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Abstract: Introduction: Jumping/falling from high structures is a common form of suicide. Mostly, these suicides occur on artificial structures. However, there are also natural formations which are used for committing suicide. It was the aim of this study to investigate the use of mountains and other natural rock formations for the means of suicide. Methods: The files of the investigations of mountain deaths from 2002 to 2016 commissioned by the public prosecutor’s office of the canton of Bern, Switzerland, or carried out by the Institute of Forensic Medicine in Bern itself, were evaluated retrospectively regarding the existence of suicides within alpine environment. Results: 20 cases were analyzed concerning various parameters such as method, age, gender and mental diagnoses. A mountain suicide occurred with a ratio of 1 to 69. The gender difference was more pronounced with 80% being male victims. Discussion: Suicide is rare in the mountains. Jumping/falling from heights was the most common manner of suicide. Most of those affected were male and a significant proportion had a psychiatric diagnosis.

Abstract Current pharmacological agents for depression have limited efficacy in achieving remission. Developing and validating new medications is challenging due to limited biological targets. This study aimed to link electrophysiological data and symptom improvement to better understand mechanisms underlying treatment response. Longitudinal changes in neural oscillations were assessed using resting-state electroencephalography (EEG) data from two Canadian Biomarker Integration Network in Depression studies, involving pharmacological and cognitive behavioral therapy (CBT) trials. Patients in the pharmacological trial received eight weeks of escitalopram, with treatment response defined as ≥ 50% decrease in Montgomery–Åsberg Depression Rating Scale (MADRS). Early (baseline to week 2) and late (baseline to week 8) changes in neural oscillation were investigated using relative power spectral measures. An association was found between an initial increase in theta and symptom improvement after 2 weeks. Additionally, late increases in delta and theta, along with a decrease in alpha, were linked to a reduction in MADRS after 8 weeks. These late changes were specifically observed in responders. To assess specificity, we extended our analysis to the independent CBT cohort. Responders exhibited an increase in delta and a decrease in alpha after 2 weeks. Furthermore, a late (baseline to week 16) decrease in alpha was associated with symptom improvement following CBT. Results suggest a common late decrease in alpha across both treatments, while modulatory effects in theta may be specific to escitalopram treatment. This study offers insights into electrophysiological markers indicating a favorable response to antidepressants, enhancing our comprehension of treatment response mechanisms in depression.

Visual search is faster when a fixed target location is paired with a spatially invariant (vs. randomly changing) distractor configuration, thus indicating that repeated contexts are learned, thereby guiding attention to the target (contextual cueing [CC]). Evidence for memory-guided attention has also been revealed with electrophysiological (electroencephalographic [EEG]) recordings, starting with an enhanced early posterior negativity (N1pc), which signals a preattentive bias toward the target, and, subsequently, attentional and postselective components, such as the posterior contralateral negativity (PCN) and contralateral delay activity (CDA), respectively. Despite effective learning, relearning of previously acquired contexts is inflexible: The CC benefits disappear when the target is relocated to a new position within an otherwise invariant context and corresponding EEG correlates are diminished. The present study tested whether global statistical properties that induce predictions going beyond the immediate invariant layout can facilitate contextual relearning. Global statistical regularities were implemented by presenting repeated and nonrepeated displays in separate streaks (mini blocks) of trials in the relocation phase, with individual displays being presented in a fixed and thus predictable order. Our results revealed a significant CC effect (and an associated modulation of the N1pc, PCN, and CDA components) during initial learning. Critically, the global statistical regularities in the relocation phase also resulted in a reliable CC effect, thus revealing effective relearning with predictive streaks. Moreover, this relearning was reflected in an enhanced PCN amplitude for repeated relative to nonrepeated contexts. Temporally ordered contexts may thus adapt memory-based guidance of attention, particularly the allocation of covert attention in the visual display.

Abstract The peptide hormone glucagon is a fundamental metabolic regulator that is also being considered as a pharmacotherapeutic option for obesity and type 2 diabetes. Despite this, we know very little regarding how glucagon exerts its pleiotropic metabolic actions. Given that the liver is a chief site of action, we performed in situ time-resolved liver phosphoproteomics to reveal glucagon signaling nodes. Through pathway analysis of the thousands of phosphopeptides identified, we reveal “membrane trafficking” as a dominant signature with the vesicle trafficking protein SEC22 Homolog B (SEC22B) S137 phosphorylation being a top hit. Hepatocyte-specific loss- and gain-of-function experiments reveal that SEC22B was a key regulator of glycogen, lipid and amino acid metabolism, with SEC22B-S137 phosphorylation playing a major role in glucagon action. Mechanistically, we identify several protein binding partners of SEC22B affected by glucagon, some of which were differentially enriched with SEC22B-S137 phosphorylation. In summary, we demonstrate that phosphorylation of SEC22B is a hepatocellular signaling node mediating the metabolic actions of glucagon and provide a rich resource for future investigations on the biology of glucagon action.

Pyrazoles are rarely found in nature but are traditionally used in the agrochemical and pharmaceutical industries, while other areas of use are also actively developing. However, they have also found numerous other applications. The search for new and efficient syntheses of these heterocycles is therefore highly relevant. The modular concept of multicomponent reactions (MCR) has paved a broad alley to heteroaromatics. The advantages over traditional methods are the broader scope and increased efficiency of these reactions. In particular, traditional multistep syntheses of pyrazoles have considerably been extended by MCR. Progress has been made in the cyclocondensation of 1,3-dielectrophiles that are generated in situ. Limitations in the regioselectivity of cyclocondensation with 1,3-dicarbonyls were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern cross-coupling and radical chemistry, as well as providing versatile synthetic approaches to pyrazoles. This overview summarizes the most important MCR syntheses of pyrazoles based on ring-forming sequences in a flashlight fashion.

Abstract The multi-staged XENON program at INFN Laboratori Nazionali del Gran Sasso aims to detect dark matter with two-phase liquid xenon time projection chambers of increasing size and sensitivity. The XENONnT experiment is the latest detector in the program, planned to be an upgrade of its predecessor XENON1T. It features an active target of 5.9 tonnes of cryogenic liquid xenon (8.5 tonnes total mass in cryostat). The experiment is expected to extend the sensitivity to WIMP dark matter by more than an order of magnitude compared to XENON1T, thanks to the larger active mass and the significantly reduced background, improved by novel systems such as a radon removal plant and a neutron veto. This article describes the XENONnT experiment and its sub-systems in detail and reports on the detector performance during the first science run.

BackgroundPemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease caused mainly by IgG autoantibodies (auto-abs) against the cadherin-type adhesion molecules desmoglein (Dsg) 1 and 3. Pathogenic anti-Dsg3 auto-abs bind to different Dsg3 epitopes, leading, among others, to signalling that is involved in pathogenic events, such as Dsg3 depletion. As central tools in research on PV, a limited number of antibodies such as AK23 are frequently used by the autoimmune bullous disease community.MethodsPreviously, we have introduced a novel Dsg3 EC5-binding antibody termed 2G4 that may potentially serve as a superior tool for numerous PV related analysis. The purpose of this study was to develop a quality-controlled production and verification process that allows I) a continuous quality improvement, and II) a verified and comprehensible overall quality with regard to pathogenic antigen-specific binding in a variety of pemphigus assays for each batch production.ResultsThus, a workflow based on a standardized operating procedure was established. This includes the verification of purity and in-vitro binding capacity (SDS-page, direct and indirect immunofluorescence) as primary parameters, and size analysis by mass-spectrometry and ex-vivo pathogenicity by monolayer dissociation assay.ConclusionWe here present an extensive point-by-point quality controlled IgG production protocol, which will serve as a basis for a standardized antibody assessment in PV research.

Abstract A key feature of cancer is the disruption of cell cycle regulation, which is characterized by the selective and abnormal activation of cyclin-dependent kinases (CDKs). Consequently, targeting CDKs via meriolins represents an attractive therapeutic approach for cancer therapy. Meriolins represent a semisynthetic compound class derived from meridianins and variolins with a known CDK inhibitory potential. Here, we analyzed the two novel derivatives meriolin 16 and meriolin 36 in comparison to other potent CDK inhibitors and could show that they displayed a high cytotoxic potential in different lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells. In a kinome screen, we showed that meriolin 16 and 36 prevalently inhibited most of the CDKs (such as CDK1, 2, 3, 5, 7, 8, 9, 12, 13, 16, 17, 18, 19, 20). In drug-to-target modeling studies, we predicted a common binding mode of meriolin 16 and 36 to the ATP-pocket of CDK2 and an additional flipped binding for meriolin 36. We could show that cell cycle progression and proliferation were blocked by abolishing phosphorylation of retinoblastoma protein (a major target of CDK2) at Ser612 and Thr82. Moreover, meriolin 16 prevented the CDK9-mediated phosphorylation of RNA polymerase II at Ser2 which is crucial for transcription initiation. This renders both meriolin derivatives as valuable anticancer drugs as they target three different Achilles’ heels of the tumor: (1) inhibition of cell cycle progression and proliferation, (2) prevention of transcription, and (3) induction of cell death.

Abstract Background Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils. Methods Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type mice. Megakaryocyte differentiation was investigated using lineage-negative bone marrow cells upon in vitro incubation with TPO/IL-1β. Cytokine concentrations in serum of mice were determined by Mouse Cytokine Array. IL-1α expression in various hematopoietic cell populations was determined by intracellular FACS analysis. RNA-seq to analyse gene expression of inflammatory cytokines was performed in isolated neutrophils from JAK2-V617F and CALR-mutated mice and patients. Bioenergetics of neutrophils were recorded on a Seahorse extracellular flux analyzer. Cell motility of neutrophils was monitored in vitro (time lapse microscopy), and in vivo (two-photon microscopy) upon creating an inflammatory environment. Cell adhesion to integrins, E-selectin and P-selection was investigated in-vitro. Statistical analysis was carried out using GraphPad Prism. Data are shown as mean ± SEM. Unpaired, two-tailed t-tests were applied. Results Strikingly, neutrophil-specific expression of JAK2-V617F, but not CALRdel, was sufficient to induce pro-inflammatory cytokines including IL-1 in serum of mice. RNA-seq analysis in neutrophils from JAK2-V617F mice and patients revealed a distinct inflammatory chemokine signature which was not expressed in CALR-mutant neutrophils. In addition, IL-1 response genes were significantly enriched in neutrophils of JAK2-V617F patients as compared to CALR-mutant patients. Thus, JAK2-V617F positive neutrophils, but not CALR-mutant neutrophils, are pathogenic drivers of inflammation in MPN. In line with this, expression of JAK2-V617F or CALRdel elicited a significant difference in the metabolic phenotype of neutrophils, suggesting a stronger inflammatory activity of JAK2-V617F cells. Furthermore, JAK2-V617F, but not CALRdel, induced a VLA4 integrin-mediated adhesive phenotype in neutrophils. This resulted in reduced neutrophil migration in vitro and in an inflamed vessel. This mechanism may contribute to the increased thrombotic risk of JAK2-V617F patients compared to CALR-mutant individuals. Conclusions Taken together, our findings highlight genotype-specific differences in MPN-neutrophils that have implications for the differential pathophysiology of JAK2-V617F versus CALR-mutant disease.

Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A FATCAT-awFC pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity (awFC)). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, awFC) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower awFC within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased awFC within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. AwFC in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the FATCAT-awFC pipeline has the benefit of providing insight on the ‘full picture’ of connectivity changes for REMs and NREMs while making for an easy intuitive approach.

Abstract Using the established synthetic methods, aroyl-S,N-ketene acetals and subsequent bi- and multichromophores can be readily synthesized. Aside from pronounced AIE (aggregation induced emission) properties, these selected examples possess distinct complexometric behavior for various metals purely based on the underlying structural motifs. This affects the fluorescence properties of the materials which can be readily exploited for metal ion detection and for the formation of different metal-aroyl-S,N-ketene acetal complexes that were confirmed by Job plot analysis. In particular, gold(I), iron(III), and ruthenium (III) ions reveal complexation enhanced or quenched emission. For most dyes, weakly coodinating complexes were observed, only in case of a phenanthroline aroyl-S,N-ketene acetal multichromophore, measurements indicate the formation of a strongly coordinating complex. For this multichromophore, the complexation results in a loss of fluorescence intensity whereas for dimethylamino-aroyl-S,N-ketene acetals and bipyridine bichromophores, the observed quantum yield is nearly tripled upon complexation. Even if no stable complexes are formed, changes in absorption and emission properties allow for a simple ion detection.

To manage Earth in the Anthropocene, new tools, new institutions, and new forms of international cooperation will be required. Earth Virtualization Engines is proposed as an international federation of centers of excellence to empower all people to respond to the immense and urgent challenges posed by climate change.

Due to large losses of seagrass meadows worldwide, restoration is proposed as a key strategy for increasing coastal resilience and recovery. The emergence of a seagrass meadow is expected to substantially amplify biodiversity and enhance benthic metabolism by increasing primary productivity and respiration. Nevertheless, open questions remain regarding the metabolic balance of aging seagrass meadows and the roles benthic communities within the seagrass ecosystem play in overall metabolism. To address these questions, we investigated a chronosequence of bare sediments and adjacent Zostera marina meadows of 3 and 7 years since restoration alongside a natural meadow located within a high-temperate marine embayment in Gåsö, Sweden. We combined continuous measurements of O2 fluxes using underwater eddy covariance with dissolved inorganic carbon (DIC) and O2 fluxes from benthic chambers during the productive season (July). Based on the ratio between O2 and DIC, we derived site-specific photosynthetic and respiratory quotients, enabling the conversion of eddy covariance fluxes to DIC. We assessed benthic diversity parameters as potential drivers of metabolic flux variability. We observed high rates of gross primary productivity (GPP) spanning −18 to −82 mmolDICm-2d-1, which increased progressively with meadow age. Community respiration (CR) mirrored the GPP trend, and all meadows were net heterotrophic (GPP < CR), with net community productivity (NCP) ranging from 16 to 28 mmolDICm-2d-1. While autotrophic biomass did not increase with meadow age, macrophyte diversity did, elucidating potential effects of niche complementarity among macrophytes on community metabolism. These findings provide valuable insights into how community composition and meadow development relate to ecosystem functioning, highlighting potential tradeoffs between carbon uptake and biodiversity.

Satellite gravimetry is used to study the global hydrological cycle. It is a key component in the investigation of groundwater depletion on the Indian subcontinent. Terrestrial mass loss caused by river sediment transport is assumed to be below the detection limit in current gravimetric satellites of the Gravity Recovery and Climate Experiment Follow-On mission. Thus, it is not considered in the calculation of terrestrial water storage (TWS) from such satellite data. However, the Ganges and Brahmaputra rivers, which drain the Indian subcontinent, constitute one of the world's most sediment-rich river systems. In this study, we estimate the impact of sediment mass loss within their catchments on local trends in gravity and consequential estimates of TWS trends. We find that for the Ganges–Brahmaputra–Meghna catchment sediment transport accounts for (4 ± 2) % of the gravity decrease currently attributed to groundwater depletion. The sediment is mainly eroded from the Himalayas, where correction for sediment mass loss reduces the decrease in TWS by 0.22 cm of equivalent water height per year (14 %). However, sediment mass loss in the Brahmaputra catchment is more than twice that in the Ganges catchment, and sediment is mainly eroded from mountain regions. Thus, the impact on gravimetric TWS trends within the Indo–Gangetic Plain – the main region identified for groundwater depletion – is found to be comparatively small (< 2 %).

Abstract We investigate the benefits of future quantum accelerometers based on cold atom interferometry (CAI) on current and upcoming satellite gravity mission concepts. These mission concepts include satellite‐to‐satellite tracking (SST) in a single‐pair (GRACE‐like) and double‐pair constellation as well as satellite gravity gradiometry (SGG, single satellite, GOCE‐like). Regarding instruments, four scenarios are considered: current‐generation electrostatic (GRACE‐, GOCE‐like), next‐generation electrostatic, conservative hybrid/CAI and optimistic hybrid/CAI. For SST, it is shown that temporal aliasing poses currently the dominating error source in simulated global gravity field solutions independent of the investigated instrument and constellation. To still quantify the advantages of CAI instruments on the gravity functional itself, additional simulations are performed where the impact of temporal aliasing is synthetically reduced. When neglecting temporal aliasing, future accelerometers in conjunction with future ranging instruments can substantially improve the retrieval performance of the Earth's gravity field (depending on instrument and constellation). These simulation results are further investigated regarding possible benefit for hydrological use cases where these improvements can also be observed (when omitting temporal aliasing). For SGG, it is demonstrated that, with realistic instrument assumptions, one is still mostly insensitive to time‐variable gravity and not competitive with the SST principle. However, due to the improved instrument sensitivity of quantum gradiometers compared to the GOCE mission, static gravity field solutions can be improved significantly.

Key Clinical Message In young infants, under the age of one‐year, cochlear malformation with profound hearing loss complicated by a perilymphatic fistula (PLF), presents a serious clinical challenge, warranting immediate audiological and surgical intervention. Timely PLF detection and closure, along with an early CI can significantly improve the prognosis of such patients and helps them in achieving their maximum hearing and developmental potential, in the long term. Abstract Inner ear malformation (IEM) with incomplete partition and cystic cochlea is mostly accompanied by profound hearing loss. It gets further complicated with other malformations such as a perilymphatic fistula (PLF). This case concerns an 8‐month‐old child cochlear malformation and profound hearing loss. Surgical intervention identified a PLF at the stapedial footplate, which was successfully closed. The surgery also included the placement of a cochlear implant (CI) in the right ear, via the round window. The left ear was equipped with hearing aids, with persistent hearing thresholds at 70–80 db. At the age of 6 years, the child showed a good hearing outcome with the CI, with only moderate speech delay. Cochlear malformation accompanied by a perilymphatic leakage warrants immediate surgical closure of the PLF, to minimize the risk of bacterial meningitis. Wherever possible, the feasibility of a CI should be explored in such cases and a CI should be placed for treatment of hearing loss. Audiological and speech outcomes may vary with the use of the CI, especially in cases of IEM. However, an early CI coupled with timely PLF detection and closure can help children with profound hearing loss, in achieving their maximum hearing and developmental potential, in the long run.

Abstract Meriolin derivatives represent a new class of kinase inhibitors with a pronounced cytotoxic potential. Here, we investigated a newly synthesized meriolin derivative (termed meriolin 16) that displayed a strong apoptotic potential in Jurkat leukemia and Ramos lymphoma cells. Meriolin 16 induced apoptosis in rapid kinetics (within 2–3 h) and more potently (IC50: 50 nM) than the previously described derivatives meriolin 31 and 36 [1]. Exposure of Ramos cells to meriolin 16, 31, or 36 for 5 min was sufficient to trigger severe and irreversible cytotoxicity. Apoptosis induction by all three meriolin derivatives was independent of death receptor signaling but required caspase-9 and Apaf-1 as central mediators of the mitochondrial death pathway. Meriolin-induced mitochondrial toxicity was demonstrated by disruption of the mitochondrial membrane potential (ΔΨm), mitochondrial release of proapoptotic Smac, processing of the dynamin-like GTPase OPA1, and subsequent fragmentation of mitochondria. Remarkably, all meriolin derivatives were able to activate the mitochondrial death pathway in Jurkat cells, even in the presence of the antiapoptotic Bcl-2 protein. In addition, meriolins were capable of inducing cell death in imatinib-resistant K562 and KCL22 chronic myeloid leukemia cells as well as in cisplatin-resistant J82 urothelial carcinoma and 2102EP germ cell tumor cells. Given the frequent inactivation of the mitochondrial apoptosis pathway by tumor cells, such as through overexpression of antiapoptotic Bcl-2, meriolin derivatives emerge as promising therapeutic agents for overcoming treatment resistance.

Abstract The regulation of mass is essential for the development and homeostasis of cells and multicellular organisms. However, cell mass is also tightly linked to cell mechanical properties, which depend on the time scales at which they are measured and change drastically at the cellular eigenfrequency. So far, it has not been possible to determine cell mass and eigenfrequency together. Here, we introduce microcantilevers oscillating in the Ångström range to monitor both fundamental physical properties of the cell. If the oscillation frequency is far below the cellular eigenfrequency, all cell compartments follow the cantilever motion, and the cell mass measurements are accurate. Yet, if the oscillating frequency approaches or lies above the cellular eigenfrequency, the mechanical response of the cell changes, and not all cellular components can follow the cantilever motions in phase. This energy loss caused by mechanical damping within the cell is described by the quality factor. We use these observations to examine living cells across externally applied mechanical frequency ranges and to measure their total mass, eigenfrequency, and quality factor. The three parameters open the door to better understand the mechanobiology of the cell and stimulate biotechnological and medical innovations.

Abstract Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With $$40\,\textrm{t}$$ 40 t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay ( $$0\upnu \upbeta \upbeta $$ 0 ν β β ), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We present here the results of simulations performed to determine the production rate of $${}^{137}$$ 137 Xe, the most crucial isotope in the search for $$0\upnu \upbeta \upbeta $$ 0 ν β β of $${}^{136}$$ 136 Xe. Additionally, we explore the contribution that other muon-induced spallation products, such as other unstable xenon isotopes and tritium, may have on the cosmogenic background.

Sequential Pd-catalyzed one-pot synthetic methodologies have emerged as a powerful and versatile approach in organic synthesis, enabling the construction of complex heterocyclic architectures with high efficiency, selectivity, and atom economy. This review discusses key advancements in multistep, sequentially Pd-catalyzed one-pot processes for accessing heterocyclic derivatives, focusing on classic reactions like Suzuki–Miyaura, Sonogashira, Heck, and hydroamination and extending to specialized techniques such as directed C-H activation. The concatenation of these steps has advanced the scope of one-pot strategies. A section is dedicated to exploring the cooperative use of palladium with other metals, particularly copper, ruthenium, and gold, which has broadened the range of accessible heterocyclic derivatives. Highlighted applications include the synthesis of biologically and pharmaceutically relevant compounds, such as tris(hetero)aryl systems, spiro-oxindoles, and indole derivatives. These one-pot strategies not only streamline synthesis but also align with green chemistry principles by minimizing purification steps and reducing waste and energy consumption. The review also addresses current challenges and limitations in these methodologies, offering insights into ongoing efforts to optimize reaction conditions and expand the applicability of sequential Pd-catalyzed processes.

IntroductionVisual search is facilitated when participants encounter targets in repeated display arrangements. This “contextual-cueing” effect is attributed to incidental learning of spatial distractor-target relations, which subsequently guides visual search more effectively toward the target location. Conversely, behaviorally significant, though task-irrelevant, negative emotional stimuli may involuntarily capture attention and thus hamper performance in visual search. This raises the question of how these two attention-guiding factors connect.MethodsTo this end, we investigated how an emotionally alerting stimulus induced by different classes of emotional (face, scene) pictures prior to the search task relates to memory-related plasticity. We tested 46 participants who were presented with repeated and non-repeated search layouts, preceded at variable (50, 500, 1,000 ms) intervals by emotional vs. neutral faces or scenes.ResultsWe found that contextual learning was increased with emotional compared to neutral scenes, which resulted in no contextual cueing was observed at all, while no modulation of the cueing effect was observed for emotional (vs. neutral) faces. This modulation occurred independent of the intervals between the emotional stimulus and the search display.DiscussionWe conclude that emotional scenes are particularly effective in withdrawing attentional resources, biasing individual participants to perform a visual search task in a passive, i.e., receptive, manner, which, in turn, improves automatic contextual learning.

Abstract Controlling the pH at the microliter scale can be useful for applications in research, medicine, and industry, and therefore represents a valuable application for synthetic biology and microfluidics. The presented vesicular system translates light of different colors into specific pH changes in the surrounding solution. It works with the two light‐driven proton pumps bacteriorhodopsin and blue light‐absorbing proteorhodopsin Med12, that are oriented in opposite directions in the lipid membrane. A computer‐controlled measuring device implements a feedback loop for automatic adjustment and maintenance of a selected pH value. A pH range spanning more than two units can be established, providing fine temporal and pH resolution. As an application example, a pH‐sensitive enzyme reaction is presented where the light color controls the reaction progress. In summary, light color‐controlled pH‐adjustment using engineered proteoliposomes opens new possibilities to control processes at the microliter scale in different contexts, such as in synthetic biology applications.

Abstract Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61% Dice score, and the best classification performance was about 80% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection.

Abstract This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals’ data. All models’ median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74–0.85). For both test sets, nn-Unet achieved the highest DSC (internal = 0.86, external = 0.93) and the lowest Hausdorff distances (10.07, 13.87 mm, respectively) for all tumor classes (p

Abstract Well-defined multicrystalline multiblock polymers are essential model polymers for advancing crystallization physics, phase separation, self-assembly, and improving the mechanical properties of materials. However, due to different chain properties and incompatible synthetic methodologies, multicrystalline multiblock polymers with more than two crystallites are rarely reported. Herein, by combining polyhomologation, ring-opening polymerization, and catalyst switch strategy, we synthesized a pentacrystalline pentablock quintopolymer, polyethylene-b-poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(L-lactide)-b-polyglycolide (PE-b-PEO-b-PCL-b-PLLA-b-PGA). The fluoroalcohol-assisted catalyst switch enables the successful incorporation of a high melting point polyglycolide block into the complex multiblock structure. Solid-state nuclear magnetic resonance spectroscopy, X-ray diffraction, and differential scanning calorimetry revealed the existence of five different crystalline phases.

Abstract The human brain displays a rich repertoire of states that emerge from the microscopic interactions of cortical and subcortical neurons. Difficulties inherent within large-scale simultaneous neuronal recording limit our ability to link biophysical processes at the microscale to emergent macroscopic brain states. Here we introduce a microscale biophysical network model of layer-5 pyramidal neurons that display graded coarse-sampled dynamics matching those observed in macroscale electrophysiological recordings from macaques and humans. We invert our model to identify the neuronal spike and burst dynamics that differentiate unconscious, dreaming, and awake arousal states and provide insights into their functional signatures. We further show that neuromodulatory arousal can mediate different modes of neuronal dynamics around a low-dimensional energy landscape, which in turn changes the response of the model to external stimuli. Our results highlight the promise of multiscale modelling to bridge theories of consciousness across spatiotemporal scales.

A library of 19 differently substituted 3-iodoindoles is generated by a consecutive four-component reaction starting from ortho-haloanilines, terminal alkynes, N-iodosuccinimide, and alkyl halides in yields of 11–69%. Initiated by a copper-free alkynylation, followed by a base-catalyzed cyclizive indole formation, electrophilic iodination, and finally electrophilic trapping of the intermediary indole anion with alkyl halides provides a concise one-pot synthesis of 3-iodoindoles. The latter are valuable substrates for Suzuki arylations, which are exemplified with the syntheses of four derivatives, some of them are blue emitters in solution and in the solid state, in good yield.

With an atmospheric concentration of approximately 2000 parts per billion (ppbV, 10−9), methane (CH4) is the second most abundant greenhouse gas (GHG) in the atmosphere after carbon dioxide (CO2). The task of long-term and spatially resolved GHG monitoring to verify whether climate policy actions are effective is becoming more crucial as climate change progresses. In this paper we report the CH4 concentration readings of our photoacoustic (PA) sensor over a 5 d period at Hohenpeißenberg, Germany. As a reference device, a calibrated cavity ring-down spectrometer, Picarro G2301, from the meteorological observatory of the German Weather Service (DWD) was employed. Trace gas measurements with photoacoustic instruments promise to provide low detection limits at comparably low costs. However, PA devices are often susceptible to cross-sensitivities related to fluctuating environmental conditions, e.g. ambient humidity. The obtained results show that for PA sensor systems non-radiative relaxation effects induced by varying humidity are a non-negligible factor. Applying algorithm compensation techniques, which are capable of calculating the influence of non-radiative relaxation effects on the photoacoustic signal, increase the accuracy of the photoacoustic sensor significantly. With an average relative deviation of 1.11 % from the G2301, the photoacoustic sensor shows good agreement with the reference instrument.

As remnants of living organisms, alkenones and isoprenoid glycerol dialkyl glycerol tetraether lipids (isoGDGTs) are widely used biomarkers for determining ocean water temperatures from the past. The organisms that these proxy carriers stem from are influenced by a number of environmental parameters, such as water depth, nutrient availability, light conditions, or seasonality, which all may significantly bias the calibration to ambient water temperatures. Reliable temperature determinations thus remain challenging, especially in higher latitudes and for undersampled regions. We analyzed 33 sediment surface samples from the southern Chilean continental margin and the Drake Passage for alkenones and isoGDGTs and compared the results with gridded instrumental reference data from the World Ocean Atlas 2005 (WOA05) and previously published data from an extended study area covering the central and western South Pacific towards the Aotearoa / New Zealand continental margin. We show that for alkenone-derived sea surface temperatures (SSTs), the widely used global core-top calibration of Müller et al. (1998) yields the smallest deviation of the WOA05-based SSTs. On the contrary, the calibration of Sikes et al. (1997), determined for higher latitudes and summer SSTs, overestimates modern WOA05-based SSTs in both the annual mean and summer. Our alkenone SSTs show a slight seasonal shift of ∼ 1 ∘C at the southern Chilean margin and up to ∼ 2 ∘C in the Drake Passage towards austral summer SSTs. Samples in the central South Pacific, on the other hand, reflect an annual mean signal. We show that for isoGDGT-based temperatures, the subsurface calibration of Kim et al. (2012a) best reflects temperatures from the WOA05 in areas north of the Subantarctic Front (SAF). Temperatures south of the SAF are, in contrast, significantly overestimated by up to 14 ∘C, irrespective of the applied calibration. In addition, we used the GDGT [2]/[3] ratios, which give an indication of the production depth of the isoGDGTs and/or potential influences from land. Our samples reflect a subsurface (0–200 m water depth) rather than a surface (0–50 m water depth) signal in the entire study area and show a correlation with the monthly dust distribution in the South Pacific, indicating terrigenous influences. The overestimation of isoGDGT surface and subsurface temperatures south of the SAF highlights the need for a reassessment of existing calibrations in the polar Southern Ocean. Therefore, we suggest a modified Southern Ocean tetraether index (TEX86)-based calibration for surface and subsurface temperatures, which shows a lower temperature sensitivity and yields principally lower absolute temperatures, which align more closely with WOA05-derived values and also OH–isoGDGT-derived temperatures.

Abstract Monitoring sleep and activity through wearable devices such as wrist-worn actigraphs has the potential for long-term measurement in the individual’s own environment. Long periods of data collection require a complex approach, including standardized pre-processing and data trimming, and robust algorithms to address non-wear and missing data. In this study, we used a data-driven approach to quality control, pre-processing and analysis of longitudinal actigraphy data collected over the course of 1 year in a sample of 95 participants. We implemented a data processing pipeline using open-source packages for longitudinal data thereby providing a framework for treating missing data patterns, non-wear scoring, sleep/wake scoring, and conducted a sensitivity analysis to demonstrate the impact of non-wear and missing data on the relationship between sleep variables and depressive symptoms. Compliance with actigraph wear decreased over time, with missing data proportion increasing from a mean of 4.8% in the first week to 23.6% at the end of the 12 months of data collection. Sensitivity analyses demonstrated the importance of defining a pre-processing threshold, as it substantially impacts the predictive value of variables on sleep-related outcomes. We developed a novel non-wear algorithm which outperformed several other algorithms and a capacitive wear sensor in quality control. These findings provide essential insight informing study design in digital health research.

Abstract Alkynylated aroyl-S,N-ketene acetals are readily synthesized in mostly excellent yields by a Sonogashira reaction resulting in a substance library of more than 20 examples. Upon expansion of the reaction sequence by deprotection and concatenating of the copper-click reaction in a one-pot fashion, a library of 11 triazole-ligated aroyl-S,N-ketene acetals is readily accessible. All derivatives show pronounced solid-state emission and aggregation-induced emission properties depending on the nature of the alkynyl or the triazole substituents.

Abstract Colloidal gels, commonly used as mesoporous intermediates or functional materials, suffer from brittleness, often showing small yield strains on the order of 1% or less for gelled colloidal suspensions. The short-range adhesive forces in most such gels are central forces—combined with the smooth morphology of particles, the resistance to yielding and shear-induced restructuring is limited. In this study, we propose an innovative approach to improve colloidal gels by introducing surface roughness to the particles to change the yield strain, giving rise to non-central interactions. To elucidate the effects of particle roughness on gel properties, we prepared thermoreversible gels made from rough or smooth silica particles using a reliable click-like-chemistry-based surface grafting technique. Rheological and optical characterization revealed that rough particle gels exhibit enhanced toughness and self-healing properties. These remarkable properties can be utilized in various applications, such as xerogel fabrication and high-fidelity extrusion 3D-printing, as we demonstrate in this study.

Wildfires are a significant source of absorbing aerosols in the atmosphere. Extreme fires in particular, such as those during the 2019–2020 Australian wildfire season (Black Summer fires), can have considerable large-scale effects. In this context, the climate impact of extreme wildfires unfolds not only because of the emitted carbon dioxide but also due to smoke aerosol released up to an altitude of 17 km. The overall aerosol effects depend on a variety of factors, such as the amount emitted, the injection height, and the composition of the burned material, and is therefore subject to considerable uncertainty. In the present study, we address the global impact caused by the exceptionally strong and high-reaching smoke emissions from the Australian wildfires using simulations with a global aerosol–climate model. We show that the absorption of solar radiation by the black carbon contained in the emitted smoke led to a shortwave radiative forcing of more than +5 W m−2 in the southern mid-latitudes of the lower stratosphere. Subsequent adjustment processes in the stratosphere slowed down the diabatically driven meridional circulation, thus redistributing the heating perturbation on a global scale. As a result of these stratospheric adjustments, a positive temperature perturbation developed in both hemispheres, leading to additional longwave radiation emitted back to space. According to the model results, this adjustment occurred in the stratosphere within the first 2 months after the event. At the top of the atmosphere (TOA), the net effective radiative forcing (ERF) averaged over the Southern Hemisphere was initially dominated by the instantaneous positive radiative forcing of about +0.5 W m−2, for which the positive sign resulted mainly from the presence of clouds above the Southern Ocean. The longwave adjustments led to a compensation of the initially net positive TOA ERF, which is seen in the Southern Hemisphere, the tropics, and the northern mid-latitudes. The simulated changes in the lower stratosphere also affected the upper troposphere through a thermodynamic downward coupling. Subsequently, increased temperatures were also obtained in the upper troposphere, causing a global decrease in relative humidity, cirrus amount, and the ice water path of about 0.2 %. As a result, surface precipitation also decreased by a similar amount, which was accompanied by a weakening of the tropospheric circulation due to the given energetic constraints. In general, it appears that the radiative effects of smoke from single extreme wildfire events can lead to global impacts that affect the interplay of tropospheric and stratospheric budgets in complex ways. This emphasizes that future changes in extreme wildfires need to be included in projections of aerosol radiative forcing.

Abstract Background Sepsis‐induced intensive care unit‐acquired weakness (ICUAW) features profound muscle atrophy and attenuated muscle regeneration related to malfunctioning satellite cells. Transforming growth factor beta (TGF‐β) is involved in both processes. We uncovered an increased expression of the TGF‐β receptor II (TβRII)‐inhibitor SPRY domain‐containing and SOCS‐box protein 1 (SPSB1) in skeletal muscle of septic mice. We hypothesized that SPSB1‐mediated inhibition of TβRII signalling impairs myogenic differentiation in response to inflammation. Methods We performed gene expression analyses in skeletal muscle of cecal ligation and puncture‐ (CLP) and sham‐operated mice, as well as vastus lateralis of critically ill and control patients. Pro‐inflammatory cytokines and specific pathway inhibitors were used to quantitate Spsb1 expression in myocytes. Retroviral expression plasmids were used to investigate the effects of SPSB1 on TGF‐β/TβRII signalling and myogenesis in primary and immortalized myoblasts and differentiated myotubes. For mechanistical analyses we used coimmunoprecipitation, ubiquitination, protein half‐life, and protein synthesis assays. Differentiation and fusion indices were determined by immunocytochemistry, and differentiation factors were quantified by qRT‐PCR and Western blot analyses. Results SPSB1 expression was increased in skeletal muscle of ICUAW patients and septic mice. Tumour necrosis factor (TNF), interleukin‐1β (IL‐1β), and IL‐6 increased the Spsb1 expression in C2C12 myotubes. TNF‐ and IL‐1β‐induced Spsb1 expression was mediated by NF‐κB, whereas IL‐6 increased the Spsb1 expression via the glycoprotein 130/JAK2/STAT3 pathway. All cytokines reduced myogenic differentiation. SPSB1 avidly interacted with TβRII, resulting in TβRII ubiquitination and destabilization. SPSB1 impaired TβRII‐Akt‐Myogenin signalling and diminished protein synthesis in myocytes. Overexpression of SPSB1 decreased the expression of early (Myog, Mymk, Mymx) and late (Myh1, 3, 7) differentiation‐markers. As a result, myoblast fusion and myogenic differentiation were impaired. These effects were mediated by the SPRY‐ and SOCS‐box domains of SPSB1. Co‐expression of SPSB1 with Akt or Myogenin reversed the inhibitory effects of SPSB1 on protein synthesis and myogenic differentiation. Downregulation of Spsb1 by AAV9‐mediated shRNA attenuated muscle weight loss and atrophy gene expression in skeletal muscle of septic mice. Conclusions Inflammatory cytokines via their respective signalling pathways cause an increase in SPSB1 expression in myocytes and attenuate myogenic differentiation. SPSB1‐mediated inhibition of TβRII‐Akt‐Myogenin signalling and protein synthesis contributes to a disturbed myocyte homeostasis and myogenic differentiation that occurs during inflammation.

Abstract Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses. Piezo1 ion channels are directly gated by mechanical forces and play an essential role in cellular mechanotransduction. However, readouts of Piezo1 activity are mainly examined by invasive or indirect techniques, such as electrophysiological analyses and cytosolic calcium imaging. Here, we introduce GenEPi, a genetically-encoded fluorescent reporter for non-invasive optical monitoring of Piezo1-dependent activity. We demonstrate that GenEPi has high spatiotemporal resolution for Piezo1-dependent stimuli from the single-cell level to that of the entire organism. GenEPi reveals transient, local mechanical stimuli in the plasma membrane of single cells, resolves repetitive contraction-triggered stimulation of beating cardiomyocytes within microtissues, and allows for robust and reliable monitoring of Piezo1-dependent activity in vivo. GenEPi will enable non-invasive optical monitoring of Piezo1 activity in mechanochemical feedback loops during development, homeostatic regulation, and disease.

Thermochemical conversion of CO2 with biomass to CO in fluidized bed gasifiers is promising for a sustainable carbon economy. Knowledge about this process is expanded by investigating experimental parameters influencing CO2 conversion in such a system and combining them to demonstrate effective conversion. Wood char and CO2 are fed to a lab-scale gasifier in 53 semi-continuous experiments. Six experimental parameters are varied: temperature, bed material type, initial bed-to-fuel ratio, initial fuel loading in the reactor, feed CO2 flow rate, and fuel particle size. The results are compiled in a semi-empirical model based on reaction kinetics. High temperatures and high fuel-gas contact times are favorable for increasing CO2 conversion, with the latter achieved through high initial fuel loadings in the reactor and low feed gas flow rates. Choosing olivine instead of silica sand as a bed material also results in higher CO2 conversions. The highest CO2 conversion demonstrated in this paper is 86.1%. This experiment produces a gas with 82.75% CO, 10.01% H2, and 5.90% CO2 (nitrogen-free and dry).

Background: Existing evidence suggests that psychiatric patients are highly noise sensitive, and that noise exposure increases the risk for adverse mental health outcomes, such as psychiatric hospitalizations and even suicide. To investigate acute effects of noise in this vulnerable population, we assessed short-term associations between fighter jet noise and on-demand sedative and analgesic drug administrations in a psychiatric clinic located close to a military airfield in Switzerland. Methods: We applied a case time series analysis with an hourly time resolution using distributed-lag models. Analysis was adjusted for long-term and seasonal trends, day of week, time of day, time-varying weather conditions and the week of stay. Noise exposure (hourly A-weighted equivalent continuous sound pressure levels (LAeq)) was modelled using detailed flight plans and noise footprints for different fighter jet and route combinations. Outcome data were available from the clinic’s records. Outcomes: During the study period (06/2016–12/2021), 23,486 flights occurred. 5,968 clinical stays with a median length of 41 days (IQR: 28d, 50d) were recorded. The odds ratio (OR) for medication administration over the lag period of 3 hours after exposure was 1.016 (95 %CI: 1.006, 1.026) per 10 dB LAeq for sedatives and 1.032 (95 %CI: 1.016, 1.048) per 10 dB for analgesics. Effects were larger in multimorbid patients. Interpretation: Case time series analysis is a novel method to investigate transient associations in observational data while minimizing risk of bias. Using an objectively recorded outcome measure, our results demonstrate that psychiatric patients are a vulnerable population, in which noise exposure can lead to symptom exacerbations and adverse events.

Rupture or dissection of thoracic aortic aneurysms is still the leading cause of death for patients diagnosed with Marfan syndrome. Inflammation and matrix digestion regulated by matrix metalloproteases (MMPs) play a major role in the pathological remodeling of the aortic media. Regnase-1 is an endoribonuclease shown to cleave the mRNA of proinflammatory cytokines, such as interleukin-6. Considering the major anti-inflammatory effects of regnase-1, here, we aimed to determine whether adeno-associated virus (AAV)–mediated vascular overexpression of the protein could provide protection from the development and progression of aortic aneurysms in Marfan syndrome. The overexpression of regnase-1 resulted in a marked decrease in inflammatory parameters and elastin degradation in aortic smooth muscle cells in vitro. Intravenous injection of a vascular-targeted AAV vector resulted in the efficient transduction of the aortic wall and overexpression of regnase-1 in a murine model of Marfan syndrome, associated with lower circulating levels of proinflammatory cytokines and decreased MMP expression and activity. Regnase-1 overexpression strongly improved elastin architecture in the media and reduced aortic diameter at distinct locations. Therefore, AAV-mediated regnase-1 overexpression may represent a novel gene therapy approach for inhibiting aortic aneurysms in Marfan syndrome.

Redox status of protein cysteinyl residues is mediated via glutathione (GSH)/glutaredoxin (GRX) and thioredoxin (TRX)-dependent redox cascades. An oxidative challenge can induce post-translational protein modifications on thiols, such as protein S-glutathionylation. Class I GRX are small thiol-disulfide oxidoreductases that reversibly catalyse S-glutathionylation and protein disulfide formation. TRX and GSH/GRX redox systems can provide partial backup for each other in several subcellular compartments, but not in the plastid stroma where TRX/light-dependent redox regulation of primary metabolism takes place. While the stromal TRX system has been studied at detail, the role of class I GRX on plastid redox processes is still unknown. We generate knockout lines of GRXC5 as the only chloroplast class I GRX of the moss Physcomitrium patens.While we find that PpGRXC5 has high activities in GSH-dependent oxidoreductase assays using hydroxyethyl disulfide or redox-sensitive GFP2 as substrates in vitro, Δgrxc5 plants show no detectable growth defect or stress sensitivity, in contrast to mutants with a less negative stromal EGSH (Δgr1). Using stroma-targeted roGFP2, we show increased protein Cys steady state oxidation and decreased reduction rates after oxidative challenge in Δgrxc5 plants in vivo, indicating kinetic uncoupling of the protein Cys redox state from EGSH. Compared to wildtype, protein Cys disulfide formation rates and S-glutathionylation levels after H2O2 treatment remained unchanged. Lack of class I GRX function in the stroma did not result in impaired carbon fixation.Our observations suggest specific roles for GRXC5 in the efficient transfer of electrons from GSH to target protein Cys as well as negligible cross-talk with metabolic regulation via the TRX system. We propose a model for stromal class I GRX function in efficient catalysis of protein dithiol/disulfide equilibria upon redox steady state alterations affecting stromal EGSH and highlight the importance of identifying in vivo target proteins of GRXC5.

IntroductionThe development of cognitive dysfunction is not necessarily associated with diet-induced obesity. We hypothesized that cognitive dysfunction might require additional vascular damage, for example, in atherosclerotic mice.MethodsWe induced atherosclerosis in male C57BL/6N mice by injecting AAV-PCSK9DY (2x1011 VG) and feeding them a cholesterol-rich Western diet. After 3 months, mice were examined for cognition using Barnes maze procedure and for cerebral blood flow. Cerebral vascular morphology was examined by immunehistology.ResultsIn AAV-PCSK9DY-treated mice, plaque burden, plasma cholesterol, and triglycerides are elevated. RNAseq analyses followed by KEGG annotation show increased expression of genes linked to inflammatory processes in the aortas of these mice. In AAV-PCSK9DY-treated mice learning was delayed and long-term memory impaired. Blood flow was reduced in the cingulate cortex (-17%), caudate putamen (-15%), and hippocampus (-10%). Immunohistological studies also show an increased incidence of string vessels and pericytes (CD31/Col IV staining) in the hippocampus accompanied by patchy blood-brain barrier leaks (IgG staining) and increased macrophage infiltrations (CD68 staining).DiscussionWe conclude that the hyperlipidemic PCSK9DY mouse model can serve as an appropriate approach to induce microvascular dysfunction that leads to reduced blood flow in the hippocampus, which could explain the cognitive dysfunction in these mice.

Abstract Objective: To compare nutritional value and aspects with environmental impact of high-protein (HP) and ‘normal-protein’ (NP) ultra-processed foods (UPF). Design: 299 HP and 286 NP products were evaluated regarding aspects of nutritional value, energy density, Nutri-Score, number of additives as well as hyper-palatability and price. Environmental impact of HP UPF was addressed by analysing protein sources and the use of environmentally persistent non-nutritive artificial sweeteners. Setting: Cross-sectional market analysis in German supermarkets and online shops. Participants: 299 HP and 286 NP UPF products. Results: HP compared to NP UPF had a lower energy density, a lower content of sugar, total and saturated fat, whereas fibre and protein content (62·2 % animal protein) were higher (all P < 0·001). HP products therefore had a higher prevalence of Nutri-Score A (67·2 % v. 21·7 %) and a lower prevalence of Nutri-Score E (0·3 % v. 11·2 %) labelling (both P < 0·001). By contrast, salt content and the number of additives (environmentally persistent sweeteners, sugar alcohols, flavourings) were higher in HP compared to NP UPF (P < 0·001). When compared to HP products, twice as many NP were identified as hyper-palatable (82·5 % v. 40·5 %; P < 0·001). The price of HP was on average 132 % higher compared to NP UPF (P < 0·001). Conclusions: While major adverse aspects of UPF regarding nutritional profile and hyper-palatability are less pronounced in HP compared to NP products, higher salt content, increased number of additives and negative environmental effects from frequent use of animal protein and environmentally persistent sweeteners are major drawbacks of HP UPF.

The increasing global plastic production has created an urgent demand for energy-efficient processes to transform mixed plastic waste into value-added products via upcycling. Compatibilization of polypropylene (PP) and poly(ethylene terephthalate) (PET), two used semi-crystalline polymers in industry, is investigated in this study. We evaluate the effectiveness of an ethylene-butylene-acrylate terpolymer (PTW) at different contents in a 70/30 PP/PET blend, examining the resulting physico-chemical characteristics. Adding PTW as compatibilizer significantly reduces the droplet size in the PP/PET blend, improving rheological and mechanical properties. Remarkably, the blend containing 1.5 % PTW exhibits maximum enhancement in mechanical properties. To understand deeply the chemical compatibilization mechanism, Fourier transform infrared spectroscopy (FTIR-ATR), Atomic Force Microscopy combined with infrared spectroscopy (AFM-IR), and Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) techniques were employed. The compatibilizer was located at the interphase, and the chemical reaction using AFM-IR and 1H NMR was tracked. These advanced techniques prove the chemical compatibilization mechanism in PP/PET blends with PTW. These findings contribute to understanding the compatibilization processes, offering valuable guidance for developing efficient upcycling processes for mixed plastic waste.

Piezoelectric poly(L-lactide) (PLLA) fibers, exhibiting high molecular chain orientation, are promising for biomedical applications. Chain orientation decreases due to fast relaxation during melt-spinning process, which implies that a second process to induce piezoelectric chain morphology is usually necessary. This work introduces a one-step melt-spinning process of piezoelectric PLLA fibers, spun directly from the melt, employing a rheological guidance for the selection of the PLLA type and process parameters, based on Rouse's relaxation time. The chain orientation and the relaxation time increased with the optical purity and average molecular weight of PLLA. The reduction of extrusion temperature from 180 °C to 150 °C facilitated in a significant way the preservation of chain orientation, and the impact of the elongation rate was as well intensified. Combining high elongation rates of ≤ 29 s−1 and reduced extrusion temperature of 150 °C led to flow-induced crystallization of oriented crystals directly from melt in a single step. This fiber exhibited piezoelectric properties in form of a deflection of 1.9 ± 0.3 µm when applying an open-circuit voltage of 210 V. The piezoelectric response was similar to that of a fiber, melt-spun at high extrusion temperature of 180 °C, with additional post-annealing in a second step.

Starting from acid chlorides, alkynes, tryptamines, and acryloyl chloride, 21 densely substituted tetrahydro-β-carbolines were prepared in a four-component, one-pot reaction. In this study, the aza-Michael addition step to generate intermediate enaminones was optimized in the presence of ytterbium triflate. Moreover, apart from acryloyl chloride, all reactants could be deployed in almost equimolar ratios, which increases the atom economy of the sequence. For mechanistic rationalization, the concluding aza-anellation was investigated by DFT calculations on potential intermediates and corresponding activation energies, revealing that the aza-anellation proceeds via ene reaction rather than via electrocyclization.

Abstract A low-energy electronic recoil calibration of XENON1T, a dual-phase xenon time projection chamber, with an internal $${}^{37}$$ 37 Ar source was performed. This calibration source features a 35-day half-life and provides two mono-energetic lines at 2.82 keV and 0.27 keV. The photon yield and electron yield at 2.82 keV are measured to be ( $$32.3\,\pm \,0.3$$ 32.3 ± 0.3 ) photons/keV and ( $$40.6\,\pm \,0.5$$ 40.6 ± 0.5 ) electrons/keV, respectively, in agreement with other measurements and with NEST predictions. The electron yield at 0.27 keV is also measured and it is ( $$68.0^{+6.3}_{-3.7}$$ 68 . 0 - 3.7 + 6.3 ) electrons/keV. The $${}^{37}$$ 37 Ar calibration confirms that the detector is well-understood in the energy region close to the detection threshold, with the 2.82 keV line reconstructed at ( $$2.83\,\pm \,0.02$$ 2.83 ± 0.02 ) keV, which further validates the model used to interpret the low-energy electronic recoil excess previously reported by XENON1T. The ability to efficiently remove argon with cryogenic distillation after the calibration proves that $${}^{37}$$ 37 Ar can be considered as a regular calibration source for multi-tonne xenon detectors.