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Abstract Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral proteins throughout MVA infection of human fibroblasts and macrophages. >690 human proteins are down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets are not shared with replication-competent vaccinia. Viral intermediate/late gene expression is necessary for MVA antagonism of innate immunity, and suppression of interferon effectors such as ISG20 potentiates virus gene expression. Proteomic changes specific to infection of macrophages indicate modulation of the inflammatory response, including inflammasome activation. Our approach thus provides a global view of the impact of MVA on the human proteome and identifies mechanisms that may underpin its abortive infection. These discoveries will prove vital to design future generations of vaccines.

Abstract Atomically thin layered van der Waals heterostructures feature exotic and emergent optoelectronic properties. With growing interest in these novel quantum materials, the microscopic understanding of fundamental interfacial coupling mechanisms is of capital importance. Here, using multidimensional photoemission spectroscopy, we provide a layer- and momentum-resolved view on ultrafast interlayer electron and energy transfer in a monolayer-WSe2/graphene heterostructure. Depending on the nature of the optically prepared state, we find the different dominating transfer mechanisms: while electron injection from graphene to WSe2 is observed after photoexcitation of quasi-free hot carriers in the graphene layer, we establish an interfacial Meitner-Auger energy transfer process following the excitation of excitons in WSe2. By analysing the time-energy-momentum distributions of excited-state carriers with a rate-equation model, we distinguish these two types of interfacial dynamics and identify the ultrafast conversion of excitons in WSe2 to valence band transitions in graphene. Microscopic calculations find interfacial dipole-monopole coupling underlying the Meitner-Auger energy transfer to dominate over conventional Förster- and Dexter-type interactions, in agreement with the experimental observations. The energy transfer mechanism revealed here might enable new hot-carrier-based device concepts with van der Waals heterostructures.

Here, the authors observe tightly bound, valley-polarized, UV-emissive trions in monolayer transition metal dichalcogenide transistors. These are quasiparticles composed of an electron from a high-lying conduction band with negative effective mass, a hole from the first valence band, and an additional charge from a band-edge state.

Abstract Atherosclerosis and its consequences cause considerable morbidity and mortality world-wide. We have previously shown that expression of the DNA glycosylase NEIL3 is regulated in human atherosclerotic plaques, and that NEIL3-deficiency enhances atherogenesis in Apoe −/− mice. Herein, we identified a time point prior to quantifiable differences in atherosclerosis between Apoe −/− Neil3 −/− mice and Apoe −/− mice. Mice at this age were selected to explore the metabolic and pathophysiological processes preceding extensive atherogenesis in NEIL3-deficient mice. Untargeted metabolomic analysis of young Apoe −/− Neil3 −/− mice revealed significant metabolic disturbances as compared to mice expressing NEIL3, particularly in metabolites dependent on the gut microbiota. 16S rRNA gene sequencing of fecal bacterial DNA indeed confirmed that the NEIL3-deficient mice had altered gut microbiota, as well as increased circulating levels of the bacterially derived molecule LPS. The mice were challenged with a FITC-conjugated dextran to explore gut permeability, which was significantly increased in the NEIL3-deficient mice. Further, immunohistochemistry showed increased levels of the proliferation marker Ki67 in the colonic epithelium of NEIL3-deficient mice, suggesting increased proliferation of intestinal cells and gut leakage. We suggest that these metabolic alterations serve as drivers of atherosclerosis in NEIL3-deficient mice.

ADP-ribosylation is regulated by HPF1 and ARH3, but the cellular target spectrum of these enzymes is not fully understood. Here, the authors use quantitative proteomics to define the HPF1- and ARH3-dependent ADP-ribosylome, providing evidence that mono-ADP-ribosylation of serine predominates in cells.

Here, the authors report on evidence of an excitonic species formed by electrons in high-energy conduction band states with a negative effective mass, explaining previous observations of quantum interference phenomena in two-dimensional semiconductors.

The world is currently dealing with a devastating pandemic. Although growing COVID-19 case numbers, deaths, and hospitalizations are concerning, this spread is particularly alarming in the United States where polarizing opinions, changing policies, and misinformation abound. In particular, American college campuses have been a venue of rampant transmission, with concerning spillover into surrounding, more vulnerable, communities. We surveyed over 600 college students from across the United States and modeled predictors of compliance with non-pharmaceutical interventions. We identified concern with severity, constitutionalism, news exposure, and religiosity as significant positive correlates with compliance, and general trust in science as a significant negative correlate. To determine how applicable nationwide modeling might be to individual local campuses we also administered this same survey to nearly 600 students at two large universities in Utah County. In this population, concern with severity was the only significant positive correlate with compliance; Additionally, feelings of inconvenience were negatively correlated. The effects of feelings of inconvenience, and news exposure were significantly different between populations. These results suggest that we should focus our efforts on increasing knowledge about the pandemic's effects on our society and informing about constitutionality amongst college students. However, we also show that nationwide surveys and modeling are informative, but if campuses are to efficiently curb the spread of COVID-19 this coming semester, they would be best served to utilize data collected from their student populations as these might significantly differ from general consensus data.

RNA quality and quantity are important factors for ensuring the accuracy of gene expression analysis and other RNA-based downstream applications. Thus far, only a limited number of methodological studies have compared sample storage and RNA extraction procedures for human cells. We compared three commercially available RNA extraction kits, i.e., (NucliSENS) easyMAG, RNeasy (Mini Kit) and RiboPure (RNA Purification Kit-blood). In addition, additional conditions, such as storage medium and storage temperature of human peripheral blood mononuclear cells were evaluated, i.e., 4 °C for RNAlater or -80 °C for QIAzol and for the respective cognate lysis buffers; easyMAG, RNeasy or RiboPure. RNA was extracted from aliquots that had been stored for one day (Run 1) or 83 days (Run 2). After DNase treatment, quantity and quality of RNA were assessed by means of a NanoDrop spectrophotometer, 2100 Bioanalyzer and RT-qPCR for the ACTB reference gene. We observed that high-quality RNA can be obtained using RNeasy and RiboPure, regardless of the storage medium, whereas samples stored in RNAlater resulted in the least amount of RNA extracted. In addition, RiboPure combined with storage of samples in its cognate lysis buffer yielded twice as much RNA as all other procedures. These results were supported by RT-qPCR and by the reproducibility observed for two independent extraction runs.

Abstract The ability of bacteriophages to kill bacteria is well known, as is their potential use as alternatives to antibiotics. As such, bacteriophages reach high doses locally through infection of their bacterial host in the human body. In this study we assessed the gene expression profile of peripheral blood monocytes from six donors for twelve immunity-related genes (i.e. CD14, CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, IL10, LYZ, SOCS3, TGFBI and TNFA) induced by Staphylococcus aureus phage ISP and four Pseudomonas aeruginosa phages (i.e. PNM, LUZ19, 14-1 and GE-vB_Pae-Kakheti25). The phages were able to induce clear and reproducible immune responses. Moreover, the overall immune response was very comparable for all five phages: down-regulation of LYZ and TGFBI, and up-regulation of CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, SOCS3 and TNFA. The observed immune response was shown to be endotoxin-independent and predominantly anti-inflammatory. Addition of endotoxins to the highly purified phages did not cause an immune response comparable to the one induced by the (endotoxin containing) phage lysate. In addition, the use of an intermediate level of endotoxins tipped the immune response to a more anti-inflammatory response, i.e. up-regulation of IL1RN and a strongly reduced expression of CXCL1 and CXCL5.

BACKGROUND:The combined impact of multiple healthy behaviors on health exceeds that of single behaviors. This study aimed to estimate trends in the prevalence of a healthy lifestyle among adults in Germany. METHODS:A data set of 18,058 adults aged 25-69 years from three population-based national health examination surveys 1990-92, 1997-99 and 2008-11 with complete information for five healthy behavior factors was used. A 'daily intake of both fruits and vegetables, 'sufficient physical exercise', 'no current smoking' and 'no current risk drinking' were assessed with self-reports and 'normal body weight' was calculated based on measured body weight and height. A dichotomous 'healthy lifestyle' indicator was defined as meeting at least four out of five healthy behaviors. Age-standardized prevalence was calculated stratified by sex, age groups (25-34, 35-44, 45-54 and 55-69 years) and education level (low, medium and high). Trends were expressed in relative change (RC) between 1990-92 and 2008-11. RESULTS:In Germany, the overall prevalence of healthy lifestyle increased from 9.3% in 1990-92 to 13.5% in 1997-99 and to 14.7% in 2008-11 (RC: +58.1%). The prevalence increased among men and women and in all age groups, with the exception of men aged 45-54 years. The RC of increasing healthy lifestyle prevalence between 1990-92 and 2008-11 was stronger albeit on a higher level among women compared to men. Therefore, the gender difference in healthy lifestyle has increased, but age-related differences have overall decreased in this period. Among high educated men the prevalence of a healthy lifestyle increased between 1990-92 and 2008-11 from 10.6% to 16.3% (p = 0.01) and among high educated women from 16.4% to 30.3% and also among medium educated women (10.9 to 16.6, p

In order to select patients most likely to benefit for thrombolysis and to predict patient outcome in acute ischemic stroke, the volumetric assessment of the infarcted tissue is used. However, infarct volume estimation on Diffusion weighted imaging (DWI) has moderate interrater variability despite the excellent contrast between ischemic lesion and healthy tissue. In this study, we compared volumetric measurements of DWI hyperintensity to a simple maximum orthogonal diameter approach to identify thresholds indicating infarct size >70 ml and >100 ml.Patients presenting with ischemic stroke with an NIHSS of ≥ 8 were examined with stroke MRI within 24 h after symptom onset. For assessment of the orthogonal DWI lesion diameters (od-values) the image with the largest lesion appearance was chosen. The maximal diameter of the lesion was determined and a second diameter was measured perpendicular. Both diameters were multiplied. Od-values were compared to volumetric measurement and od-value thresholds identifying a lesion size of > 70 ml and > 100 ml were determined. In a selected dataset with an even distribution of lesion sizes we compared the results of the od value thresholds with results of the ABC/2 and estimations of lesion volumes made by two resident physicians.For 108 included patients (53 female, mean age 71.36 years) with a median infarct volume of 13.4 ml we found an excellent correlation between volumetric measures and od-values (r2 = 0.951). Infarct volume >100 ml corresponds to an od-value cut off of 42; > 70 ml corresponds to an od-value of 32. In the compiled dataset (n = 50) od-value thresholds identified infarcts > 100 ml / > 70 ml with a sensitivity of 90%/ 93% and with a specificity of 98%/ 89%. The od-value offered a higher accuracy in identifying large infarctions compared to both visual estimations and the ABC/2 method.The simple od-value enables identification of large DWI lesions in acute stroke. The cutoff of 42 is useful to identify large infarctions with volume larger than 100 ml. Further studies can analyze the therapeutic utility of this new method.ClinicalTrials.org NCT00715533.

The positive association between education level and health outcomes can be partly explained by dietary behaviour. We investigated the associations between education and several indices of food intake and potential influencing factors, placing special emphasis on physical-activity patterns, using a representative sample of the German adult population.The German National Health Interview and Examination Survey 1998 (GNHIES98) involved 7,124 participants aged between 18 and 79. Complete information on the exposure (education) and outcome (nutrition) variables was available for 6,767 persons. The associations between 'education' and indices of 'sugar-rich food', 'fat-rich food', 'fruit-and-vegetable' and 'alcohol' intake were analysed separately for men and women using multivariate logistic regression analysis. Odds ratios (OR) of education level on nutrition outcomes were calculated and adjusted for age, region (former East/West Germany), occupation, income and other influencing factors such as physical activity indicators.Men and women with only a primary education had a more frequent intake of sugar-rich and fat-rich foods and a less frequent intake of fruit and vegetables and alcohol than people with a tertiary education. 'Physical work activity' partly explained the associations between education and sugar-rich food intake. The interference with physical work activity was stronger among men than women. No significant associations between education and energy-dense food intake were observed in the retirement-age group of persons aged 65+ and among persons with low energy expenditure.In Germany, adults with a low level of education report that they consume energy-dense foods more frequently - and fruit and vegetables and alcohol less frequently - than adults with a high education level. High levels of physical work activity among adults with a low education level may partly explain why they consume more energy-dense foods.

The present study investigated whether changes in gene expression in the right ventricle following pulmonary hypertension can be attributed to hypoxia or pressure loading.To distinguish hypoxia from pressure-induced alterations, a group of rats underwent banding of the pulmonary trunk (PTB), sham operation, or the rats were exposed to normoxia or chronic, hypobaric hypoxia. Pressure measurements were performed and the right ventricle was analyzed by Affymetrix GeneChip, and selected genes were confirmed by quantitative PCR and immunoblotting. Right ventricular systolic blood pressure and right ventricle to body weight ratio were elevated in the PTB and the hypoxic rats. Expression of the same 172 genes was altered in the chronic hypoxic and PTB rats. Thus, gene expression of enzymes participating in fatty acid oxidation and the glycerol channel were downregulated. mRNA expression of aquaporin 7 was downregulated, but this was not the case for the protein expression. In contrast, monoamine oxidase A and tissue transglutaminase were upregulated both at gene and protein levels. 11 genes (e.g. insulin-like growth factor binding protein) were upregulated in the PTB experiment and downregulated in the hypoxic experiment, and 3 genes (e.g. c-kit tyrosine kinase) were downregulated in the PTB and upregulated in the hypoxic experiment.Pressure load of the right ventricle induces a marked shift in the gene expression, which in case of the metabolic genes appears compensated at the protein level, while both expression of genes and proteins of importance for myocardial function and remodelling are altered by the increased pressure load of the right ventricle. These findings imply that treatment of pulmonary hypertension should also aim at reducing right ventricular pressure.

Abstract Genomic surveillance (GS) programmes were crucial in identifying and quantifying the mutating patterns of SARS-CoV-2 during the COVID-19 pandemic. In this work, we develop a Bayesian framework to quantify the relative transmissibility of different variants tailored for regions with limited GS. We use it to study the relative transmissibility of SARS-CoV-2 variants in Chile. Among the 3443 SARS-CoV-2 genomes collected between January and June 2021, where sampling was designed to be representative, the Gamma (P.1), Lambda (C.37), Alpha (B.1.1.7), B.1.1.348, and B.1.1 lineages were predominant. We found that Lambda and Gamma variants’ reproduction numbers were 5% (95% CI: [1%, 14%]) and 16% (95% CI: [11%, 21%]) larger than Alpha’s, respectively. Besides, we observed a systematic mutation enrichment in the Spike gene for all circulating variants, which strongly correlated with variants’ transmissibility during the studied period (r = 0.93, p-value = 0.025). We also characterised the mutational signatures of local samples and their evolution over time and with the progress of vaccination, comparing them with those of samples collected in other regions worldwide. Altogether, our work provides a reliable method for quantifying variant transmissibility under subsampling and emphasises the importance of continuous genomic surveillance.

Abstract The emergence of alternative stable states in forest systems has significant implications for the functioning and structure of the terrestrial biosphere, yet empirical evidence remains scarce. Here, we combine global forest biodiversity observations and simulations to test for alternative stable states in the presence of evergreen and deciduous forest types. We reveal a bimodal distribution of forest leaf types across temperate regions of the Northern Hemisphere that cannot be explained by the environment alone, suggesting signatures of alternative forest states. Moreover, we empirically demonstrate the existence of positive feedbacks in tree growth, recruitment and mortality, with trees having 4–43% higher growth rates, 14–17% higher survival rates and 4–7 times higher recruitment rates when they are surrounded by trees of their own leaf type. Simulations show that the observed positive feedbacks are necessary and sufficient to generate alternative forest states, which also lead to dependency on history (hysteresis) during ecosystem transition from evergreen to deciduous forests and vice versa. We identify hotspots of bistable forest types in evergreen-deciduous ecotones, which are likely driven by soil-related positive feedbacks. These findings are integral to predicting the distribution of forest biomes, and aid to our understanding of biodiversity, carbon turnover, and terrestrial climate feedbacks.

Abstract In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp3-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a powerful approach for the light-mediated B-alkyl Suzuki−Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes were easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring under photocatalytic conditions. This methodology eliminates the need for expensive catalytic systems and sensitive organometallic compounds, operating efficiently at room temperature within just 30 min. We further demonstrate the translation of the present protocol to continuous-flow conditions, enhancing scalability, safety, and overall efficiency of the method. This versatile approach offers significant potential for accelerating drug discovery efforts by enabling the introduction of complex aliphatic fragments in a straightforward and reliable manner.

Abstract Solution-based memristors deposited by inkjet printing technique have a strong technological potential based on their scalability, low cost, environmentally friendlier processing by being an efficient technique with minimal material waste. Indium-gallium-zinc oxide (IGZO), an oxide semiconductor material, shows promising resistive switching properties. In this work, a printed Ag/IGZO/ITO memristor has been fabricated. The IGZO thickness influences both memory window and switching voltage of the devices. The devices show both volatile counter8wise (c8w) and non-volatile 8wise (8w) switching at low operating voltage. The 8w switching has a SET and RESET voltage lower than 2 V and − 5 V, respectively, a retention up to 105 s and a memory window up to 100, whereas the c8w switching shows volatile characteristics with a low threshold voltage (Vth

Abstract Site-specific recombinases such as the Cre-LoxP system are routinely used for genome engineering in both prokaryotes and eukaryotes. Importantly, recombinases complement the CRISPR-Cas toolbox and provide the additional benefit of high-efficiency DNA editing without generating toxic DNA double-strand breaks, allowing multiple recombination events at the same time. However, only a handful of independent, orthogonal recombination systems are available, limiting their use in more complex applications that require multiple specific recombination events, such as metabolic engineering and genetic circuits. To address this shortcoming, we develop 63 symmetrical LoxP variants and test 1192 pairwise combinations to determine their cross-reactivity and specificity upon Cre activation. Ultimately, we establish a set of 16 orthogonal LoxPsym variants and demonstrate their use for multiplexed genome engineering in both prokaryotes (E. coli) and eukaryotes (S. cerevisiae and Z. mays). Together, this work yields a significant expansion of the Cre-LoxP toolbox for genome editing, metabolic engineering and other controlled recombination events, and provides insights into the Cre-LoxP recombination process.

The constructivist acquisition of language by children has been elaborately documented by researchers in psycholinguistics and cognitive science. However, despite the centrality of human-like communication in the field of artificial intelligence, no faithful computational operationalizations of the mechanisms through which children learn language exist to date. In this article, we fill part of this void by introducing a mechanistic model of the constructivist acquisition of language through syntactico-semantic pattern finding. Concretely, we present a methodology for learning grammars based on similarities and differences in the form and meaning of linguistic observations alone. The resulting grammars consist of form-meaning mappings of variable extent and degree of abstraction, called constructions, which facilitate both language comprehension and production. Applying our methodology to the CLEVR benchmark dataset, we provide a proof of concept that demonstrates the online, incremental, data-efficient, transparent and effective learning of item-based construction grammars from utterance–meaning pairs.

Abstract Political knowledge is crucial for well-functioning democracies, with most scholars assuming that people at the political extremes are more knowledgeable than those at the center. Here, we adopt a data-driven approach to examine the relationship between political orientation and political knowledge by testing a series of polynomial curves in 45 countries (N = 63,544), spread over 6 continents. Contrary to the dominant perspective, we found no evidence that people at the political extremes are the most knowledgeable about politics. Rather, the most common pattern was a fourth-degree polynomial association in which those who are moderately left-wing and right-wing are more knowledgeable than people at the extremes and center of the political spectrum. This pattern was especially, though not exclusively, prevalent in Western countries. We conclude that the relationship between political orientation and political knowledge is more context-dependent and complex than assumed, and caution against (implicit) universal conclusions in social sciences.

Abstract Recent and potential future health-care users (i.e., the public) are important stakeholders in the transition toward environmentally sustainable healthcare. However, it remains unclear whether, according to the public, there is room for sustainable innovations in materials for plastic medical devices (PMD). This study explores preferences regarding conventional or bio-based PMD, and psychological mechanisms underlying these preferences. We administered two surveys among Dutch adults from a research panel. Results from the first survey (i.e., open-text survey on attitude elements; N Study1 = 66) served as input for the second survey (i.e., Likert-scale survey on beliefs, emotions, perceived control, social norms, trust, related to current and bio-based PMD, and health and age; N Study2 = 1001; M age = 47.35; 54.4% female). The second survey was completed by 501 participants who, in the last two years, received care in which PMD were used, and 500 participants who did not. Cross-sectional psychological networks were estimated with data from the second study using the EBICglasso method. Results showed that participants preferred bio-based over conventional PMD, and this applied regardless of whether devices are used inside or outside of the body. Results also showed emotions play an important role, with emotions regarding bio-based PMD being strongly related to preference. Furthermore, comparing recent and potential future receivers of PMD revealed differences in preference but comparable relations between preference and other psychological variables. This study shows that receivers’ perspectives should not be seen as potential barriers, but as additional motivation for transitioning toward sustainable healthcare. Recommendations for implementation are discussed.

Abstract Anthropogenic climate change, particularly seawater warming, is expected to drive quick shifts in marine species distribution transforming coastal communities. These shifts in distribution will be particularly noticeable in biogeographical transition zones. The continental Portuguese coast stretches from north to south along 900 km. Despite this short spatial scale, the strong physical gradient intensified by the Iberian upwelling creates a transition zone where seaweed species from boreal and Lusitanian-Mediterranean origin coexist. On the northern coast, kelp marine forests thrive in the cold, nutrient-rich oceanic waters. In the south, communities resemble Mediterranean-type seaweed assemblages and are dominated by turfs. Recent evidence suggests that in these coastal areas, marine intertidal species are shifting their distribution edges as a result of rising seawater temperatures. Taking advantage of previous abundance data collected in 2012 from subtidal seaweed communities, a new sampling program was carried out in the same regions in 2018 to assess recent changes. The results confirmed the latitudinal gradient in macroalgal assemblages. More importantly we found significant structural and functional changes in a short period of six years, with regional increases of abundance of warm-affinity species, small seaweeds like turfs. Species richness, diversity, and biomass increase, all accompanied by an increase of community temperature index (CTI). Our findings suggest that subtidal seaweed communities in this transitional area have undergone major changes within a few years. Evidence of “fast tropicalization” of the subtidal communities of the Portuguese coast are strong indication of the effects of anthropic climate change over coastal assemblages.

Abstract Phospholipase D3 (PLD3) polymorphisms are linked to late-onset Alzheimer’s disease (LOAD). Being a lysosomal 5’-3’ exonuclease, its neuronal substrates remained unknown as well as how a defective lysosomal nucleotide catabolism connects to AD-proteinopathy. We identified mitochondrial DNA (mtDNA) as a major physiological substrate and show its manifest build-up in lysosomes of PLD3-defective cells. mtDNA accretion creates a degradative (proteolytic) bottleneck that presents at the ultrastructural level as a marked abundance of multilamellar bodies, often containing mitochondrial remnants, which correlates with increased PINK1-dependent mitophagy. Lysosomal leakage of mtDNA to the cytosol activates cGAS–STING signaling that upregulates autophagy and induces amyloid precursor C-terminal fragment (APP-CTF) and cholesterol accumulation. STING inhibition largely normalizes APP-CTF levels, whereas an APP knockout in PLD3-deficient backgrounds lowers STING activation and normalizes cholesterol biosynthesis. Collectively, we demonstrate molecular cross-talks through feedforward loops between lysosomal nucleotide turnover, cGAS-STING and APP metabolism that, when dysregulated, result in neuronal endolysosomal demise as observed in LOAD.

Gaseous and semi-volatile organic compounds emitted by the transport sector contribute to air pollution and have adverse effects on human health. To reduce harmful effects to the environment as well as to humans, renewable and sustainable bio-hybrid fuels are explored and investigated in the cluster of excellence "The Fuel Science Center" at RWTH Aachen University. However, data on the effects of bio-hybrid fuels on human health is scarce, leaving a data gap regarding their hazard potential. To help close this data gap, this study investigates potential toxic effects of a Ketone-Ester-Alcohol-Alkane (KEAA) fuel blend on A549 human lung cells. Experiments were performed using a commercially available air-liquid interface exposure system which was optimized beforehand. Then, cells were exposed at the air-liquid interface to 50-2000 ppm C3.7 of gaseous KEAA for 1 h. After a 24 h recovery period in the incubator, cells treated with 500 ppm C3.7 KEAA showed significant lower metabolic activity and cells treated with 50, 250, 500 and 1000 ppm C3.7 KEAA showed significant higher cytotoxicity compared to controls. Our data support the international occupational exposure limits of the single KEAA constituents. This finding applies only to the exposure scenario tested in this study and is difficult to extrapolate to the complex in vivo situation.

Temperature shapes the adaptation and composition of microbiomes, but whether their enzymes drive the thermal response remains unknown. Using an analysis of seven enzyme classes from worldwide marine microbiome data, this study shows that enzyme thermal properties explain microbial thermal plasticity and they are both finely tuned by the thermal variability of the environment.

A mismatch between quasi-Fermi level splitting and open-circuit voltage is detrimental to wide bandgap perovskite pin solar cells. Here, through theoretical and experimental approaches, the authors optimize n- and p-type interfaces to achieve open-circuit voltage of 1.29 V and T80 of 3500 h at 85 °C.

In this Bayesian inference study, the authors aim to quantify the impact of the men’s 2020 UEFA Euro Football Championship on COVID-19 spread in twelve participating countries. They estimate that 0.84 million cases and 1,700 deaths were attributable to the championship, with most impacts in England and Scotland.

Abstract The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55–74 at enrollment in 1993–2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consent. Genotyping on high-density arrays and imputation was performed, and GWAS were conducted using a custom semi-automated pipeline. Association summary statistics were generated from a total of 110,562 participants of European, African and Asian ancestry. Application programming interfaces (APIs) and open-source software development kits (SKDs) enable exploring, visualizing and open data access through the PLCO Atlas GWAS Explorer website, promoting Findable, Accessible, Interoperable, and Re-usable (FAIR) principles. Currently the GWAS Explorer hosts association data for 90 traits and >78,000,000 genomic markers, focusing on cancer and cancer-related phenotypes. New traits will be posted as association data becomes available. The PLCO Atlas is a FAIR resource of high-quality genetic and phenotypic data with many potential reuse opportunities for cancer research and genetic epidemiology.

Abstract It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (N total = 12,553) from 6 continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions—warmth and competence—plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges.

Alginate based biofilms are widely used for designing edible food packaging while its application for developing inedible waterproof food packaging has not been studied enough. Both, cellulose fiber and alginate are attractive natural materials that could be used for developing natural fiber-based food packaging. In this research the cellulose/alginate biocomposites were produced by eco-friendly technique bi-layer lamination of prepared cellulose (C) fiber plates with sodium (SA) and calcium alginates (CA) containing glycerol as plasticizer. The morphology, moisture content, solubility in water, water vapor permeability (WVP), surface hydrophobicity and mechanical characteristics of prepared cellulose/alginates biocomposites were evaluated and compared. The biocomposite surface morphology evaluation showed that all analyzed samples had smooth surfaces without cracks. Moreover, obtained results showed that plasticizer is essential in developing biocomposites with improved characteristics. The concentration of glycerol had a positive effect on gloss, flexibility, moisture content, solubility in water and negative effect to surface hydrophobicity of C/SA and C/CA biocomposites. It was observed that samples had partly hydrophobic surfaces which contact angles varies from 37° to 63°. Mechanical characteristics revealed that the most promising are C/CA biocomposites that could be further modified for waterproof food packaging developing.

Abstract This study evaluates the use of rice husk ash (RHA)-eggshell lime (ESL) and RHA-commercial lime (CL) as alternative binders for clayey soil stabilization, as well as the performance of soil-binder mixtures under acidic attack. A central composite design was carried out to analyze the reactivity by batch tests with a sulfuric acid solution. Physical and mechanical behavior was evaluated by compaction test and unconfined compressive strength (UCS). Reactivity tests demonstrated better neutralization of contaminant acidity for mixtures with ESL. The highest compressive strength, reactivity and partial encapsulation of toxic elements are associated with application of 30% RHA and 6% ESL in the soil. A C–S–H gel is observed in poorly crystalline phases through the XRD pattern. The application of RHA-ESL in soils exposed to acidic attack has environmental feasibility. Analysis of RHA grinding processes combined with the mixture strength over time, and its application tests in impermeable barriers, in landfills, are recommended.

Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022. Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance. Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models. Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks. Funding: AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 (https://www.nfdi4health.de/task-force-covid-19-2) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z).

Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.

Abstract This work presents an alternative method of getting tracking, and the impact point of the actual flight of a rocket, by telemetry data and slant-range device. The tracking and impact point data were obtained from an actual flight path by merging the angular components of a telemetry antenna (Azimuth, and Elevation) and the radial distance information provided by the slant-range device. The position components were analyzed with the telemetry antenna in automatic mode, target tracking, comparing with the tracking results performed by the radar. The result obtained by the composition of the coordinates of the telemetry/slant-range set, it was observed that the point of impact generated by this group had a distance of 237.64 (meters), in relation to the impact generated by the tracking of the radar. Indicating a significant reduction of the search area and can be used as na alternative form of use. It allows you to provide additional location information for payload recovery around the actual point of impact.

A good way to identify microscopic conduction regimes where current flow deviates from Ohm’s law is still lacking. Here, the authors identify Sondheimer oscillations as a quantitative probe of the length scale of relaxing electron scattering in studying the non-ohmic electron flow of WP2 crystals.

Quando falamos em inserir ferramentas tecnológicas na educação, devemos entender que o uso das tecnologias de informação e comunicação (TIC) no ensino visa trazer para a sala de aula as ferramentas que os alunos já utilizam, como telefones celulares e até algumas redes sociais. O objetivo deste trabalho é trazer informações acerca de algumas ferramentas tecnológicas e como elas podem contribuir no processo de ensino e aprendizagem nas aulas de química. Ao produzir este artigo, visou-se buscar e analisar trabalhos científicos na área de Química que trouxessem a tecnologia como ferramenta didática podendo estimular e aproximar o aluno do conteúdo de química de forma menos tradicional. Para isso foram consultadas as plataformas Capes Periódicos, SciElo e Química nova na escola encontrando-se 513 trabalhos, dos quais 506 foram excluídos devido não se adequarem ao tema abordado, restando 07 trabalhos que foram objeto de estudo. Foi possível identificar que uso das ferramentas tecnológicas, uma grande aliada no ensino da química, pois apresentaram resultados bastantes satisfatórios, como contribuição com aprendizagem do conteúdo, maior participação nas aulas, despertar um espírito solidário e companheirismo, maior domínio dos conteúdos, proporcionar maior trabalho em equipe, aulas mais dinâmicas, melhores desempenhos nas avaliações dentre outras.

Test, trace, and isolate programmes are central to COVID-19 control. Here, Viola Priesemann and colleagues evaluate how to allocate scarce resources to keep numbers low, and find that if case numbers exceed test, trace and isolate capacity, there will be a self-accelerating spread.

AGO2 binds to miRNAs to repress expression of cognate target mRNAs. Here the authors report that heterozygous AGO2 mutations result in defects in neurological development and impair RNA interference.

O conhecimento da alimentação natural de peixes é importante para compreender o hábito alimentar das espécies, como elas se comportam e interagem com o meio ambiente. Além disso, pesquisas desse tipo podem fornecer dados quanto ao aperfeiçoamento da captura desses animais, tendo em vista a sua importância econômica e social. O presente estudo objetivou analisar a composição alimentar da espécie Larimus breviceps proveniente do litoral norte da cidade de Cabedelo-PB, avaliando a importância de cada item alimentar para sua dieta. Os espécimes de L. breviceps foram advindos da pesca artesanal da região. No laboratório, os indivíduos foram identificados, suas medidas morfométricas foram retiradas, e, posteriormente, o conteúdo estomacal de cada espécime foi removido e examinado. Foram realizadas três análises da dieta, porcentagem por frequência de ocorrência, por número e por peso, além do cálculo de importância alimentar (IRI%). Ao todo, foram analisados 30 conteúdos estomacais; identificou-se 15 itens alimentares distintos, sendo os mais representativos deles, fragmentos de peixes, Copepoda, Gammaridea, Decapoda (camarão), material vegetal e material sintético. Diante dos resultados, constatou-se que a dieta desta espécie se torna diversificada à medida que seus indivíduos alcançam a fase adulta, e que estes ingerem lixo marinho, o que indica um impacto antrópico.

Abstract In the study of utilitarian morality, the sacrificial dilemma paradigm has been the dominant approach for years. However, to address some of the most pressing issues in the current research literature, the present studies adopt an alternative approach by using a minimal group paradigm in which participants have to make decisions about the allocation of resources. This approach allows not only to pit utilitarianism against equality-based morality, but also to study these modes of morality for both harm and benefit, and to directly address the role of group identity affecting the (im)partial nature of ‘utilitarian’ (i.e., outcome maximizing) decisions. In our experiments, across four different samples (total N = 946), we demonstrate that although participants generally prefer equality-based allocations over maximizing distributions, outcome maximizing choices become more prevalent when they served to minimize harm compared to maximizing benefit. Furthermore, reducing the objective value of the equal distribution outcomes further prompts participants to adopt a more utilitarian approach in situations involving harm, but has little effect in situations where benefits have to be distributed. Finally, the introduction of (minimal) group identity consistently demonstrates that decisions that maximize the overall outcome are more likely if they also serve the ingroup compared to when they rather serve the outgroup. We discuss how these findings have meaningful implications that may be especially relevant for recent movements that advocate a utilitarian approach to charity, and for our understanding of (im)partiality in lay people’s ‘utilitarian’ decision making.

This study examines how broad attitude networks are affected by tailored interventions aimed at variables selected based on their connectiveness with other variables. We first computed a broad attitude network based on a large-scale cross-sectional COVID-19 survey (N = 6,093). Over a period of approximately 10 weeks, participants were invited five times to complete this survey, with the third and fifth wave including interventions aimed at manipulating specific variables in the broad COVID-19 attitude network. Results suggest that targeted interventions that yield relatively strong effects on variables central to a broad attitude network have downstream effects on connected variables, which can be partially explained by the variables the interventions were aimed at. We conclude that broad attitude network structures can reveal important relations between variables that can help to design new interventions.

Cryptorchidism is the most common congenital sex development disorder in dogs. Despite this, little progress has been made in understanding its genetic background. Extensive genetic testing of dogs through consumer and veterinary channels using a high-density SNP genotyping microarray coupled with links to clinical records presents the opportunity for a large-scale genome-wide association study to elucidate the molecular risk factors associated with cryptorchidism in dogs. Using an inter-breed genome-wide association study approach, a significant statistical association on canine chromosome 10 was identified, with the top SNP pinpointing a variant of HMGA2 previously associated with adult weight variance. In further analysis we show that incidence of cryptorchidism is skewed towards smaller dogs in concordance with the identified variant's previous association with adult weight. This study represents the first putative variant to be associated with cryptorchidism in dogs.

The spread of a contagious disease clearly depends on when infected individuals come into contact with susceptible ones. Such effects, however, have remained largely unexplored in the study of epidemic outbreaks. In particular, it remains unclear how the timing of contacts interacts with the latent and infectious stages of the disease. Here, we use real-world physical proximity data to study this interaction and find that the temporal statistics of actual human contact patterns (i) destabilize epidemic outbreaks and (ii) modulate the basic reproduction number R _0 . We explain both observations by distinct aspects of the observed contact patterns. On the one hand, we find the destabilization of outbreaks to be caused by the temporal clustering of contacts leading to over-dispersed offspring distributions and increased probabilities of otherwise rare events (zero- and super-spreading). Notably, our analysis enables us to disentangle previously elusive sources of over-dispersion in empirical offspring distributions. On the other hand, we find the modulation of R _0 to be caused by a periodically varying contact rate. Both mechanisms are a direct consequence of the memory in contact behavior, and we showcase a generative process that reproduces these non-Markovian statistics. Our results point to the importance of including non-Markovian contact timings into studies of epidemic outbreaks.