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Magnetic nanoparticles (MNPs) provide new opportunities for enzyme-free biosensing of nucleic acid biomarkers and magnetic actuation by patterning on DNA origami, yet how the DNA grafting density affects their dynamics and accessibility remains poorly understood. Here, we performed surface functionalization of MNPs with single-stranded DNA (ssDNA) via click chemistry with a tunable grafting density, which enables the encapsulation of single MNPs inside a functional polymeric layer. We used several complementary methods to show that particle translational and rotational dynamics exhibit a sigmoidal dependence on the ssDNA grafting density. At low densities, ssDNA strands adopt a coiled conformation that results in minor alterations to particle dynamics, while at high densities, they organize into polymer brushes that collectively influence particle dynamics. Intermediate ssDNA densities, where the dynamics are most sensitive to changes, show the highest magnetic biosensing sensitivity for the detection of target nucleic acids. Finally, we demonstrate that MNPs with high ssDNA grafting densities are required to efficiently couple to DNA origami. Our results establish ssDNA grafting density as a critical parameter for the functionalization of MNPs for magnetic biosensing and functionalization of DNA nanostructures.

Climate services aim to provide climate information to aid decision-making. However, in practice their effectiveness is hampered by factors such as incompatibility with decisions, neglect of user’s context, and limited understanding of the information provided. Enhancing climate services’ user orientation necessitates capacity building to bolster the knowledge and collaborative skills among actors in the climate production chain. This study introduces a learning framework for capacity building in climate services that was developed using iterative systematic cycles for educational design research. The framework contains seven steps, along with relevant guiding questions, derived from the evaluation of case studies and the trainer’s experiences in 21 training events conducted under the User Learning Services (ULS) of the Copernicus Climate Change (C3S). Overall, this study offers a learning framework that can guide the content and design of capacity building in future climate information services. This contributes significantly to the ongoing effort to enhance and understand the impact of climate services on decision making.

Purpose/Background: Prostate-specific membrane antigen (PSMA) radioligand therapy has emerged as a promising treatment for advanced prostate cancer. Prior to the administration of radioligand therapy, precise assessment of PSMA expression and tumor localization is essential. Technetium-99m ( 99mTc) imaging is cost-effective and widely available. This study presents the first experiences of using [99mTc]TcO-ABX474 in patients with advanced prostate cancer, with the aim of providing valuable insights into its clinical utility and feasibility. Methods: Patients with advanced prostate cancer, who were scheduled for PSMA radioligand therapy, were referred to PSMA-Imaging. All patients underwent whole-body 99m Tc-PSMA ligand single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. Qualitative and semi-quantitative assessments of [99mTc]TcO-ABX474 uptake were performed, and the results were compared with 18F-PSMA-1007 PET/CT scans. Furthermore, ratios of at least 5 tumor lesions and salivary glands, spleen and kidneys to blood pool, muscle and liver were calculated for each patient. PSMA tumor uptake for evaluation of radioligand therapy was assessed using PROMISE V2 criteria. Results: In total 10 patients received a [99mTc]TcO-ABX474 SPECT/CT imaging prior to PSMA targeted radioligand therapy. Dynamic imaging at 3 time points were performed in 4 patients. In 6 patients image acquisition was performed starting 60 minutes after injection. There was a washout of activity within normal tissue (blood pool, liver and salivary glands) from 10 to 60 and 180 Minutes after injection. The ratios of tumor lesions and the kidneys to normal tissue uptake increased over the same period, whereas the ratios of the slivary glands and spleen decreased. According to PROMISE V2 85, 10 and 5% of the measured lesions showed a PSMA Score of 3, 2 and 1, therefore 95% were eligible for PSMA radioligand therapy. Conclusion: This study represents the first clinical experien

Semi-arid farming systems in India are facing an increasing frequency of climate change-induced extreme weather events. With the aim of improving their climate resilience, we retrospectively assess climate resilience in two case studies in Maharashtra, India. We considered a 15-year period and multiple interventions in both. The systems showed improved climate resilience when agricultural productivity-enhancing interventions were combined with those related to water management, soil health, livelihood diversification, and food and nutrition security. Further, we recommend embedding a monitoring, evaluation and learning component within the design of all interventions to help with adaptive decision-making.

Field-effect transistors are capable of detecting electromagnetic radiation from less than 100 GHz up to very high frequencies reaching well into the infrared spectral range. Here, we report on frequency coverage of up to 30THz, thus reaching the technologically important frequency regime of CO2 lasers, using GaAs/AlGaAs high-electron-mobility transistors. A detailed study of the speed and polarization dependence of the responsivity allows us to identify a cross over of the dominant detection mechanism from ultrafast non-quasistatic rectification at low Terahertz frequencies to slow rectification based on a combination of the Seebeck and bolometric effects at high frequencies, occurring at about the boundary between the Terahertz frequency range and the infrared at 10THz.

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Objectives: Positron Emission Tomography (PET) is a non-invasive molecular imaging technique, which continues to find increasing application and further development for diagnosis of a broad range of disorders and dysfunctions. Since their involvement in pathophysiological processes that lead to cancer, for example, monocarboxylate transporters (MCTs) are of interest for the development of new radioligands for PET, such as [18F]FACH [1, 2] and its deuterated isotopologue [18F]FACH-d6. Both candidates have been already examined previously in preclinical PET studies in healthy mice and piglets, also with regard to their biodistribution and metabolic fate [3]. However, the general finding that in piglets both radioligands showed significant lower metabolic stability than in mice left some important unanswered questions, especially those relevant to potential clinical application. Therefore, this study aimed to further explore the metabolic properties of both radioligands by means of in vitro examinations, which besides discovering species dependency in some respects, might allow predictions for their metabolic stability in humans. Methods: [18F]FACH, [18F]FACH-d6 as well as their corresponding non-radioactive references were incubated with murine (mouse MLM and rat RLM) and human (HLM) liver microsomes and with pig and human S9 fractions, in presence of NADPH, but also other co-factors (e.g. UDPGA). After collection of samples at defined time points, subsequently prepared samples were investigated by radio-HPLC, UV-HPLC or LC-MS/MS. Obtained data allowed calculation of basic metabolic parameters and identification of metabolites formed in vitro. Results: [18F]FACH, incubated in presence of NADPH at 37°C for up to 60 min, showed highest stability in MLM (t1/2= 29913 min), whereas lowest stability was found in RLM (t1/2= 201 min). A moderate stability was found for both HLM (t1/2= 948 min) and pig S9 fraction (t1/2= 522 min). However, in a recent head-to-head comparis

The development of cannabinoid receptor type 2 (CB2R) radioligands for positron emission tomography (PET) imaging was intensively explored. To overcome the low metabolic stability and simultaneously increase the binding affinity of known CB2R radioligands, a carborane moiety was used as a bioisostere. Here we report the synthesis and characterization of carboranebased 1,8-naphthyridinones and thiazoles as novel CB2R ligands. All tested compounds showed low nanomolar CB2R affinity, with (Z)-N-[3-(4-fluorobutyl)-4,5-dimethylthiazole-2(3H)-ylidene]-(1,7-dicarba-closo-dodecaboranyl)-carboxamide (LUZ5) exhibiting the highest affinity (0.8 nM). Compound [18F]LUZ5-d8 was obtained with an automated radiosynthesizer in high radiochemical yield and purity. In vivo evaluation revealed the improved metabolic stability of [18F]LUZ5-d8 compared to that of [18F]JHU94620. PET experiments in rats revealed high uptake in spleen and low uptake in brain. Thus, the introduction of a carborane moiety is an appropriate tool for modifying literature-known CB2R ligands and gaining access to a new class of high-affinity CB2R ligands, while the in vivo pharmacology still needs to be addressed.

Semi-arid regions in India are characterized by poor natural resources, smallholder farmers and an increasing frequency of extreme weather events. The vulnerability of semi-arid farming systems to climate change and the state of agrarian distress in India underscore the need to assess their climate resilience. We observe weaknesses in existing frameworks for assessing resilience, such as a bias toward assessing a system’s status quo and the lack of clarity between assessing resilience to specific stresses and a system’s more general resilience attributes. The need for context-specific tools and frameworks has also been highlighted in literature on climate resilience. To address these gaps, we develop a context-specific framework to assess the climate resilience of semi-arid farming systems in India and evaluate its relevance. The Climate Resilience In Semi-arid India (CRISI) framework, with customized system functions, indicators, resilience capacities and attributes, has been developed by combining insights from existing literature, from the local knowledge and expertise of the research team and from a case study application. Considering emerging climate change risks, the case study further shows us there is an urgent need to build the resilience capacities of adaptability and transformability of the farming system. CRISI’s inclusiveness in identifying stakeholder needs, its systemic understanding of resilience and its provision of information for decision-making make it useful for the farming community, practitioners and policymakers in assessing and building climate resilience.

Objectives: Epigenetic mechanisms like methylation and acetylation of histones regulate the gene expression on the chromatin level. Thus, the degree of acetylation of lysine residues on histones influences the accessibility of DNA and furthermore the gene expression. Histone deacetylases (HDACs) are overexpressed in various tumour diseases, resulting in the interest in HDAC inhibitors (HDACi) for cancer therapy. The aim of this work is the development of a novel ¹⁸F-labelled HDAC1-selective inhibitor with an ortho-aminoanilide zinc-binding group (ZBG) to visualize this enzyme in brain tumours by positron emission tomography (PET). Methods: Based on the selective HDAC1-3 inhibitors tacedinaline and entinostat, a series of fluorine-containing derivatives was synthesized and the IC₅₀ values were determined by an in-house biochemical enzyme assay. Out of several ligands with high inhibitory potency and selectivity for HDAC1, N-(2-amino-5-(thiophen-3-yl)phenyl)-4-((2-fluoropropanamido)methyl)benzamide (BA3, Figure 1A) was selected for radiofluorination. The two-step one-pot radiosynthesis of [¹⁸F]BA3 was performed by a nucleophilic aliphatic substitution reaction of the protected 2-bromopropionyl precursor 2 and subsequent deprotection. The process was successfully transferred to a TRACERlab FX2 N radiosynthesizer (Figure 1B). For the characterization of BA3, the in vitro stability in mouse and human liver microsomes and the cell toxicity in glioblastoma cell lines (U251-MG, F98) were assessed. In parallel, the in vivo metabolism of [¹⁸F]BA3 was investigated (mouse plasma and brain samples, 30 min p.i.) as well as PET studies in mice were carried out. Results: BA3, containing a PAMBA linker (para-aminomethylbenzoic acid), shows a high inhibitory activity against HDAC1 and high selectivity towards HDAC3 and HDAC6 (see Table 1). The cell viability of U251-MG and F98 cells after incubation with 50 µM BA3 for 72h was only 64% and 36%, respectively. The automated radiosynthes

Objectives: During the last 15 years several PSMA PET ligands for prostate cancer imaging have been developed resulting in the recent approvals of 68Ga-PSMA-11, 18F-PSMA-1007 and 18F-DCFPyL.[1,2] However, 99mTc remains a popular radiometal for SPECT imaging due to its longer half-life and availability from 99Mo/99mTc generators especially in outpatient imaging centers. Due to the widespread availability of SPECT cameras PSMA SPECT ligands have the potential to substantially extend the availability of PSMA-based imaging, but currently no PSMA SPECT ligand is approved. MIP-1404, PSMA-I&S and HYNIC-iPSMA are rare examples of PSMA SPECT tracers in clinical development. Accordingly, the aim of our study was to develop a PSMA ligand for 99mTc SPECT imaging of prostate cancer based on an N2S2 chelator, which enables reliable radiolabeling to form stable 99mTc complexes.[3] Methods: A number of compounds, which contain the PSMA binding motif Glu-urea-Lys, a varying linker and a bisaminothiol (BAT)-type N2S2 chelator, were synthesized. Selected compounds were radiolabeled with 99mTc, followed by assessment of in vitro stability of the formed complexes via radio-HPLC. The specific binding affinity towards PSMA and the internalization of the radioligands were examined in LNCaP cells, supplemented by autoradiographic studies. Tissue distribution and tumor accumulation were evaluated in LNCaP-tumor bearing mice via quantitative SPECT/CT imaging, benchmarked with [99mTc]Tc-PSMA-I&S[4] and [68Ga]Ga-PSMA-11. Results: Among the six 99mTc radioligands synthesized and examined, [99mTc]TcO-ABX474 showed most favorable properties. Radiolabeling of ABX474 (50 µg) was achieved starting from [99mTc]NaTcO4 (0.2-2 GBq) in saline (1.4 mL) using SnCl2 (1 µg in 0.01 M HCl) as reducing agent, in presence of calcium-D-heptagluconate (10 µg) and D-mannitol (1 mg) at pH 5-6. Incubation at r.t. for 20 min followed by heating at 80°C for 20 min afforded the product-containing solution with a radioche