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Varved lake sediments are exceptional archives of paleoclimatic information due to their precise chronological control and annual resolution. However, quantitative paleoclimate reconstructions based on the biogeochemical composition of biochemical varves are extremely rare, mainly because the climate–proxy relationships are complex and obtaining biogeochemical proxy data at very high (annual) resolution is difficult. Recent developments in high-resolution hyperspectral imaging (HSI) of sedimentary pigment biomarkers combined with micro X-ray fluorescence (µXRF) elemental mapping make it possible to measure the structure and composition of varves at unprecedented resolution. This provides opportunities to explore seasonal climate signals preserved in biochemical varves and, thus, assess the potential for annual-resolution climate reconstruction from biochemical varves. Here, we present a geochemical dataset including HSI-inferred sedimentary pigments and µXRF-inferred elements at very high spatial resolution (60 µm, i.e. > 100 data points per varve year) in varved sediments of Lake Żabińskie, Poland, over the period 1966–2019 CE. We compare these data with local meteorological observations to explore and quantify how changing seasonal meteorological conditions influenced sediment composition and varve formation processes. Based on the dissimilarity of within-varve multivariate geochemical time series, we classified varves into four types. Multivariate analysis of variance shows that these four varve types were formed in years with significantly different seasonal meteorological conditions. Generalized additive models (GAMs) were used to infer seasonal climate conditions based on sedimentary variables. Spring and summer (MAMJJA) temperatures were predicted using Ti and total C (Radj2=0.55; cross-validated root mean square error (CV-RMSE) = 0.7 ∘C, 14.4 %). Windy days from March to December (mean daily wind speed > 7 m s−1) were predicted using mass accumulation rate (MAR) and Si (Radj2=0.48; CV-RMSE = 19.0 %). This study demonstrates that high-resolution scanning techniques are promising tools to improve our understanding of varve formation processes and climate–proxy relationships in biochemical varves. This knowledge is the basis for quantitative high-resolution paleoclimate reconstructions, and here we provide examples of calibration and validation of annual-resolution seasonal weather inference from varve biogeochemical data.

Abstract The change of a quantum state can generally only be fully monitored through simultaneous measurements of two non-commuting observables $$\hat{X}$$ X ̂ and $$\hat{Y}$$ Y ̂ spanning a phase space. A measurement device that is coupled to the thermal environment provides at a time a pair of values that have a minimal uncertainty product set by the Heisenberg uncertainty relation, which limits the precision of the monitoring. Here, we report on an optical ensemble measurement setup that is able to monitor the time-dependent change of the quantum state’s displacement in phase space ( $$\langle \hat{X}(t)\rangle ;\langle \hat{Y}(t)\rangle$$ ⟨ X ̂ ( t ) ⟩ ; ⟨ Y ̂ ( t ) ⟩ ) with an imprecision 10 dB below the Heisenberg uncertainty limit. Our setup provides pairs of values (X(t i ); Y(t i )) from simultaneous measurements at subsequent times t i . The measurement references are not coupled to the thermal environment but are established by an entangled quantum state. Our achievement of a tenfold reduced quantum imprecision in monitoring arbitrary time-dependent displacements supports the potential of the quantum technology required for entanglement-enhanced metrology and sensing as well as measurement-based quantum computing.

Objective The aim of this study was to examine the associations between characteristics of physicians working in primary care emergency units (PCEUs) and the outcome of assessments of the medical records. Design Data from a previous case-control study was used to evaluate factors related to medical errors. Setting Ten Norwegian PCEUs were included. Subjects Physicians that had evoked a patient complaint, and a random sample of three physicians from the same PCEU and time period as the physician who had evoked a complaint. Recorded physician characteristics were: gender, seniority, citizenship at, and years after authorization as a physician, specialty in general practice, and workload at the PCEU. Main outcome measures: Assessments of the medical records: errors that may have led to harm, no medical error, or inconclusive. Results In the complaint group 77 physicians were included, and in the random sample group 217. In the first group, 53.2% of the medical records were assessed as revealing medical errors. In the random sample group, this percentage was 3.2. In the complaint group the percentages for no-error and inconclusive for the female physicians were 30.8 and 15.4; and for the male physicians 9.8 and 27.3, p = 0.027. Conclusion In the group of complaints there was a higher percentage with no assessed medical error, and a lower percentage with inconclusive assessments of medical errors, among female physicians compared to their male colleagues. We found no other physician factors that were associated with assessed medical errors. Future research should focus on the underlying elements of these findings.Key points Medical errors are among the leading causes of death and they are essentially avoidable. Primary care emergency units are a vulnerable arena for committing medical errors. By assessing the medical records of a group of physicians who had evoked a complaint, no differences related to physician factors were revealed in the incidence of medical errors. In the group of female physicians, the proportion of no-errors, was higher, and the percentage of inconclusive medical records was lower than for their male colleagues. The Norwegian regulations on independent participation in PCEUs may have modulated these results.

Abstract Magnesium-based lightweight structural materials exhibit potential for energy savings. However, the state-of-the-art quest for novel compositions with improved properties through conventional bulk metallurgy is time, energy, and material intensive. Here, the opportunities provided by combinatorial thin film materials design for the sustainable development of magnesium alloys are evaluated. To characterise the impurity level of (Mg,Ca) solid solution thin films within grains and grain boundaries, scanning transmission electron microscopy and atom probe tomography are correlatively employed. It is demonstrated that control of the microstructure enables impurity levels similar to bulk-processed alloys. In order to substantially reduce time, energy, and material requirements for the sustainable development of magnesium alloys, we propose a three-stage materials design strategy: (1) Efficient and systematic investigation of composition-dependent phase formation by combinatorial film growth. (2) Correlation of microstructural features and mechanical properties for selected composition ranges by rapid alloy prototyping. (3) Establishment of synthesis–microstructure–property relationships by conventional bulk metallurgy.

The personalisation principle is a design recommendation and states that multimedia presentations using personalised language promote learning better than those using formal language (e.g., using "your" instead of "the"). It is often assumed that this design recommendation affects motivation and therefore allocation of attention. To gain further insight into the processes underlying personalisation effects we conducted an eye tracking experiment with 37 German university students who were presented with either personalised or formal learning materials. We examined group differences in attention allocation parameters (fixation rate, mean fixation duration, transition count, reading depth). The eye-tracking data was combined with self-reports concerning motivation, cognitive load, and learning outcomes. Eye-tracking data revealed a higher reading depth for the main picture areas of interest in the personalised condition. Additionally, participants found the personalised version more appealing and inviting. For learning outcomes, there was a positive effect of personalisation. However, after Bonferroni correction effects and therefore the pattern expected did not reach significance. The results are discussed in regard to their importance for methodological and practical implications for instructional design.

Although recent evidence indicates that CD4+ T cells responding to chronic viral infection are functionally heterogenous, our understanding of the developmental relationships between these subsets, and a determination of how their transcriptional landscape compares to their acute infection counterparts remains unclear. Additionally, whether cell-intrinsic factors such as TCR usage influence CD4+ T cell fate commitment during persistent infection has not previously been studied. Herein, we perform single-cell RNA sequencing (scRNA-seq) combined with single-cell T cell receptor sequencing (scTCR-seq) on virus-specific CD4+ T cells isolated from mice infected with chronic lymphocytic choriomeningitis virus (LCMV) infection. We identify several transcriptionally distinct states among the Th1, Tfh, and memory-like T cell subsets that form at the peak of infection, including the presence of a previously unrecognized Slamf7+ subset with cytolytic features. We further show that the relative distribution of these populations differs substantially between acute and persistent LCMV infection. Moreover, while the progeny of most T cell clones displays membership within each of these transcriptionally unique populations, overall supporting a one cell-multiple fate model, a small fraction of clones display a biased cell fate decision, suggesting that TCR usage may impact CD4+ T cell development during chronic infection. Importantly, comparative analyses further reveal both subset-specific and core gene expression programs that are differentially regulated between CD4+ T cells responding to acute and chronic LCMV infection. Together, these data may serve as a useful framework and allow for a detailed interrogation into the clonal distribution and transcriptional circuits underlying CD4+ T cell differentiation during chronic viral infection.

Burkholderia pseudomallei and the closely related species, Burkholderia mallei, produce similar multifaceted diseases which range from rapidly fatal to protracted and chronic, and are a major cause of mortality in endemic regions. Besides causing natural infections, both microbes are Tier 1 potential biothreat agents. Antibiotic treatment is prolonged with variable results, hence effective vaccines are urgently needed. The purpose of our studies was to compare candidate vaccines that target both melioidosis and glanders to identify the most efficacious one(s) and define residual requirements for their transition to the non-human primate aerosol model. Studies were conducted in the C57BL/6 mouse model to evaluate the humoral and cell-mediated immune response and protective efficacy of three Burkholderia vaccine candidates against lethal aerosol challenges with B. pseudomallei K96243, B. pseudomallei MSHR5855, and B. mallei FMH. The recombinant vaccines generated significant immune responses to the vaccine antigens, and the live attenuated vaccine generated a greater immune response to OPS and the whole bacterial cells. Regardless of the candidate vaccine evaluated, the protection of mice was associated with a dampened cytokine response within the lungs after exposure to aerosolized bacteria. Despite being delivered by two different platforms and generating distinct immune responses, two experimental vaccines, a capsule conjugate + Hcp1 subunit vaccine and the live B. pseudomallei 668 ΔilvI strain, provided significant protection and were down-selected for further investigation and advanced development.

Aiming to address clinical requirements subsequent to SARS-CoV-2-related pulmonary disease, multiple research groups and industry groups carried out intensive studies to develop pandemic ventilators (PDVs). In vitro testing to critically evaluate the specific performance of the developed apparatuses is an essential requirement. This study presents a test protocol which promotes a test-oriented, iterative, and agile assessment and consecutive development of such PDVs. It allows for fast identification of specific characteristics of each PDV in the individual test features. The test protocol includes an evaluation of the accuracy of control systems and instruments at changing parameters, the oxygen dynamics, and the response to trigger signals. The test environment is a mechanical lung, which allows reproducing various lung mechanics and to simulate active breathing cycles. A total of three PDVs that are under development were iteratively tested, with a Hamilton T1 as a reference. Continuous testing of the PDVs under development enables quick identification of critical application aspects that deserve further improved. Based on the present test protocol, the ventilators demonstrate a promising performance justifying continued development.

Clouds play an important role in the climate system; nonetheless, the relationship between climate change in general and regional cloud occurrence is not yet well understood. This particularly holds for remote areas such as the iconic Galapagos archipelago in Ecuador. As a first step towards a better understanding, we analyzed the spatio-temporal patterns of cloud cover over Galapagos. We found that cloud frequency and distribution exhibit large inter- and intra-annual variability due to the changing influence of climatic drivers (trade winds, sea surface temperature, El Niño/La Niña events) and spatial variations due to terrain characteristics and location within the archipelago. The highest cloud frequencies occur in mid-elevations on the slopes exposed to the southerly trade winds (south-east slopes). Towards the highlands ( >900 m a.s.l), cloud frequency decreases, with a sharp leap towards high-level crater areas mainly on Isabela Island that frequently immerse into the trade inversion layer. With respect to the diurnal cycle, we found a lower cloud frequency over the islands in the evening than in the morning. Seasonally, cloud frequency is higher during the hot season (January–May) than in the cool season (June–December). However, spatial differences in cloudiness were more pronounced during the cool season months. We further analyzed two periods beyond average atmospheric forcing. During El Niño 2015, the cloud frequency was higher than usual, and differences between altitudes and aspects were less pronounced. La Niña 2007 led to negative anomalies in cloud frequency over the islands, with intensified differences between altitude and aspect.

In this paper, the high strength and lightweight Al–Cu–Li alloy (AA2099) is considered in as-built and preheated conditions (440 °C, 460 °C, 480 °C, 500 °C, and 520 °C). The purpose of this study is to investigate the influence of laser powder bed fusion (LPBF) in situ preheating on precipitation microstructure, mechanical and corrosive properties of LPBF-printed AA2099 alloy compared to the conventionally processed and heat-treated (T83) alloy. It is shown that precipitations evolve with increasing preheating temperatures from predominantly globular Cu-rich phases at lower temperatures (as-built, 440 °C) to more plate and rod-like precipitates (460 °C, 480 °C, 500 °C and 520 °C). Attendant increase with increasing preheating temperatures are the amount of low melting Cu-rich phases and precipitation-free zones (PFZ). Hardness of preheated LPBF samples peaks at 480 °C (93.6 HV0.1), and declines afterwards, although inferior to the T83 alloy (168.6 HV0.1). Preheated sample (500 °C) shows superior elongation (14.1%) compared to the T83 (11.3%) but falls short in tensile and yield strength properties. Potentiodynamic polarization results also show that increasing preheating temperature increases the corrosion current density (Icorr) and corrosion rate. Indicated by the lower oxide resistance (Rox), the Cu-rich phases compromise the integrity of the oxide layer.

Abstract We argue that symmetry and unification can emerge as byproducts of certain physical constraints on dynamical scattering. To accomplish this we parameterize a general Lorentz invariant, four-dimensional theory of massless and massive scalar fields coupled via arbitrary local interactions. Assuming perturbative unitarity and an Adler zero condition, we prove that any finite spectrum of massless and massive modes will necessarily unify at high energies into multiplets of a linearized symmetry. Certain generators of the symmetry algebra can be derived explicitly in terms of the spectrum and three-particle interactions. Furthermore, our assumptions imply that the coset space is symmetric.

Las concepciones sobre el aprendizaje autorregulado en educación superior son determinantes para develar las prácticas de los profesores en relación con el proceso de aprendizaje de sus estudiantes, considerando su historia personal y los elementos del sistema que influyen en la praxis pedagógica. Numerosos análisis han identificado que la percepción del docente sobre el aprendizaje influye radicalmente en cómo aborda sus procesos pedagógicos en educación superior, donde es fundamental reconocer que debe haber una perspectiva que incluya el aprendizaje autorregulado como un modelo transversal de la práctica educativa, que comprenda los factores determinantes para la configuración de estrategias de aprendizaje que respondan a las demandas del sistema educativo. Esta investigación se propuso identificar esas percepciones de los profesores (licenciados) de educación superior acerca del aprendizaje autorregulado. Para esto, se diseñó una entrevista semiestructurada que recoge las principales categorías de la conceptualización del aprendizaje autorregulado, y se hizo un análisis cualitativo de las relaciones categoriales en función de dicha percepción. Se encontró que el aprendizaje autorregulado se percibe como un ideal educativo, en comparación con el aprendizaje autónomo, determinado por la influencia de factores emocionales en la construcción de elementos de autorregulación del aprendizaje.

Abstract Wildlife‐friendly produce shows promise in addressing the disconnect between consumers' choices and the loss of biodiversity from agriculture. However, the scope of programs and their contribution to conservation remain limited. An improved understanding of specific markets, combined with auspicious scenarios, could address this. In Australia's Murray‐Darling Basin, rice fields support the largest known breeding population of the Australasian bittern, a globally endangered waterbird. We surveyed 1478 Australian consumers about their values for “bittern‐friendly” rice. To help support successful bittern breeding, consumers' mean willingness‐to‐pay for a 1‐kg product, normally $3.00, was $4.12—a premium of 37%—while the inferred valuation for their nearest neighbor was $3.79, a 26% premium. In a choice experiment, rice directly sourced from bittern‐friendly rice growers attracted the highest premium, approaching 200%, but conventional rice with indirect support for bittern‐friendly growers was also highly valued. Consumers valued endorsement and certification labels from all organizations more than individual ones, and would pay additional premiums for reduced pesticide use or organic products. Feasibility of broad‐scale, consumer‐funded incentive programs is emphasized by an engaging narrative and a supportive, cohesive rice industry. Similar opportunities likely exist where consumers can be central to endangered species conservation, expanding wildlife‐friendly farming coverage.

Due to the COVID-19 pandemic, university students worldwide have experienced drastic changes in their academic and social lives, with the rapid shift to online courses and contact restrictions being reported among the major stressors. In the present study, we aimed at examining students’ perceived stress over the course of the pandemic as well as individual psychological and social coping resources within the theoretical framework of the Transactional Model of Stress and Coping in the specific group of STEM students. In four cross-sectional studies with a total of 496 computer science students in Germany, we found that students reported significantly higher levels of perceived stress at both measurement time points in the second pandemic semester (October/November 2020; January/February 2021) as compared to the beginning of the first (April/May 2020), indicating that students rather became sensitized to the constant pandemic-related stress exposure than habituating to the “new normal”. Regarding students’ coping resources in the higher education context, we found that both high (a) academic self-efficacy and (b) academic online self-efficacy as well as low (c) perceived social and academic exclusion among fellow students significantly predicted lower levels of students’ (d) belonging uncertainty to their study program, which, in turn, predicted lower perceived stress at the beginning of the first pandemic semester. At the beginning of the second pandemic semester, we found that belonging uncertainty still significantly mediated the relationship between students’ academic self-efficacy and perceived stress. Students’ academic online self-efficacy, however, no longer predicted their uncertainty about belonging, but instead had a direct buffering effect on their perceived stress. Students’ perceived social and academic exclusion among fellow students only marginally predicted their belonging uncertainty and no longer predicted their perceived stress 6 months into the pandemic. We discuss the need and importance of assessing and monitoring students’ stress levels as well as faculty interventions to strengthen students’ individual psychological and social coping resources in light of the still ongoing pandemic.

ABSTRACT Toxin-antitoxin (TA) systems are genetic modules that consist of a stable protein-toxin and an unstable antitoxin that neutralizes the toxic effect. In type II TA systems, the antitoxin is a protein that inhibits the toxin by direct binding. Type II TA systems, whose roles and functions are under intensive study, are highly distributed among bacterial chromosomes. Here, we identified and characterized a novel type II TA system PrrT/A encoded in the chromosome of the clinical isolate 39016 of the opportunistic pathogen Pseudomonas aeruginosa. We have shown that the PrrT/A system exhibits classical type II TA characteristics and novel regulatory properties. Following deletion of the prrA antitoxin, we discovered that the system is involved in a range of processes including (i) biofilm and motility, (ii) reduced prophage induction and bacteriophage production, and (iii) increased fitness for aminoglycosides. Taken together, these results highlight the importance of this toxin-antitoxin system to key physiological traits in P. aeruginosa. IMPORTANCE The functions attributed to bacterial TA systems are controversial and remain largely unknown. Our study suggests new insights into the potential functions of bacterial TA systems. We reveal that a chromosome-encoded TA system can regulate biofilm and motility, antibiotic resistance, prophage gene expression, and phage production. The latter presents a thus far unreported function of bacterial TA systems. In addition, with the emergence of antimicrobial-resistant bacteria, especially with the rising of P. aeruginosa resistant strains, the investigation of TA systems is critical as it may account for potential new targets against the resistant strains.

Two epigenetic pathways of transcriptional repression, DNA methylation and polycomb repressive complex 2 (PRC2), are known to regulate neuronal development and function. However, their respective contributions to brain maturation are unknown. We found that conditional loss of the de novo DNA methyltransferase Dnmt3a in mouse excitatory neurons altered expression of synapse-related genes, stunted synapse maturation, and impaired working memory and social interest. At the genomic level, loss of Dnmt3a abolished postnatal accumulation of CG and non-CG DNA methylation, leaving adult neurons with an unmethylated, fetal-like epigenomic pattern at ~222,000 genomic regions. The PRC2-associated histone modification, H3K27me3, increased at many of these sites. Our data support a dynamic interaction between two fundamental modes of epigenetic repression during postnatal maturation of excitatory neurons, which together confer robustness on neuronal regulation.