Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

es hat kein aussagekräfiges Abstract vorgelegen

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es hat kein aussagefähiges Abstract vorgelegen

Large magnetocaloric effects can be observed in materials with first-order magneto-structural phase transition. However, materials with large thermal hysteresis show a reduced effect in moderate fields (~2 T) because the external field is insufficient to induce a fully reversible transformation. The hysteresis can be overcome or even exploited by applying a second external stimulus. A multistimuli test bench has been built to demonstrate the multicaloric effect in FeRh alloy using a pulsed magnetic field up to 9 T and a uniaxial stress of up to 700 MPa. A cyclic multicaloric effect of ±2.5 K could be observed for a sequential application of a pulsed field of 3 T and a uniaxial stress of 700MPa. The interplay among external field strength, thermal hysteresis, and the transition width enables the use of pulsed magnetic fields and allows a decoupling of the applied magnetic field and the heat transfer process in the multi-stimuli cycle.

The comminution of lithium-ion batteries (LIBs) produces a powder containing the active cell components, commonly referred to as “black mass.” Recently, flotation has emerged as a promising method to simultaneously recover graphite and cathode active particles (CAMs) from black mass, thus increasing the recycling rate of LIBs. However, to ensure an effective separation, both CAMs and graphite particles must be free of organic binder (i.e., polyvinylidene fluoride) which gives them similar wettabilities. While pyrolysis pre-treatment has proven effective in removing organic binders, it raises environmental concerns, including generation and release of toxic hydrogen fluoride gas and carcinogenic polynuclear and halogenated hydrocarbons. In response, this study proposes an environmentally benign method for the removal of an organic binder: using the non-toxic and green solvent Cyrene™ (dihydroleveglucosenone). Comparative analysis were performed by pretreating industrial black mass with either pyrolysis or Cyrene™ solvent before froth flotation, aiming to provide insights into a sustainable approach to enhance LIBs recycling.

Effluents generated from Li-ion battery recycling often contain high concentrations of lithium. This study focused on characterizing the composition of process water obtained from battery recycling and conducting ion-exchange experiments using synthetic Li-rich water (1 g/L). Employing a weak-acid chelating cationic resin, fast Li exchange kinetics were observed, consistent with a pseudo-second order model. The equilibrium isotherm revealed a notable maximum Li sorption capacity of 70.1 mg/g according to the Langmuir model. Notably, as battery recycling effluents typically contain minimal competing ions, these results underscore the potential of employing ion exchange as a viable method to recover and concentrate lithium before precipitating Li-salts. This approach holds promise for enhancing the efficiency of lithium recovery processes

Lithium iron phosphate (LFP) batteries are gaining prominence in the growing EV market due its long life cycle, cost-effectiveness, and safety. Consequently, its influx in the battery waste stream is anticipated, which necessitates a tailored recycling process. Froth flotation is a promising technique to separate the cathode and anode active material of black mass from lithium-ion batteries before downstream recycling processes. However, unlike previously studied chemistries (e.g., NMC, LCO), LFP presents a more intricate challenge due to its fine particle sizes (d10-d90 of 0.5-6.0 µm), rendering them susceptible to entrainment and thereby affecting float fraction recovery. In this work, the effective separation of LFP black mass into graphite-rich and LiFePO4-rich fraction was investigated by implementing a flocculant, polyacrylamide (PAM). Initial results reveal improved selectivity with the use of flocculants in model black mass (pristine and liberated particles of LFP and graphite) flotation. However, complexities arise when PAM was employed in an industrially pyrolyzed black mass, impacting flotation performance and material recovery dynamics.

Implementing circular economy using secondary resources from mining tailings and industrial slags -
MIMAC seminar

Implementing circular economy using secondary resources from mining tailings and industrial slags at HIF, HZDR

Remining the historic tailings for energy materials recovery using circular economy and sustainable chemistry approaches

“Circular economy in practice using process metallurgy

75. BHT – Freiberger Universitätsforum 2024, 05.06.2024, Freiberg, Deutschland

Electric micromobility, or e-scooters and e-bikes may offer an alternative to the use of private cars. These micromobility devices, while lighter and less resource-intensive than cars, still require different metals and minerals. In this paper, we build a dynamic material flow model for shared e-scooters and private e-bikes in Finland, with an emphasis on their batteries, as these contain many critical raw materials. Our aim is to quantify the future urban mining potential of micromo-bility. We use Weibull distributions to model the lifetimes of micromobility devices and their batteries and discrete-time Bass diffusion to model the uptake of e-bikes as an innovation. In our baseline scenario, the outflow of used e-scooter batteries will be approximately 25,400 units and the outflow of used e-bike batteries some 217,000 units annually. For both types of devices, the main drivers of uncertainty are battery lifetime and the volume of future sales.

ntroduction:

Accelerated brain ageing is associated with increased risks of dementia and mortality, and can be assessed
with machine learning and structural brain MRI data to determine the predicted age difference (brain-PAD)
between biological and chronological age[1]. Advanced brain-PAD approaches aim to increase accuracy and
sensitivity to specific pathologies by adding sequences able to assess cerebrovascular health, a contributor to
cognitive decline[2].
Improved brain-PAD accuracy, and classification of Alzheimer's Disease (AD) patients, were shown with
Cerebrovascular Brain-age by adding Arterial Spin Labeling (ASL) perfusion MRI to T1w and FLAIR data in a
single-site study[3,4]. Such a pre-trained model has, however, a limited value for data from different MRI
vendors or acquired with different parameters. While combining (ASL) studies is often a prerequisite to reach
sufficient sample sizes for machine learning, acquisition differences can lead to a systematic bias of brain-PAD.
The impact of commonly used harmonisation techniques on this bias is not sufficiently studied.

Ziel: Entwicklung eines Theranostikums für die Radiomarkierung mit 99mTc/188Re gegen das Prostatakarzinom zur Umgehung von Lieferengpässen anderer therapeutischer Radionuklide.
Methoden: Zwei verschiedene Radiotracer (MIP-1404 und N3S-PSMA), die bekannterweise sehr gute Markierungsausbeuten mit 99mTc aufweisen, wurden auf unterschiedliche Markierungsstrategien mit 188Re überprüft. Zellaufnahmen und Internalisierung der markierten Radiotracer wurden an LNCaP Zellen gegen [68Ga]Ga-PSMA-11 als Vergleich getestet.
Ergebnisse: Die Zweistufen-Radiosynthese von [188Re]Re-MIP-1404 wurde zunächst erfolgreich optimiert, erwies sich jedoch ungeeignet bei Anwendung von therapeutischen Aktivitäten >3 GBq. Zu viele Nebenprodukte bildeten sich, die auch nicht mittels HPLC abtrennbar waren. Auch die Radiosynthese des Markierungsbausteins [188Re]Re-Tricarbonyl war ohne erkennbaren Grund bei höheren Aktivitäten von starken Ausbeuteschwankungen geprägt. Demgegenüber standen die sehr guten Markierungsergebnisse mit 99mTc sowohl zur Bildung des [99mTc]Tc-Tricarbonyls als auch zur Bildung von [99mTc]Tc-MIP-1404. Die direkte Radiomarkierung des N3S-PSMAs lieferte sowohl für Aktivitäten von >1 GBq 99mTc als auch für Aktivitäten bis zu 10 GBq 188Re sehr hohe radiochemische Ausbeuten und Reinheiten. In anschließenden Zellversuchen waren vergleichbare bis bessere Anreicherungen und Internalisierungen des [99mTc]Tc/[188Re]Re-N3S-PSMAs gegen [68Ga]Ga-PSMA -11 und [99mTc]Tc-MIP-1404 zu verzeichnen, die über 24 h hinaus noch deutlich zunahmen.
Schlussfolgerungen: Das N3S-PSMA eignet sich exzellent für Radiomarkierungen mit diagnostischen und therapeutischen Aktivitätsmengen und besitzt auch eine zum [68Ga]Ga-PSMA-11 vergleichbare bzw. verbesserte Zellaufnahme über 24 h hinaus. [188Re]Re-N3S-PSMA würde als Ausweichtherapeutikum zur Verfügung stehen, falls andere therapeutische Radionuklide nicht zur Verfügung stehen. Dosimetrische Untersuchungen mit [99mTc]Tc-N3S-PSMA sollen Rückschlüsse auf die therapeutisch einsetzbare Aktivität geben, gerade in Bezug auf Nierendosis bzw. -toxizität bei 188Re.

Keywords: Alzheimer's Disease, Arterial spin labelling, Blood-brain barrier, Biomarkers

Motivation: Blood-brain barrier (BBB) permeability changes may be implicated in Alzheimer’s Disease (AD) pathophysiology.

Goal(s): To investigate if the exchange time (Tex) of water across the BBB is associated with cognitive and amyloid status.

Approach: We measured Tex with a multi-echo arterial spin labeling MRI sequence in 116 adults older than 50 years and studied its association with cognition (cognitively normal vs mild cognitive impaired) and amyloid (A- vs A+) status.

Results: BBB water permeability is increased in A+ participants and in patients with MCI, compared to healthy controls

Impact: Our results suggest that multi-TE ASL MRI BBB water permeability can be used as a potential early imaging biomarker of AD pathophysiology.

Keywords: Tumors (Pre-Treatment), Arterial spin labelling

Motivation: Blood brain barrier arterial spin labeling (BBB-ASL) could assess BBB integrity. However, the assumption of homogeneous T2 in data fitting might be broken in gliomas.

Goal(s): To evaluate the BBB integrity in gliomas with regional tissue-specific T2.

Approach: A mono-exponential T2 fitting was used to obtain tissue-specific T2 values to estimate time of water exchange (Tex) and perfusion (CBF) in the tumor, normal-appearing white (NAWM), and gray matter (NAGM) using ExploreASL.

Results: Higher Tex in NAWM, and lower Tex in the tumor and NAGM were observed and the tumor heterogeneity was better depicted when tissue-specific T2 values were used.

Impact: Water exchange and perfusion maps are highly affected by the tissue T2 value used in BBB-ASL data processing. Applying tissue-specific T2 correction has resulted in a more reliable evaluation of BBB integrity in gliomas.

Ziel: Die Kombination des γ-Strahlers Blei-203 (SPECT) und dem Therapienuklid Blei-212 (Kaskade mit β- und α) ist ein ideales theranostisches Matched Pair. Es wurden bereits einige Untersuchungen mit verschiedenen Radiotracern durchgeführt, wobei die meisten auf DOTA-ähnlichen Chelatoren basieren.[1] In unseren vorherigen Untersuchungen wurde festgestellt, dass sich der Chelator macropa (mcp) ebenfalls hervorragend zur Komplexierung von Blei eignet.[2] Verschiedene 225Ac-markierte mcp-PSMA-Konjugate wurden bereits untersucht.[3] In dieser Studie soll die Bioverteilung der 203Pb-markierten mcp-PSMA-Konjugate untersucht werden für die mögliche theranostische Anwendung dieser Konjugate mit Blei-203 und Blei-212.
Methoden: Es erfolgte die Synthese von PSMA-617, PSC-PSMA (PSC – bleispezifischer Chelator), mcp-M-PSMA, mcp-D-PSMA, sowie der modifizierten PSMA-Konjugate mit Albuminbinder mcp-M-alb-PSMA und mcp-D-alb-PSMA. Mit allen PSMA-Konjugaten wurden Radiomarkierungen durchgeführt. Anschließend erfolgten SPECT-Bildgebung und Bioverteilung.
Ergebnisse: Alle PSMA-Konjugate wurden mit Blei-212 und Blei-203 markiert. Dabei wurden molare Aktivitäten von bis zu 10 GBq/nmol bei Blei-203 und 1 GBq/nmol bei Blei-212 mit den PSMA Derivaten erreicht. Für die SPECT-Bildgebung an LNCaP-tumortragenden Mäusen wurden 10 MBq/nmol je 203Pb-PSMA-Radiokonjugat injiziert und bei verschiedenen Zeitpunkten (1 h, 1 d, 2 d, 3 d, 5 d und 7 d), die Bioverteilung untersucht. Mithilfe zusätzlicher Ex-vivo-Experimente wurden die Bioverteilungen der 203Pb-PSMA-Konjugate quantifiziert.
Schlussfolgerungen: Die beiden Bleiisotope 203Pb und 212Pb zeigten quantitative Radiomarkierungen bis c = 10-6 – 10-7 M. Die SPECT-Bildgebung zeigen eine hohe Anreicherung der Radiotracer im Tumor, eine hohe Ausscheidung über die Niere und Blase, aber wenig in den anderen Organen, weshalb eine Therapiestudie mit 212Pb-PSMA-Konjugaten angestrebt wird.

Keywords: Arterial Spin Labelling, Arterial spin labelling, Challenge; multi-PLD ASL

Motivation: The OSIPI ASL Challenge is a community initiative motivated by open science principles that aim to establish good practices in ASL image analysis and Cerebral Blood Flow (CBF) quantification.

Goal(s): The second ASL challenge's main goal is to provide a thorough comparison of existing post-processing pipelines focusing on Multi-PLD methodology.

Approach: The second roadmap will provide different datasets; a population dataset which will bring real variability to the challenge and synthetic data which allows straightforward ground truth comparison.

Results: The second edition of the ASL Challenge will contribute to gaining new insights into the potential sources of variability within the multi-PLD analysis pipeline.

Impact: Through the second edition of the ASL Challenge, we seek to enhance our understanding of multi-PLD analysis in the ASL community. Its success could establish a consensus on the processing of multi-PLD ASL data, positively influencing clinical and scientific practices.

Keywords: Arterial Spin Labelling, Perfusion, Arterial Spin Labelling, Normal Development

Motivation: There is lacking understanding of hemodynamic changes in children and their impact on MRI perfusion quantification.

Goal(s): We aim to investigate age-related hemodynamic changes in developing brain.

Approach: Perfusion parameters from single- and multi-delay Arterial Spin Labeling (ASL) MRI of MR-negative children are analyzed.

Results: We found significant age-dependent differences between perfusion quantification with single- and multi-delay approaches. ATT followed a non-linear distribution in age and was heterogeneous across vascular territories Our findings support the use of multi-delay ASL for improved perfusion assessment in children and provide better understanding of hemodynamic changes in developing brain.

Impact: This is the first study to investigate age-related arterial transit-time changes in children and their impact on perfusion quantification with perfusion MRI. Our findings prompt improved understanding of age-related perfusion changes and standardization of hemodynamic parameters in the pediatric cohort.

Motivation: Structural brain ageing models are associated with cognitive decline, and the addition of arterial spin labelling (ASL)-derived improved brain-age estimation accuracy, but the relation between cerebrovascular ageing and cognitive decline is not yet fully understood.

Goal(s): To assess the contribution of ASL in the relationship between brain-age estimates and cognitive decline.

Approach: Brain-age estimation accuracy and linear relationships with composite cognitive scores were compared between structural-only (T1w and FLAIR), ASL-only, and structural+ASL models.

Results: Combined structural and ASL brain-age models showed the highest accuracy and increased effect sizes with composite cognitive scores, however, ASL-only models showed unexpected relationships.

Impact: Combined structural-ASL brain-age models might present a surrogate biomarker in an earlier stage of cognitive decline, aiding in diagnosis and treatment monitoring. Possible mediation effects of ASL on the association of structural decline with cognitive domains should be investigated further.

Introduction
Mid-life cardiovascular and late-life structural cerebrovascular pathology play a major role in accelerating cognitive decline in normal aging and dementia. Cerebral blood flow (CBF) may be a critical intermediate biomarker of future cognitive decline, however our understanding of normal CBF variability and its relation with mid-life cardiovascular and late-life structural cerebrovascular parameters is limited. The MRC National Survey of Health and Development neuroimaging sub-study ‘Insight 46’ provides a unique opportunity to study the effects of cardiovascular and cerebrovascular health on CBF in a cohort with a fixed chronological age. We explored associations of life-long cardiovascular parameters and WMH volume with ASL MRI CBF in this cognitively healthy population-based sample.
Methods
3D T1-weighted, FLAIR, and pseudo-continuous ASL (labeling duration = 1800ms; post-labelling delay = 1800ms) data (3T) were acquired in 295 participants (Table 1). Clinical data included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and the Framingham Risk Score (FRS). MRI scans were processed with ExploreASL. Grey matter (GM), white matter (WM) and white matter hyperintensity (WMH) volume were segmented from the T1w and FLAIR images. ASL- derived partial volume-corrected CBF and the spatial coefficient of variation (sCoV) were obtained in whole-brain GM and WM. Linear regression models examined associations between life-long cardiovascular health (ages 43, 53, 60-64, 69, and 69-71 years), ASL metrics (at 69-71 years), and WMH load (at 69-71 years). Models were corrected for sex, and sex interactions were tested if applicable.
Results
While mid-life cardiovascular parameters were associated with late-life sCoV and CBF, the strongest associations were seen at 69-71 years. At this time point, higher SBP and MAP were associated with lower GM CBF in men (1A-B, β=-0.16,-0.28) and relatively stable GM CBF in women (1A-B, β=0.02,-0.02); higher DBP was associated with lower GM CBF (β=-0.18). Higher WMH volume was related to higher GM and WM CBF (2A-B, β=2.04,1.45), and lower GM and WM sCoV (2C-D, β=-0.04,0.05).
Discussion
These sex-dependent associations encourage further investigation into the potential mediatory role of CBF between mid-life cardiovascular and late-life structural decline of cerebrovascular health, leading to cognitive

Processing samples from the Ruwai skarn deposit, the largest polymetallic skarn deposit in Indonesia, were analyzed to assess mass balances, recovery rates, and deportments of selected critical elements in order to understand their distribution and behaviour within the deposit. These samples included feed ore, Pb scavenger and final Pb concentrates, Zn scavenger and final Zn concentrates, and final tailings. They underwent bulk geochemical, mineralogical, and mineral chemical analyses.
The analyses revealed that Ag and Bi are the predominant critical elements in the samples, with highest recoveries occurring in the Pb concentrate at 75-90% and 78-90%, respectively. This observation is consistent with the results of the Ag and Bi deportments, as these elements are mainly hosted in solid solution within galena (PbS), whereas particulate Ag- and Bi-bearing minerals, such as acanthite (Ag2S), freibergite ((Ag,Cu,Fe)12(Sb,As)4S13), pyrargyrite (Ag3SbS3), bismuthinite (Bi2S3), native bismuth (Bi), and cosalite (Pb2Bi2S5) are commonly associated with galena.
The majority of In reported to the Zn concentrate (61-84%), suggesting an association with sphalerite. However, a notable portion, approximately 13-33%, was lost to the final tailings. A significant proportion of Sb (44-62%) was lost to the final tailings, while only 33-52% reported to the Pb concentrate. Recovery rates of Se in the Pb and Zn concentrate reach 30-61% and 32-63%, respectively. Meanwhile, 56-77% of Te was recovered in the Pb concentrate, and 16-34% was lost to the final tailings. Sphalerite is expected to be the primary carrier of In, whereas freibergite and pyrargyrite have been identified as carriers of Sb, and pilsenite/tsumoite (Bi4Te3/BiTe), hessite (Ag2Te) and BiTeAg host Te. Additionally, it is possible that some gangue minerals are responsible for carrying some of these elements to the final tailings.

The presence of open-volume defects, such as vacancies, can significantly alter the functional properties of a material, including its
structure and electronic transport. This study employs ion irradiation using inert ions (Ar+) and transition metal ions (Co+) at fluences
of 1012 – 1015 ions∙cm-2 to achieve systematic disorder in the multilayer structure of MAX-phase Cr2AlC. It is shown that the magnitude
of the paramagnetic response of Cr2AlC increases with ion fluence, regardless of the dopant used. A combination of isolated moments in
defect sites with J = ½ and magnetic clusters are used to explain this behavior. Low-temperature (< 30 K) resistivity measurements show
local minima and sudden up(down)-turns with decreasing temperature, which, together with unusual MR in this temperature range,
suggest the presence of quantum transport effects, such as the Kondo effect.

Introduction
Arterial spin labeling (ASL) MRI, a non-invasive technique for imaging perfusion, now allows studying BBB permeability. The DEveloping BBB-ASL as a non-Invasive Early biomarker of Alzheimer's Disease (DEBBIE-AD) multi-cohort study integrates this modified BBB-ASL technique in several healthy and diseased populations (Table 1) to study methodological and clinical research questions (Table 2) on the ability of BBB-ASL as an early AD biomarker.
Methods
DEBBIE-AD will enroll various cohorts with subjective cognitive decline, mild cognitive impairment, and AD dementia, as well as age-matched healthy controls, at seven sites (Table 1). Our newly developed BBB-ASL sequence — implemented with the vendor-independent MRI framework gammaSTAR — will be added to multiple MRI protocols. The BBB-ASL sequence combines time-encoded multi-post labeling delay pseudo-continuous ASL with a multi-echo 3D GRASE readout, allowing estimating CBF, ATT, and the BBB time of exchange (Tex). Data analyses will be conducted using ExploreASL. Beyond MRI standard sequences, including T1w, T2w, FLAIR, DWI, the DEBBIE clinical outcomes include amyloid-PET and blood and CSF fluid biomarkers (Table 1).
Expected Results
Preliminary testing of the BBB-ASL has been conducted on 3T systems (different Siemens Heathineers scanners) in different cohorts at multiple sites. Data processing with ExploreASL includes FSL-FABBER4 for quantification, allowing harmonized image processing. An example of the mean and standard deviation Tex maps of two DEBBIE cohorts is shown in Figure 1 to illustrate the similarities of the Tex patterns from two cohorts of similar-aged healthy adults from different sites.
Discussion
The DEBBIE-AD study aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies. The presented sequence may provide novel and unique insights into the staging of BBB permeability changes in groups at greater risk of developing AD, which may, in turn, provide new targets for treatment.

Ziel/Aim: Hepatocellular carcinoma (HCC) is one of the most common cancer entities worldwide. Glypican-3 (GPC-3) has been proposed as HCC biomarker, since it is selectively overexpressed in HCC tumor tissue. Several peptides targeting GPC-3 have been reported, however with contradictory binding and in vitro properties [1] [2]. Taking this into account, we selected the peptide TJ12P2 as a starting point for tracer development.

Methodik/Methods: The 12-mer peptide TJ12P2 (SNDRPPNILQKR) and two derivatives with a NODAGA chelator were synthesized using Fmoc-based solid-phase peptide synthesis. The resulting compounds were radiolabeled with Ga-67/Ga-68 and their serum stability investigated. Binding affinities were studied using surface plasmon resonance (SPR) and a radioligand binding assay with HepG2 cells, which express a high level of GPC-3. PET imaging in mice bearing a HepG2-tumor was conducted to examine in vivo distribution and uptake pattern of the constructs.

Ergebnisse/Results: The two peptide conjugates were successfully synthesized, characterized, and radiolabeled. The peptide SNDRPPNILQKR-Sar3-K(NODAGA)-NH2 was found to be stable in serum over 24 h. In contrast, the peptide NODAGA-SNDRPPNILQKR-NH2 was degraded rapidly (half-life of 17.6 min), leading to the formation of one radiometabolite. Specific binding to GPC-3 could not be confirmed, neither by SPR nor in a radioligand binding assay. Similarly, no tracer uptake could be observed in the target-positive tumor in vivo. Tumor-to-liver and tumor-to-muscle ratios after 1 h were quite low (0.36-0.46 and 0.31-2.22).

Schlussfolgerungen/Conclusions: Using various techniques, we were not able to confirm GPC-3 binding of TJ12P2 and its derivatives. Therefore, we conclude that the peptide is not a suitable starting point for the development of an HCC specific radiotracer.

The Ruwai Pb-Zn skarn deposit is hosted by Jurassic limestones of the Ketapang Complex and Cretaceous granitoids of the Sukadana Complex (part of the Schwaner Mountain Complex), in Central Kalimantan, Indonesia. It is the largest polymetallic skarn deposit in Indonesia with estimated resources of 14 Mt. of ore at ~5 wt.% Zn, ~3 wt.% Pb, ~108 g/t Ag. In order to understand the metal deportment and optimize critical metal recovery (Ag, Bi, Sb, In, Te), pulp samples from 6 main stages of the processing plant, including feed, Pb concentrate, Pb scavenger, Zn concentrate, Zn scavenger, and tailings, were analysed.
The bulk geochemistry, mineralogy and mineral chemistry were obtained using several analytical techniques. These include, X-ray fluorescence (XRF), inductively coupled plasma optical emission spectroscopy (ICP-OES), inductively coupled plasma mass spectrometry (ICP-MS) and instrumental neutron activation analysis (INAA) for bulk geochemistry, mineral liberation analysis (MLA) coupled with x-ray diffraction analysis (XRD) for mineralogy and electron probe microanalysis (EPMA) to determine the concentrations of the major and minor elements within individual minerals.
This assessment presents the deportment and distribution of silver and bismuth in the processing products of the Ruwai skarn deposit. The data show that the primary host of silver is galena (PbS), whereas other minerals such as acanthite (Ag2S), freibergite ((Ag,Cu,Fe)12(Sb,As)4S13), pyrargyrite (Ag3SbS3), hessite (Ag2Te), silver-rich cossalite (Pb2Bi2S5) and BiTeAg contribute subordinate amounts due to their low abundance. The major Bi-bearing phases include galena, bismuthinite (Bi2S3), native bismuth (Bi), cossalite, silver-rich cossalite, pilsenite (Bi4Te3)/tsumoite (BiTe), BiTeAg and bismite (Bi2O3). Further analytical work using laser ablation ICP-MS is planned for all samples to also enable the evaluation of the resource potential of the other critical elements of interest (Sb, In, Te).

es hat kein aussagefähiges Abstract vorgelegen

es hat kein aussagekräftiges Abstract vorgelegen

es hat kein aussagefähiges Abstract vorgelegen

In this work, we present the formation of superconducting phases of Ga-precipitates in hyperdoped SiGe with different ratios of Si/Ge composition. Using ion implantation and flash lamp annealing (FLA) in the millisecond range, we explore the coherent coupling of Ga network within the bulk instead at the SiO2/Si or SiO2/Ge interfaces. As the Si concentration in the alloy increases, but with an identical Ga concentration, the samples show a transition from a superconducting to a non-superconducting phase due to the change of the Ga solubility in the SiGe alloy. We found hyperdoped Si0.3Ge0.7 with 13 % of Ga shows superconducting transition temperature of 3.5 K, critical magnetic field of 1 T and a critical current of approximately 250 μA.

Numerical simulations of two-phase flows offer a versatile alternative for designing and sizing process plants, especially when complex phase interactions are involved. Thermal separation units with two-phase feeds often face undeveloped flows without tailored prediction methods. Industrial-scale experiments are costly and typically limited to water/air systems. Modern numerical models like VoF and AIAD enable free surface flow simulations across scales for validated pipe geometries. This work evaluates their effectiveness in predicting developing two-phase flow patterns in straight pipes and horizontal bends of two diameters under two operating conditions. Discrepancies between the codes and AIAD's velocity field limitations near bends were identified. Comparison with experimental data showed satisfactory agreement in average phase fractions. The numerical results were further applied to feed inlet device selection.

Phenomena involving complex multiphase gas-liquid flows, encompassing elements such as bubbles and free surface flows, are commonly encountered in various industrial processes. When it comes to Computational Fluid Dynamics (CFD) simulations, capturing the transition from low to high void fraction conditions presents a formidable challenge, primarily due to the escalating intricacies at the gas-liquid interface. For instance, gas volume fractions within the range where churn-turbulent and slug flows are dominated by exceedingly deformable bubbles. In this intricate scenario, a generalized multiphase CFD modeling approach known as GENTOP stands out. GENTOP adopts the concept of a fully-resolved continuous gas phase, wherein this continuous gas phase encompasses all gas structures that are sufficiently large to be resolved within the computational mesh. On the other side smaller structures are simulated using the dispersed gas phase.

Various academic cases and experiments were utilzed to validate the GENTOP concept in ANSYS Fluent.

However, it is important to note that for a typical user, delving into the complexities and technical nuances of setting up multiphase flow simulations can be quite challenging and laborious.

Ziel: Die an der Eicosanoid-Synthese beteiligten Enzyme Cyclooxygenase-2 (COX-2) und 5-Lipoxygenase (5-LO) spielen bei Entwicklung und Wachstum, aber auch bei Metastasierung und Radioresistenz zahlreicher Tumoren eine wichtige Rolle.1,2 In Vorarbeiten wurde, ausgehend von RWJ-63556 als Leitstruktur, das vielversprechende Carboran-basierte Derivat MetCMs (Abbildung 1) als dualer COX-2/5-LO-Inhibitor identifiziert. 3 Ziel dieser Arbeit war die Synthese und Radiomarkierung von I-MetCMs.

Methoden: Die Iodierung von MetCMs erfolgte durch Umsatz mit Chloramin-T und NaI in DMSO/H2O und Reinigung durch semi-präparative HPLC. Die Reaktionsbedingungen zur Radioiodierung wurden, ausgehend von 10–24 MBq no-carrier-added [123I]NaI in Gegenwart von Chloramin-T, hinsichtlich der Menge des Oxidationsmittels und Präkursors optimiert. Der radiochemische Umsatz (RCC) im Reaktionsgemisch wurde mittels Radio-DC und -HPLC analysiert. Die optimierten Reaktionsbedingungen wurden auf eine manuelle Radiosynthese mit semi-präparativer HPLC-Reinigung und Festphasenextraktion übertragen.

Ergebnisse: I-MetCMs wurde in 30–60 % Ausbeute erhalten. 1H-, 11B- und 11B{1H}-NMR-Analysen der Referenzsubstanz zeigten, dass die Iodierung abseits des Carboran-Clusters am Thiophen erfolgt. Für die Synthese von [123I]I-MetCMs erwies sich Chloramin-T als optimales Oxidationsmittel, welches RCC(HPLC) von 81–97 % bis zu einer minimalen Konzentration von 0,4 mM MetCMs lieferte. Bei Übertragung auf die finale Radiosynthese wurde eine deutliche Tendenz zur Radiodeiodierung bereits nach semi-präparativer HPLC-Reinigung beobachtet, welche jedoch durch Zugabe von Ascorbinsäure erfolgreich minimiert werden konnte (radiochemische Reinheit 88–100 %). Nach Synthese und Separierung wurde [123I]I-MetCMs in radiochemischen Ausbeuten (RCY) von 58±9 % erhalten.

Schlussfolgerungen: Iodierung und Radioiodierung des dualen COX-2/5-LO-Inhibitors MetCMs konnten optimiert werden. Aktuelle Arbeiten richten sich auf die In-vitro- und In-vivo-Charakterisierung von I-MetCMs und [123I]I-MetCMs.

Background
Cyclooxygenase-2 (COX 2) and 5-lipoxygenase (5 LO) convert arachidonic acid to prostanoids and leukotrienes respectively. Both enzymes are involved in tumorigenesis and show overexpression in cancer which makes them promising targets for radioligands [1,2]. Herein, we present radioiodination of two dual COX 2/5 LO inhibitors featuring a closo-dicarbadodecaborane(12) moiety as metabolically stable phenyl mimetic and the results of preliminary in vitro and in vivo investigations.
Materials and Methods
Enzyme inhibition of I 1 and I 2 (Figure 1) was determined using a fluorescence-based COX assay. 1 and 2 were radioiodinated using chloramine T and purified by semipreparative HPLC followed by solid-phase extraction. Radiotracer formulations contained ascorbic acid (AA) or gentisic acid (GA). Stability in ethanol, isotonic saline (0.9% NaCl), phosphate-buffered saline pH 7.4 (PBS) and human plasma was investigated for up to 11 h. Cell uptake studies were performed using U87 glioblastoma, U87 COX 2–knockout, and A2058 melanoma cells. Distribution in U87 tumour-bearing NMRI nu/nu mice was investigated using single-photon emission computed tomography (SPECT).
Results
Radiosynthesis gave high radiochemical yield (41–67 %). Radiochemical purity (RCP) depended on addition of antioxidants (none 62–100 %, AA > 88 %, GA > 97 %). Formulations in EtOH were stable for more than 10 h at room temperature. In isotonic saline and PBS, radiodeiodination was decelerated by antioxidants. Radiotracers exhibited stability during incubation with human plasma (RCP > 95 % up to 5 h at 37°C with GA). Cell uptake was observed and partially blocked by inhibitors of COX 2 and 5 LO. A SPECT imaging pilot study showed tracer excretion via hepatobiliary and renal routes within 2 h, and thyroid uptake resulting mainly from residual [123I]iodide in the tracer formulation. Furthermore, [123I]I 2 formulated with AA, but not GA, showed uptake in the marginal region of COX 2-positive tumours 24 h after injection (maximum standardised uptake value SUVmax = 9.1).
Conclusions
Two radioiodinated closo-dicarbadodecaborane(12)-based COX 2/5 LO inhibitors were characterised in vitro and underwent first explorative SPECT studies in vivo. Interestingly, binding of [123I]I 2 at the marginal tumour region was observed in presence of AA but not GA, potentially indicating partial specificity by blocking COX-2 in GA-treated mice. Further investigations, such as an intact cell 5 LO assay and in vivo experiments, will allow to validate these initial observations and to assess the applicability of COX 2/5 LO inhibitors as tumour radiotracers.

Aim: Parkinson’s disease is caused by degeneration of nigro-striatal dopaminergic neurons and denervation of the target neurons in the neostriatum. The resulting disruption of dopaminergic modulation produces an imbalance between antagonistic pathways in the basal ganglia leading to rigidity, tremor, and bradykinesia [1]. One state-of-the-art treatment option is the so called deep-brain-stimulation (DBS), whereby an electrode is implanted to re-equilibrate the nervous pathways. Though highly effective, DBS is linked to a complex surgical procedure and can lead to adverse neurological effects [2,3]. The goal of this project is to enable a selective stimulation of striatal dopaminoceptive neurons from outside the brain through polymeric photovoltaic nanoparticles which are transported to the neostriatum using engineered M13 bacteriophage as nanocarrier. To monitor its biodistribution in the organism, the engineered bacteriophages are going to be radiolabeled.
Materials and methods: To allow the radiolabeling with a radiometal, a chelator has to be conjugated to the bacteriophage. Phage conjugates with different chelators were produced, but stability analysis by agarose gel electrophoresis revealed a significantly increased and unexpected aggregation of the radiolabeled conjugates, in comparison to the unconjugated phage, when incubated with 50% human serum. To address this problem and avoid aggregation, a chelator-free radiolabeling approach was chosen instead, by radioiodination of the tyrosine residues using [123I]NaI and Iodogen.
Results: The achieved radiochemical purity was > 96% and the molar activity was 11 MBq/pmol. Stability analysis using agarose gel electrophoresis indeed revealed a low aggregation in serum. C57BL mice were intravenously injected with ~ 30 MBq/mouse of [123I]I-M13 and imaged with SPECT/CT after 20 min, 40 min, 60 min and 18 h. A high amount of activity was observable in the heart of the mice over the whole duration of the experiment, indicating circulation of bacteriophages. In the necropsy after 18 h, a portion of 15% of the activity was still found in the blood. Another accumulation was observed in the lungs, however the signal originated from the blood circulation in the organ, which was confirmed by the necropsy. After 18 h, 5% of the activity was also found in the thyroid, indicating moderate deiodination over time. According to blood samples collected over time the biological half-life was calculated to be ~ 9 h.
Conclusion: In this study, for the first time the successful radioiodination of M13 bacteriophages using [123I]NaI is described. Using the radioiodinated M13, the biodistribution of the phages was studied in vivo and a striking long serum half-life of the [123I]I-M13 was discovered.

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Spin crossover (SCO) complexes have been shown to exhibit giant mechanocaloric effects. Due to the change of magnetization at the spin crossover transition, they are also expected to show magnetocaloric effects. However, experimental studies on the magnetocaloric properties in SCOs are scarce. Here, we have studied the magnetocaloric response in the SCO complex {Fe(L)₂}(BF₄)₂, {L = 2,6-di(pyrazol-1-yl)pyridine} using pulsed magnetic fields. We show that applying a magnetic field can induce a partial transformation from the low spin to the high spin state. We directly measure the adiabatic temperature change of the transformation for different initial sample temperatures and magnetic fields and compare them with calculations using the Clausius–Clapeyron equation. While we found a large change in entropy of 70 Jkg⁻¹K⁻¹ at 50 T, the corresponding temperature change of 1.5 K is small due to the weak dependence of the transformation temperature on the magnetic field. Our study enhances the knowledge of caloric effects in SCO complexes, which so far have mainly focused on mechanocaloric studies.

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We present comprehensive high magnetic field studies of the alternating weakly coupled ferroantiferromagnetic (FM-AFM) spin-1/2 chain compound Cu₂(OH)₃Br, with the structure of the natural mineral botallackite. Our measurements reveal a broad magnetization plateau at about half of the saturation value, strongly suggesting that the FM chain sublattice becomes fully polarized, while the AFM chain sublattice remains barely magnetized, in magnetic fields at least up to 50 T. We confirm a spin-reorientation transition for magnetic fields applied in the ac* plane, whose angular dependence is described in the framework of the mean-field theory. Employing high-field THz spectroscopy, we reveal a complex pattern of high-frequency spinon-magnon bound-state excitations. On the other hand, at lower frequencies we observe two modes of antiferromagnetic resonance, as a consequence of the long-range magnetic ordering.We demonstrate that applied magnetic field tends to suppress the long-range magnetic ordering; the temperature-field phase diagram of the phase transition is obtained for magnetic fields up to 14 T for three principal directions (a, b, c*).

The pressure and temperature conditions at which precipitation of diamond occurs from hydrocarbon mixtures is important for modelling the interior dynamics of icy planets. However, there is substantial disagreement from laboratory experiments, with those using dynamic compression techniques finding much more extreme conditions are required than in static compression. Here we report the time-resolved observation of diamond formation from statically compressed polystyrene, (C8H8)n, heated using the 4.5 MHz X-ray pulse trains at the European X-ray Free Electron Laser facility. Diamond formation is observed above 2,500 K from 19 GPa to 27 GPa, conditions representative of Uranus’s and Neptune’s shallow interiors, on 30 μs to 40 μs timescales. This is much slower than may be observed during the ∼10 ns duration of typical dynamic compression experiments, revealing reaction kinetics to be the reason for the discrepancy. Reduced pressure and temperature conditions for diamond formation has implications for icy planetary interiors, where diamond subduction leads to heating and could drive convection in the conductive ice layer that has a role in their magnetic fields.

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X-ray free electron laser (XFEL) sources coupled to high-power laser systems offer an avenue to study the structural dynamics of materials at extreme pressures and temperatures. The recent commissioning of the DiPOLE 100-X laser on the high energy density (HED) instrument at the European XFEL represents the state-of-the-art in combining x-ray diffraction with laser compression, allowing for compressed materials to be probed in unprecedented detail. Here, we report quantitative structural measurements of molten Sn compressed to 85(5) GPa and  ~3500 K. The capabilities of the HED instrument enable liquid density measurements with an uncertainty of ~1% at conditions which are extremely challenging to reach via static compression methods. We discuss best practices for conducting liquid diffraction dynamic compression experiments and the necessary intensity corrections which allow for accurate quantitative analysis. We also provide a polyimide ablation pressure vs input laser energy for the DiPOLE 100-X drive laser which will serve future users of the HED instrument.

We present in situ measurements of spectrally resolved X-ray scattering and X-ray diffraction from monocrystalline diamond samples heated with an intense pulse of heavy ions. In this way, we determine the samples’ heating dynamics and their microscopic and macroscopic structural integrity over a timespan of several microseconds. Connecting the ratio of elastic to inelastic scattering with state-of-the-art density functional theory molecular dynamics simulations allows the inference of average temperatures around 1300 K, in agreement with predictions from stopping power calculations. The simultaneous diffraction measurements show no hints of any volumetric graphitization of the material, but do indicate the onset of fracture in the diamond sample. Our experiments pave the way for future studies at the Facility for Antiproton and Ion Research, where a substantially increased intensity of the heavy ion beam will be available.

Die Therapie der Akuten Myeloischen Leukämie (AML) bleibt eine große Herausforderung. Intensive Chemotherapien und allogene hämatopoetische Stammzelltransplantationen bieten
manchen Patienten Heilungschancen, sind aber mit einer hohen Morbidität verbunden und kommen v.a. für ältere und morbide Patienten oft nicht infrage. Insbesondere die rezidiviert/
refraktäre AML weist weiterhin eine schlechte Prognose auf. Folglich ist der Bedarf an neuen innovativen und sicheren Therapieansätzen hoch. CAR T-Zellen konnten einen Durchbruch in
der Behandlung akuter lymphatischer Leukämien und Lymphome erzielen, sich aber bei der Behandlung der AML in klinischen Studien bislang nicht durchsetzen. Die Suche nach Ziel-
strukturen auf AML-Blasten erweist sich als schwierig, nicht zuletzt da deren Expression auf gesunden myeloischen Zellen mit einer Myelosuppression unter Therapie einhergehen kann.
Die UniCAR T-Zell-Therapie ist eine Adapter CAR-Plattform, welche innovative Lösungsansätze zur Therapie der AML offeriert. Das UniCAR-System basiert auf der Quervernetzung
von UniCAR T-Zellen mit Tumorzellen durch molekulare Adapter, sog. Targetmodule (TM). Da der UniCAR keine Tumorassoziierten Antigene, sondern das kurze E5B9-Peptidepitop des TM erkennt, ist das UniCAR-System in Abwesenheit der TM inaktiv. Dies erlaubt eine rasche, reversible Schaltbarkeit des Systems im Falle von Nebenwirkungen wie dem CRS oder der
Myelosuppression. Die TM vermitteln die spezifische Bindung an Zielstrukturen der AML. Zudem können durch Kombinationen von TM verschiedener Spezifität mehrere Zielstrukturen
der AML zeitgleich angegriffen werden. In der AG Bachmann wurden bereits scFv-basierte TM mit kurzer Halbwertszeit (HWZ) zur UniCAR T-Zell-Therapie der AML entwickelt. Beachtliche Ergebnisse konnten u. a. das CD33- und CD123-spezifische scFv TM zeigen, sodass Letzteres bereits in einer multizentrischen klinischen Phase 1 Studie evaluiert wird (NCT04230265). Eine weitere Zielstruktur der AML ist FLT3. Es handelt sich um eine Tyrosinkinase, welche von AML-Blasten überexprimiert wird. Darüber hinaus ist die interne Tandemduplikation von FLT3 eine der häufigsten Treibermutationen der AML, welche mit einer schlechten Prognose assoziiert ist. Dies macht FLT3 zu einem geeigneten Angriffspunkt der UniCAR T-Zell-Therapie. In dieser Arbeit wurden FLT3-spezifische TM verschiedener Größe für die UniCAR T-Zell-Therapie der AML entwickelt. Während kleine scFv-basierte TM aufgrund ihrer kurzen in vivo HWZ eine rasche Kontrolle von Nebenwirkungen ermöglichen, könnten sich größere HWZ-verlängerte TM für spätere Therapiephasen anbieten, in denen die AML-Blastenzahl und das Nebenwirkungs-Risiko wesentlich reduziert sind. Durch ihre verlängerten HWZ könnten die Abstände zwischen den TM-Infusionen verlängert werden, was ambulante Therapien ermöglichen könnte. In dieser Arbeit wurde eine Verlängerung der in vivo HWZ durch das Einfügen konstanter Domänen humaner IgG-Moleküle erreicht. So konnten zusätzlich zum FLT3-scFv TM mit kurzer HWZ ein FLT3-Minibody (Mb) TM, FLT3-IgG4 TM sowie FLT3-IgG4mut TM mit steigendem Molekulargewicht und somit längerer HWZ gebildet werden. Um deren Immunogenität im Patienten im Hinblick auf eine klinische Translation zu reduzieren, wurden alle FLT3-spezifischen TM humanisiert und funktionell mit den murinen TM verglichen. Es konnten erfolgreich murine und humanisierte FLT3-scFv TM, FLT3-Mb TM, FLT3-IgG4 TM und FLT3-IgG4mut TM kloniert und durch lentivirale Transduktion stabil in das Genom eukaryotischer Zelllinien eingebracht werden. Die von den Zelllinien exprimierten TM konnten durch Affinitätschromatografien in hoher Reinheit und Konzentration gewonnen werden. Im direkten in vitro Vergleich erwiesen sich die humanisierten FLT3 TM (huFLT3 TM) als funktionell gleichwertig zu den murinen Varianten. In weiteren Funktionalitätsstudien konnten die potenziell weniger immunogenen huFLT3 TM eingehender charakterisiert werden. Sämtliche huFLT3 TM erwiesen sich in vitro an verschiedenen AML-Zelllinien mit unterschiedlicher FLT3-Expression als sehr effektiv. Alle huFLT3 TM konnten spezifisch an FLT3+ AML-Zellen binden und im Folgenden UniCAR T-Zellen aktivieren. Diese setzten
daraufhin proinflammatorische Zytokine frei. UniCAR T-Zellen lysierten nach huFLT3 TM-vermittelter Quervernetzung spezifisch AML-Zellen bei geringen E:T-Verhältnissen, wofür
halbmaximale Wirkkonzentrationen der huFLT3 TM im picomolaren Bereich ermittelt wurden. Darüber hinaus konnten isolierte primäre AML-Blasten drei verschiedener AML-Patienten in
vitro durch die FLT3-spezifische UniCAR T-Zell-Therapie lysiert werden. Die höchste Effektivität konnte dabei das huFLT3-scFv TM erzielen. Bei der in vivo Behandlung von AML-
Tumoren im Mausmodell erwiesen sich das huFLT3-scFv TM sowie das huFLT3-IgG4 TM am wirksamsten. Letzteres konnte die Tumore binnen etwa einer Woche vollständig eradizieren.
Abschließend wurde durch PET-Untersuchungen die in vivo Pharmakokinetik der huFLT3 TM in einem immundefizienten murinen AML-Xenograftmodell evaluiert. Es konnte die sukzessive HWZ-Verlängerung im Blut für das huFLT3-Mb TM, das huFLT3-IgG4 TM und das huFLT3-IgG4mut TM entsprechend ihres steigenden Molekulargewichts im Vergleich zum huFLT3-scFv TM bestätigt werden. Alle huFLT3 TM reicherten sich hochspezifisch in den FLT3+ AML-Tumoren an und persistierten dort. Aufgrund dieser Eigenschaften könnten sich die TM evtl. auch durch Markierung mit geeigneten Radionukliden für eine Radioimmuntherapie eignen.
Insgesamt legt diese Doktorarbeit das Potenzial der neuen huFLT3 TM für die UniCAR T-Zell-Therapie der AML dar. Am wirksamsten erwiesen sich sowohl in vitro bei der Behandlung
primärer AML-Blasten als auch in vivo an AML-Tumoren im Mausmodell das huFLT3-scFv TM sowie das huFLT3-IgG4 TM als Vertreter eines huFLT3 TM mit kurzer und langer in vivo HWZ. Mit der erfolgreichen HWZ-Verlängerung der TM könnten langfristige UniCAR T-Zell-Erhaltungstherapien residualer AML-Blasten ermöglicht werden. Die in dieser Arbeit akquirierten
PET-Daten legen zudem die Eignung der huFLT3 TM für theranostische Ansätze nahe.

Femtosecond high-intensity laser pulses at intensities surpassing 1014 W/cm2 can generate a diverse range of functional surface nanostructures. Achieving precise control over the production of these functional structures necessitates a thorough understanding of the surface morphology dynamics with nanometer-scale spatial resolution and picosecond-scale temporal resolution. In this study, we show that single XFEL pulses can elucidate structural changes on surfaces induced by laser-generated plasmas using grazing-incidence small-angle X-ray scattering (GISAXS). Using aluminium-coated multilayer samples we distinguish between sub-picosecond (ps) surface morphology dynamics and subsequent multi-ps subsurface density dynamics with nanometer-depth sensitivity. The observed subsurface density dynamics serve to validate advanced simulation models representing matter under extreme conditions. Our findings promise to open new avenues for laser material-nanoprocessing and high-energy-density science.

Immunotherapy encompasses a wide array of strategies, spanning from cytokines to antibodies and their derivatives, extending to engineered immune cells. A highly promising
avenue in immunotherapy involves T or NK cell engineering to express chimeric antigen receptors (CARs), which redirect immune cells to specific antigens, triggering effector cell
activation and subsequent elimination of target cells. CAR technology has demonstrated significant therapeutic potential in both preclinical and clinical studies. This success
encourages the application of CAR-expressing immune effector cells for the treatment of GBM, a highly aggressive malignant brain tumor. Despite the success of CAR T cells, clinical trials have unveiled various toxicities and therapy-related adverse events in cancer patients. These side effects derive primarily from the inability to regulate the activity of CAR T cells post-administration and the expression of tumor-associated antigens (TAAs) on non-malignant cells, leading to the unspecific attack of healthy tissues. Additionally, effective targeting of solid tumors using CAR technology encounters challenges posed by the structural complexities, immunosuppressive microenvironment, and heterogeneity of the disease. To address these challenges, a novel modular and switchable CAR platform, named reversible CAR (RevCAR), has been developed by our group. Unlike conventional CARs, the RevCAR engineered effector cells that exhibits a peptide epitope (E7B6 or E5B9) in their extracellular domain (ECD) derived from the nuclear protein La-SS/B; instead of the scFv expressed on conventional CARs. This special modular design of RevCAR system is responsible for its switchability as it only interacts with target cancer cells through a RevTM, which simultaneously bind with one arm to the RevCAR epitope on effector cells and with the other arm to the TAA. This RevTM-induced cross-linkage facilitates the activation of the modified T cells, leading to the subsequent elimination of the tumor cells. Besides its safety mechanism, the system serves as a versatile platform for targeting multiple antigens by employing different RevTMs with distinct antigen specificities, thus overcoming tumor heterogeneity and antigen escape without the need to re-engineer T cells. Two formats of RevCAR T cells (RevCAR E5B9 and RevCAR E7B6) have been used in this thesis in order to target disialoganglioside (GD2) and/or epidermal growth factor receptor (EGFR) antigens that are overexpressed on GBM. For this purpose, GD2 and EGFR RevTMs were developed to redirect the corresponding RevCAR T cells towards tumor cells. In vitro functional tests have demonstrated a successful redirection of RevCAR T cells and therefore, a specific elimination of GBM cells and release of proinflammatory cytokines in an antigen-specific and RevTM concentration-dependent manner. While both RevTMs exhibited high killing efficiency, the half-maximal effective concentration (EC50) value for RevTM-5B9 was in the pM range, whereas RevTM-7B6 was in the nM range. In addition, also regarding the cytokine release the RevCAR-E5B9 system was superior compared to the RevCAR-E7B6 system. Following the successful application of OR-gated GBM targeting, I aimed to validate the concept of combinatorial targeting for more specific killing of GBM. Therefore, I employed the established Dual-RevCAR system, which follows the AND-gated targeting strategy. This novel framework includes a splitted version of the activation and costimulatory signaling domains into two RevCARs: the signaling (SIG) RevCARs that initiate the CD3 signal and the co-stimulatory (COS) RevCARs that initiate the CD28 signal. The full activation of the modified Dual-RevCAR T cells is only achieved through simultaneous cross-linking with cancer cells via two RevTMs upon recognition of two antigens. Through this combinatorial targeting of GBM cells displaying two TAAs, Dual-RevCARs reduce the risk of "on-target, off-tumor" toxicities. In this study, RevTMs against GD2 and EGFR were developed in different structures based on EGFR-nb (~45 KDa), GD2-scFv (~57 KDa) and GD2-IgG4 (~160 KDa), and they were linked to either 5B9- or 7B6-scFv. Structural different RevTMs provide different properties and biodistribution profiles for fast or retained elimination of RevTM. The performed functional analyses revealed that only in the simultaneous presence of RevTM GD2-5B9 or GD2-IgG4-5B9 and RevTM EGFR-7B6, Dual-RevCAR T cells significantly triggered the secretion of proinflammatory cytokines and efficiently eliminated GD2- and EGFR-expressing GBM cells in the nM range. This effect was completely absent using control cells lacking the expression of one or both TAAs, thereby indicating the precision targeting of Dual-RevCARs against GBM cells. Additionally, RevTM GD2 in the IgG4 and scFv formats were radiolabeled with 64Cu. Positron emission tomography (PET) analysis of the radiolabeled RevTM GD2 in tumor-bearing mice revealed that the different formats exhibits different pharmacokinetic profiles but both showed enrichment in GD2-expressing GBM cells, making them a suitable theranostic tool for GBM. Furthermore, I modified NK-92 cells with our RevCAR constructs to target GBM. NK-92 cell line can be used as “off-the-shelf” allogeneic therapy, which potentially lower the manufacturing costs and time, and reduce the likelihood of side effects due to their short lifespan. Due to the heterogenic nature of GBM, we decided to target an additional TAA, called fibroblast growth factor-inducible 14 (Fn14), which is overexpressed on GBM as indicated by previous studies. For this reason, Fn14-specific RevTMs were created to redirect the switchable RevCAR NK-92 cells, as well as RevCAR T cells, resulting in the specific killing of Fn14-expressing GBM cells in vitro and in vivo.
In conclusion, this thesis illustrates the significant potential of the switchable RevCAR system - as a mono or dual therapy - to specifically target different GBM cell models in a specific, safe and flexible manner.

Controlling the formation and stoichiometric content of the desired phases of materials has become of central interest for a variety of fields. The possibility of accessing metastable states by initiating reactions by X-ray-triggered mechanisms over ultrashort time scales has been enabled by the development of X-ray free electron lasers (XFELs). Utilizing the exceptionally high-brilliance X-ray pulses from the EuXFEL, we report the synthesis of a previously unobserved yttrium hydride under high pressure, along with nonstoichiometric changes in hydrogen content as probed at a repetition rate of 4.5 MHz using time-resolved X-ray diffraction. Exploiting non-equilibrium pathways, we synthesize and characterize a hydride in a Weaire–Phelan structure type at pressures as low as 125 GPa, predicted using a crystal structure search, with a hydrogen content of 4.0–5.75 hydrogens per cation, that is enthalpically metastable on the convex hull.

Das La Protein ist ein abundantes Protein, welches unter physiologischen Bedingungen im Zellkern lokalisiert ist. Dort ist es mit verschiedenen RNAs assoziiert und arbeitet einerseits
als Chaperone und stellt andererseits die korrekte Prozessierung der RNAs sicher. Außerhalb des Zellkerns ist das La Protein an der IRES-abhängigen Translation zellulärer
Proteine beteiligt, welche unter Bedingungen wie oxidativem Stress oder Apoptose auftritt. La ist allerdings nicht nur mit zellulären RNAs assoziiert, sondern auch mit viralen RNAs
und ist außerdem an der Translation viraler Proteine beteiligt. Abgesehen von der Möglichkeit der Re-lokalisation in das Cytoplasma wurde auch gezeigt, dass das La Protein
an die Zelloberfläche gelangen kann. Im Kontext der Krebstherapie wurde La als mögliches Zielantigen untersucht, weil es zum einen in maligne-transformierten Zellen überexprimiert ist und zum anderen wegen der Möglichkeit, die Re-lokalisation von La an die Zelloberfläche durch beispielsweise Bestrahlung oder Chemotherapie auszulösen. An der Zelloberfläche wäre das La Protein dann zugänglich für die Bindung durch La Antikörper (Ak). In der Gruppe von Prof. Bachmann wurden in den letzten Jahren verschiedene Ak gegen das La Protein charakterisiert. Die beiden bekanntesten dieser Ak, 5B9 und 7B6, erkennen jeweils kurze Peptid-Epitope. Die Interaktion dieser Ak mit den Peptid-Epitopen wurde verifiziert durch den Einsatz in immuntherapeutischen Ansätzen wie den Adapter-CAR Systemen UniCAR und RevCAR. Sowohl der 5B9 als auch der 7B6 Ak sind nicht in der Lage natives La Protein in Immunpräzipitations-experimenten zu erkennen, was bedeutet, dass die erkannten Epitope im nativen Protein kryptisch sind. Ein anderer La Ak, der von besonderem Interesse ist, ist der Ak 312B, welcher sowohl humanes als auch murines La Protein erkennt und demnach ein wirklicher Auto-Ak ist. Der 312B Ak erkennt ein Konformationsepitop, welches auch im nativen Protein zugänglich ist. Interessant an diesem Ak ist die geringe Anzahl an Mutationen in den variablen Regionen im Vergleich zu der vorhergesagten Keimbahnsequenz.
Im ersten Teil dieser Studie wurde der 312B Ak genauer untersucht, wobei besonderes Augenmerk auf die variablen Sequenzen des Ak gelegt wurde. Diese zeigen zum einen somatische Hypermutationen und zum anderen eingefügte N-Nukleotide, welche den Leserahmen und somit die Sequenz der CDR3 der schweren Ak-Kette bestimmen. Es wurde gezeigt, dass das Zurückmutieren der AS zurück zu der vorhergesagten Keimbahnsequenz, unter Beibehalten der N-Nukleotide, dazu führt, dass der erhaltene Keimbahn-312B Ak seine Reaktivität gegen La verliert. Das bedeutet, dass die Hypermutationen verantwortlich für die anti-La Reaktivität des 312B Ak sind. Durch das Rückmutieren der einzelnen AS des Keimbahn-312B Ak zu der Sequenz des urprünglichen Ak konnte gezeigt werden, dass der Austausch eines Asparaginsäure-Restes (D) in der CDR3 der schweren Kette gegen einen Tyrosin-Rest (Y) die anti-La Reaktivität wiederherstellt. Das resultierende Konstrukt konnte in Immunoblot Experimenten wieder sein Antigen erkennen. Mit Hilfe von Immunpräzipitation und ELISA konnte bestätig werden, dass diese eine D zu Y Mutation ausreichend ist, um die Bindungseigenschaften des reifen 312B Ak wiederherzustellen und dass diese Mutation einen wesentlichen Anteil an der anti-La Reaktivität dieses Ak trägt. Zusätzlich zur Charakterisierung des 312B Ak hat sich der zweite Teil dieser Arbeit mit den vier zuvor beschriebenen La Ak A3A9, A6F12, A1E5 und A9E9 befasst. Diese wurden in den 1980er Jahren etabliert, aber bisher nicht näher charakterisiert. Für diese Ak wurden zum einen die variablen Sequenzen identifiziert. Außerdem wurden die Bindeeigenschaften der Ak gegen humanes und murines La untersucht, wobei bestätigt wurde, dass alle Ak gegen humanes La reaktiv sind, allerdings nur der Ak A1E5 auch mit murinem Protein reagiert. In Immunpräzipitationsexperimenten wurde gezeigt, dass zwei der Ak, A3A9 und A9E9, natives La Protein erkennen, was bedeutet, dass diese Epitope im nativen Protein zugänglich sind. Um die Epitope der Ak zu bestimmen, wurden Immunoblot Experimente mit La-Deletionsmutanten durchgeführt, für eine genauere Bestimmung wurden die Ak zu der Firma PEPperPRINT geschickt. Für die Ak A3A9 und A6F12 konnten kurze Peptid-Epitope bestimmt werden, welche in der Linker-Region zwischen LaN und LaC,
beziehungsweise im RRM1 lokalisiert sind. Die Ak A1E5 und A9E9 erkennen jeweils Konformationsepitope, wobei das Epitop des Ak A1E5 im Bereich des RRM1 liegt und das
A9E9-Epitop in LaC lokalisiert ist. Da bekannt ist, dass manche der La Ak das Protein redox-abhängig erkennen, wurde auch für die vier in dieser Arbeit charakterisierten Ak die Redox-
Sensitivität untersucht. Die beiden Ak A3A9 und A6F12 zeigten keine redox-abhängigen Unterschiede in der Bindung an La. Für die Ak A1E5 und A9E9 konnte eine Redox-Sensitivität festgestellt werden, wobei der A1E5 Ak eine höhere Affinität zu oxidiertem La zeigt und der A9E9 Ak vorzugsweise an reduziertes La bindet. Weitere Experimente mit dem A9E9 Ak haben bestätigt, dass die Redox-Sensitivität durch die Cystein-Reste in LaC vermittelt wird. Für die beiden Ak A3A9 und A9E9, welche kurze Peptid-Epitope erkennen, wurde dann
getestet, ob sie auch für den Einsatz in einem Adapter-CAR System geeignet wären. Dafür wurden CARs entwickelt, welche extra-zellulär den anti-La scFv tragen, und Target Module
(TMs), die gegen das Tumorantigen PSMA gerichtet sind und das jeweilige La-Epitop-Tag tragen. Die neuen CARs wurden mit einer PSMA-positiven Zelllinie getestet, wobei beide
La CARs zusammen mit dem jeweiligen TM eine Lyse der Tumorzellen auslösen konnten. Beide CARs wurden auch für die Lyse von Tumorzellen, die La auf ihrer Oberfläche tragen,
eingesetzt. Dabei wurde eine unspezifische Lyse von La-gelabelten Zellen durch die A6F12 CARs beobachtet, die A3A9 CARs hingegen zeigten eine signifikante spezifische Lyse dieser Tumorzellen. Obwohl die neuen CARs in beiden Ansätzen eine Tumorzell-Lyse induzieren konnten, ist ein Adapter-CAR System einem direkten Targeting Ansatz vorzuziehen, da es sich besser kontrollieren lässt.
Zusammenfassend wurden in dieser Arbeit verschiedene La Ak charakterisiert. Es wurde gezeigt, dass die Reaktivität des 312B Ak hauptsächlich von einer AS-Mutation in der CDR3
der schweren Ak-Kette abhängt. Für die vier neuen Ak konnten die Sequenzen identifiziert und die Epitope bestimmt werden. Außerdem wurden die Bindungseigenschaften dieser Ak
untersucht. Des Weiteren wurden neue CARs entwickelt, die sowohl als Adapter CARs als auch für das direkte Targeting von La genutzt werden können.

H2O transforms to two forms of superionic (SI) ice at high pressures and temperatures, which contain highly mobile protons within a solid oxygen sublattice. Yet the stability field of both phases remains debated. Here, we present the results of an ultrafast X-ray heating study utilizing MHz pulse trains produced by the European X-ray Free Electron Laser to create high temperature states of H2O, which were probed using X-ray diffraction during dynamic cooling. We confirm an isostructural transition during heating in the 26-69 GPa range, consistent with the formation of SI-bcc. In contrast to prior work, SI-fcc was observed exclusively above ~50 GPa, despite evidence of melting at lower pressures. The absence of SI-fcc in lower pressure runs is attributed to short heating timescales and the pressure-temperature path induced by the pump-probe heating scheme in which H2O was heated above its melting temperature before the observation of quenched crystalline states, based on the earlier theoretical prediction that SI-bcc nucleates more readily from the fluid than SI-fcc. Our results may have implications for the stability of SI phases in ice-rich planets, for example during dynamic freezing, where the preferential crystallization of SI-bcc may result in distinct physical properties across mantle ice layers.

Immuntherapien zählen zu den vielversprechendsten neuartigen Ansätzen zur Behandlung von Krebserkrankungen. Ihr Ziel ist es, die Limitationen konventioneller Therapien zu überwinden, indem sie Zellen des Immunsystems reaktivieren und Tumorzellen auf diese Weise hoch spezifisch sowie effizient eliminieren. Dabei konnten insbesondere mit CAR T-Zellen enorme Fortschritte in der Immuntherapie liquider Tumorerkrankungen erzielt werden. CARs sind artifizielle Rezeptoren, die aus drei wesentlichen Komponenten aufgebaut sind: (i) eine Tumorantigen-bindende scFv-basierte EZD, (ii) eine TMD sowie (iii) eine intrazelluläre Signaldomäne. Letztere besteht häufig aus einer aktivierenden, signalgebenden (z. B. CD3z) sowie kostimulatorischen (z. B. CD28 oder CD137) Domäne. Die Ausstattung humaner T-Zellen mit CARs erlaubt die spezifische Erkennung von Tumorantigenen unabhängig vom endogenen TZR. Die Erkennung Zielantigen-präsentierender Tumorzellen resultiert in der spezifischen Aktivierung der CAR T-Zelle sowie die daraus folgende zytotoxische Elimination der Tumorzellen. Die klinische Zulassung von bislang sechs CAR T-Zellprodukten hat zur Entwicklung neuer, experimenteller CAR T-Zelltechnologien geführt, um u. a. die Expansion, Zytokinsekretion, Zytotoxizität und in vivo Persistenz von CAR T-Zellen zu optimieren. Dabei gibt es insbesondere auch großes Interesse an der Entwicklung sogenannter Adapter CAR Plattformen, um die Flexibilität, Tumor-spezifität sowie Kontrollierbarkeit von CAR T-Zelltherapien zu verbessern. Ziel dieser Ansätze ist es, die Tumorantigen-Bindedomäne von der intrazellulären Signaldomäne des CARs auf zwei Komponenten aufzuteilen, um die Aktivierung des CARs über Adaptermoleküle zu steuern. Adapter CARs, wie z. B. die in der AG Bachmann entwickelte UniCAR Plattform, weisen durch ihren modularen Aufbau wesentliche Vorteile, wie beispielsweise eine erhöhte Kontrollierbarkeit durch Dosierung der
Adaptermoleküle sowie Flexibilität in Hinblick auf die Antigenspezifität auf. Die entwickelten Ansätze nutzen allerdings mehrheitlich scFv-basierte Adapter CARs. Eine scFv-basierte EZD, wie sie auch in konventionellen CARs verwendet wird, kann zu tonischer Signalgebung führen. In der Folge werden CAR T-Zellen konstitutiv aktiviert und es kann im Patienten zu einer verringerten Persistenz der T-Zellen sowie Beeinträchtigung der antitumoralen Antwort kommen. Eine weitere Herausforderung der CAR T-Zelltherapie ist die Tumorspezifität. Die meisten Zielstrukturen von konventionellen sowie Adapter CARs sind TAAs. Diese werden in geringem Maß auch auf gesunden Zellen präsentiert, sodass die Anwendung von konventionellen und Adapter CAR T-Zellen ein Risiko für on target, off-tumor Toxizität birgt. Um die Tumorspezifität zu erhöhen, werden derzeit u. a. gated Targetingstrategien mit UND Logik evaluiert. Das Prinzip dieser Ansätze ist es, die signalgebende sowie kostimulatorische Domäne eines CARs auf zwei separate CARs mit unterschiedlicher Spezifität aufzuteilen und somit eine vollumfängliche Aktivierung von CAR T-Zellen nur dann zu vermitteln, wenn beide Zielantigene auf Tumorzellen präsentiert und erkannt werden. Der Erfolg dieser Ansätze wird durch den scFv-basierten CAR Aufbau jedoch durch gleich zwei Faktoren beeinträchtigt: einerseits limitiert die Größe der CAR Transgene die Transduktionseffizienz bei simultaner Ausstattung von T-Zellen mit zwei CARs, andererseits besteht weiterhin die Gefahr tonischer Signalgebung.
Unter Berücksichtigung dieser Kriterien wurde in der vorliegenden Dissertation die alternative, modulare RevCAR Plattform zum universellen Einsatz in der Tumorimmuntherapie entwickelt. Im Gegensatz zu konventionellen CARs oder UniCARs tragen RevCARs im extrazellulären Bereich keine scFv-Domäne, sondern eines der beiden Peptidepitope E5B9 oder E7B6. Beide Epitope stammen vom humanen nukleären La/SS-B Protein und resultieren durch ihre Länge von nur 10 bzw. 18 AS in einer signifikant verkürzten EZD in RevCARs. Damit einhergehend weisen RevCAR-kodierende Gene eine starke Reduktion im Vergleich zu Genen konventioneller scFv-basierter CARs auf. Es wurden E5B9- und E7B6-spezifische RevCAR Konstrukte mit CD3z Signaldomäne und CD28 KoD, sowie STOP RevCARs ohne intrazelluläre Signaldomäne als Kontrolle generiert. Zur Kreuzvernetzung RevCAR-armierter
T-Zellen mit TAA+ Tumorzellen bedarf es der Anwesenheit von Adaptermolekülen. Zu diesem Zweck wurden im Rahmen der Dissertation RevTMs generiert. RevTMs sind rekombinante bsAk, bei denen sich eine Bindedomäne jeweils gegen das RevCAR Peptidepitop E5B9 oder E7B6 richtet, während die andere Bindedomäne eines der beiden Prostatakarzinom-TAAs PSCA oder PSMA erkennt. Die RevTM-vermittelte Kreuzvernetzung von RevCAR-armierten T-Zellen mit TAA+ Tumorzellen resultiert in der spezifischen Aktivierung der RevCAR T-Zellen. Dies hat sowohl in vitro, als auch in vivo im Xenotransplantat-Mausmodell die effiziente zytotoxische Eliminierung von Tumorzellen zur Folge, welche strikt Peptidepitop- sowie TAA-spezifisch erfolgt. Zur Zytolyse der Tumorzellen nutzen RevCAR T-Zellen sowohl die Interaktion von Todesliganden wie TRAIL und FasL mit den entsprechenden Todesrezeptoren, als auch die Sekretion von Perforin und Granzym B. Darüber hinaus resultiert die spezifische Aktivierung der RevCAR T-Zellen in der Sekretion proinflammatorischer und proliferationsfördernder Zytokine. Die antitumorale Antwort der RevCAR T-Zellen ist dabei über die Dosierung der RevTM Konzentration ein- und ausschaltbar bzw. steuerbar. Durch die Gabe von RevTMs mit unterschiedlicher TAA-Spezifität kann die flexible RevCAR Plattformtechnologie für eine gated Targetingstrategie mit ODER Logik genutzt werden und ist darüber hinaus breit anwendbar gegen verschiedenste Tumorantigene und Tumorerkrankungen.
Zusätzlich zu den RevCARs E5B9-28/3z und E7B6-28/3z wurden auch Konstrukte mit CD137 KoD generiert, um zu evaluieren, in welchem Maß die Wahl der KoD die Funktionalität von RevCAR T-Zellen beeinflusst. RevCAR E5B9-137/3z und E7B6-137/3z T-Zellen konnten TAA+ Tumorzellen mit vergleichbarer Spezifität und Effizienz wie CD28-basierte RevCAR T-Zellen eliminieren. Insgesamt zeigten CD28- und CD137-basierte RevCAR T-Zellen in Hinblick auf T-Zell-Aktivierung sowie Differenzierung zu spezialisierten Gedächtnispopulationen und die Sekretion proinflammatorischer bzw. proliferationsfördernder Zytokine eine vergleichbare Funktionalität. Lediglich in Hinblick auf die Proliferation und Expansion der T-Zellen zeigten RevCARs mit CD28 KoD eine geringfügige Überlegenheit im Vergleich zu CD137-basierten RevCARs. Im Einsatz gegen solide Tumore wie dem Prostatakarzinom, welches im Rahmen der vorliegenden Dissertation im Fokus stand, ist die Wirksamkeit von CAR T-Zelltherapien u. a. durch das immunsuppressive Mikromilieu meist stark limitiert. Um dies zu überwinden, wurde die stärkere Kostimulation durch CD28 als vorteilhaft angesehen.
Trotz großer Erfolge ist die konventionelle CAR T-Zelltherapie oft mit lebensbedrohlichen Nebenwirkungen, wie z. B. on-target, off-tumor Effekten gegen gesundes Normalgewebe assoziiert. Um die Tumorspezifität der CAR T-Zelltherapie zu erhöhen, wurden gated Targetingstrategien nach dem Prinzip der UND Logik entwickelt. Dabei werden T-Zellen mit zwei unterschiedlichen CARs ausgestattet, sodass die Tumorzellen ausschließlich nach Erkennung von zwei unterschiedlichen Antigenen eliminiert werden. RevCARs zeichnen sich durch eine stark verkürzte EZD aus und basieren daher auf kurzen RevCAR-kodierenden Genen. Diese Voraussetzungen begünstigen die Generierung von dualen RevCAR T-Zellen (bzw. einer RevCAR Plattform) zum gated Targeting von Prostatakarzinomzellen nach dem Prinzip der UND Logik. Zu diesem Zweck wurden T-Zellen simultan mit zwei RevCARs unterschiedlicher Spezifität ausgestattet, die unterschiedliche Signale (einerseits die signalgebende CD3z und andererseits die kostimulatorische CD28 Domäne) vermitteln. Um das ideale SIG und COS Rezeptorpaar zu identifizieren, wurde eine Vielzahl unterschiedlicher RevCARs basierend auf verschiedenen Struktureinheiten neu generiert und in Kombination miteinander getestet.
Entscheidend war dabei, dass SIG und COS RevCARs keine Heterodimere bilden, um einen cross-talk zwischen beiden Rezeptoren zu verhindern und zu gewährleisten, dass das CD3z und CD28 Signal nach Erkennung unterschiedlicher Tumorantigene getrennt voneinander vermittelt werden. Gleichzeitig musste gewährleistet werden, dass eine komplette Aktivierung der RevCAR T-Zellen ausschließlich infolge beider Signale (und nicht bereits nach Vermittlung eines der beiden Signale allein) erfolgte. Hier erwies sich die schwächere Expression der SIG RevCARs infolge der Einführung der HiD des humanen IgG4 sowie der TMD vom humanen CD4 als vorteilhaft für die Implementierung der UND Logik. In dieser Arbeit ist es gelungen, eine neuartige RevCAR Plattform zum gated Targeting nach dem Prinzip der UND Logik am Beispiel des Prostatakarzinoms zu entwickeln. RevCAR T-Zellen mit dualer Spezifität
wurden sowohl durch Ko-Transduktion des COS und SIG RevCARs, als auch durch Transduktion eines bicistronischen Vektors, der gleichzeitig für COS und SIG RevCAR kodiert, generiert. Infolge des gated Targetings von PSCA und PMSA durch gleichzeitige RevTM-vermittelte Stimulation von COS und SIG RevCAR, zeigten bispezifische RevCAR T-Zellen eine gesteigerte Aktivierung, Zytotoxizität, Zytokinsekretion sowie Proliferation und Expansion. Dabei wurde beobachtet, dass die Generierung dualer E7B6-3z-E5B9-28 RevCAR T-Zellen infolge der Transduktion mit dem bicistronischen Vektor in einer verstärkten Expression des COS RevCARs resultiert. Dies wirkte sich vorteilhaft auf die strikte Implementierung der UND Logik aus. Duale E7B6-3z-E5B9-28 RevCAR T-Zellen wurden ausschließlich infolge des simultanen Targetings von PSCA und PSMA zu einer effizienten T-Zell-Aktivierung und
Zytokinsekretion sowie Tumorzellelimination angeregt. Die Analysen haben demonstriert, dass duale RevCAR T-Zellen entsprechend den Regeln der booleschen Algebra programmierbar sind und sich zur Anwendung einer gated Targetingstrategie mit UND Logik eignen. Zusammenfassend wurde in dieser Arbeit erstmalig die neue Adapter RevCAR Plattformtechnologie entwickelt, die ein- und ausschaltbar, vielseitig anwendbar und programmierbar ist, um eine effiziente, tumorspezifische und sichere personalisierte Immuntherapie von Tumorerkrankungen zu ermöglichen.

Resonant inelastic x-ray scattering (RIXS) is a widely used spectroscopic technique, providing access to the electronic structure and dynamics of atoms, molecules, and solids. However, RIXS requires a narrow bandwidth x-ray probe to achieve high spectral resolution. The challenges in delivering an energetic monochromated beam from an x-ray free electron laser (XFEL) thus limit its use in few-shot experiments, including for the study of high energy density systems. Here we demonstrate that by correlating the measurements of the self-amplified spontaneous emission (SASE) spectrum of an XFEL with the RIXS signal, using a dynamic kernel deconvolution with a neural surrogate, we can achieve electronic structure resolutions substantially higher than those normally afforded by the bandwidth of the incoming x-ray beam. We further show how this technique allows us to discriminate between the valence structures of Fe and Fe2O3, and provides access to temperature measurements as well as M-shell binding energies estimates in warm-dense Fe compounds.

Extensive efforts have been done in the area of immunotherapies to develop approaches that restore the ability of immune cells to recognize and eliminate malignant cells. These strategies range from the use of antibodies to the genetic modification of immune cells with cytotoxic potential. A strategy with great potential is T cell engineering with chimeric antigen receptors (CARs), which allows T cell redirection to recognize and eliminate cells expressing a certain tumor-associated antigen (TAA). Although CAR T cells have shown astonishing results in the treatment of CD19+ B-cell malignancies, their success targeting other TAAs has been overshadowed by life-threating adverse effects experienced by patients. Two main causes for such dangerous side-effects are the lack of control over the activity of the CAR T cells once they are administered to the patient and the fact that certain TAAs can also commonly be expressed on non-malignant cells. This results in an unspecific and uncontrolled ablation of healthy tissue. Aiming to address these relevant flaws of conventional CAR T cells and to develop a safer and more specific approach, the group of Prof. Bachmann and Dr. Feldmann developed the adaptor RevCAR system. Compared to conventional CAR T cells, RevCAR T cells do not display a scFv on their surface but a peptide epitope (E5B9 or E7B6) derived from the nuclear protein La-SS/B. Therefore, RevCAR T cells remain inert and their ability to recognize a cancer cell depends on the presence of a reverse target module (RevTM). The structure of a RevTM is similar to a bispecific antibody (bsAb), recognizing and binding
simultaneously to the peptide epitope on the RevCAR T cell and to a specific TAA. The crosslinking of cancer cells and RevCAR T cells mediated by the RevTM promotes the activation of
the modified T cells and the subsequent killing of the target cells. The RevCAR system represents a safer approach because the modified T cells can be reversely switched on and
off after their infusion into the patient, which allows the management of secondary effects upon their onset. Moreover, the targeted TAA can be easily exchanged by the administration of
different RevTMs without the need to re-engineer the T cells, which can be very practical if cancer cells downregulate the targeted TAA. Yet, the risk of “on-target, off-tumor” toxicities is
not completely circumvented by the RevCAR system. Aiming to increase the specificity of the CAR T cell killing potential towards tumor cells, multiple CAR technologies have been
developed, incorporating Boolean logic circuits (AND, OR, NOT). In this line of thought, the group of Prof. Bachmann and Dr. Feldmann further developed the RevCAR system to be
governed by an AND-gate Boolean logic. This new platform termed as Dual-RevCAR system incorporates two types of RevCARs: the signaling (SIG) RevCARs triggering the CD3 signal
and the co-stimulatory (COS) RevCARs triggering the CD28 signal. Only their simultaneous cross-linking with cancer cells via RevTMs can promote a full activation of the modified Dual-
RevCAR T cells. This allows a combinatorial targeting of tumor cells expressing two TAAs and should spare those cells lacking of a specific TAA expression pattern and thus reducing the
risk of “on-target, off-tumor” toxicities. The present work aims to demonstrate that the Dual-RevCAR system can be used for the targeting of hematological malignancies, like acute myeloid leukemia (AML), as well as, solid tumors like colorectal cancer (CRC). The AML-related antigens CD33 and CD123 were chosen as targets and existing anti-CD33 and anti-CD133 RevTMs were used. In vitro functional assays revealed that only the simultaneous presence of anti-CD33 and anti-CD123 RevTMs promoted the secretion of proinflammatory cytokines by Dual-RevCAR T cells and specific killing of CD33+ CD123+ cancer cells. Besides immortalized AML target cell lines, which have their limitations to recapitulate the high heterogenicity observed in samples of AML patients, Dual-RevCAR T cells were also able to eliminate AML patient-derived blasts following a true AND-gate targeting.
To further prove that the RevCAR system can also be used to precisely recognize and eliminate solid tumors, this thesis focuses also on the targeting of CRC. Since the structure of
the RevTMs has a direct effect on certain properties, such as biodistribution and pharmacokinetics, and considering that different formats could be useful at diverse time points
during treatment, a novel monomeric scFv-based and a homodimeric IgG4-based RevTMs targeting the carcinoembryonic antigen (CEA) were developed. In vitro and in vivo functional
assays showed that both RevTM formats successfully redirect RevCAR T cells towards CEA+ malignant cells in an antigen-specific and RevTM-dependent manner, which results in the
secretion of proinflammatory cytokines and killing of target cells. Although both RevTMs showed high efficiency in a dose-dependent manner, the EC50 value from RevTM CEA-IgG4-
7B6 was in the picomolar range, whereas the one from RevTM CEA-7B6 was in the nanomolar range. In addition, results demonstrate that the RevTM CEA-IgG4-7B6 promoted enhanced
cytokine secretion and a more robust effect in preventing tumor growth than the RevTM CEA-7B6. To further increase the precision of CRC targeting, a novel Dual-RevCAR system was
established targeting the epithelial cell adhesion molecule (EpCAM) in combination with CEA following an AND-gate logic. Therefore, two novel and structurally different anti-EpCAM
RevTMs were created: an IgG1-based and a minibody (Mb)-based format. In vitro and in vivo assays validated that only the simultaneous presence of RevTM CEA-IgG4-7B6 and either
anti-EpCAM RevTM triggered the specific elimination of CEA+ EpCAM+ malignant cells along with cytokine secretion. Moreover, phenotyping of Dual-RevCAR T cells after a first short-term challenge showed that the modified T cells mainly retained a non-exhausted TCM phenotype.
Taken together, this thesis demonstrates the remarkable potential of the Dual-RevCAR system to target diverse cancer entities following a true AND-gate Boolean logic, which represents a
safer approach circumventing off-target toxicities. Moreover, the adaptor nature of the system allows a quick switch on/off and a flexible targeting of different TAAs without re-engineering of
the T cells.

Optimizing grain boundary characteristics in polycrystalline materials can improve their properties. Many processing methods have been developed for grain boundary manipulation, including the use of intense radiation in certain applications. In this work, we used X-ray free electron laser pulses to irradiate single-crystalline bismuth selenide (Bi2Se3) and observed grain boundary formation and subsequent grain rotation in response to the X-ray radiation. Our observations with simultaneous transmission X-ray microscopy and X-ray diffraction demonstrate how intense X-ray radiation can rapidly change size and texture of grains.

Recently, we established the controllable modular UniCAR platform technology to advance the
efficacy and safety of CAR T cell therapy. The UniCAR system is composed of (i) target
modules (TMs) and (ii) UniCAR armed T cells. TMs are bispecific molecules that are able to
bind to the tumor cell surface and simultaneously to UniCAR T cells. For interaction with
UniCAR T cells, TMs contain a peptide epitope sequence which is recognized by UniCAR T
cells. So far, a series of TMs against a variety of tumor targets including against the prostate
stem cell antigen (PSCA) were constructed and functionally characterized. In order to facilitate
their purification all these TMs are expressed as recombinant proteins equipped with an oligo-
His-tag. The aim of the here presented manuscript was to learn whether or not the oligo-His-
tag of the TM influences the UniCAR system. For this purpose, we constructed TMs against
PSCA equipped with or lacking an oligo-His-tag. Both TMs were compared side by side
including for functionality and biodistribution. According to our data, an oligo-His-tag of a
UniCAR TM has only little if any effect on its binding affinity, in vitro and in vivo killing capability
and in vivo biodistribution.

Abstract
T-cell Acute Lymphoblastic Leukemia (T-ALL) is characterized by aggressive proliferation of
malignant T cells. It accounts for a pronounced percentage of around 25% of ALL in adult and
pediatric cases. Despite the advances in treatment, conventional T-ALL therapies like
chemotherapy remain with high relapse rates. Thus, there is the need for an alternative
treatments. CAR T cell therapy emerges as a promising approach, however faces its challenges
with T-ALL. In general, CAR T cell therapy associated with toxicities like cytokine release
syndrome (CRS) and neurotoxicity. In the case of treating T-ALL with CAR T cells, an
additional challenge is posed by tumor cells sharing surface markers with T cells, raising
further issues like fratricide and T cell aplasia. To overcome such limitations and risks posed
by conventional CAR T cell therapy, modular CAR T cell systems, for T-ALL in specific,
present a compelling treatment option as it may limit the fratricide, and mainly because it can
be switched off, thus long term destruction of T cells could be avoided. Therefore, the primary
aim of this thesis is to utilize the modular UniCAR T cell system to target CD7, a surface
antigen overexpressed in T-ALL. The objective is to evaluate the in vitro efficacy as a potential
therapeutic option for T-ALL. In this project, UniCAR T cells could be successfully redirected
towards CD7-expressing T-ALL cell lines via four different TMs; single chain fragment
variable (scFv)-based and IgG4-based; each with a murine version and a humanized version of
the TM. Purified TMs showed binding to CD7 on tumor cell lines and successful tumor cell
lysis was achieved with negligible fratricide. Given the results, the UniCAR T cell platform
confirms potential of targeting CD7 expressing tumor cells while also addressing the
limitations of conventional CAR T cell therapy. Offering a new scope of T-ALL targeted
therapy.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. The survival rate of PDAC is
extremely low. For treatment of PDAC still an urgent unmet clinical need exists to develop novel
innovative treatment options. An improved understanding of the genetics of PDAC has lead to the new
targeted and immune based therapies that are available to improve the survival and quality of life. There
have been several advancements that have been made in the field of cancer immunotherapy in recent
years. The development of the chimeric antigen receptor (CAR) became a revolutionary idea in cancer
treatment. Exemplary treatment efficacy was showcased by the genetically engineer CAR-T cells given
to the patients by adoptive transfer. However, there are certain barriers such as severe life-threatening
toxicities such as Cytokine release syndrome (CRS) and Tumor lysis syndrom (TLS), antigen escape,
restricted trafficking, and limited tumor infiltration of the T-cells. To overcome these limitations,
adapter CAR-T cells were developed which specifically target the tumor cells in the presence of adapter
molecules. In this study the modular adapter UniCAR-T-cell system was employed which has been
preclinically validated and even shown successful anti-tumor responses in cancer patients.

In this study, we focused on the target antigen ICA512, also known as Islet cell autoantigen 512, which
belongs to a family of receptor-type protein tyrosine phosphatase (PTPs) associated with Type 1
diabetes are known to be expressed in pancreatic beta cells. Recent studies showed that any disruptions
in these regulatory pathways lead to uncontrolled cell growth in pancreatic and glioblastoma cancer
cells. Several monoclonal antibodies (mAbs) are available to target ICA512. Here we used the murine
mAb anti-ME1-ICA512 to generate a novel TM to target ICA512 on cancer cells by the UniCAR-T-
cell system and analyzed its functionality in vitro. Therefore, in this thesis the novel ICA512-specific,
IgG4-based UniCAR TM, named as anti-ICA512-IgG4-E5B9 TM, was cloned, produced and
characterized in vitro. For proof of concept, cancer cell lines were used as a robust cellular test model
that stably overexpress ICA512. It was shown that the anti-ICA512-IgG4-E5B9 TM specifically binds
to the ICA512-positive cancer cells as well as to the UniCAR-T cells. Remarkably, this study
demonstrate that the novel anti-ICA512-IgG4-E5B9 TM can specifically and efficiently redirect
UniCAR-T-cells to kill ICA512-expressing cancer cell lines in vitro. In principle, these data provide a
proof of concept that ICA512 cancer cells can be immunotherapeutically targeted by the UniCAR
approach and thus ICA512 might be a suitable target for tumor immunotherapy.

Der hohe Energiebedarf thermischer Trennverfahren erfordert eine stetige Weiterentwicklung der Einbauten, um den übergeordneten Zielen zur Energieeinsparung näher zu kommen. In Bodenkolonnen betrifft dies unter anderem Ventilböden mit Fixed Valves, bei denen im Gegensatz zu den in der Literatur bereits ausführlich untersuchten Siebböden noch großes Forschungspotential besteht.

Einen wichtigen Einfluss auf die Fluiddynamik von Böden hat das Strömungsverhalten der Flüssigkeit auf dem Boden, das maßgeblich durch die verschiedenen Bodenelemente beeinflusst wird. Die experimentelle Untersuchung der Strömung auf Kolonnenböden ist Bestandteil von einigen Untersuchungen in der Literatur, welche jedoch häufig nur auf qualitativen Beobachtungen des Strömungsverhaltens basieren.

Im Rahmen des IGF-Vorhabens "Werkzeuge und Methoden zur verbesserten fluiddynamischen Auslegung von Querstromböden mit Hochleistungsventilen" wurde am Helmholtz-Zentrum Dresden-Rossendorf (HZDR) ein Tracer-Feldsensor entwickelt, der mithilfe von 360 Leitfähigkeitssonden das Strömungsverhalten auf einer parallelen Ebene über dem Boden ortsaufgelöst erfassen kann. Die eigens dafür entwickelte Sondengeometrie ermöglicht eine zuverlässige Messung der auf dem Boden vorliegenden Flüssigkeitsströmung. Beim eingespeisten Tracer handelt es sich um eine Natriumsulfat-Lösung, die über eine entsprechende Vorrichtung über die ganze Breite des Schachts eingespeist wird. Basierend auf der anschließenden Auswertung lässt sich das Strömungsverhalten in Bezug auf die mittlere Punktverweilzeit, die mittlere Varianzverteilung sowie die unidirektionalen Geschwindigkeiten auf dem Boden charakterisieren.

Die Messungen wurden in einem Gas/Flüssig-Kolonnenversuchsstand am Lehrstuhl für Anlagen- und Prozesstechnik der TU München durchgeführt, der einen Durchmesser von 1,2 m aufweist und mit dem Stoffsystem Luft/Wasser betrieben wurde. Vermessen wurden verschiedene Konfigurationen von Sieb- und Fixed-Valve-Böden mit und ohne Push Valves, die unter Berücksichtigung von relevanten in der Industrie eingesetzten Ventiltypen ausgewählt wurden. Zusätzlich wurden Variationen in der Wehrhöhe und -geometrie durchgeführt.

Die Ergebnisse der Untersuchungen mit dem Tracer-Sensor ermöglichen detaillierte Aussagen zum Strömungsverhalten verschiedener Bodenkonfigurationen bei unterschiedlichen Belastungszuständen. Zudem konnten mit dem im letzten Jahr vorgestellten Sensor zur Messung der Phasenverteilung umfassende Untersuchungen zum Aufbau der Zweiphasenschicht durchgeführt werden. Durch die Verknüpfung der Messergebnisse beider Sensoren können abschließend wertvolle Aussagen zum fluiddynamischen Verhalten der untersuchten Böden getroffen werden.

A new AMS system called HAMSTER (Helmholtz Accelerator Mass Spectrometer Tracing Environmental Radionuclides) will be installed in Dresden-Rossendorf to expand the capabilities of radionuclide measurements at HZDR. It consists of a 1MV pelletron tandem accelerator and has a conventional ion source for classic AMS operation and two additional injection lines: One injection line holds an ion cooler for additional purposes of isobar suppression (Ion Linear Trap for Isobar Suppression ILTIS), the other is a SIMS (Secondary Ion Mass Spectrometer) moved from its original 6MV DREAMS facility to perform Super-SIMS measurements at the new machine.
The facility will be placed in a new building that holds space for the experimental area and control room of the AMS as well as for two
chemistry laboratories. Installation of the first injector beamline with the ILTIS is foreseen for early 2024 and we expect HAMSTER to be
in operation by summer. In this contribution we will introduce the surrounding infrastructure and layout of the new facility.

As nickel (Ni), cobalt (Co), and scandium (Sc) play crucial roles in driving essential technologies for sustainable energy and transportation, Indonesian laterites have emerged as prominent sources for these metals. In the present case study, new geological data on the laterites from Sebuku Island (SE Kalimantan, Indonesia) are presented.
The Sebuku ore deposits extend over an area of more than 30 km2 and contain a JORC-compliant resource of ~390 Mt at 42.5 wt.% Fe, 0.9 wt.% Ni, and 0.15 wt.% Co. Orebodies are mostly limonitic and oxide-dominated. They are formed by weathering of Jurassic-Cretaceous ophiolites. Despite mining has been underway since 2006 (primarily for iron ore), limited mineralogical and geochemical data exist, hindering the optimization of beneficiation processes and the recovery of critical metals.
Typical laterite profiles at Sebuku include a weathered bedrock composed of serpentinized dunites and harzburgites, overlain by a saprolite zone ranging from 0.2 to 7 meters thick, a yellow limonite zone spanning 2 to 8.5 meters, and a red-limonite zone measuring 1 to 3.5 meters thick. These soil horizons exhibit complex relationships among themselves, characterized by irregular boundaries, lenticular beds, and lateral variations.
X-ray diffraction (XRD) and mineral liberation analysis (MLA) data reveal a complex ore mineralogy, encompassing oxides and oxi-hydroxides such as goethite, gibbsite/bayerite, chromite, various iron oxides (maghemite, hematite, magnetite), manganese minerals (asbolane and lithiophorite), and silicates comprising serpentine/talc, chlorite, pyroxene, garnet, quartz, and smectites. Combined MLA, electron probe microanalysis (EPMA), and X-ray fluorence (XRF) allowed to determine the deportment of Ni, Co, and Sc in those minerals.
Based on these new findings, beneficiation strategies were developed, with the ultimate goal of enhancing the efficiency of the existing processing flowchart.

Indonesian laterites are a major global source of nickel (Ni) and cobalt (Co). Here, we present new geological data on the laterites from Sebuku Island (SE Kalimantan, Indonesia). The ore deposits at Sebuku extend over an area of more than 30 km2 and contain a resource of ~390 Mt at 42.5 wt.% Fe, 0.9 wt.% Ni, and 0.15 wt.% Co. They are mostly limonitic, oxide-dominant Fe-Ni-Co-rich bodies, which formed by weathering of Jurassic-Cretaceous ophiolites. Although the Fe ore has been mined since 2006, little mineralogical and geochemical data are available, which would allow for optimization of beneficiation and recovery of Ni, Co, and scandium (Sc).
Typical laterite profiles at Sebuku consist of: 1) weathered bedrock mainly composed of serpentinites overlain by 2) a 0.2-7 m-thick saprolite zone, 3) a 2-8.5 m-thick yellow limonite zone, and 4) a 1-3.5 m-thick red-limonite zone. These horizons show complex relationships between each other.
XRF analysis shows a decrease in Mg and Si and an increase in Fe moving upwards through the laterite profile. Scandium concentrations are locally high (up to ~120 ppm in some samples), highlighting its potential as a by-product. XRD and mineral liberation analysis (MLA) data show a complex ore assemblage, which includes oxides and (oxi)-hydroxides such as goethite, maghemite, hematite, magnetite, chromite, gibbsite/bayerite, and various Mn-minerals, and silicates consisting of serpentine, chlorite, talc, quartz, pyroxene, garnet, and smectites. Critical metal deportment was calculated through MLA, coupled with electron probe microanalysis (EPMA): Ni is hosted by various minerals, including goethite, Mn-hydroxides, Fe-oxides, serpentine, and smectites, whereas Co is mainly hosted by Mn-hydroxides. It is still unclear in which minerals Sc is primarily hosted.
On the basis of these results, new beneficiation concepts will be developed, which are ultimately aimed at improving the efficiency of the current processing flowsheet.

The Gorno mining district is an example of Mississippi Valley-type (MVT) deposit in the Italian Orobic Alps. It consists of stratabound Zn-Pb-Ag (± fluorite ± barite) mineralization extending for over ~100 km2. A complex series of dolomitization, silicification, brecciation, dissolution, and cementation phenomena affected the lower Carnian stratigraphic succession in the region. Here, high-grade sulfide ore is hosted in the basal portion of the Gorno Formation, consisting of a few meters-thick interval of clay-rich sediments known as “black shales”. Other major orebodies are hosted in the underlying peritidal limestones of the Breno and Calcare Metallifero Bergamasco formations. Mineralization types encompass replacements, dissolution cavity fillings, and breccia cements.

Microthermometry of primary fluid inclusions in dolomite, sphalerite, and fluorite, integrated with sphalerite trace-element geothermometry, allow to infer moderately hot formation temperatures. Moreover, fluid inclusion data (supported by Raman spectroscopy data) document the involvement of high-salinity brines and gaseous hydrocarbons in ore deposition. The isotopic values of carbon, oxygen, and strontium indicate that the ore fluid likely originated as seawater and modified through contact with the underlying Permian clastic sediments and/or with the metamorphic basement.

The association of sulfide bodies with organic-rich shales imply a notable role of organic carbon in ore deposition. Organic matter and associated hydrocarbons likely served as reactive barriers, leading to the reduction of the ore fluid and initiating the precipitation of sulfide minerals.

Relative to bulk material, bismuth oxide nanoparticles (Bi2O3–NPs), as spheres or rods, have shown quantum confinement effects and unique optical, electrical, and magnetic properties, as well as high surface reactivity, high refractive index, good photoconductivity, and wide energy band gaps. In this work, we present the first observation and report on the synthesis of Bi2O3 nanorings by using a simple and inexpensive sonochemical route. In the presence of trisodium citrate (TSC), the hydrothermal treatment of Bi(NO3)3 gives rise to a controlled spherical morphology of Bi2O3–NPs, while the absence of TSC leads to the formation of nanorods, highlighting the critical role of the coating layer in influencing the crystal growth of NPs. Subsequently, exposing the spherical Bi2O3–NPs to ultrasonication in water led to a rearrangement and self-assembly of toroidally shaped particles, giving rise to the formation of nanorings, as observed through scanning electron microscopy (SEM). The UV–vis analysis demonstrated enhanced absorption of nanorings in the near-infrared (NIR) range compared to other solid structures. Moreover, we demonstrated the direct role of the pore size on the light-absorbing properties of Bi2O3 nanorings. Additionally, we showed that the band gap energies of Bi2O3 nanoparticles can be effectively tuned, depending on their structure. With the distinctive features and hollow morphology of Bi2O3 nanorings, they hold great potential for innovative anticancer treatments. The pronounced absorption of nanorings in the visible and NIR regions can translate into high photothermal conversion efficiency, which can lead to effective hyperthermia-based destruction of the cancer cells. Moreover, the unique hollow architecture of the nanorings makes them highly suitable as excellent nanoscale carriers for chemotherapeutic agents, offering high encapsulation efficiency, as well as stimuli-responsive drug release and targeted delivery against cancer cells.

The COVID-19 pandemic, caused by SARS-CoV-2, remains a significant threat, particularly for immunocompromised individuals and other high-risk groups. Despite the success of conventional vaccines in the general population, they frequently fail to generate a robust immune response in these vulnerable individuals, leaving them at heightened risk for severe illness. Consequently, there is still a pressing need for the development of novel therapeutic strategies against SARS-CoV-2.
To overcome the challenges posed by current COVID-19 treatments, we have developed two novel recombinant antibody constructs comprising the angiotensin-converting enzyme 2 (ACE2). The first construct is based on an IgG4 backbone, whereas the second one utilizes a human IgA backbone. The latter was selected due to its crucial role in mucosal immunity, which is particularly relevant in the context of respiratory infections like COVID-19. Both, the ACE2-IgG4 and ACE2-IgA construct effectively bind to cells harboring the receptor-binding domain (RBD) of SARS-CoV-2. Moreover, they feature an epitope tag that can be recognized by immune cells genetically modified to express an adaptor chimeric antigen receptor (CAR), known as UniCAR. This enables UniCAR-expressing immune cells to kill RBD-positive cells with high specificity and efficacy.
Overall, this approach not only facilitates a robust cellular immune response to SARS-CoV-2 but also offers a promising alternative strategy to overcome the limitations of current vaccines which is particularly important for immunocompromised individuals. Thereby, both ACE2-based constructs represent a significant advancement in the combat against COVID-19 and will protect, especially, vulnerable populations who are at a higher risk for severe COVID-19.
This work was funded by the Else-Kröner-Fresenius-Stiftung (project COGNID).

The 1:10,000 geological map of the Arera-Vedra Valley area covers an area of about 12 km2 in the Orobic Alps (Lombardy, N Italy), and is accompanied by five underground maps corresponding to different levels of historic mining works. The area is characterized by a Triassic stratigraphic succession that hosts one of the most important Zn-Pb mining districts in Italy (Gorno district). Original surface and underground geological mappings have been integrated with the analysis of drillhole stratigraphies and historic underground geological maps. Detailed geological cross sections correlating surface map data with those of the underground mining tunnels have been done. This work proposes a new map representation that is consistent with new interpretation of the geometry of the orebodies at depth, to serve as a tool for mining purposes (targets definition, mine design) and for a better understanding of the genesis of the Gorno “Alpine-type” deposits.

Arterial spin labelling (ASL) enables non-invasive quantification of regional brain perfusion using MRI. ASL was used in the Reducing Pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR) multi-centre trial to pilot the assessment of the effects of the anti-hypertension drug losartan on cerebral blood flow (CBF). In the multi-centre setting, disparities in ASL implementation on scanners from different manufacturers lead to inherent differences in measured CBF and its associated parameters (e.g. spatial coefficient of variation (sCoV) of CBF, a proxy of arterial arrival times). In addition, differences in ASL acquisition parameter settings can also affect the measured quantitative perfusion values. In this study, we used data from the RADAR cohort as a case study to evaluate the site-dependent systematic differences of CBF and sCoV, and show that variations in the readout module (2D or 3D) and the post-labelling delay acquisition parameter introduced artifactual group differences. When accounting for this effect in data analysis, we show that it is still possible to combine ASL data across sites to observe the expected relationships between grey matter CBF and cognitive scores. In summary, ASL can provide useful information relating to CBF difference in multi-centre therapeutic trials, but care must be taken in data analysis to account for the inevitable inter-site differences in scanner type and acquisition protocol.

Laser-plasma accelerators (LPAs) hold great promise for generating high-charge, low-emittance electron beams with various applications in science and industry. However, their integration into high-demand applications requires precise control of the properties of the generated electron beams, which is not yet fully achieved and requires further understanding of the underlying dynamics. Three-dimensional particle-in-cell (PIC) simulations are the leading method to model relativistic laser-plasma interactions and probing the dynamics of these LPAs.

In this study, a realistic experimental setup of a laser wakefield accelerator (LWFA) employing self-truncated ionization injection was recreated using the open-source PIC code PIConGPU. Translating experimental conditions into simulations is inherently difficult due to the large number of possibly unknown laser and plasma parameters and their fluctuation in the experiment. To address this challenge, a Bayesian optimization campaign was conducted, employing an iterative feedback loop to explore the parameter space efficiently. This optimization framework was implemented with Snakemake, a Python-based workflow engine that automated and simplified the submission process of the simulations.

The recreated experimental setup enabled not only a better understanding of the experiment, but also a detailed multi-dimensional mapping of laser and plasma parameters to electron beam properties. This study offers a comprehensive, highly detailed analysis of LWFA electron beam characteristics, uncovering complex multi-parameter dependencies. The findings provide valuable guidance for experimentalists, enabling optimized input parameters and improved efficiency in achieving high-quality electron beams.

The application of plasma polymerized silicon-based coatings on plastic substrates is an effective way to adjust the permeability of the substrate. However, the mechanisms of permeation are yet not fully understood. Here, the activation energy of permeation can offer valuable insights. In order to understand how the activation energy of permeation depends on the coating structure five silicon-based coatings with varying oxygen content were analysed, which led to properties modification ranging from silicon-oxidic to silicon-organic. Positron annihilation spectroscopy was employed to characterise the free volume and quartz crystal microbalance measurements were used to determine the density of the coating. These results were compared to water vapor permeation measurements with a temperature variation in the range of 15 °C – 50 °C. As expected, the more silicon-organic coatings do not significantly impact the permeation rates, while the silicon-oxidic coatings exhibit a barrier effect. The density of the coatings increases for the more silicon-oxidic coatings. A coating with an unusual high oxygen to precursor ratio forms the exception both in permeation and density. The free volume appears to increase for the more silicon-organic coatings. The pore wall chemistry is also affected, hinting at a phase shift from silicon-organic to silicon-oxidic. With this approach, we aim for an in-depth understanding of the chemical structure of silicon-based thin film coatings and its influence on gas permeation through those coatings.

Presentation of a Bayesian optimization algorithm to reproduce experimental results of laser electron accelerators using STII with PIConGPU. Demonstration of the effect of a background plasma to reduce the divergence of the electron beam.

In this study, we probe the coupling between magnetism and lattice dynamics in UO₂, a 3k antiferromagnet that undergoes magnetic ordering below its Néel temperature (T_N) of 30.8 K. Ultrasound measurements provide insights into the interplay between the material’s magnetic properties and lattice vibrations in response to the applied high magnetic field. A model analysis based on ab initio calculated superexchange interactions predicts a change in the magnetic structure from 3k to 2k at around 50 T. Although this change is not evident in the magnetization curve, we observe a crossover of ultrasound velocity Δv/v using a phase-sensitive pulse-echo technique in pulsed magnetic fields of up to 65 T. We show that at H_z > 50 T, the structure remains antiferromagnetic in the xy plane and becomes ferromagnetic in the z direction. A further transition into the 1k structure is theoretically predicted to take place at a magnetic field of ∼104 T.

Modern laser-plasma accelerators require large-scale particle-in-cell (PIC) simulations to realistically model the three-dimensional relativistic laser-plasma interactions. The large number of possibly unknown laser and target parameters and their uncertainties in experimental setups prevent a simple translation of experimental setups into simulations and thus make meaningful statements about the prevailing dynamics difficult. In order to efficiently reproduce experiments PIC simulations were performed and their deviation from experimental results evaluated. To minimize this deviation, a feedback loop using Bayesian optimization was used to determine the next set of input parameters. We employed this method to self-truncated ionization injection experiments for electron acceleration at HZDR. It resulted in good agreement between simulation and experimental results after only a few simulations. Thus, saving computational resources compared to random parameter sampling. The simulations were performed using the open-source software PIConGPU, a multi-GPGPU PIC code that generates openPMD output at high throughput. It allows the simulation of dispersive lasers and their propagation over hundreds of thousands of time steps through complex targets. The iterative optimization scheme was implemented using Snakemake, a Python-based workflow engine that allows any number of computational jobs to be organized in a directed acyclic graph (DAG) and submitted to different compute clusters. The combination of PIConGPU and Snakemake allowed simulations to be compiled, run, and evaluated in an automated and parallel fashion, and the results used directly in the Bayesian optimization algorithm to obtain new input parameters. The developed workflow interface can be easily applied to any other multi-parameter PIConGPU simulation campaign and is now part of the publicly available PIConGPU codebase.

Magnetic skyrmions are nanometer-sized whirling spin textures in the magnetic material, which have the potential to revolutionize the field of spintronics. This study explores the influence of pressure on the structural properties of the PtMnGa hexagonal system, recognized for hosting Néel skyrmions. By employing pressuredependent synchrotron x-ray powder diffraction (SXRPD), we reveal an isostructural phase transition in this system at approximately 6 GPa. The isostructural transition is evidenced by a deviation of the lattice parameter from the linear dependence, change of trend in the in-plane to out-of-plane lattice parameter ratio, and a description of the pressure-unit cell volume data by two distinct second-order Birch-Muraghan equation of states. The PtMnGa system, however, exhibits reversible structural behavior when pressure is released. Analysis of combined pressure and temperature-dependent SXRPD data provides indirect evidence that the application of moderate pressure (0.8–1.09 GPa) shifts the thermodynamically stable skyrmion regime near to room temperature in the Néel skyrmion-host PtMnGa system. Theoretical calculations on band structure, magnetic moment, and density of states (DOS) under pressure further corroborate the experimental findings, offering a comprehensive understanding of the material’s response to pressure changes. The combination of experimental findings and theoretical calculations demonstrates the potential for engineering materials supporting stable skyrmions even at elevated temperatures and nominal pressures, which can be attained in the materials using chemical substitution or epitaxial thin films by strain controlling of the substrate-film lattice parameter mismatch.

The ytterbium-based delafossite NaYbSe₂ is discussed as a prototype for a spin-orbit entangled, effective spin-1/2 triangular spin lattice with emerging antiferromagnetic correlations and a quantum spin liquid (QSL) ground state. We report on a comprehensive study of the static and dynamic anisotropic magnetism in singlecrystalline samples of NaYbSe₂ using NMR spectroscopy as a local-probe technique. We performed ²³Na and ⁷⁷Se NMR measurements in magnetic fields up to 16 T, applied along the in-plane and out-of-plane crystallographic directions and at temperatures from 300 down to 0.3 K. We could determine the anisotropic hyperfine contributions from the angular dependence of the ²³Na and ⁷⁷Se NMR spectra. In the paramagnetic regime, we probed the temperature dependence of the ²³Na and ⁷⁷Se spectral shift and the hyperfine coupling constants for fields applied along the principal crystal axes. The spin-lattice relaxation-rate data indicate critical spin fluctuations and the absence of long-range magnetic order at low magnetic fields and temperatures down to 0.3 K, evidenced by a monotonic increase of 1/T₁ and associated spectral broadening. This is clear proof of the evolution of a critical QSL ground state with residual fluctuations down to lowest temperatures. At elevated fields, we observe the emergence of long-range order as the temperature-dependent 1/T₁ rate passes through a pronounced maximum at T_N at a given field, followed by a decrease at lower temperatures. Further, we find an inhomogeneous broadening of the ²³Na spectra below T_N, probing the histogram of the local-field distribution in the presence of the field-induced order.

Präsentation der Ergebnisse:

• Fokus: Radiopharmazie stärken
• Ziele: Regulation vereinfachen/standardisieren | Isotopenverfügbarkeit sichern | Diagnostische Breitenversorgung ausbauen | Radiopharmazeutische Kompetenz strukturell verstärken
• Handlungsfelder und Maßnahmen:

Motivated by by the recent discovery of dielectric relaxation by quantum critical magnons in Cs₂Cu₂Mo₃O₁₂, we conduct a detailed analysis of its dielectric response and compare it to that in the isostructural compound Rb₂Cu₂Mo₃O₁₂. Measurements in the vicinity of the field-induced magnon softening show that its description in terms of a three-dimensional Bose-Einstein condensation quantum critical point is unaltered by the presence of dielectric relaxation. We also demonstrate the existence of dielectric relaxation anomalies at 19 K in Rb₂Cu₂Mo₃O₁₂ and discuss the implications for the microscopic origin of dielectric activity in two compounds.

In the last century, targeted theranostic procedures were developed for both diagnostic and therapeutic purposes in nuclear medicine. The term "Theranostics" was first defined by John Funkhouser, CEO of PharmaNetics, which refers to the ability to influence therapy or treatment of a disease state based on diagnosis. The approval of targeted radiopharmaceuticals for certain cancers, such as prostate cancer and neuroendocrine tumors, has led to the consolidation of radionuclide theranostics. The introduction of radium-223 for alpha therapy and gallium-68 PET/CT imaging has been significant milestones in patient care, and the approval of lutetium-177 labeled Lutathera for peptide receptor radionuclide therapy of neuroendocrine tumors is of utmost importance in the field. The approval of Detectnet in 2020, i.e. copper-64 labelled DOTA-TATE, marks a significant milestone for copper-64 ligand PET/CT. This presents opportunities in CopperNostics for theranostics. Other tracers such as PSMA-11, PSMA-1007, and Pylarify have also been approved in recent years, improving diagnosis of prostate cancer patients. Pluvicto, or [177Lu]Lu-PSMA-617 approved in 2022 for radioligand therapy (RLT) of prostate cancer patients, further cements the concept of radionuclide Theranostics. However, the supply of lutetium-177 for beta therapy and actinium-225 for alpha therapy is becoming a pressing issue due to increasing demand.
Radionuclide Theranostics is facing a challenge due to the shortage of Theranostics Centers worldwide, despite the increasing number of clinical trials and opportunities for therapeutic radiopharmaceuticals for various types of cancers. Consolidation of radionuclide theranostics with applied radiopharmaceutical sciences is crucial to improve patient outcomes. Non-invasive molecular imaging by means of PET/CT can complement blood marker diagnostics and radiological procedures well, enabling early diagnosis and aiding surgery. Recent clinical findings have led to new ideas in applied basic research, which lead to the design of the PSMA-11 PET tracer conjugated to a fluorescent dye for PET/CT prestaging and subsequent fluorescence-guided surgery of patients suffering from early stages of prostate cancer. Therapeutic nuclear medicine, or endoradiotherapy, uses ionizing radiation to induce an immune response and provides targeted systemic radioligand therapy options beyond beta therapy. Alpha therapy has shown promise in chemotherapy-naive patients. Research is being conducted to make short-lived alpha emitters more available for clinical use. Terbium-161 and copper-67 are promising beta emitters with properties similar to lutetium-177, and efforts are underway to make copper-67 more clinically available. It is crucial to consider the properties of radionuclides and appropriate binding vectors when selecting therapy options for a particular biological target.
The use of radiometals in radiolabelling requires complexing agents. One such agent is sarcophagine, which has been used to develop highly stable copper complexes that are inert kinetically. These complexes have been conjugated with PSMA inhibitors and octreotate derivatives for clinical development. Our group is working on combining the macropa ligand with the PSMA-617 binding motif for use with actinium-225. We have also established the cyclotron-based production of the PET nuclide lanthanum-133 as a diagnostic match for actinium-225.
In radiopharmaceutical cancer research, identifying the right unmet clinical need is crucial, which requires an understanding of the tumor microenvironment. The development of non-peptidic radiotracers that target fibroblast activation protein alpha (FAPalpha) has shown promising results in the non-invasive visualization and potential therapeutic targeting of a wide variety of cancers. The development of new tracer classes, e.g. for the non-invasive imaging of programmed cell death ligand 1 (PD-L1) shows a high clinical need for molecular imaging of the PD-1/PD-L1 axis to make therapeutic decisions for immune checkpoint therapy. All in all radiopharmacutical sciences offer all facets in further developing radionuclide theranostics in nuclear medicine.

Germanium (Ge) is a good candidate for designing near-infrared photodetectors because of its bandgap (0.66 eV), which exhibits a large absorption coefficient at near-infrared wavelengths. Also, Ge has excellent compatibility with parallel processing common in silicon technology [1,2]. Photodetectors based on Ge material have been fabricated with different structures such as metal-semiconductor-metal (MSM) and p−n junctions. On the other hand, the observation of high responsivity in semiconductor nanowires with a high surface-to-volume ratio has attracted growing interest in using nanowires in photodetectors. So far, significant efforts have been made to fabricate single nanowire-based photodetectors with different materials such as Si, Ge, and GaN to achieve miniaturized devices with high responsivity and short response time [3-5]. Hence, Ge nanowires are excellent candidates to fabricate single nanowire-based near-infrared photodetectors.

In this work, we report on the fabrication and characterization of an axial p−n junction along Ge nanowires. First, through a resist mask created by electron beam lithography (EBL), the p-type top Ge layer of germanium-on-insulator (GeOI) substrates was locally doped with phosphorus ions using ion beam implantation followed by rear-side flash lamp annealing. Then, single Ge nanowire-based photodetectors containing an axial p−n junction were fabricated using EBL and inductively coupled plasma reactive ion etching. The fabricated single Ge nanowire devices demonstrate the rectifying current−voltage characteristic of a p−n diode in dark conditions. Moreover, the photoresponse of the axial p−n junction-based photodetectors was investigated under light illumination with three different wavelengths: 637 nm, 785 nm, and 1550 nm. The experiments indicated that the fabricated photodetectors operate at zero bias and room temperature under ambient conditions. A high responsivity of 3.7×102 AW-1 and a detectivity of 1.9×1013 cmHz1/2W-1 were determined at zero bias under illumination of a 785 nm laser diode. The fabricated photodetectors exhibit a high-frequency response up to 1 MHz under pulsed excitation of the 1550 nm laser at zero bias, which makes them promising candidates for lightwave communication and optical switches [6].

[1] L. Virot, D. Benedikovic, B. Szelag, et al. Opt. Express 25(2017), 19487–19496.
[2] W. Chen, R. Liang, S. Zhang, et al. Nano Res. 13(2020), 127–132.
[3] K. Das, S. Mukherjee, S. Manna, et al. Nanoscale (6)2014,11232–11239.
[4] S. Cuesta, M. Spies, V. Boureau, et al. Nano Lett. 19(2019), 5506−5514.
[5] S. Mukherjee, K. Das, S. Das, and S. K. Ray, ACS Photonics 5(2018), 4170−4178.
[6] C. Xie, B. Nie, L. Zeng, et al. 8 ACS Nano (2014), 4015-4022.

Germanium (Ge) is a promising candidate for designing near-infrared photodetectors because of its bandgap (0.66 eV), which exhibits a large absorption coefficient at near-infrared wavelengths. Also, Ge has excellent compatibility with parallel processing common in silicon technology [1,2]. The observation of high responsivity in semiconductor nanowires (NWs) with a high surface-to-volume ratio has attracted growing interest in using NWs in photodetectors. So far, significant efforts have been made to fabricate single NW-based photodetectors with different materials such as Si, Ge, and GaN to achieve miniaturized devices with high responsivity and short response time [3-5]. Hence, Ge nanowires are excellent candidates to fabricate single nanowire-based near-infrared photodetectors.
In this work, we report on the fabrication and characterization of an axial p−n junction along Ge NWs. First, Ge layers were locally doped with phosphorus ions using ion implantation followed by rear-side flash lamp annealing. Then, single Ge NWs with an axial p--n junction were fabricated via the top-down approach. The fabricated devices demonstrate the rectifying current−voltage characteristic of a p−n diode in dark conditions. Moreover, the response characteristics of the axial p−n junction-based photodetectors were investigated under light illumination of 850 nm laser. The experiments indicated that the fabricated photodetectors could be operated at zero bias under illumination and high responsivity of 1.72 AW-1 was determined at reverse bias. Moreover, the fabricated photodetectors exhibit a high-frequency response with 3dB cut-off frequency of 2.4 GHz, which makes them promising candidates for light-wave communication switches [6].

[1] L. Virot, D. Benedikovic, B. Szelag, et al. Opt. Express, 25, 19487–19496, (2017).
[2] W. Chen, R. Liang, S. Zhang, et al. Nano Res. 13, 127–132.
[3] K. Das, S. Mukherjee, S. Manna, et al. Nanoscale, 6,11232–11239, (2014).
[4] S. Cuesta, M. Spies, V. Boureau, et al. Nano Lett., 19, 5506−5514, (2019).
[5] S. Mukherjee, K. Das, S. Das, and S. K. Ray, ACS Photonics, 5, 4170−4178, (2018).
[6] C. Xie, B. Nie, L. Zeng, et al., ACS Nano, 8, 4015-4022, (2014).

Silicon nanowires have been effectively utilized in innovative electronic devices such as sensors, solar cells, and logic circuits [1]. Field-effect transistors (FETs) based on silicon nanowires are widely used for sensing applications due to their compact nanostructures, which provides excellent control of the electrostatic potential across the nanowire channel and increased sensitivity from high surface-to-volume ratio [2]. One such example is the junctionless nanowire transistor (JNT) [3]. A JNT features a highly doped nanowire channel without p-n junctions, where the gate electrode controls the flow of charge carriers. Typically, JNTs function as either p-type or n-type devices, depending on the doping type. In this study, we optimize the doping concentration of silicon JNT devices to function as ambipolar FETs by using the back gate for control. The use of both top and back gates allows for enhanced polarity tuning in JNT devices, resulting in unipolar behaviour similar to electrostatic doping in reconfigurable field-effect transistors (RFETs). The dual polarity of JNTs is advantageous for sensing applications. Previously, silicon JNTs have demonstrated excellent sensitivity to very low concentrations of the protein streptavidin in the liquid phase [4]. However, they have not yet been used as gas sensors. In this work, we also investigate the sensing properties of ambipolar JNTs in gaseous atmosphere.

Lightly p-doped silicon-on-insulator (SOI) substrates are implanted with phosphorus (n-type) dopant, followed by millisecond range flash lamp annealing (FLA) for dopant activation and defect healing. Nanowires are fabricated using a top-down approach using electron beam lithography with HSQ resist and reactive ion etching. Dielectric deposition is employed using rapid thermal oxidation (RTO) for SiO2 and atomic layer deposition (ALD) for Al2O3. UV lithography and metal evaporation form 50 nm Nickel (Ni) source-drain contacts, while TiN top gate is fabricated using EBL, metal evaporation and lift-off (Figure 1) [5,6]. Electrical characterization of JNTs is performed by back-gating after rapid thermal annealing (RTA) of the contacts leading to ambipolarity in the devices (figure 2a) The devices exhibit an excellent on/off ratio of ~ 108. To investigate the ambipolar nature of JNT, output characteristics are measured showing Schottky barrier based behaviour (Figure 2b). Furthermore, Hall Effect measurements with van-der-Pauw configuration on n-type-doped SOI confirm the carrier concentration (~ 6 x 1017 /cm3) and hall mobility (~ 51 cm2/Vs). Tuning the unipolar behaviour of the JNT is achieved with both the back and the top gate. In this setup, the back gate acts as a program gate, adjusting the device polarity, while the top gate functions as the control gate, regulating the carrier flow. Figure 3 illustrates the band diagram and transfer characteristics of such a device. JNT sensor tests exhibited characteristic shifts in the transfer curve and systematic increase and decrease of p- and n-type current, respectively, under the influence of different gases like NO2 (shown in figure 4) and NH3 confirming the potential suitability of ambipolar JNTs as gas sensors. Additionally these devices can be functionalized to display versatility of gas sensing applications, e.g. for the detection of atmospheric free radicals.

Research in cancer therapies is rapidly advancing and demands the
exploration of innovative approaches to further improve the efficacy of
treatment. Here a multimodal approach for cancer therapy is reported which
combines bioactive targeting, magnetic hyperthermia, and controlled drug
release. For this, a nanoformulation MNP-Chi-Dox-Ab, is bioengineered by
conjugating CA 15-3 antibodies to doxorubicin-loaded functionalized magnetic
nanoparticles (MNPs). Solvothermally synthesized MNPs of uniform
spherical shape and size are functionalized with thermo-pH-responsive
chitosan. The nanoformulation showed higher drug release of ≈65% at pH 5
and 42 °C temperature compared to the release at physiological pH and
temperature. Furthermore, in an alternating magnetic field drug release is
enhanced to 74%. Cytotoxicity studies in MCF-7 breast cancer cells confirm
the active targeting potential of the nanoformulation. For the nanoformulation
without bioactive molecule (anti-CA 15-3) only 18% cancer cell death is noted
whereas with the conjugation of anti-CA 15-3, 43% cell death is recorded.
Flow cytometry studies revealed an increased apoptotic population at
hyperthermic temperature (42 °C) compared to the physiological temperature.
These results suggest that MNP-Chi-Dox-Ab nanoformulation represents a
promising multimodal platform for synergistic breast cancer therapy by
combining active targeting, controlled drug release, and hyperthermia.

Yttrium iron garnet (YIG) is a prototypical material in spintronics due to its exceptional magnetic properties. To exploit these properties, high quality thin films need to be manufactured. Deposition techniques like sputter deposition or pulsed laser deposition at ambient temperature produce amorphous films, which need a postannealing step to induce crystallization. However, not much is known about the exact dynamics of the formation of crystalline YIG out of the amorphous phase. Here, we conduct extensive time and temperature series to study the crystallization behavior of YIG on various substrates and extract the crystallization velocities as well as the activation energies needed to promote crystallization. We find that the type of crystallization as well as the crystallization velocity depend on the lattice mismatch to the substrate. We compare the crystallization parameters found in literature with our results and find excellent agreement with our model. Our results allow us to determine the time needed for the formation of a fully crystalline film of arbitrary thickness for any temperature.

a general introduction about doping semiconductors by ion implantation

CrSBr is rapidly gaining attention as a prominent candidate within the family of van der Waals magnetic semiconductors [1-3]. Below the Néel temperature of 132 K, the material is supposed to exhibit prototypical A-type antiferromagnetic order, as predicted by mean-field theory years ago. Recently, however, several groups reported the observation of unusual magnetic signatures indicating a second magnetic phase transition at temperatures around 40 K. In this contribution, we are going to discuss: (1) whether these signatures reflect an intrinsic property of the material or are caused by extrinsic influences; (2) if not the former, whether one can tailor the magnetic properties after growth.

We start with the single crystals grown by the group of Z. Sofer. Surprisingly, by extensive magnetization measurement utilizing SQUID magnetometry, we cannot detect the second, 40K magnetic phase transition [4]. Our magnetometry measurements confirm the theoretically predicted magnetic phase diagram and thus demonstrate that the 40K phase observed by other groups is not an intrinsic element of the magnetic phase diagram of CrSBr. The pure antiferromagnetic CrSBr crystals and flakes were then subjected to non-magnetic ion irradiation, which produces structural defects in the crystals in a controllable way. We observe a transition from antiferromagnetic to ferromagnetic behavior in CrSBr [5]. Already at moderate fluences, ion irradiation induces a remanent magnetization with hysteresis adapting to the easy-axis anisotropy of the pristine magnetic order up to a critical temperature of 110 K. Structure analysis of the irradiated crystals in conjunction with density functional theory calculations suggest that the displacement of constituent atoms due to collisions with ions and the formation of interstitials favors ferromagnetic order between the layers. Increasing irradiation fluences gradually lowers the Curie temperature, reflecting the impact of crystalline degradation. This suggests that by finely tuning the irradiation parameters and employing precise lithography techniques, it's possible to selectively modulate induced ferromagnetism in CrSBr in terms of magnetization strength, critical temperature, and spatial distribution. However, in our opinion, the origin and nature of the second phase with a transition temperature around 40 K in pristine CrSBr samples by various studies still remains elusive.

[1] N. P. Wilson, K. Lee, J. Cenker et al., Nat. Mater. 20 (12), 1657 (2021).
[2] F. Dirnberger, J.M. Quan, R. Bushati et al., Nature 620, 533 (2023).
[3] K. Lin, X. Sun, F. Dirnberger et al., ACS Nano 18, 2898–2905 (2024).
[4] F. Long, K. Mosina, et al., Appl. Phys. Lett. 123, 222401 (2023).
[5] F. Long, M.Ghorbani-Asl, K. Mosina, et al., Nano Lett. 23, 8468–8473 (2023).

Tellurium is one of the deep-level impurities in Si, leading to states of 200-400 meV below the conduction band. Non-equilibrium methods allow for doping deep-level impurities in Si well above the solubility limit, re-ferred as hyperdoping, that can result in exotic properties, such as extrinsic photo-absorption well below the Si bandgap [1]. The hyperdoping is realized by ion implantation and pulsed laser melting. We will present the re-sulting optical and electrical properties as well as perspective applications for infrared photodetectors.
With increasing the Te concentration, the samples undergo an insulator to metal transition [2]. The electron concentration obtained in Te-hyperdoped Si is approaching 1021 cm-3 and does not show saturation [3]. It is even higher than that of P or As doped Si, and mid-infrared localized surface plasmon resonances (LSPR) are also observed [4]. Using Te-doped Si, we demonstrate the room-temperature operation of infrared photodetectors with both vertical and planar device geometries [5,6]. The key parameters, such as the detectivity, the bandwidth and the rise/fall time, show competitiveness with commercial products. To understand the micro-scopic picture, we have performed Rutherford backscattering/channeling angular scans and hard x-ray spectros-copies [4, 7]. The Te-dimer complex sitting on adjacent Si lattice sites is the most preferred configuration at high doping concentration. Those substitutional Te-dimers are effective donors, leading to the insulator-to-metal tran-sition, the non-saturating carrier concentration as well as the sub-band photoresponse. Our results are promising for the integration of active and passive photonic elements on a single Si chip, leveraging the advantages of pla-nar CMOS technology.
This work was financially supported by the German Research Foundation (WA4804/1-1, 445049905).

References
[1] J. M. Warrender, Appl. Phys. Rev. 3, 031104 (2016).
[2] M. Wang, Y. Berencén, E. García-Hemme, S. Prucnal, et al., Phys. Rev. Appl. 10, 024054 (2018).
[3] M. Wang, A. Debernardi, Y. Berencén, R. Heller, et al., Phys. Rev. Appl. 11, 054039 (2019).
[4] M. Wang, Y. Yu, S. Prucnal, Y. Berencen, et al., Nanoscale 14, 2826-2836 (2022).
[5] M. Wang, E. García-Hemme, Y. Berencén, R. Hübner, et al., Adv. Opt. Mater. 9, 2001546 (2020).
[6] M. S. Shaikh, S. Wen, M. Catuneanu, M. Wang, et al., Optics Express 31, 26451-26462 (2023).
[7] M. Hoesch, O. Fedchenko, M. Wang, C. Schlueter, et al., Appl. Phys. Lett. 122, 252108 (2023).

CrSBr is rapidly gaining attention as a prominent candidate within the family of van der Waals magnetic semiconductors [1-3]. Below the Néel temperature of 132 K, the material is supposed to exhibit prototypical A-type antiferromagnetic order, as predicted by mean-field theory years ago. Recently, however, several groups reported the observation of unusual magnetic signatures indicating a second magnetic phase transition at tem-peratures around 40 K. In this contribution, we are going to discuss: (1) whether these signatures reflect an in-trinsic property of the material or are caused by extrinsic influences; (2) if not the former, whether one can tailor the magnetic properties after growth.

We start with CrSBr single crystals synthesized by chemical vapor transport. Surprisingly, by extensive magnetization measurement utilizing SQUID magnetometry, we cannot detect the second, 40 K magnetic phase transition [4]. Our magnetometry measurements confirm the theoretically predicted magnetic phase diagram and thus demonstrate that the 40 K phase observed by other groups is not an intrinsic element of the magnetic phase diagram of CrSBr. The pure antiferromagnetic CrSBr crystals and flakes were then subjected to non-magnetic ion irradiation, which produces structural defects in the crystals in a controllable way. We observe a transition from antiferromagnetic to ferromagnetic behavior in CrSBr (see Fig. 1 below) [5]. Already at moderate fluences, ion irradiation induces a remanent magnetization with hysteresis adapting to the easy-axis anisotropy of the pris-tine magnetic order up to a critical temperature of 110 K. Structure analysis of the irradiated crystals in conjunc-tion with density functional theory calculations suggest that the displacement of constituent atoms due to colli-sions with ions and the formation of interstitials favor ferromagnetic order between the layers. Increasing irradi-ation fluences gradually lowers the Curie temperature, reflecting the impact of crystalline degradation. This suggests that by finely tuning the irradiation parameters and employing precise lithography techniques, it is pos-sible to selectively modulate induced ferromagnetism in CrSBr in terms of magnetization strength, critical tem-perature, and spatial distribution. However, in our opinion, the origin and nature of the second phase with a tran-sition temperature around 40 K reported in pristine CrSBr samples by various studies still remains elusive.
References
[1] N. P. Wilson, K. Lee, J. Cenker et al., Nat. Mater. 20, 1657 (2021).
[2] F. Dirnberger, J.M. Quan, R. Bushati et al., Nature 620, 533 (2023).
[3] K. Lin, X. Sun, F. Dirnberger et al., ACS Nano 18, 2898–2905 (2024).
[4] F. Long, K. Mosina, et al., Appl. Phys. Lett. 123, 222401 (2023).
[5] F. Long, M.Ghorbani-Asl, K. Mosina, et al., Nano Lett. 23, 8468–8473 (2023).

In the present study, we use optical pump-probe spectroscopy in reflection geometry to unravel the dynamics of charge carriers in the magnetic kagome metals GdMn6Sn6 and TbMn6Sn6. The measured pump-probe traces reveal two exponential decay processes and a slow thermal relaxation, similarly to what has been observed in other kagome metals. The exponential decays occur on quite different time scales, and we ascribe them to the dynamics of different types of charge carriers present in the compounds. Additionally, a damped oscillation feature appears during the first 15-20 picoseconds. It can be explained in the context of acoustic strain waves, generated due to a thermal expansion at the sample’s surface that is induced by the pump pulse. We also present temperature and pump fluence dependence for both compounds that helps to understand better the relaxation mechanisms.

Layered magnetic materials are becoming a major platform for future spin-based applications. Particularly the air-stable van der Waals compound CrSBr is emerging as a new star in this family [1]. Pristine CrSBr is a semiconductor with a direct bandgap of around 1.35 eV. Bulk CrSBr is antiferromagnetic below its Néel temperature of 132 K [1, 2]. Due to its direct-band gap and magnetic order, pronounced correlations between magnons, photons, electrons, and phonons are revealed in CrSBr. Using low-temperature photoluminescence spectroscopy, we have measured the effective coupling between excitons and phonons in nanometer-thick CrSBr [3]. Upon irradiation by high-energy, non-magnetic ions, CrSBr undergoes a transition from antiferromagnetic to ferromagnetic [4], which suggests the important role of intrinsic defects in altering the magnetic coupling. Therefore, CrSBr presents an excellent avenue to exploit optoelectronic and spintronic applications based on 2D materials.

[1] F. Dirnberger, et al., Magneto-optics in a van der Waals magnet tuned by self-hybridized polaritons. Nature 620, 533–5377 (2023).
[2] F. Long, et al., Intrinsic magnetic properties of the layered antiferromagnet CrSBr, Appl. Phys. Lett. 123, 222401 (2023).
[3] K. Lin, et al., Strong Exciton-Phonon Coupling as a Fingerprint of Magnetic Ordering in van der Waals Layered CrSBr, ACS Nano 18, 2898-2905 (2024).
[4] F. Long, et al, Ferromagnetic interlayer coupling in CrSBr crystals irradiated by ions, Nano Lett. 23, 8468–8473 (2023).

CrSBr is rapidly gaining attention as a prominent candidate within the family of van der Waals magnetic semiconductors [1-3]. Below the Néel temperature of 132 K, the material is supposed to exhibit prototypical A-type antiferromagnetic order, as predicted by mean-field theory years ago. Recently, however, several groups reported the observation of unusual magnetic signatures indicating a second magnetic phase transition at tem-peratures around 40 K. In this contribution, we are going to discuss: (1) whether these signatures reflect an in-trinsic property of the material or are caused by extrinsic influences; (2) if not the former, whether one can tailor the magnetic properties after growth.

We start with CrSBr single crystals synthesized by chemical vapor transport. Surprisingly, by extensive magnetization measurement utilizing SQUID magnetometry, we cannot detect the second, 40 K magnetic phase transition [4]. Our magnetometry measurements confirm the theoretically predicted magnetic phase diagram and thus demonstrate that the 40 K phase observed by other groups is not an intrinsic element of the magnetic phase diagram of CrSBr. The pure antiferromagnetic CrSBr crystals and flakes were then subjected to non-magnetic ion irradiation, which produces structural defects in the crystals in a controllable way. We observe a transition from antiferromagnetic to ferromagnetic behavior in CrSBr [5, 6]. Already at moderate flu-ences, ion irradiation induces a remanent magnetization with hysteresis adapting to the easy-axis anisotropy of the pristine magnetic order up to a critical temperature of 110 K. Structure analysis of the irradiated crystals in conjunction with density functional theory calculations suggest that the displacement of constituent atoms due to collisions with ions and the formation of interstitials favor ferromagnetic order between the layers. Increasing irradiation fluences gradually lowers the Curie temperature, reflecting the impact of crystalline degradation. This suggests that by finely tuning the irradiation parameters and employing precise lithography techniques, it is pos-sible to selectively modulate induced ferromagnetism in CrSBr in terms of magnetization strength, critical tem-perature, and spatial distribution. However, in our opinion, the origin and nature of the second phase with a tran-sition temperature around 40 K reported in pristine CrSBr samples by various studies still remains elusive.
References
[1] N. P. Wilson, K. Lee, J. Cenker et al., Nat. Mater. 20, 1657 (2021).
[2] F. Dirnberger, J.M. Quan, R. Bushati et al., Nature 620, 533 (2023).
[3] K. Lin, X. Sun, F. Dirnberger et al., ACS Nano 18, 2898–2905 (2024).
[4] F. Long, K. Mosina, et al., Appl. Phys. Lett. 123, 222401 (2023).
[5] F. Long, M.Ghorbani-Asl, K. Mosina, et al., Nano Lett. 23, 8468–8473 (2023).
[6] F. Long, et al. Adv. Phys. Res., https://doi.org/10.1002/apxr.202400053 (2024)

Tellurium is one of the deep-level impurities in Si, leading to states of 200-400 meV below the conduction band. Non-equilibrium methods allow for doping deep-level impurities in Si well above the solubility limit, re-ferred as hyperdoping, that can result in exotic properties, such as extrinsic photo-absorption well below the Si bandgap [1]. The hyperdoping is realized by ion implantation and pulsed laser melting. We will present the re-sulting optical and electrical properties as well as perspective applications for infrared photodetectors.
With increasing the Te concentration, the samples undergo an insulator to metal transition [2]. The electron concentration obtained in Te-hyperdoped Si is approaching 1021 cm-3 and does not show saturation [3]. It is even higher than that of P or As doped Si, and mid-infrared localized surface plasmon resonances (LSPR) are also observed [4]. Using Te-doped Si, we demonstrate the room-temperature operation of infrared photodetectors with both vertical and planar device geometries [5,6]. The key parameters, such as the detectivity, the bandwidth and the rise/fall time, show competitiveness with commercial products. To understand the micro-scopic picture, we have performed Rutherford backscattering/channeling angular scans and hard x-ray spectros-copies [4, 7]. The Te-dimer complex sitting on adjacent Si lattice sites is the most preferred configuration at high doping concentration. Those substitutional Te-dimers are effective donors, leading to the insulator-to-metal tran-sition, the non-saturating carrier concentration as well as the sub-band photoresponse. Our results are promising for the integration of active and passive photonic elements on a single Si chip, leveraging the advantages of pla-nar CMOS technology.
This work was financially supported by the German Research Foundation (WA4804/1-1, 445049905).

References
[1] J. M. Warrender, Appl. Phys. Rev. 3, 031104 (2016).
[2] M. Wang, Y. Berencén, E. García-Hemme, S. Prucnal, et al., Phys. Rev. Appl. 10, 024054 (2018).
[3] M. Wang, A. Debernardi, Y. Berencén, R. Heller, et al., Phys. Rev. Appl. 11, 054039 (2019).
[4] M. Wang, Y. Yu, S. Prucnal, Y. Berencen, et al., Nanoscale 14, 2826-2836 (2022).
[5] M. Wang, E. García-Hemme, Y. Berencén, R. Hübner, et al., Adv. Opt. Mater. 9, 2001546 (2020).
[6] M. S. Shaikh, S. Wen, M. Catuneanu, M. Wang, et al., Optics Express 31, 26451-26462 (2023).
[7] M. Hoesch, O. Fedchenko, M. Wang, C. Schlueter, et al., Appl. Phys. Lett. 122, 252108 (2023).

The astrophysical site of the r-process remains an open question in nuclear astrophysics. Pure
r-process radionuclides present in the solar system today that cannot originate from primordial
events due to their comparably short half-lives (e.g. 244Pu t1/2 ∼ 81 Myr) act as fingerprints
of recent r-process events in the solar neighbourhood. The discovery of live 244Pu via single-atom
counting with accelerator mass spectrometry (AMS) in deep-sea ferromanganese crusts has recently
confirmed such r-process activity. We now aim to extend our search for interstellar 244Pu and also
supernova-produced 60Fe (t1/2 = 2.6 Myr) to a different archive, lunar soil, which allows to map out
the interstellar influx up to hundreds of millions of years ago. The proper characterization of the
soil’s exposure history and composition is important here. Alongside various analytical methods we
measure cosmogenic radionuclides with half-lives in the order of million years via AMS. 10Be, 26Al,
and 41Ca are measured at HZDR and 53Mn at ANU. This contribution presents initial findings from
the measurements of these radionuclides in a set of lunar regolith samples, discussing their role in
determining the sample’s exposure history. Additionally, we will provide insights into preliminary
60Fe data and updates on the quest for interstellar 244Pu.

Despite being responsible for the nucleosynthesis of half of all heavier nuclides in the galaxy, the site of the r-process is still an open question in nuclear astrophysics. The detection of the pure r-process nuclide 244Pu, live, in deep-sea ferromanganese crusts already demonstrated ongoing r-process events. A complementary archive for 244Pu is lunar soil - lacking in time resolution, but offering a proposed exposure time to interstellar dust deposition ranging from a few up to hundreds of million years. In this project we aim for the detection of interstellar 244Pu and 60Fe in lunar soil. Important will be the proper characterization of lunar soil for exposure history and composition. Among various additional analytical methods, we measure cosmogenic 10Be, 26Al, 41Ca and 53Mn.

This talk presents first results of the cosmogenic radionuclides 10Be, 26Al and 53Mn measured in a set of lunar samples and discusses their use in characterizing the exposure history of the samples.

Graphite based conductors are promising low cost and light-weight alternatives to copper but current challenges
are among others the improvement of the conductivity of graphite films (GF). Therefore, in this work the in-
fluence of copper(II) chloride and nickel(II) chloride on the graphitization of graphene oxide and the electrical
conductivity of the resulting GF was studied. The electrical conductivity was measured at different scales by
contactless eddy current method and four point probe scanning tunneling microscopy transport measurements.
The macroscopic and nanoscopic transport measurements were complemented by network-based simulations,
which allowed us to estimate the microscopic material properties of the GF with and without additives.
Annealing temperatures between 1600 ◦C to 2850 ◦C and varying metal chloride concentrations revealed an
optimum at 2850 ◦C and a concentration of 8.8 mmol/l NiCl2 in the aqueous dispersion. These GFs displayed an
electrical conductivity of 609 kS/m, around 30 % higher than the GFs without any metal chloride addition. The
graphitization morphology was analyzed by x-ray diffraction and scanning electron microscopy respectively. The
precipitation effect of carbon from Ni supports the growth of graphitic structures, whereas the catalytic activity
of Cu known from chemical vapor deposition does not promote graphitic structures. Rather, the annealing
temperature is the crucial parameter for achieving highly conductive films. Furthermore, the influence of applied
pressure during compression was studied. High pressures of at least 250 MPa are needed to obtain compact GFs
with an electrical conductivity 3 times larger than before compression