Die Charité – Universitätsmedizin Berlin unterstützt ihre angehörigen Autor*innen beim Publizieren im Open Access seit 2018 finanziell und ist daran interessiert, auch in nachhaltige Infrastruktur für eine offene Wissenschaft zu investieren. Im Rahmen des Programms „Open-Access-Publikationskosten“ werden Mittel zur Deckung von Mehrkosten beantragt, die der Charité als publikationsstarker Einrichtung in der Transformation zu einem artikelbasierten Abrechnungs- und Finanzierungssystem entstehen. Strukturen und Prozesse für das Monitoring von Publikations- und Kostendaten sollen weiterentwickelt und technisch optimiert werden. Angestrebt werden größtmögliche Transparenz der Kosten und Finanzierungsströme sowie Standardisierung der Publikationsdaten zur einfachen Weiterverarbeitung in verschiedenen internen und externen Kontexten. Eine umfassende Unterstützung von Wissenschaftler*innen beim Open Access Publizieren und eine unkomplizierte Förderung sollen dauerhaft sichergestellt werden.

Clathrin-mediated endocytosis (CME) is the predominant endocytic pathway in eukaryotic cells and a major regulator of cell physiology as it facilitates the internalization of receptors, channels, and transporters and viral entry. The clathrin terminal domain acts as a central protein interaction hub within the endocytic protein network. Previously described inhibitors of CME display off-target activities that result in cytotoxicity, providing limitations to their use. We report the development and characterization of next-generation small molecule inhibitors of clathrin terminal domain function. These compounds termed Pitstop 2c and Pitstop 2d occupy the binding site within the clathrin terminal domain for endocytic protein ligands including epsin, resulting in potent inhibition of receptor-mediated endocytosis and reduced entry of vesicular stomatitis virus (VSV) with minimal cytotoxic side effects. Next-generation Pitstops thus provide an improved toolset to address clathrin function in cell physiology with potential applications as inhibitors of virus and pathogen entry.

A multi-element isotope (N, O, Ti, and Cr) study was conducted on C1 and CM-like clasts hosted in achondrites and chondrite breccias to understand the genesis of these chondritic clasts. The mineralogy, O, and N isotopes confirm that CM-like clasts in howardites and polymict eucrites closely resemble CM chondrite-like material. The O and Cr isotope composition of C1 clasts in CR chondrites overlaps with those of CR chondrites, implying either formation in a similar nebular environment or resemblance to local CR material that underwent more extensive in situ alteration. Notably, these clasts are less enriched in 15N than bulk CR chondrites. In contrast, C1 clasts in ureilites are enriched in 15N relative to the Earth's atmosphere by ~100‰ setting them apart from any other known solar system material. They display elevated 17O and 18O values and lie along the CCAM line. In addition, a C1 clast from an ureilite represents the most 54Cr-enriched and 50Ti-depleted endmember among the carbonaceous chondrites. Altogether, these isotopic characteristics suggest that C1 clasts in ureilites represent material not sampled by any known meteorite group. Overall, this study highlights the presence of primitive, isotopically distinct materials in the early outer solar system, some of which were transported to the inner solar system to the accretion region of the host parent bodies.

Domestic animals are moved for reasons that are mutually beneficial to the animal and the farmer. Some examples include the need for fresh grazing grounds and watering points, or the need to access livestock markets for income to sustain farmers’ livelihoods. However, livestock mobility is a key risk factor for the transmission of transboundary animal diseases. Contact tracing of individual animals and flocks is very challenging, especially in most low-income countries, due to a lack of efficient livestock traceability systems. Despite these challenges, low-income countries, such as Uganda, issue paper-based animal movement permits (AMPs) to ensure only clinically healthy animals are moved following a physical inspection. In this study, we used national approximately 9 years of (2012–2020) small ruminant movement data obtained from archived AMPs in Uganda to describe small ruminant movement networks. The movement networks were described using social network analysis (SNA) approaches implemented in R software to identify and visualize relationships between individual and groups districts in Uganda. Lira, Kaberamaido, Nabilatuk, Mbarara, Kiruhura, Kampala, and Wakiso were identified as districts with the highest degree (in and out-degree) and betweenness among other centrality measures. Our results suggest these districts could be the most important bridges connecting the various regions of the country. Tailoring control interventions to such districts with high incoming and high outgoing shipments, or bridges, would accelerate the nation’s ability to timely detect outbreaks, prevent or mitigate further spread, and contain diseases in their original foci, respectively. We also identified areas for active surveillance, vaccination, quarantine, and biosecurity measures-staging depending on prevailing circumstances. These findings will be used to guide the national small ruminant infectious diseases control strategies and subsequently contribute to national and global initiatives, such as the 2030 Peste des petits ruminants (PPR) eradication program.

Dynamical backaction cooling has been demonstrated to be a successful method for achieving the motional quantum ground state of a mechanical oscillator in the resolved-sideband regime, where the mechanical frequency is significantly larger than the cavity decay rate. Nevertheless, as mechanical systems increase in size, their frequencies naturally decrease, thus bringing them into the unresolved-sideband regime, where the effectiveness of the sideband cooling approach decreases. Here we demonstrate, however, that this cooling technique in the unresolved-sideband regime can be significantly enhanced by utilizing a nonlinear cavity as shown in the experimental work of Zoepfl et al. [Phys. Rev. Lett. 130, 033601 (2023)]. The above arises due to the increased asymmetry between the cooling and heating processes, thereby improving the cooling efficiency. In addition, we show that injecting a squeezed vacuum into the nonlinear cavity paves the way to ground-state cooling of the mechanical mode. Notably, the required squeezing parameters are far less stringent than in the linear case, simplifying experimental implementation.

Prevailing anthropocentric frameworks of animal husbandry in archaeological research are increasingly critiqued for their inability to capture the full spectrum of human–non-human systems. In west Siberia and northern Mongolia, reindeer herding communities practise an entwined multi-species lifeways with the subarctic boreal and forest ecosystems—but these practices lack secure archaeological chronologies and time depth in northeast Asia. Traces of reindeer herding and reindeer remains themselves are often under-represented in the depositional record, requiring alternative avenues for tracing the archaeology of reindeer herding. Here, we explore the potential of documenting these complex dynamics archaeologically through a proof-of-concept analysis of stable isotopic carbon and nitrogen in faunal bone collagen, which can represent a possible nexus of multi-species practices. In doing so, we seek to expand investigative potentials into both human and non-human community members, providing valuable, nuanced insights into past practices, hunter–herder interactions and domestication dynamics.

We investigate quotients by radical monomial ideals for which T2, the second cotangent cohomology module, vanishes. The dimension of the graded components of T2, and thus their vanishing, depends only on the combinatorics of the corresponding simplicial complex. We give both a complete characterization and a full list of one dimensional complexes with T2=0. We characterize the graded components of T2 when the simplicial complex is a uniform matroid. Finally, we show that T2 vanishes for all matroids of corank at most two and conjecture that all connected matroids with vanishing T2 are of corank at most two.

Background

Effective biosecurity measures prevent the spread of pathogens, thereby reducing the need for antibiotic use on livestock farms. However, quantitative data on these practices and health outcomes in semi-intensive broiler farms in low-income settings is limited. A longitudinal study in Wakiso, Uganda, aimed to evaluate biosecurity practices, health performance, and antibiotic use in such farms.

Methods

The FarmUSE survey tool was used to collect data from 19 farms over two production cycles. A biosecurity risk assessment tool was used to quantify biosecurity. Blood samples (n = 342) were collected and analyzed using the ProFLOK® assay to assess antibody responses to vaccines for Newcastle disease (NCD), Infectious Bronchitis (IB), and Infectious bursal disease (IBD).

Results

Median biosecurity scores were 26.3 % for external measures, 55.6 % for internal measures, and an overall score of 38.5 %. Sixteen farms reported respiratory signs, and 12 had gastrointestinal issues, with median mortality rates of 2.9 % in the first cycle and 4.6 % in the second. Antibiotic use was reported by 84 % and 77 % of farms in the first and second cycles, respectively. The most used antibiotics were tetracyclines, fluoroquinolones, and macrolides, with the highest usage occurring during the brooding phase. Good antibody responses were reported in only 10.5 % of flocks for NCD and 16 % for IBD, while all farms had poor responses against IB.

Conclusion

Recurrent clinical signs could be attributed to insufficient biosecurity and inadequate vaccination outcomes, resulting in high antibiotic usage despite low mortality rates. Improving diagnostic access and strengthening the vaccine supply chain are essential. Identifying feasible and cost-effective biosecurity practices for semi-intensive broiler farms can enhance health outcomes, reduce antibiotic use, and boost productivity.

The main goal of this work is to provide a description of transitions from uniform to non-uniform snychronization in diffusions based on large deviation estimates for finite time Lyapunov exponents. These can be characterized in terms of moment Lyapunov exponents which are principal eigenvalues of the generator of the tilted (Feynman–Kac) semigroup. Using a computer assisted proof, we demonstrate how to determine these eigenvalues and investigate the rate function which is the Legendre–Fenchel transform of the moment Lyapunov function. We apply our results to two case studies: the pitchfork bifurcation and a two-dimensional toy model, also considering the transition to a positive asymptotic Lyapunov exponent.

Variational quantum algorithms (VQAs) are hybrid quantum-classical approaches used for tackling a wide range of problems on noisy intermediate-scale quantum (NISQ) devices. Testing these algorithms on relevant hardware is crucial to investigate the effect of noise and imperfections and to assess their practical value. Here, we implement a variational algorithm designed for optimized parameter estimation on a continuous variable platform based on squeezed light, a key component for high-precision optical phase estimation. We investigate the ability of the algorithm to identify the optimal metrology process, including the optimization of the probe state and measurement strategy for small-angle optical phase sensing. Two different optimization strategies are employed, the first being a gradient descent optimizer using Gaussian parameter shift rules to estimate the gradient of the cost function directly from the measurements. The second strategy involves a gradient-free Bayesian optimizer, fine-tuning the system using the same cost function and trained on the data acquired through the gradient-dependent algorithm. We find that both algorithms can steer the experiment towards the optimal metrology process. However, they find minima not predicted by our theoretical model, demonstrating the strength of variational algorithms in modelling complex noise environments, a non-trivial task.

The coupling between electrons and phonons is one of the fundamental interactions in solids, underpinning a wide range of phenomena, such as resistivity, heat conductivity and superconductivity. However, direct measurements of this coupling for individual phonon modes remain a substantial challenge. In this work, we introduce a new technique for mapping phonon dispersions and electron–phonon coupling (EPC) in van der Waals (vdW) materials. By generalizing the quantum twisting microscope1 (QTM) to cryogenic temperatures, we demonstrate its capability to map not only electronic dispersions through elastic momentum-conserving tunnelling but also phononic dispersions through inelastic momentum-conserving tunnelling. Crucially, the inelastic tunnelling strength provides a direct and quantitative measure of the momentum and mode-resolved EPC. We use this technique to measure the phonon spectrum and EPC of twisted bilayer graphene (TBG) with twist angles larger than 6°. Notably, we find that, unlike standard acoustic phonons, whose coupling to electrons diminishes as their momentum tends to zero, TBG exhibits a low-energy mode whose coupling increases with decreasing twist angle. We show that this unusual coupling arises from the modulation of the interlayer tunnelling by a layer-antisymmetric ‘phason’ mode of the moiré system. The technique demonstrated here opens the way for examining a large variety of other neutral collective modes that couple to electronic tunnelling, including plasmons2, magnons3 and spinons4 in quantum materials.

Designing nanomaterials for drug encapsulation is a crucial, yet challenging, aspect for pharmaceutical development. An important step is synthesizing amphiphiles that form stable supramolecular systems for efficient drug loading. In the case of fluorinated drugs, these have superior properties and also a tendency toward reduced water solubility. For the first time, we report here fluorinated hexosome carriers made from nonionic dendritic amphiphiles, capable of encapsulating the fluorinated drug Leflunomide with high efficiency (62 ± 3%) and increasing its solubility by 12-fold. We synthesized amphiphiles with varying tail groups (fluorinated/alkylated), and their supramolecular self-assembly was investigated using cryogenic transmission electron microscopy and small-angle X-ray scattering. Furthermore, Leflunomide and its equivalent nonfluorinated counterpart were encapsulated within fluorinated and nonfluorinated assemblies. Self-assembly and encapsulation mechanisms were well supported by coarse-grained molecular simulations, yielding a fundamental understanding of the new systems.

Electron paramagnetic resonance (EPR) is an accurate and efficient technique to probe unpaired electrons in many applications across materials science, chemistry, and biology. Dynamic processes are investigated using EPR; however, these applications are limited by the use of resonator-based spectrometers such that the entire process must be confined to the resonator. The EPR-on-a-chip (EPRoC) device circumvents this limitation by integrating the entire EPR spectrometer into a single microchip. In this approach, the coil of a voltage-controlled oscillator (VCO) is used as the microwave source and detector simultaneously, operating under a protective coating such that the device may be placed in the sample solution directly. Additionally, improvements in sensitivity via rapid scan EPR (RS-EPR/RS-EPRoC) increase the accessible applications where SNR per measurement time is the fundamental limit. The herein reported device combines a dipstick EPRoC sensor with the enhanced sensitivity of frequency-swept frequency modulated rapid scan to measure triarylmethyl (trityl, Ox071) oxygen-sensitive probes dissolved in aqueous solutions. EPR spectra of Ox071 solutions were recorded using the RS-EPRoC sensor while varying the oxygen concentration of the solution between normal atmosphere and after purging the solution with nitrogen gas. We demonstrate that EPRoC may be employed to monitor dissolved oxygen in fluid solution in an online fashion.

Scholars and pundits focusing on the changing international order and its possible fragmentation often pay little attention to the manifold relationships between international organizations (IOs). Neglecting inter-organizational relationships, we argue, biases discussions towards doomsday predictions and reinforces the perception of global fragmentation. In this Forum, we address these biases by bringing together two strands of IR scholarship: power rivalry/transition and regime complexity. We do so by introducing the concept of organizational (dis)entanglements. An examination of how more and less powerful national and international policymakers engage and disengage IOs, highlights processes of reinforcing, muddling through, or undermining various ongoing order-making initiatives. The individual contributions examine organizational (dis)entanglements by highlighting actors’ various multilateral order-making attempts across IOs, global and regional ordering dynamics through IOs, and the roles international bureaucrats play in these processes. These contributions help identify new directions of inquiry in the study of IOs and international order by, for example, demonstrating that actors can engage with competition and cooperation simultaneously. Not all ordering attempts are equally likely to radically change global politics.

In the recent years, studies on health consequences of smartphone usage time have increased, yet findings on the effectiveness of usage interventions remain unclear. This preregistered study investigates the effectiveness of a planning intervention to reduce total smartphone usage time. Additionally, it examines the interventions’ underlying mechanisms of self-efficacy, intention, action, and coping planning. A primary analysis of a randomized controlled trial, with data collected at three measurement points was conducted. Three cohorts of university students were recruited during the period prior to the end-of-term exams. A total of N = 787 participants were allocated to either an intervention condition (n = 389) or a control condition (n = 398). At baseline measurement (T1) the intervention condition formed up to three actions and three coping plans. Self-reported self-efficacy, intention, action, and coping planning as well as objectively measured smartphone usage were assessed up to a three-weeks follow-up. The effectiveness of the intervention and the mediating mechanisms were evaluated using linear mixed models. The analysis revealed no significant effect on total smartphone usage time. With respect to the interventions underlying mechanisms, results show a significant indirect effect of self-efficacy at T2, on a reduction in total smartphone usage time at T3 but no evidence for intention, action, or coping planning.

The molecular and serological prevalence of Toxoplasma gondii infection was investigated among rodents living in desertic areas in the Tataouine district, in the south of Tunisia. A total number of 43 rodents were captured from four sites classified as arid and Saharan climatic zones. Sera, hearts, spleens and brains were collected from each rodent. Sera were tested for the presence of anti-T. gondii IgG by the ELISA technique. PCR was used to detect T. gondii DNA from different tissues. Two rodent species were identified as Ctenodactylus gundi (Rodentia, Ctenodactylidae) (N = 28; 65%) and Psammomys obesus (Rodentia, Muridae) (N = 15; 35%). The overall molecular prevalence of T. gondii was 39% (17/43). Infection prevalences were higher in C. gundi (53.6%; 15/28) compared to P. obesus (13.3%; 2/15). In both species, the brain was the most infected organ (p = 0.02). No significant difference was recorded for the two rodent species according to gender and sampling sites (p > 0.05). The overall seroprevalence was up to 34.9% (15/43). It was higher in C. gundi (43%; 12/28) compared to P. obesus (20; 3/15) (p = 0.02). These results highlight a high infection level of T. gondii in desertic rodents. More investigations are required to understand the role of other desertic mammals and to identify the genotype circulating in the Tunisian Sahara.

Background: A comorbidity between Borderline Personality Disorder (BPD) and Posttraumatic Stress Disorder (PTSD) is common, severely disabling, and hard to treat. The choice of an optimal psychotherapy based on patient characteristics remains challenging.

Objective: This study develops models to predict the outcome of two psychotherapies for comorbid BPD and PTSD.

Method: Data from two trials comparing Narrative Exposure Therapy (NET, N = 40) with Dialectical Behavior Therapy-based treatment (DBT-bt, N = 40) was analysed. A cross-validated genetic algorithm was used to detect baseline predictors of change in PTSD symptoms.

Results: In the NET group higher education, more baseline PTSD symptoms, more traumatic experiences, fewer baseline BPD symptoms, and not taking antipsychotic medication predicted better treatment outcome. This model (RMSE = 8.98) outperformed the prediction of PTSD symptom reduction with baseline PTSD symptoms alone (RMSE = 10.07) or with all available predictor variables (RMSE = 12.97). Only more baseline PTSD symptoms were selected to predict a better treatment outcome after DBT-bt. This model (RMSE = 9.41) outperformed the prediction of change in PTSD symptoms with all available predictor variables (RMSE = 14.43).

Conclusion: Differences in treatment outcome between NET and DBT-bt may be predictable at baseline, to identify which one of both treatments may be most beneficial for individual patients. The small sample size may restrict the generalizability of the results.

Learning, particularly vocal learning, is often a social process. In human infants, it is well-established that social interactions influence speech acquisition and are hypothesized to modulate attentiveness and sensory processes, thereby affecting the speech-learning process. However, our understanding of how social interactions shape vocal ontogenetic processes in non-human mammals, particularly those which vocally learn, remains limited. In the bat Saccopteryx bilineata, pups acquire the adult vocal repertoire through a distinctive babbling behavior that shows interesting similarities to human infant babbling. While babbling encompasses many different syllable types, it is particularly noteworthy that pups learn song syllables by imitating adult singing males. The pups' social environment involves frequent interactions with their mothers, whereas adult males mainly serve as the primary source of acoustic input. We monitored the vocal ontogeny of wild pups, investigating whether their social environment influenced three aspects of babbling: the amount of vocal practice, the pups’ final syllable repertoire size and the production of the syllable types acquired through vocal learning. The results demonstrate that maternal behavioral displays significantly influence the amount of vocal practice, the presence and versatility of song syllable types in babbling and the percentage of mature song syllables. Our findings show that maternal feedback plays a significant role in the vocal ontogeny and learning processes of S. bilineata, thus enhancing our understanding of the relationship between social feedback and vocal development in mammalian vocal learners.

Quantum machine learning aims to improve learning methods through the use of quantum computers. If it is to ever realize its potential, many obstacles need to be overcome. A particularly pressing one arises at the prediction stage because the outputs of quantum learning models are inherently random. This creates an often considerable overhead, as many executions of a quantum learning model have to be aggregated to obtain an actual prediction. In this work, we analyze when quantum learning models can evade this issue and produce predictions in a near-deterministic way—paving the way to single-shot quantum machine learning. We give a rigorous definition of single shotness in quantum classifiers and show that the degree to which a quantum learning model is near deterministic is constrained by the distinguishability of the embedded quantum states used in the model. Opening the black box of the embedding, we show that if the embedding is realized by quantum circuits, a certain depth is necessary for single shotness to be even possible. We conclude by showing that quantum learning models cannot be single shot in a generic way and trainable at the same time.

Who makes it to the top? We use the leading socio-economic survey in Germany, supplemented by extensive data on the rich, to answer this question. We identify the key predictors for belonging to the top 1 percent of income, wealth, and both distributions jointly. Although we consider many, only a few traits matter: Entrepreneurship and self-employment in conjunction with a sizable inheritance of company assets is the most important covariate combination across all rich groups. Our data suggest that all top 1 percent groups, but especially the joint top 1 percent, are predominantly populated by intergenerational entrepreneurs.