of ⁶⁸Ga-PSMA-11 PET/CT, this imaging method has rapidly spread and is now regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). The aim of this study was to analyse the influence of several variables with possible influence on PSMA ligand uptake in a large cohort. Methods We performed a retrospective analysis of 1007 consecutive patients who were scanned with ⁶⁸Ga-PSMA-11 PET/CT (1 h after injection) from January 2014 to January 2017 to detect recurrent disease. Patients with untreated primary PCa or patients referred for PSMA radioligand therapy were excluded. The possible effects of different variables including PSA level and PSA doubling time (PSA_DT), PSA velocity (PSA_Vel), Gleason score (GSC, including separate analysis of GSC 7a and 7b), ongoing androgen deprivation therapy (ADT), patient age and amount of injected activity were evaluated. Results In 79.5% of patients at least one lesion with characteristics suggestive of recurrent PCa was detected. A pathological (positive) PET/CT scan was associated with PSA level and ADT. GSC, amount of injected activity, patient age, PSA_DT and PSA_Vel were not associated with a positive PET/CT scan in multivariate analysis. Conclusion ⁶⁸Ga-PSMA-11 PET/CT detects tumour lesions in a high percentage of patients with recurrent PCa. Tumour detection is clearly associated with PSA level and ADT. Only a tendency for an association without statistical significance was found between higher GSC and a higher probability of a pathological PET/CT scan. No associations were found between a pathological ⁶⁸Ga-PSMA-11 PET/CT scan and patient age, amount of injected activity, PSA_DT or PSA_Vel.

Purpose Since the introduction of ⁶⁸Ga-PSMA-11 PET/CT for imaging prostate cancer (PC) we have frequently observed mediastinal lymph nodes (LN) showing tracer uptake despite being classified as benign. The aim of this evaluation was to further analyze such LN. Methods Two patient groups with biphasic ⁶⁸Ga-PSMA-11 PET/CT at 1 h and 3 h p.i. were included in this retrospective evaluation. Group A (n = 38) included patients without LN metastases, and group B (n = 43) patients with LN metastases of PC. SUV of mediastinal/paraaortal LN of group A (n = 100) were compared to SUV of LN metastases of group B (n = 91). Additionally, 22 randomly selected mediastinal and paraaortal LN of patients without PC were immunohistochemically (IHC) analyzed for PSMA expression. Results In group A, 7/38 patients (18.4%) presented with at least one PSMA-positive mediastinal LN at 1 h p.i. and 3/38 (7.9%) positive LN at 3 h p.i. with a SUV_max of 2.3 ± 0.7 at 1 h p.i. (2.0 ± 0.7 at 3 h p.i.). A total of 11 PSMA-positive mediastinal/paraaortal LN were detected in nine patients considering both imaging timing points. SUV_max of LN-metastases was 12.5 ± 13.2 at 1 h p.i. (15.8±17.0 at 3 h p.i.). SUV_max increased clearly (> 10%) between 1 h and 3 h p.i. in 76.9% of the LN metastases, and decreased significantly in 72.7% of the mediastinal/paraaortal LN. By IHC, PSMA-expression was observed in intranodal vascular endothelia of all investigated LN groups and to differing degrees within germinal centers of 15/22 of them (68.1%). Expression was stronger in mediastinal nodes (p = 0.038) and when follicular hyperplasia was present (p = 0.050). Conclusion PSMA-positive mediastinal/paraaortal benign LN were visible in a notable proportion of patients. PSMA-positivity on the histopathological level was associated with the activation state of the LN. However, in contrast to LN metastases of PC, they presented with significantly lower uptake, which, in addition, usually decreased over time.

A recently discovered modified low-temperature baking leads to reduced surface losses and an increase of the accelerating gradient of superconducting TESLA shape cavities. We will show that the dynamics of vacancy-hydrogen complexes at low-temperature baking lead to a suppression of lossy nanohydrides at 2 K and thus a significant enhancement of accelerator performance. Utilizing Doppler broadening Positron Annihilation Spectroscopy, Positron Annihilation Lifetime Spectroscopy and instrumented nanoindentation, samples made from European XFEL niobium sheets were investigated. We studied the evolution of vacancies in bulk samples and in the sub-surface region and their interaction with hydrogen at different temperature levels during in-situ and ex-situ annealing.

The role of vacancies in hardening of Fe–Al intermetallic alloys were studied in the present work for a wide range of Al concentrations from 20 to 50 at%. The alloys quenched from 1000 ◦C as well as those annealed subsequently at 520 ◦C for 1 h were subject to study. Slow-positron beam experiments combined with Vicker’s microhardness tests were utilised. Hardness of Fe–Al alloys exhibited a somewhat complex dependence on Al content which could not be fully explained purely by consideration of intermetallic phases formed. This happens due to additional hardening effect caused by quenched-in vacancies. The concentrations of vacancies were estimated from positron back-diffusion data and found to rise for Al content above 25 at%. Correlation of vacancy concentrations with hardness data for the quenched and annealed alloys has revealed that hardening of alloys with a low Al content (< 30 at%) is originated predominantly by anti-phase boundaries while hardening induced by quenched-in vacancies dominates for alloys with a higher Al content (30–50 at%).

Rare earths (RE = Sm, Gd, Ho) doped ZnO thin films were grown by pulsed laser deposition in oxygen ambient at pressure of 10 Pa on fused silica and Si(100) substrates at room temperature. A good optical quality of the films was confirmed by transmittance measurement in the visible spectral region. Photoluminescence suggested RE3+ oxidation state as confirmed at ZnO:Sm, where local structure was inhomogeneous. ZnO:Sm film exhibited the highest electrical resistivity while ZnO:Ho the lowest. Nanocrystalline structure of the films was observed by atomic force microscopy and X-ray diffraction. Defects structure was examined by variable energy positron annihilation spectroscopy. All ZnO:RE films exhibited significantly higher values of the S parameter as well as shorter positron diffusion lengths compared to ZnO monocrystal reference due to trapping of positrons at open volumes associated with grain boundaries. We observed the impact of the type of RE dopant on optical and electrotransport properties while the defect structure remained unchanged.

Understanding the photocatalytic–activity–defects relationship of titanium oxynitride nanotubes (TiON-NTs) is important for tailoring their photocatalytic performance. Herein, we fabricated highly ordered and vertically aligned nanotube arrays of TiON-NT-functionalized with iridium nanoparticles denoted as (Ir/TiON-NTs) for solar-driven water splitting. Positron annihilation lifetime spectroscopy (PALS) and variable-energy positron annihilation spectroscopy (VEPAS) were performed to quantify the vacancy-type defects of Ir/TiON-NTs relative to TiON-NTs and TiO2-NTs. The results display that the Ir/TiON-NTs exhibit abundant defects such as small nitrogen vacancies, larger size vacancy clusters, and small voids. The obtained photocurrent density of the Ir/TiON-NTs (11.3 mA cm−2) is about 3.97, 5, and 11.89 times higher than that of Ir/TiO2-NTs, TiON-NTs, and TiO2-NTs, respectively. The Mott–Schottky analysis revealed the highest significant negative shift in the band potential and the lowest donor density of Ir/TiON-NTs compared to its counterparts. This result is attributed to the unique structural and compositional merits of Ir/TiON-NTs despite the abundant defects, which delay the charge recombination and improve the photocatalytic activity. The presented study may open new frontiers on engineering the defects of metal oxynitrides with metal-based catalysts for photocatalytic applications.

Chapter "Ions and small molecules as radiopharmaceuticals" in the Encyclopedia of Nuclear Medicine and Molecular Imaging, Volume 1: Basic principles and instrumentation

Purpose The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer ⁶⁸Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, ⁶⁸Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of ¹⁸F-labelled analogs. ¹⁸F-PSMA-1007 was selected among several ¹⁸F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of ¹⁸F-PSMA-1007 in human volunteers and patients. Methods Radiation dosimetry of ¹⁸F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent ¹⁸F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining. Results With an effective dose of approximately 4.4–5.5 mSv per 200–250 MBq examination, ¹⁸F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other ¹⁸F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, ¹⁸F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to ¹⁸F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2–3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. ¹⁸F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter. Conclusion ¹⁸F-PSMA-1007 performs at least comparably to ⁶⁸Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of ⁶⁸Ga-labelled PSMA-targeted tracers.

1:1 metal complexes of small crown ethers are structurally similar to extraframework sites in metal-exchanged zeolites. Using ab initio calculations, we show that adsorbed molecular hydrogen follows the same trends in adsorption energies and vibrational frequencies at both types of metal sites. Unlike zeolites, crown ethers can be characterized in the gas phase, which opens new possibilities for understanding the bonding of dihydrogen at undercoordinated metal sites to help guide the rational design of porous materials for hydrogen isotope separation. Because more strongly binding adsorbates affect the geometry of the hosts, the similarity of crown ethers and zeolites with regard to the vibrational spectra of the adsorbed molecule seems to be limited to H₂.

Without Abstract

[¹⁸F]6-Fluoro-N-[2-(diethylamino)ethyl]nicotinamide [¹⁸F]MEL050 is a novel nicotinamide-based radiotracer, designed to target random metastatic dissemination of melanoma tumours by targeting melanin. Preclinical studies suggest that [¹⁸F]MEL050 has an excellent potential to improve diagnosis and staging of melanoma. Here we report the radiochemical optimization conditions of [¹⁸F]MEL050 and its large scale automated synthesis using a GE FXFN automated radiosynthesis module for clinical, phase-1 investigation. [¹⁸F]MEL050 was prepared via a one-step synthesis using no-carrier added K[¹⁸F]F-Kryptofix® 222 (DMSO, 170° C, 5 min) followed by HPLC purification. Using 6-chloro-N-[2-(diethylamino)ethyl]nicotinamide as precursor, [¹⁸F]MEL050 was obtained in 40-46% radiochemical yield (non-decay corrected), in greater than 99.9% radiochemical purity and specific activity ranging from 240 to 325 GBq µmol(-1). Total synthesis time including formulation was 40 min and [¹⁸F]MEL050 was stable (99.8%) in PBS for 6 h.

Biochemical recurrence (BCR) is a concern for prostate cancer patients after local treatment. ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA) ligands have significantly improved prostate cancer imaging. However, several ¹⁸F-labeled ligands that were developed as fluorinated tracers might present advantages. In this study, we analyzed the potential of ¹⁸F-PSMA-1007 in patients with BCR. Methods: Twelve patients with BCR after local treatment underwent PET/CT scans 1 and 3 h after injection of ¹⁸F-PSMA-1007. Results: ¹⁸F-PSMA-1007 PET/CT detected lesions in 9 of 12 patients (75%). A significant difference was observed when comparing the tracer uptake in ¹⁸F-PSMA-1007–positive lesions 1 and 3 h after injection (median SUV_max, 7.00 vs. 11.34; P < 0.001; n = 76). Fortyfour (88%) of 50 ¹⁸F-PSMA-1007–positive lymph nodes had a shortaxis diameter of less than 8 mm. Conclusion: In this pilot study, ¹⁸F-PSMA-1007 PET/CT presented high potential for localization of recurrent disease in prostate cancer patients with BCR.

The introduction of ¹⁸F-labeled prostate-specific membrane antigen (PSMA)–targeted PET/CT tracers, first ¹⁸F-DCFPyL (2-(3-{1-carboxy-5-[(6-¹⁸F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) andmore recently ¹⁸F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-¹⁸F-fluoronicotinamido)butanamido)butanamido)methyl)phenyl)-3-(naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane-10,14,16-tricarboxylic acid)), have demonstrated promising results for the diagnostic workup of prostate cancer. This clinical study presents an intraindividual comparison to evaluate tracer-specific characteristics of ¹⁸F-DCFPyL versus ¹⁸F-PSMA-1007. Methods: Twelve prostate cancer patients, drug-na¨ıve or before surgery, received similar activities of about 250 MBq of ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007 48 h apart and were imaged 2 h after injection on the same PET/CT scanner using the same reconstruction algorithm. Normal-organ biodistribution and tumor uptake were quantified using SUV_max. Results: PSMA-positive lesions were detected in 12 of 12 prostate cancer patients. Both tracers, ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007, detected the same lesions. No statistical significance could be observed when comparing the SUV_max of ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007 for local tumor, lymph node metastases, and bone metastases. With regard to normal organs, ¹⁸F-DCFPyL had statistically significant higher uptake in kidneys, urinary bladder, and lacrimal gland. Vice versa, significantly higher uptake of ¹⁸F-PSMA-1007 in muscle, submandibular and sublingual gland, spleen, pancreas, liver, and gallbladder was observed. Conclusion: Excellent imaging quality was achieved with both ¹⁸F-DCFPyL and ¹⁸F-PSMA-1007, resulting in identical clinical findings for the evaluated routine situations. Nonurinary excretion of ¹⁸F-PSMA-1007 might present some advantage with regard to delineation of local recurrence or pelvic lymph node metastasis in selected patients; the lower hepatic background might favor ¹⁸F-DCFPyL in late stages, when rare cases of liver metastases can occur.

⁶⁸Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT represents an advanced method for the staging of primary prostate cancer (PCa) and diagnosis of recurrent or metastatic PCa. However, because of the narrow availability of ⁶⁸Ga the development of alternative tracers is of high interest. The objective of this study was to examine the value of the new PET tracer ¹⁸F-PSMA-1007 for the staging of local disease by comparing it with multiparametric MRI (mpMRI) and radical prostatectomy (RP) histopathology. Methods: In 2016, ¹⁸F-PSMA-1007 PET/CT was performed in 10 men with biopsy-confirmed high-risk PCa. Nine patients underwent mpMRI in the process of primary diagnosis. Consecutively, RP was performed in all 10 men. Agreement analysis was performed retrospectively. PSMA staining was added for representative sections in RP specimen slices. Localization and agreement analysis of ¹⁸F-PSMA-1007 PET/CT, mpMRI, and RP specimens was performed by dividing the prostate into 38 sections as described in the prostate imaging reporting and data system (PI-RADS) (version 2). Sensitivity, specificity, positive predictive values, negative predictive values (NPVs), and accuracy were calculated for total and near-total agreement. Results: ¹⁸F-PSMA-1007 PET/CT had an NPV of 68% and an accuracy of 75%, and mpMRI had an NPV of 88% and an accuracy of 73% for total agreement. Near-total agreement analysis resulted in an NPV of 91% and an accuracy of 93% for ¹⁸F-PSMA-1007 PET/CT and 91% and 87% for mpMRI, respectively. Retrospective combination of mpMRI and PET/CT had an accuracy of 81% for total and 93% for near-total agreement. Conclusion: Comparison with RP histopathology demonstrates that ¹⁸F-PSMA-1007 PET/CT is promising for accurate local staging of PCa.

In recent years, several radiotracers targeting the prostate-specific membrane antigen (PSMA) have been introduced. Some of them have had a high clinical impact on the treatment of patients with prostate cancer. However, the number of ¹⁸F-labeled tracers addressing PSMA is still limited. Therefore, we aimed to develop a radiofluorinated molecule resembling the structure of therapeutic PSMA-617. Methods: The nonradioactive reference compound PSMA-1007 and the precursor were produced by solid-phase chemistry. The radioligand ¹⁸F-PSMA-1007 was produced by a 2-step procedure with the prosthetic group 6-¹⁸F-fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester. The binding affinity of the ligand for PSMA and its internalization properties were evaluated in vitro with PSMA-positive LNCaP (lymph node carcinoma of the prostate) cells. Further, organ distribution studies were performed with mice bearing LNCaP and PC-3 (prostate cancer cell line; PSMA-negative) tumors. Finally, small-animal PET imaging of an LNCaP tumor–bearing mouse was performed. Results: The identified ligand had a binding affinity of 6.7 ± 1.7 nM for PSMA and an exceptionally high internalization ratio (67% ± 13%) in vitro. In organ distribution studies, high and specific tumor uptake (8.0 ± 2.4 percentage injected dose per gram) in LNCaP tumor–bearing mice was observed. In the small-animal PET experiments, LNCaP tumors were clearly visualized. Conclusion: The radiofluorinated PSMA ligand showed promising characteristics in its preclinical evaluation, and the feasibility of prostate cancer imaging was demonstrated by small-animal PET studies. Therefore, we recommend clinical transfer of the radioligand ¹⁸F-PSMA-1007 for use as a diagnostic PET tracer in prestaging and monitoring of prostate cancer.

PET imaging with the prostate-specific membrane antigen (PSMA)–targeted radioligand ⁶⁸Ga-PSMA-11 is regarded as a significant step forward in the diagnosis of prostate cancer (PCa). More recently, a PSMA ligand was developed that can be labeled with ⁶⁸Ga, ¹¹¹In, ¹⁷⁷Lu, and ⁹⁰Y. This ligand, named PSMA-617, therefore enables both diagnosis and therapy of PCa. The aims of this evaluation were to clinically investigate the distribution of ⁶⁸Ga-PSMA-617 in normal tissues and in PCa lesions as well as to evaluate the radiation exposure by the radioligand in PET imaging. Methods: Nineteen patients, most of them with recurrent PCa, were referred for ⁶⁸Ga-PSMA-617 PET/CT. The quantitative assessment of tracer uptake of several organs and of 53 representative tumor lesions was performed in 15 patients at 1 and 3 h after injection. In 4 additional patients, the same procedure was conducted at 5 min, 1 h, 2 h, 3 h, 4 h, and 5 h after injection. On the basis of the data for these 4 patients (mean injected dose, 231 MBq), the radiation exposure of a ⁶⁸Ga-PSMA-617 PET/CT was identified. Results: Intense tracer uptake was observed in the kidneys and salivary glands. In 14 of 19 patients (73.7%), at least 1 lesion suspected of being a tumor was detected at 3 h after injection. Of 53 representative tumor lesions selected at 3 h after injection, 47 lesions were visible at 1 h after injection. The mean tumor-to-background ratio for maximum standardized uptake value was 20.4 ± 17.3 (range, 2.3–84.0) at 1 h after injection and 38.2 ± 38.6 (range, 3.6–154.3) at 3 h after injection. The average radiation exposure (effective dose) was approximately 0.021 mSv/MBq. Conclusion: Within healthy organs, the kidneys and salivary glands showed the highest ⁶⁸Ga-PSMA-617 uptake. The radiation exposure was relatively low. ⁶⁸Ga-PSMA-617 shows PCa lesions with high contrast. Images obtained between 2 and 3 h after injection seem to be the best option with regard to radiotracer uptake and tumor contrast. Later images can help to clarify unclear lesions.

For the time period from 1.5 to 4 Myr before present we found in deep ocean ferromanganese crusts a 53Mn excess concentration in terms of 53Mn/Mn of about 4 x 10^-14 over that expected for cosmogenic production. We conclude that this 53Mn is of supernova origin because it is detected in the same time window, about 2.5 Myr ago, where 60Fe has been found earlier. This overabundance confirms the supernova origin of that 60Fe. For the first time supernova-formed 53Mn has been detected and it is the second positively identified radioisotope from the same supernovae. The ratio 53Mn/60Fe of about 14 is consistent with that expected for a SN with a 11 - 25 Mʘ progenitor mass and solar metallicity.

Treatment resistance of cancer cells is a multifaceted process in which DNA repair emerged as potential therapeutic target. DNA repair is predominantly conducted by nuclear events; yet, how extra-nuclear cues impact the DNA damage response is largely unknown. Here, using a high-throughput RNAi-based screen in three-dimensionally grown cell cultures of head and neck squamous cell carcinoma (HNSCC), we identified novel focal adhesion proteins controlling DNA repair, including the intermediate filament protein synemin. We demonstrate that synemin critically regulates the DNA damage response by non-homologous end joining repair. Mechanistically, synemin forms a protein complex with DNA-PKcs through its C-terminal tail domain for determining DNA repair processes upstream of this enzyme in an ATM–dependent manner. Our study discovers a critical function of the intermediate filament protein synemin in the DNA damage response fundamentally supporting the concept of cytoarchitectural elements as co-regulators of nuclear events.

Epothilone B was shown to have promising chemo- and radiosensitizing effects on cells, but the mechanisms underlying cell death remain ambiguous. The aim of the study was to examine selected cell death pathways on the basis of FaDu and A549 cells. Western blot analyses were used for investigation of specific apoptotic markers. Immunofluorescence imaging and flow cytometry were utilized for examination of cell death mechanisms. DNA-staining was used for studying influence of epothilone B on micronucleus rate. We showed that epothilone B can initiate cell death via apoptosis and mitotic catastrophe, but induction of cell death was cell type specific.

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The Nconga Formation of the Mesoarchean (~2.96-2.84 Ga) Mozaan Group of the Pongola Supergroup of southern Africa contains the world’s oldest known granular iron formation. Three dimensional reconstructions of the granules using micro-focus X-ray computed tomography reveal that these granules are microstromatolites coated by magnetite and calcite, and can therefore be classified as oncoids. The reconstructions also show damage to the granule coatings caused by sedimentary transport during formation of the granules and eventual deposition as density currents. The detailed, three dimensional morphology of the granules in conjunction with previously published geochemical and isotope data indicate a biogenic origin for iron precipitation around chert granules on the shallow shelf of one of the oldest supracratonic environments on Earth almost three billion years ago. It broadens our understanding of biologically-mediated iron precipitation during the Archean by illustrating that it took place on the shallow marine shelf coevally with deeper water, below-wave base iron precipitation in micritic iron formations.

Es wird Verfahren zur Auswahl eines Sensors (1) aus einer Mehrzahl von Sensoren zur sensorbasierten Sortierung eines Materialgemischs (10) anhand einer Materialeigenschaft zur Konzentration eines Wertstoffes vorgeschlagen, wobei in einem ersten Schritt aus dem Materialgemisch (10) repräsentative Einzelproben gewonnen werden (20), in einem zweiten Schritt Materialeigenschaften der Einzelproben gemessen werden (30), in einem dritten Schritt auf Grundlage der gemessenen Materialeigenschaften eine Mehrzahl von simulierten Sortierungen anhand jeweils unterschiedlicher Materialeigenschaften simuliert wird (40), in einem vierten Schritt eine simulierte Sortierung mit einer hohen Wertstoffkonzentration aus der Mehrzahl von simulierten Sortierungen ausgewählt wird, in einem fünften Schritt ein Sensor (1) zur Messung der Materialeigenschaft ausgewählt wird (50), welcher geeignet ist, mindestens eine der Materialeigenschaften, welche für die ausgewählte simulierte Sortierung genutzt wurde, zu messen.

Die Erfindung betrifft einen Reaktor, ein Verfahren und die Verwendung dieses Reaktors in dem Verfahren zur Gewinnung amphiphiler Siderophore aus einer Mikroorganismenkultur. Der Reaktor umfasst die Bauteile: (a) Vorrichtung (40) zum Rühren und/oder Begasen, und (b) Ablauf (70) für Schaum, enthaltend die amphiphilen Siderophore, in der Seitenwand des Reaktors, (c) Deckel (90) wobei die Unterkante des Ablaufs (70) für Schaum als Überlauf in einer Höhe liegt, die im Bereich von 40-75% der Gesamthöhe des Reaktors (10), von unten gemessen, liegt, und wobei der Ablauf (70) für Schaum horizontal nach außen oder schräg nach unten außen verläuft oder als Überlauf ausgestaltet ist.

Verschiedene Ausführungsformen betreffen ein Verfahren (700) zum Betreiben einer Kühlvorrichtung (300), das Verfahren (700) aufweisend: ein erstes Verändern eines elektrischen Feldes (304) in einem Feldbereich (306), wobei in dem Feldbereich (306) mindestens ein Magnetsystem mit magnetoelektrischer Kopplung angeordnet ist, und dadurch Erwärmen des mindestens einen Magnetsystems; und, anschließend, ein zweites Verändern des elektrischen Feldes (304) in dem Feldbereich (306) und dadurch Abkühlen des mindestens einen Magnetsystems.

Die Erfindung betrifft eine Schichtabfolge zur Erzeugung von Elektrolumineszenz und deren Verwendung, beispielsweise in einem Pixelarray oder in textilen Materialien. Die Aufgabe eine Schichtstruktur anzugeben, die einfach realisierbar bzw. herstellbar sowie einfach aufgebaut ist, mit der Elektrolumineszenz einfach erzeugt werden kann und langzeitstabil einsetzbar ist, wird durch eine Schichtabfolge zur Erzeugung von Elektrolumineszenz gelöst, die mindestens eine polykristalline Seltene-Erd-Manganat-Schicht sowie einen ersten Kontakt, der auf einer Seite der Seltene-Erd-Manganat-Schicht angeordnet ist sowie einen zweiten Kontakt, der auf der gegenüberliegenden Seite des ersten Kontaktes oder auf der gleichen Seite wie der erste Kontakt angeordnet ist, aufweist, wobei in der Seltene-Erd-Manganat-Schicht zwischen dem ersten Kontakt und dem zweiten Kontakt ein Widerstand größer als 100 Ohm ausgebildet ist und wobei die Seltene-Erd-Manganat-Schicht geeignet ist, bei Anlegen einer elektrischen Gleichspannung, lokal im Bereich des sich zwischen den beiden elektrisch leitenden Kontakten ausbildenden elektrischen Feldes in der Seltene-Erd-Manganat-Schicht eine Elektrolumineszenz aufgrund von Stoßionisation auszubilden.

Die Erfindung betrifft ein Fluidik-Detektionssystem zur magnetisch-elektrischen Messung einer fluiden Probe, wobei das System jeweils mindestens ein Probenmodul, einen Magnetfeldsensor und einen Magneten umfasst, welche voneinander beabstandet angeordnet sind. Dabei weist das Probenmodul mindestens einen Kanal auf, der zum Befördern einer fluiden Probe entlang einer Fließrichtung ausgebildet ist. Der Magnet erzeugt ein Magnetfeld in einem Mess- und Anregungsbereich des Kanals. Dabei entspricht der Detektionsbereich des Magnetfeldsensors dem Mess- und Anregungsbereich des Kanals. Beim Befördern der fluiden Probe im Mess- und Anregungsbereich des Kanals wird das Magnetfeld von der zu untersuchenden fluiden Probe modifiziert, wobei der Magnetfeldsensor das modifizierte Magnetfeld erfasst. Die Erfindung betrifft weiterhin ein Verfahren zum Betrieb des erfindungsgemäßen Fluidik-Detektionssystems zur magnetisch-elektrischen Messung einer fluiden Probe.

Die Erfindung betrifft eine Verbindung der allgemeinen Formel I worin R¹ aus der Gruppe ausgewählt ist, die aus einer C₁-C₁₂-Alkylgruppe, einer C₃-C₁₂-Cycloalkylgruppe und einer Hetrocycloalkylgruppe mit 5 bis 12 Ringatomen, wobei die Ringatome Kohlenstoff und 1 bis 4 Heteroatome, ausgewählt aus N, O und S, sind, besteht; R² Wasserstoff oder Fluor ist, R³ eine Gruppe der Formel II oder eine Gruppe der Formel III ist: X¹ aus der Gruppe ausgewählt ist, die aus -(CR⁵R⁶)ₘ-, -(CR⁵R⁶)ₙC(O)-(CR⁵R⁶)ₚ- und -(CR⁵R⁶)q-X2-(CR⁵R⁶)ᵣ- besteht, wobei m, n, p, q und r unabhängig voneinander jeweils 0 oder eine Ganzzahl von 1 bis 6 sind; R⁴ aus der Gruppe ausgewählt ist, die aus einer Arylgruppe, einer Heteroarylgruppe mit 5 bis 12 Ringatomen, wobei die Ringatome Kohlenstoff und 1 bis 4 Heteroatome, ausgewählt aus N, O und S, sind, einer C₃-C₁₂-Cycloalkylgruppe und einer Heterocycloalkylgruppe mit 5 bis 12 Ringatomen, wobei die Ringatome Kohlenstoff und 1 bis 4 Heteroatome, ausgewählt aus N, O und S, sind, besteht; Ring A eine Arylgruppe oder eine Heteroarylgruppe mit 5 bis 12 Ringatomen, wobei die Ringatome Kohlenstoff und 1 bis 4 Heteroatome, ausgewählt aus N, O und S, sind, ist.

Die Erfindung beschreibt ein Verfahren zur Rekonfiguration einer Vortex-Dichte in einem Seltene-Erd-Manganat sowie einen nichtflüchtigen Impedanzschalter mit rekonfigurierbarer Impedanz. Die Aufgabe ein Verfahren anzugeben, mittels dem in speziellen Materialien deren Impedanz in Abhängigkeit von einer Vortex-Dichte ohne großen Aufwand beeinflusst und eingestellte werden kann, wird durch ein Verfahren zur Rekonfiguration einer Vortex-Dichte in einem Seltene-Erd-Manganat gelöst, wobei ein einmaliges Spannungs-Zeit-Profil zwischen einem ersten und einem zweiten, an das Seltene-Erd-Manganat angebrachten elektrisch leitenden Kontakt angelegt wird, so dass das Seltene-Erd-Manganat in einem Bereich eines sich zwischen den beiden elektrisch leitenden Kontakten ausbildenden elektrischen Feldes während eines Abkühlvorganges während und nach Anlegen des Spannungspulses oder der Spannungsrampe eine Ordnungstemperatur durchläuft und damit die Vortex-Dichte lokal im Bereich des sich zwischen den beiden elektrisch leitenden Kontakten ausbildenden elektrischen Feldes beeinflusst und eingestellt wird.

Die Erfindung betrifft einen Festbettreaktor (1) mit einem rohrförmigen Reaktionsbehälter (2), der einen Rohrmantel (7), der einen Innenraum (14) begrenzt, und eine Längsachse (B) aufweist, die gegen die Horizontale geneigt ist und um die der Reaktionsbehälter (2) drehbar ist. Dabei ist vorgesehen, dass in dem Innenraum (14) ein Verdrängungskörper (15) unter Ausbildung eines umlaufenden Spaltes (20) zwischen dem Verdrängungskörper (15) und dem Rohrmantel (7) angeordnet ist, wobei im Betriebszustand des Festbettreaktors (1) ein Festbett (13) aus einem Katalysatormaterial in dem Spalt (20) fixiert ist, das von zumindest einer Flüssigkeit (51) und zumindest einem Gas (52) durchströmt ist.

Die Erfindung betrifft ein multisensorisches therapeutisch-diagnostisches System zum Monitoring des orthopädischen Trainings und der sportlichen Leistung mit voneinander beabstandeten elektrischen Komponenten, welche eine Datenverarbeitungseinrichtung, einen Energiespeicher, ein Sensorsystem zur Erfassung von Daten sowie eine Trageeinrichtung aufweisen, wobei die elektrischen Komponenten zumindest teilweise in oder an der Trageeinrichtung angeordnet sind. Weiterhin betrifft die Erfindung ein Verfahren zum Monitoring des orthopädischen Trainings und der sportlichen Leistung sowie ein Computerprogrammprodukt zur Durchführung des Verfahrens.

Die Erfindung stellt ein mehrstufiges Verfahren bereit, zur selektiven, umweltfreundlichen und kostengünstigen Rückgewinnung von Nichteisenmetallen aus Industrieabwässern. Das Verfahren basiert auf dem Prinzip der Komplexierung der Nichteisenmetalle, Abtrennung der Komplexe und anschließender Dekomplexierung der Nichteisenmetalle. Zur Anwendung kommen als Komplexbildner Siderophore, die innerhalb des Prozesses zurückgewonnen werden. Das Verfahren ist insbesondere auch bei geringen Nichteisenmetall-Konzentrationen anwendbar. Es ist effizient, umweltfreundlich und kostengünstig.

Die Erfindung betrifft einen transparenten Objektträger. Die Aufgabe der Erfindung einen Objektträger anzugeben, an dem die Reichweite sowie die Stärke der oberflächennahen, elektrostatischen Kräfte, während eines Herstellungsprozesses des Objektträgers zu beeinflussen und einzustellen sind, wird durch einen transparenten Objektträger gelöst, welcher eine aufnahmeseitige Oberfläche und eine von der Aufnahmeseite abgewandte, also rückseitige Oberfläche ausweist und mindestens drei Schichten umfasst: eine elektrisch isolierende erste Schicht, eine auf der ersten Schicht angeordnete siliziumhaltige zweite Schicht sowie eine auf der zweiten Schicht angeordnete elektrisch isolierende dritte Schicht, wobei sich jeweils eine Grenzfläche zwischen der ersten und zweiten Schicht sowie zwischen der zweiten und dritten Schicht ausbildet, wobei die Grenzfläche zwischen der ersten und zweiten Schicht eine erste Flächenladungsdichte aufweist und die Grenzfläche zwischen der zweiten und dritten Schicht eine zweite Flächenladungsdichte aufweist, wobei die erste und zweite Flächenladungsdichte gleiche oder unterschiedliche Vorzeichen aufweisen und der Objektträger oberflächennahe, elektrostatischen Kräfte auf beiden Oberflächenseiten aufweist, deren Reichweite sowie Stärke während des Herstellungsprozesses zu beeinflussen und einzustellen sind.

Die Erfindung betrifft ein Verfahren zur kontinuierlichen Bestimmung sämtlicher Komponenten eines Widerstandstensors von Dünnschichten, wie Dünnschichtwiderständen und Dünnschichtsensoren aller Art. Durch die Erfindung soll ein Verfahren zur kontinuierlichen Bestimmung sämtlicher Komponenten eines Widerstandstensors von Dünnschichten, wie Dünnschichtwiderständen und Dünnschichtsensoren aller Art, geschaffen werden, bei dem mit einer minimierten Anzahl von Kontakten eine kontinuierliche Bestimmung aller Komponenten des Widerstandstensors ohne Umschalten der Kontaktpunkte ermöglicht wird. Erreicht wird das dadurch, dass ein beliebig geformtes homogenes Teilstück (T) der Dünnschicht mit mindestens drei in Abständen zueinander angeordneten Kontaktpunkten (K₁ bis K₃) versehen wird, wobei an jedem der Kontaktpunkte (K₁ bis K₃) eine Eingangsspannung Uᵢ(t) angelegt wird, dass die die Kontaktpunkte (K₁ bis K₃) durchfließenden Ströme Iᵢ(t) erfasst werden und dass aus den Spannungs- und Stromwerten der vollständige Widerstandstensor p des Teilstücks (T) der Dünnschicht bestimmt wird.

Die Erfindung betrifft ein Teilchenspektrometer und Teilchenspektrometrieverfahren zum Analysieren eines entlang eines Teilchenpfades verlaufenden Teilchenpulses, wobei der Teilchenpuls an einer Kreuzungsposition zur Überlagerung mit einem Photonenpuls gebracht wird, sodass ein Teil der Teilchen des Teilchenpulses mittels des Photonenpulses elektrisch umgeladen wird, und wobei anschließend mittels eines Analysators die umgeladenen Teilchen separiert und die umgeladenen oder die nicht umgeladenen Teilchen separat mittels eines Teilchendetektors detektiert werden.

We report high-resolution dilatometry on high-quality single crystals of NiTiO₃ grown by means of the optical floating-zone technique. The anisotropic magnetic phase diagram is constructed from thermal expansion and magnetostriction studies up toB=15 T and magnetization studies in static (15-T) and pulsed (60-T) magnetic fields. Our data allow us to quantitatively study magnetoelastic coupling and to determine uniaxial pressure dependencies. While the entropy changes are found to be of magnetic nature, Grüneisen analysis implies only one relevant energy scale in the whole low-temperature regime. Thereby, our data suggest that the observed structural changes due to magnetoelastic coupling and previously reported magnetodielectric coupling [L. Balhorn, J. Hazi, M. C. Kemei, and R. Seshadri, Phys. Rev. B93, 104404(2016)] are driven by the same magnetic degrees of freedom that lead to long-range magnetic order in NiTiO₃.

We report on the nonequilibrium monopole dynamics in the classical spin ice Dy₂Ti₂O₇ detected by means of high-resolution magnetostriction measurements. Significant lattice changes occur at the transition from the kagome-ice to the saturated-ice phase, visible in the longitudinal and transverse magnetostriction. A hysteresis opening at temperatures below 0.6 K suggests a first-order transition between the kagome and saturated state. Extremely slow lattice relaxations, triggered by changes of the magnetic field, were observed. These latticerelaxation effects result from nonequilibrium monopole formation or annihilation processes. The relaxation times extracted from our experiment are in good agreement with theoretical predictions with decay constants of the order of 10⁴ s at 0.3K.

The thermodynamics in spin-ice systems are governed by emergent magnetic monopole excitations and, until now, the creation of a pair of these topological defects was associated with one specific pair-creation energy. Here, we show that the electric dipole moments inherent to the magnetic monopoles lift the degeneracy of their creation process and lead to a splitting of the pair-creation energy. We consider this finding to extend the model of magnetic relaxation in spin-ice systems and show that an electric dipole interaction in the theoretically estimated order of magnitude leads to a splitting which can explain the controversially discussed discrepancies between the measured temperature dependence of the magnetic relaxation times and previous theory. By applying our extended model to experimental data of, various spin-ice systems, we show its universal applicability and determine a dependence of the electric dipole interaction on the systemparameters, which is in accordance with the theoretical model of electric dipole formation.

In the field of mineral resources extraction, one main challenge is to meet production targets in terms of geometallurgical properties. These properties influence the processing of the ore and are often represented in resource modeling by coregionalized variables with a complex relationship between them. Valuable data are available about geometalurgical properties and their interaction with the beneficiation process given sensor technologies during production monitoring. The aim of this research is to update resource models as new observations become available. A popular method for updating is the ensemble Kalman filter. This method relies on Gaussian assumptions and uses a set of realizations of the simulated models to derive sample covariances that can propagate the uncertainty between real observations and simulated ones. Hence, the relationship among variables has a compositional nature, such that updating these models while keeping the compositional constraints is a practical requirement in order to improve the accuracy of the updated models. This paper presents an updating framework for compositional data based on ensemble Kalman filter which allows us to work with compositions that are transformed into a multivariate Gaussian space by log-ratio transformation and flow anamorphosis. This flow anamorphosis, transforms the distribution of the variables to joint normality while reasonably keeping the dependencies between components. Furthermore, the positiveness of those variables, after updating the simulated models, is satisfied. The method is implemented in a bauxite deposit, demonstrating the performance of the proposed approach.

In the present study, we assessed the capabilities of Eulerian-Eulerian CFD two-phase flow simulation with the homogeneous Multiple Size Group Model (MUSIG) and consideration of breakup and coalescence under transient three-dimensional flow conditions. We compared void fraction, bubble size and bubble velocity distributions against experimental data from vertical gas-disperse two-phase flow in a pipe with a flow obstruction. The simulation results generally agree well upstream the obstacle, where we have a typically developed pipe flow. Downstream of the obstacle void fraction is overpredicted while bubble velocity is underpredicted. The bubble size distribution has no clear trend. With higher liquid velocities, the deviations increase. As a conclusion, the simulation has difficulties to balance the gas fraction in the strong vortex in the shadow of the obstacle. Here further model improvement is needed.

Purpose: The aim of the study was to improve abdominal tumor detection by use of a dual radiologic contrast protocol. Procedures: eXia160® (Benitio international) was mixed with 2-deoxy-2-[¹⁸F]fluoro-D-glucose or 3′-[¹⁸F]fluoro-3′-deoxythymidine for intravenous (IV) injections. Omnipaque® 300 (GE healthcare) was used for intraperitoneal (IP) injections. Positron emission tomography/computed tomography (PET/CT) scans were acquired on a Siemens Biograph® equipped with point spread function reconstruction. The optimal concentration and injection schedule of IP contrast agent was studied in 12 mice. The impact of IP contrast media on PET quantitative accuracy was investigated by phantom studies and by imaging six mice before and after IP injection of Omnipaque®. The impact of a dual contrast media protocol on tumor delineation and quantitation was evaluated in 15 tumor-bearing mice using ex vivo counting as the reference. Results: The optimal sequence was a mixture of tracer plus IV contrast agent followed by 1 mL of IP contrast agent (20 mg iodine/mL) administered 10 min before PET/CT acquisition. Phantom studies showed that the use of a 20-mg iodine/mL concentration of Omnipaque® led to a 4.8% overestimation of radioactivity concentration, as compared to saline. This was confirmed by animal studies that demonstrated a 4.3% overestimation. Tumor detection was excellent and correlation between PET/CT quantitative data and ex vivo counting was good (r²=0.91, slope=0.7). Conclusions: A dual radiologic contrast protocol is useful in PET/CT scanning of mice bearing abdominal tumors. Contrast agents used in this manner lead to a small but acceptable overestimation of quantitative PET data.

Targeting the mammalian target of rapamycin (mTOR) pathway is a potential means of overcoming cisplatin resistance in ovarian cancer patients. Because mTOR inhibition affects cell proliferation, we aimed to study whether 39-deoxy-39-¹⁸F-fluorothymidine (¹⁸F-FLT) PET could be useful for monitoring early response to treatment with mTOR inhibitors in an animal model of cisplatin-resistant ovarian tumor. Methods: BALB/c nude mice bearing subcutaneous human SKOV3 ovarian cancer xenografts were treated with either the mTOR inhibitor everolimus (5 mg/kg) or vehicle, and ¹⁸F-FLT PET was performed at baseline, day 2, and day 7 of treatment. ¹⁸F-FLT uptake was evaluated by calculation of mean standardized uptake value (SUVmean) corrected for partial-volume effect. Ex vivo immunohistochemistry studies were performed on separate cohorts of mice treated as above and sacrificed at the same time points as for the PET studies. The ex vivo analysis included bromodeoxyuridine incorporation as a marker of cell proliferation, and phosphorylation of ribosomal protein S6 as a downstream marker of mTOR activation. Results: During the treatment period, no significant change in tumor ¹⁸F-FLT uptake was observed in the vehicle group, whereas in everolimus-treated mice, ¹⁸F-FLT SUVmean decreased by 33% (P = 0.003) at day 2 and 66% (P < 0.001) at day 7, compared with baseline. Notably, the reduction of ¹⁸F-FLT uptake observed at day 2 in the everolimus group preceded changes in tumor volume, and a significant difference in ¹⁸F-FLT uptake was observed between vehicle and drug-treated tumors at both day 2 (P = 0.0008) and day 7 (P = 0.01). In ex vivo studies, everolimus treatment resulted in a 98% reduction in phosphorylated ribosomal protein S6 immunostaining at day 2 (P = 0.02) and 91% reduction at day 7 (P = 0.003), compared with the vehicle group. Bromodeoxyuridine incorporation was reduced by 65% at day 2 (not significant) and by 41% at day 7 (P = 0.02) in drug versus vehicle groups. Conclusion: Reduction in ¹⁸F-FLT uptake correlates well with the level of mTOR inhibition by everolimus in the SKOV3 ovarian tumor model. These data suggest that early treatment monitoring by ¹⁸F-FLT PET may be of use in future preclinical or clinical trials evaluating treatment of cisplatinresistant ovarian tumors by mTOR inhibitors.

The efficacy of differing routes of administration of ¹⁸F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (¹⁸F-MEL050), a new benzamide-based PET radiotracer for imaging regional lymph node metastasis in melanoma, was assessed. Methods: B16-Black/6 metastatic melanoma cells harboring an mCherry transgene were implanted into the left-upper-foot surface of 49 C57 Black/6 mice as a model of popliteal lymph node (PLN) metastasis. Ultrasound scanning of the left PLN was performed at baseline and in combination with 18F-MEL050 PET on days 5, 9, and 14. Mice were divided into 2 groups to compare the results of tracer administration either subcutaneously at the tumor site (local) or in the lateral tail vein (systemic). After PET on each imaging day, 5 mice per group—including any with evidence of metastasis—were sacrificed for ex vivo validation studies including assessment of retained radioactivity and presence of the mCherry transgene as a surrogate of nodal tumor burden. Results: Nine mice were judged as positive for PLN metastasis by ultrasound at day 5, and 8 PLNs were positive on ¹⁸F-MEL050 PET, 3 after systemic and 5 after local administration. Ex vivo analysis showed that ultrasound correctly identified 90% of positive PLNs, with 1 false-positive. ¹⁸F-MEL050 PET correctly identified 60% of positive PLNs after systemic administration and 100% after local administration with no false-positive results by either route. The average node-to-background ratio for positive PLNs was 6.8 in the systemic-administration group and correlated with disease burden. In the local-administration group, the mean uptake ratio was 48, without clear relation to metastatic burden. Additional sites of metastatic disease were also correctly identified by ¹⁸F-MEL050 PET. Conclusion: In addition to its potential for systemic staging, perilesional administration of ¹⁸FMEL050 may allow sensitive and specific, noninvasive identification of regional lymph node metastasis in pigmented malignant melanomas.

Ventilation–perfusion (V/Q) scintigraphy is established for regional assessment of lung function in a variety of diseases, including pulmonary embolism (PE). PET/CT may further improve the accuracy and utility of V/Q imaging because of its superior technical characteristics. This pilot study assessed the feasibility of performing V/Q PET/CT and compared diagnostic utility with conventional V/Q imaging in patients with clinical suspicion of PE. Methods: Ten patients undergoing conventional V/Q imaging were prospectively recruited. PET/CT V/Q imaging was performed after inhalation of ⁶⁸Ga-carbon nanoparticles (“Galligas”) and administration of ⁶⁸Ga-macroaggregated albumin. Blinded to the results of the other study, SPECT/CT (n = 9) or SPECT (n = 1) images and PET/CT images were graded by a predefined scoring system for scan quality. The number of matched or unmatched defects and diagnosis were also measured and compared with a final diagnosis. Results: PET image quality was equivalent or superior to SPECT in all patients, with more homogeneous radiotracer distribution for both ventilation and perfusion studies (P < 0.01). Based on conventional V/Q imaging, the diagnosis was acute PE in 2 patients and no PE in 7 patients, and the imaging results were nondiagnostic in 1 patient. The PET/CT diagnosis was concordant in 8 patients, and these studies demonstrated a similar number and distribution of matched and unmatched defects. In 1 discordant case, a patient with a SPECT/CT study that was nondiagnostic because of severe airway disease showed no PE on PET/CT. In another, the diagnosis of PE established on SPECT/CT was not reported on PET/CT 2 d later, possibly because of interval clot lysis or migration. Conclusion: This intraindividual comparative study demonstrated that V/Q PET/CT with ⁶⁸Ga-labeled radiotracers can be performed in clinical practice. Compared with conventional V/Q imaging, advantages include higher-resolution, fully tomographic images with potentially better regional quantitation of lung function. The short half-life of ⁶⁸Ga also enables more flexible acquisition protocols with the option of performing ventilation studies selectively on patients with abnormal perfusion. On the basis of our results, further studies are indicated to assess whether V/Q PET/CT can improve diagnostic algorithms for patients with suspected PE.

International efforts have been focused on the development of new 9Cr Ferritic/Martensitic steels capable of operating at temperatures above 700 ºC to improve thermal efficiency of new power plants. The distribution and size of the MX nanoprecipitates present in these steels have been reported to be the key factor for improving the thermal stability of the microstructure during creep. Bearing in mind these findings, three different heat resistant steels were designed to have a higher number density of MX nanoprecipitates than commercial 9Cr ferritic/martensitic steels. The manufacturing and subsequent microstructural characterization carried out showed that this goal was achieved. Preliminary high temperature strength results performed by means of Small Punch Creep Tests (SPCT) demonstrated that these new steels improve significantly the high temperature strength without an important loss of ductility as compared to a current commercial 9Cr Ferritic/Martensitic steel.

Chimeric antigen receptor (CAR) T cells show remarkable therapeutic effects in some hematological malignancies. However, CAR T cells can also cause life-threatening side effects. In order to minimize off-target and on-target/off-tumor reactions, improve safety, enable controllability, provide high flexibility, and increase tumor specificity, we established a novel humanized artificial receptor platform termed RevCARs. RevCAR genes encode for small surface receptors lacking any antigen-binding moiety. Steering of RevCAR T cells occurs via bispecific targeting molecules (TMs). The small size of RevCAR-encoding genes allows the construction of polycistronic vectors. Here, we demonstrate that RevCAR T cells efficiently kill tumor cells, can be steered by TMs, flexibly redirected against multiple targets and used for combinatorial targeting following the “OR” and “AND” gate logic.

The noncentrosymmetric superconductor α-PdBi is a candidate material for the realization of topological superconductivity. Here, we present a detailed de Haas–van Alphen (dHvA) study together with band-structure calculations within the framework of density functional theory. The rich dHvA spectra are a manifestation of the 13 bands that cross the Fermi energy E_F . We find excellent agreement between calculated and experimentally observed dHvA frequencies with moderately enhanced effective masses. One of the bands crossing EF, the so-called α band, exhibits topological character with Weyl nodes lying 43 meV below E_F .

The crystal-electric field and exchange parameters are determined for the (Nd_0.5Dy_0.5)₂Fe₁₄B compound by analyzing experimental magnetization curves obtained in high magnetic fields up to 58 T. The series (Nd_xDy_1-x)₂Fe₁₄B compounds were analyzed theoretically to achieve a temperature stability while maintaining a large maximum energy product (BH)_max. We demonstrate that computational simulations is an important tool in the materials design.

The magnetocaloric effect in the Fe₄₉Rh₅₁ alloy was systematically studied using three different approaches: in-field differential scanning calorimetry, standard direct measurement of the adiabatic temperature change, and a non-contact method based on a thermo-optical phenomenon, the mirage effect, which was able to directly test the magnetocaloric response induced by a fast magnetic field variation. The metamagnetic phase transition of Fe₄₉Rh₅₁ was studied in the temperature range of 290–330 K at magnetic fields up to 1.8 T through magnetic and calorimetric measurements. The estimated parameters of phase transition were comparable with the literature data. The values of adiabatic temperature change obtained with the three methods (calorimetry, standard direct measurement, and mirage-based technique), which explore three different time scales of the field variation (static field, 1 T s⁻¹, 770 T s⁻¹), were consistent, proving the absence of dynamic constraints in the first-order magnetostructural transition at the maximum field sweep rate.

Prostate-specific membrane antigen (PSMA)–targeted PET imaging recently emerged as a new method for the staging and restaging of prostate cancer. Most published studies investigated the diagnostic potential of ⁶⁸Ga-labeled PSMA agents that are excreted renally ¹⁸F-PSMA-1007 is a novel PSMA ligand that has excellent preclinical characteristics and that is only minimally excreted by the urinary tract, a potential advantage for pelvic imaging. The aim of this study was to investigate the diagnostic efficacy of ¹⁸F-PSMA-1007 for biochemical recurrence (BCR) after radical prostatectomy. Methods: From 3 academic centers, 251 patients with BCR after radical prostatectomy were evaluated in a retrospective analysis. Patients who had received second-line androgen deprivation therapy (ADT) or chemotherapy were excluded, but prior first-line ADT exposure was allowed. The median prostate-specific antigen (PSA) level was 1.2 ng/mL (range, 0.2–228 ng/mL). All patients underwent PSMA PET/CT at 92 ± 26 min after injection of 301 ± 46 MBq of ¹⁸FPSMA-1007. The rate of detection of presumed recurrence sites was correlated with the PSA level and original primary Gleason score. A comparison to a subset of patients treated previously with ADT was undertaken. Results: Of the 251 patients, 204 (81.3%) had evidence of recurrence on ¹⁸F-PSMA-1007 PET/CT. The detection rates were 94.0% (79/84), 90.9% (50/55), 74.5% (35/47), and 61.5% (40/65) for PSA levels of greater than or equal to 2, 1 to less than 2, 0.5 to less than 1, and 0.2 to less than 0.5 ng/mL, respectively. ¹⁸FPSMA-1007 PET/CT revealed local recurrence in 24.7% of patients (n = 62). Lymph node metastases were present in the pelvis in 40.6% of patients (n = 102), in the retroperitoneum in 19.5% of patients (n = 49), and in supradiaphragmatic locations in 12.0% of patients (n = 30). Bone and visceral metastases were detected in 40.2% of patients (n = 101) and in 3.6% of patients (n = 9), respectively. In tumors with higher Gleason scores (≤7 vs. ≥8), detection efficacy trended higher (76.3% vs. 86.7%) but was not statistically significant (P = 0.32). However, detection efficacy was higher in patients who had received ADT (91.7% vs. 78.0%) within 6 mo before imaging (P = 0.0179). Conclusion: ¹⁸F-PSMA-1007 PET/CT offers high detection rates for BCR after radical prostatectomy that are comparable to or better than those published for ⁶⁸Ga-labeled PSMA ligands.

Introduction: Ga-68 DOTATATE (Ga-octreotate, GaTate) positron emission tomography (PET)/CT has multiple advantages compared with conventional and In-111 octreotide imaging for neuroendocrine tumours and other somatostatin-receptor expressing tumours. This study assesses the management impact of incremental diagnostic information obtained from this technique compared with conventional staging. Methods: Fifty-nine GaTate PET/CT studies were performed over an 18-month period (52 proven or suspected gastro-entero-pancreatic or bronchial neuroendocrine tumours and seven neural crest/mesenchymal tumours). A retrospective blinded review was performed on the number of abnormalities (1, 2–5 or >5) within defined regions with comparison to conventional imaging to assess incremental diagnostic information. Subsequent management impact (high, moderate or low) was determined by clinical review and follow up to assess pre-PET stage, treatment intent and post-PET management change. Results: Eighty-eight percent of GaTate studies were abnormal. Compared with conventional and In-111 octreotide imaging, additional information was provided by GaTate PET/CT in 68 and 83% of patients, respectively. Management impact was high (inter-modality change) in 47%, moderate (intra-modality change) in 10% and low in 41% (not assessable in 2%). High management impact included directing patients to curative surgery by identifying a primary site and directing patients with multiple metastases to systemic therapy. Conclusion: GaTate PET/CT imaging provides additional diagnostic information in a high proportion of patients with consequent high management impact. GaTate PET/CT could replace 1In-111 octreotide scintigraphy at centres where it is available given its superior accuracy, faster acquisition and lower radiation exposure. Rapid implementation could be achieved by allowing substitutional funding in the Medicare Benefit Schedule.

Many supernova remnants (SNRs), such as G296.5+10.0, exhibit an axisymmetric or barrel shape. Such morphologies have previously been linked to the direction of the Galactic magnetic field, although this remains uncertain. These SNRs generate magnetohydrodynamic shocks in the interstellar medium, modifying its physical and chemical properties. The ability to study these shocks through observations is difficult due to the small spatial scales involved. In order to answer these questions, we perform a scaled laboratory experiment in which a lasergenerated blast wave expands under the influence of a uniform magnetic field. The blast wave exhibits a spheroidal shape, whose major axis is aligned with the magnetic field, in addition to a more continuous shock front. The implications of our results are discussed in the context of astrophysical systems.

Purpose The imaging potential of a new ¹⁸F-labelled methionine derivative, S-(3-[¹⁸F]fluoropropyl)-D-homocysteine (¹⁸F-D-FPHCys), and its selectivity for amino acid transporter subtypes were investigated in vitro and by imaging of human tumour xenografts. Methods Expression of members of the system L (LAT isoforms 1–4 and 4F2hc) and ASCT (ASCT isoforms 1 and 2) amino acid transporter subclasses were assessed by quantitative real-time PCR in four human tumour models, including A431 squamous cell carcinoma, PC3 prostate cancer, and Colo 205 and HT-29 colorectal cancer lines. The first investigations for the characterization of ¹⁸F-D-FPHCys were in vitro uptake studies by comparing it with [1-¹⁴C]-L-methionine (¹⁴C-MET) and in vivo by PET imaging. In addition, the specific involvement of LAT1 transporters in ¹⁸F-DFPHCys accumulation was tested by silencing LAT1 mRNA transcription with siRNAs. To determine the proliferative activity in tumour xenografts ex vivo, Ki-67 staining was used as a biomarker. Results A431 cells showed the highest ¹⁸F-D-FPHCys uptake in vitro and in vivo followed by Colo 205, PC3 and HT-29. A similar pattern of retention was observed with ¹⁴C-MET. ¹⁸F-D-FPHCys retention was strongly correlated with LAT1 expression both in vitro R²=0.85) and in vivo (R²=0.99). Downregulation of LAT1 by siRNA inhibited ¹⁸F-DFPHCys uptake, demonstrating a clear dependence on this transporter for tumour uptake. Furthermore, ¹⁸F-D-FPHCys accumulation mirrored cellular proliferation. Conclusion The favourable properties of ¹⁸F-D-FPHCys make this tracer a promising imaging probe for detection of tumours as well as for the noninvasive evaluation and monitoring of tumour growth.

Purpose The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. Methods A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [¹⁸F]fluorodeoxyglucose or [¹⁸F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions –5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of ⁶⁸Ga-ethylenediaminetetraacetic acid (EDTA). Results For typical lesion sizes of 7–8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SORair and SORwater were 5.3 and 7.5%, respectively. A strong correlation (r2=0.97, p<0.0001) between quantitative data obtained in mice imaged alone and simultaneously in a group of three was found following PSF reconstruction. The correlation between ex vivo counting and PET/CT data was better with PSF reconstruction (r2=0.98; slope=0.89, p<0.0001) than without (r2=0.96; slope=0.62, p<0.001). Valid time-activity curves of the blood pool, kidneys and bladder could be derived from ⁶⁸Ga-EDTA dynamic acquisition.Conclusion New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available.

The aim of this study was to evaluate the novel probe ¹⁸F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (¹⁸F-MEL050) for the imaging of primary and metastatic melanoma. Methods: PET using ¹⁸F-MEL050 was performed in murine models of melanoma. The specificity of ¹⁸F-MEL050 was studied by comparing its accumulation in pigmented B16-F0 allograft tumors with that of human amelanotic A375 xenografts using PET and high-resolution autoradiography. ¹⁸F-MEL050 PET results were compared with ¹⁸F-FDG PET, the current standard in melanoma molecular imaging. To test the ability of ¹⁸F-MEL050 to assess the metastatic spread of melanoma, a murine model of lung metastasis was imaged by PET/CT, and results correlated with physical assessment of tumor burden in the lungs. Results: In pigmented B16-F0 grafts, ¹⁸F-MEL050 PET yielded a tumor-to-background ratio of approximately 20:1 at 1 h and greater than 50:1 at 2 and 3 h. In the B16-F0 melanoma allograft model, tumor-to-background ratio was more than 9-fold higher for ¹⁸F-MEL050 than for ¹⁸F-FDG (50.9 ± 6.9 vs. 5.8 ± 0.5). No uptake was observed in the amelanotic melanoma xenografts. Intense uptake of ¹⁸F-MEL050 was evident in metastatic lesions in the lungs of B16-BL6 tumor–bearing mice on PET at 2 h after tracer injection, with high concordance between ¹⁸F-MEL050 accumulation on PET/CT and tumor burden determined at necroscopy. Conclusion: ¹⁸F-MEL050 has a rapid tumor uptake and high retention with specificity for melanin, suggesting great potential for noninvasive clinical evaluation of suspected metastatic melanoma.

The high melanoma uptake and rapid body clearance displayed by our series of [¹²³I]iodonicotinamides prompted the development of [¹⁸F]N-(2-(diethylamino)ethyl)-6-fluoronicotinamide ([¹⁸F]2), a novel radiotracer for PET melanoma imaging. Significantly, unlike fluorobenzoates, [¹⁸F]fluorine incorporation on the nicotinamide ring is one step, facile, and high yielding. [¹⁸F]2 displayed high tumor uptake, rapid body clearance via predominantly renal excretion, and is currently being evaluated in preclinical studies for progression into clinical trials to assess the responsiveness of therapeutic agents.

Low-cost, non-noble-metal electrocatalysts are required for direct methanol fuel cells, but their development has been hindered by limited activity, high onset potential, low conductivity, and poor durability. A surface electronic structure tuning strategy is presented, which involves doping of a foreign oxophilic post-transition metal onto transition metal aerogels to achieve a non-noble-metal aerogel Ni₉₇Bi₃ with unprecedented electrocatalytic activity and durability in methanol oxidation. Trace amounts of Bi are atomically dispersed on the surface of the Ni₉₇Bi₃ aerogel, which leads to an optimum shift of the d-band center of Ni, large compressive strain of Bi, and greatly increased conductivity of the aerogel. The electrocatalyst is endowed with abundant active sites, efficient electron and mass transfer, resistance to CO poisoning, and outstanding performance in methanol oxidation. This work sheds light on the design of high-performance non-noble-metal electrocatalysts

One of the paradigm-shifting phenomena triggered in laser-plasma interactions at relativistic intensities is the so-called relativistic transparency. As the electrons become heated by the laser to relativistic energies, the plasma becomes transparent to the laser light even though the plasma density is sufficiently high to reflect the laser pulse in the non-relativistic case. This paper highlights the impact that relativistic transparency can have on laser-matter interactions by focusing on a collective phenomenon that is associated with the onset of relativistic transparency: plasma birefringence in thermally anisotropic relativistic plasmas. The optical properties of such a system become dependent on the polarization of light, and this can serve as the basis for plasma-based optical devices or novel diagnostic capalibities.

Using three-dimensional kinetic simulations, we examine the emission of collimated γ-ray beams from structured laser-irradiated targets with a prefilled cylindrical channel and its scaling with laser power (in the multi-PW range). The laser power is increased by increasing the laser energy and the size of the focal spot while keeping the peak intensity fixed at 5×1022W/cm2. The channel radius is increased proportionally to accommodate the change in laser spot size. The efficiency of conversion of the laser energy into a beam of MeV-level γ rays (with a 10âˆ&tild; opening angle) increases rapidly with the incident laser power P before it roughly saturates above P≈4PW. Detailed particle tracking reveals that the power scaling is a result of enhanced electron acceleration at higher laser powers. One application that directly benefits from such a strong scaling is pair production via two-photon collisions. We investigate two schemes for generating pairs through the linear Breit-Wheeler process: Colliding two γ-ray beams and colliding one γ-ray beam with black-body radiation. The two scenarios project up to 104 and 105 pairs, respectively, for the γ-ray beams generated at P=4PW. A comparison with a regime of laser-irradiated hollow channels corroborates the robustness of the setup with prefilled channels.

Calculations on the dynamics of ions and electrons in near-infrared laser fields at intensities up to 3×1023W/cm2 are presented. We explore the acceleration of ions in a laser focus by conservation of canonical momentum during ionization events and by the ponderomotive force in the f/1 focal geometry required to reach such intensity. At intensities exceeding 1023W/cm2, highly charged ions are expelled from the laser focus before they can interact with the laser pulse at peak intensity, decreasing the predicted ionization yields of deeply bound states. We consider the interaction of a tightly focused, f/1 laser pulse with krypton at an intensity of 3×1023W/cm2 and a pulse duration of 140 fs. We find that the ions and electrons are accelerated to energies in excess of 2 MeV/nucleon and 1.4 GeV, respectively. Ponderomotive expulsion of the parent ions decreases the total number of ultrarelativistic above-threshold ionization electrons produced by tunneling ionization from the K-shell states of krypton but does not change their energy spectrum.
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With the latest configuration, the Ti:Sa laser system ARCTURUS (Düsseldorf University, Germany) operates with a double-chirped pulse amplification (CPA) architecture delivering pulses with an energy of 7 J before compression in each of the two high-power beams. By the implementation of a plasma mirror system, the intrinsic laser contrast is enhanced up to on a time scale of hundreds of picoseconds, before the main peak. The laser system has been used in various configurations for advanced experiments and different studies have been carried out employing the high-power laser beams as a single, high-intensity interaction beam (), in dual- and multi-beam configurations or in a pump-probe arrangement.

A high-repetition rate laser-driven proton source from a continuously operating cryogenic hydrogen cluster target is presented. We demonstrate a debris-free, Coulomb-explosion based acceleration in the 10s of kilo-electron-volt range with a stability of about 10% in a 5 Hz operation. This acceleration mechanism, delivering short pulse proton bursts, represents an ideal acceleration scheme for various applications, for example, in materials science or as an injector source in conventional accelerators. Furthermore, the proton energy can be tuned by varying the laser and/or cluster parameters. 3D numerical particle-in-cell simulations and an analytical model support the experimental results and reveal great potential for further studies, scaling up the proton energies, which can be realized with a simple modification of the target.
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When an ultrashort laser pulse is tightly focused to a size approaching its central wavelength, the properties of the focused spot diverge from the diffraction-limited case. Here, we report on this change in behavior of a tightly focused petawatt-class laser beam by an f ㄍ1 off-axis parabolic mirror (OAPM). Considering the effects of residual aberration, the spatial profile of the near-field, and pointing error, we estimate the deviation in peak intensities of the focused spot from the ideal case. We verify that the estimated peak intensity values are within an acceptable error range of the measured values. With the added uncertainties in target alignment, we extend the estimation to infer on-target peak intensities of ≥1022 Wㄍcm2 for a target at the focal plane of this f ㄍ1 OAPM.

The generation of high-order harmonics in ultraviolet spectral range by targets of periodic modulation interacting with relativistic, high contrast laser pulse ( 2 = 10 20 W/cm 2 · μm 2 ) was investigated experimentally and numerically. The spectral intensity of the 2nd- and 3rd-order harmonic emission from grating of different periodicities (250, 410, and 480 nm) is presented. The enhancement of the 3rd harmonic order compared with 2nd was observed for a grating of 480 nm periodicity. The experimental results indicate the role of the grating periodicity on the emission efficiency of different higher order harmonics in the UV spectral range. The higher order harmonics are emitted at the grating surface separated from the specular reflection of the laser pulse, due of the interference effects. In addition, 2D numerical PIC simulations demonstrate a complex angular distribution of the higher harmonics (HH) spectral intensity and confirm the strong dependence of the HH efficiency of a specific order on the grating periodicity, as observed experimentally. These special features of the high harmonic emission by periodically modulated targets open the route toward the control of HH spectral composition and of the emission efficiency of the lower order harmonics. Copyright © Cambridge University Press 2019.

A solid density target irradiated by a high-intensity laser pulse can become relativistically transparent, which then allows it to sustain an extremely strong laser-driven longitudinal electron current. The current generates a filament with a slowly varying MT-level azimuthal magnetic field that has been shown to prompt efficient emission of multi-MeV photons in the form of a collimated beam required for multiple applications. This work examines the feasibility of using an x-ray beam from the European x-ray free electron laser for the detection of the magnetic field via the Faraday rotation. Post-processed three dimensional particle-in-cell simulations show that, even though the relativistic transparency dramatically reduces the rotation in a uniform target, the detrimental effect can be successfully reversed by employing a structured target containing a channel to achieve a rotation angle of 10-4rad. The channel must be relativistically transparent with an electron density that is lower than the near-solid density in the bulk. The detection setup has been optimized by varying the channel radius and focusing the laser pulse driving the magnetic field. We predict that the Faraday rotation can produce 103 photons with polarization orthogonal to the polarization of the incoming 100 fs long probe beam with 5 × 1012 x-ray photons. Based on the calculated rotation angle, the polarization purity must be much better than 10-8 in order to detect the signal above the noise level.