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The temporal relationship between global glaciations and the Great Oxidation Event (GOE) suggests that climate change played an important role in Earth's oxygenation. The potential role of temperature is captured by the stratigraphic proximity between glacial deposits and sediments containing mass‐independent fractionation of sulfur isotopes (MIF‐S). We use a time‐dependent one‐dimensional photochemical model to investigate whether temperature changes associated with global glaciations can drive oscillations in atmospheric O2 levels and MIF‐S production across the GOE. We find that extreme climate change can cause atmospheric O2 to oscillate between pre (<10−6 times the present atmospheric level, PAL) and post‐GOE (>10−5 PAL) levels. Post‐glacial hot‐moist greenhouse climates lead to post‐GOE O2 levels because the abundant H2O vapor and oxidizing radicals drive the depletion of reduced species. This pattern is generally consistent with the MIF‐S signal observed in the sedimentary record, suggesting a link between global glaciations and O2 oscillations across the GOE. Plain Language Summary: The Great Oxidation Event was the most significant environmental and chemical transformation in Earth's history, marking the first time oxygen accumulated in the atmosphere around 2.4 billion years ago. Oxygen increased from below one millionth (low) to at least one‐thousandth of a percent (intermediate) of the present oxygen concentration during this event. However, measurements of geochemical oxygen proxies suggest that oxygen levels oscillated between low and intermediate levels before stabilizing after this event. The first rise of atmospheric oxygen occurred during a period of extreme climate variability indicated by the presence of glacial rock deposits around this time. In this study, we use a time‐dependent photochemical model to show that extreme temperature changes caused by global glaciations can drive oscillations in atmospheric oxygen levels across the Great Oxidation Event (GOE). Our results can help explain why atmospheric oxygen shows drastic changes across the GOE in a way that is consistent with the geochemical record. Key Points: Across the Great Oxidation Event (GOE), extreme climate change linked to global glaciations can drive oscillations in atmospheric O2 levels and mass‐independent fractionation of sulfur isotopes (MIF‐S) productionGlacial climates and hot‐moist greenhouse climates were likely characterized by pre‐GOE and post‐GOE O2 levels respectivelyTemperature changes associated with global glaciations can help explain the MIF‐S record across the GOE [ABSTRACT FROM AUTHOR]

Prepolarized MRI (PMRI) is a long‐established technique conceived to counteract the loss in signal‐to‐noise ratio (SNR) inherent to low‐field MRI systems. When it comes to hard biological tissues and solid‐state matter, PMRI is severely restricted by their ultra‐short characteristic relaxation times. Here we demonstrate that efficient hard‐tissue prepolarization is within reach with a special‐purpose 0.26 T scanner designed for ex vivo dental MRI and equipped with suitable high‐power electronics. We have characterized the performance of a 0.5 T prepolarizer module, which can be switched on and off in 200 μs. To this end, we have used resin, dental and bone samples, all with T1 times of the order of 20 ms at our field strength. The measured SNR enhancement is in good agreement with a simple theoretical model, and deviations in extreme regimes can be attributed to mechanical vibrations due to the magnetic interaction between the prepolarization and main magnets. [ABSTRACT FROM AUTHOR]

Aim: Genome‐wide genetic data can provide key input for both taxonomy and conservation, but its use in this context remains limited. In this study, we performed the first genome‐wide assessment of genetic variation in two populations of the Eurasian lynx, the Balkan population, the most threatened, and the Caucasian population, a possible glacial refugium, with the aim to place them in the context of the species, investigate their demographic history and evaluate their genetic status. Location: The Balkans and the Caucasus. Methods: We obtained whole genome resequencing data from seven Balkan and 12 Caucasian lynx, and analysed them along with novel and existing data from other populations. Based on a total 105 whole genome and 114 mitogenome sequences, we reconstructed phylogenetic and historical relationships, ancient and recent demography, and patterns of genetic diversity and inbreeding. Results: Both the Balkan and the Caucasian lynx appear as distinct mitochondrial lineages that diverged from the rest of the Eurasian lynx lineages ca. 92.6 kya, and from each other ca. 46.4 kya. Autosomal data suggest, however, that the Balkan lynx is closely related with the Carpathian population, and revealing alarmingly low genetic diversity and high inbreeding. In contrast, the Caucasian lynx shows a longer history of relative isolation from the rest of lynx populations and high genetic diversity, consistent with its large long‐term effective population size. Main conclusions: The taxonomic status of the Balkan lynx remains unresolved due to the evidence of long‐term isolation in the mitogenome, contrasting with extensive autosomal admixture and intense recent genetic drift in the nuclear genome. Our results alert on genetic risks and call for the consideration of genetic rescue from closely related Carpathian lynxes. In contrast, substantial mitogenomic and autosomal divergence with no signs of genetic drift supports the identification of the Caucasian lynx as a separate subspecies with good genetic health. [ABSTRACT FROM AUTHOR]

The use of modern discretization technologies such as hybrid high‐order (HHO) methods, coupled with appropriate linear solvers, allow for the robust and fast solution of partial differential equations (PDEs). Although efficient linear solvers have recently been made available for simpler cases, complex geometries remain a challenge for large scale problems. To address this problem, we propose in this work a geometric multigrid algorithm for unstructured non‐nested meshes. The non‐nestedness is handled in the prolongation operator through the use of the L2‐orthogonal projection from the coarse elements onto the fine ones. However, as the exact evaluation of this projection can be computationally expensive, we develop a cheaper approximate implementation that globally preserves the approximation properties of the L2‐orthogonal projection. Additionally, as the multigrid method requires not only the coarsening of the elements, but also that of the faces, we leverage the geometric flexibility of polytopal elements to define an abstract non‐nested coarsening strategy based on element agglomeration and face collapsing. Finally, the multigrid method is tested on homogeneous and heterogeneous diffusion problems in two and three space dimensions. The solver exhibits near‐perfect asymptotic optimality for moderate degrees of approximation. [ABSTRACT FROM AUTHOR]

Demographic bottlenecks generally reduce genetic diversity through more intense genetic drift, but their net effect may vary along the genome due to the random nature of genetic drift and to local effects of recombination, mutation, and selection. Here, we analyzed the changes in genetic diversity following a bottleneck by comparing whole‐genome diversity patterns in populations with and without severe recent documented declines of Iberian (Lynx pardinus, n = 31) and Eurasian lynx (Lynx lynx, n = 29). As expected, overall genomic diversity correlated negatively with bottleneck intensity and/or duration. Correlations of genetic diversity with divergence, chromosome size, gene or functional site content, GC content, or recombination were observed in nonbottlenecked populations, but were weaker in bottlenecked populations. Also, functional features under intense purifying selection and the X chromosome showed an increase in the observed density of variants, even resulting in higher θW diversity than in nonbottlenecked populations. Increased diversity seems to be related to both a higher mutational input in those regions creating a large collection of low‐frequency variants, a few of which increase in frequency during the bottleneck to the point they become detectable with our limited sample, and the reduced efficacy of purifying selection, which affects not only protein structure and function but also the regulation of gene expression. The results of this study alert to the possible reduction of fitness and adaptive potential associated with the genomic erosion in regulatory elements. Further, the detection of a gain of diversity in ultra‐conserved elements can be used as a sensitive and easy‐to‐apply signature of genetic erosion in wild populations. [ABSTRACT FROM AUTHOR]

The role of the inflammasomes in aging and progeroid syndromes remain understudied. Recently, MCC950, a NLRP3 inhibitor, was used in Zmpste24−/− mice to ameliorate the phenotypes. However, the safety of MCC950 was questioned due to liver toxicity observed in humans. Nevertheless, inhibition of the inflammasomes would be a beneficial therapy for progeria. Here, we show that OLT1177 (dapansutrile), other NLRP3 inhibitor, improved cellular and animal phenotypes using progeroid fibroblasts and a LmnaG609G/G609G mouse model. In both cases dapansutrile reduced progerin accumulation, NLRP3‐inflammasome activation and secretory phenotype of senescence, extended the lifespan of progeroid animals, preserved bodyweight, and reduced kyphosis, inflammation, and senescence. Interestingly, dapansutrile further improved the effect of lonafarnib, the only FDA‐approved drug for the progeria. The combination of both drugs reduced the inflammation and senescence, extended survival and ameliorated various progeroid defects both in vitro and in vivo, compared with treatment using lonafarnib alone. These findings and the safety of dapansutrile demonstrated in several clinical trials proposes it as a possible co‐adjuvant treatment with lonafarnid in HGPS. [ABSTRACT FROM AUTHOR]

Malaria remains a major cause of mortality in the world and an efficient vaccine is the best chance of reducing the disease burden. Vaccination strategies for the liver stage of disease that utilise injection of live radiation‐attenuated sporozoites (RAS) confer sterile immunity, which is mediated by CD8+ memory T cells, with liver‐resident memory T cells (TRM) being particularly important. We have previously described a TCR transgenic mouse, termed PbT‐I, where all CD8+ T cells recognize a specific peptide from Plasmodium. PbT‐I form liver TRM cells upon RAS injection and are capable of protecting mice against challenge infection. Here, we utilize this transgenic system to examine whether nonliving sporozoites, killed by heat treatment (HKS), could trigger the development of Plasmodium‐specific liver TRM cells. We found that HKS vaccination induced the formation of memory CD8+ T cells in the spleen and liver, and importantly, liver TRM cells were fewer in number than that induced by RAS. Crucially, we showed the number of TRM cells was significantly higher when HKS were combined with the glycolipid α‐galactosylceramide as an adjuvant. In the future, this work could lead to development of an antimalaria vaccination strategy that does not require live sporozoites, providing greater utility. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N2O) is a long‐lived greenhouse gas that affects atmospheric chemistry and climate. In this work, we use satellite measurements of N2O, ozone (O3), and temperature from the Aura Microwave Limb Sounder (MLS) instrument to calculate stratospheric loss of N2O, and thus its atmospheric lifetime. Using three chemistry transport models simulating the Aura period 2005–2017, we verify the stratospheric sink using MLS data and follow that loss signal down to the surface and compare with surface observations. Stratospheric loss has a strong seasonal cycle and is further modulated by the Quasi‐Biennial Oscillation (QBO); these cycles are seen equally in both observations and the models. When filtered for interannual variability, the modeled surface signal is QBO‐caused, and it reproduces the observed pattern, highlighting the potential role of the QBO in tropospheric chemistry and composition, as well as in model evaluation. The observed annual surface signal in the northern hemisphere matches well with the models run without emissions, indicating the annual cycle is driven mostly by stratosphere‐troposphere exchange (STE) flux of N2O‐depleted air and not surface N2O emissions. In the southern hemisphere (SH), all three models disagree and thus provide no guidance, except for indicating that modeling annual STE in the SH remains a major model uncertainty. Parallel model simulations of CFCl3, which has greater stratospheric loss that N2O and possibly surreptitious emissions, show that its interannual variations parallel those of N2O, and thus the observed N2O variability can identify the stratospheric component of the observed CFCl3 variability. Plain Language Summary: Nitrous oxide (N2O) is a long‐lived greenhouse gas that drives climate change and ozone depletion, posing a threat to society's health and well‐being. The abundance of N2O at Earth's surface, where we can measure it most precisely, fluctuates over seasons and years due to increasing human emissions, variable natural emissions, varying stratospheric destruction, and the movement of air throughout the atmosphere. Scientists use these fluctuations to separate natural from human emissions and quantify what humans can do to reduce the growth in N2O. In this work, we model the physical side of atmospheric N2O that drives fluctuations through chemistry and atmospheric transport. Our model simulations match most of the observed seasonal and multi‐year fluctuations seen in satellite and surface observations, indicating that N2O loss is causing the dominating signal, not emissions. Unfortunately, in the southern hemisphere, the annual cycle of the models is in disagreement and cannot help us interpret the observed fluctuations. In addition to helping understand the human role in N2O increases, we find that the N2O observations provide a valuable test of models and guidance to improve them. Key Points: Losses of nitrous oxide (N2O) and chlorofluorocarbon (CFCl3) are modulated (±5% amplitude) by the Quasi‐Biennial OscillationStratospheric air depleted in N2O and CFCl3 is transported down to the surface where it affects the observed surface variabilityThe seasonal cycle of surface N2O in the northern hemisphere is driven mostly by stratospheric loss rather than surface emissions [ABSTRACT FROM AUTHOR]

Disentangling the contribution of long‐term evolutionary processes and recent anthropogenic impacts to current genetic patterns of wildlife species is key to assessing genetic risks and designing conservation strategies. Here, we used 80 whole nuclear genomes and 96 mitogenomes from populations of the Eurasian lynx covering a range of conservation statuses, climatic zones and subspecies across Eurasia to infer the demographic history, reconstruct genetic patterns, and discuss the influence of long‐term isolation and/or more recent human‐driven changes. Our results show that Eurasian lynx populations shared a common history until 100,000 years ago, when Asian and European populations started to diverge and both entered a period of continuous and widespread decline, with western populations, except Kirov, maintaining lower effective sizes than eastern populations. Population declines and increased isolation in more recent times probably drove the genetic differentiation between geographically and ecologically close westernmost European populations. By contrast, and despite the wide range of habitats covered, populations are quite homogeneous genetically across the Asian range, showing a pattern of isolation by distance and providing little genetic support for the several proposed subspecies. Mitogenomic and nuclear divergences and population declines starting during the Late Pleistocene can be mostly attributed to climatic fluctuations and early human influence, but the widespread and sustained decline since the Holocene is more probably the consequence of anthropogenic impacts which intensified in recent centuries, especially in western Europe. Genetic erosion in isolated European populations and lack of evidence for long‐term isolation argue for the restoration of lost population connectivity. [ABSTRACT FROM AUTHOR]

Ultra‐high performance fiber reinforced concrete (UHPFRC) is a unique class of fiber‐reinforced concrete featuring ultra‐high compressive strength and ductile tensile strain hardening behavior, accompanied by multiple narrow cracking. Although many studies have confirmed its superior mechanical and damage tolerance properties under monotonic or blast loading, limited research has been carried out on the cyclic performance of UHPFRC structural members. This paper proposes the use of UHPFRC to improve the cyclic performance of structural elements. An experimental program was carried out on a large number of UHPFRC beam‐column joint specimens under a cyclic lateral load. After the cyclic loading test, the following results were obtained: (a) hysterical performance, (b) maximum load, (c) maximum displacement, (d) the maximum energy dissipation (measured by hysteresis cycles), (e) stiffness degradation, (f) the cracking pattern, and (g) the cracking area. The analysis showed that UHPFRC specimens have at least 157% higher energy dissipation than nonfiber conventional reinforced concrete (RC). The initial stiffness of UHPFRC specimens without fibers (NF) was at least 23% higher than the RC specimen. For UHPFRC with fiber, initial stiffness was at least 45% higher than RC specimen. [ABSTRACT FROM AUTHOR]

In order to address environmental aspects during redesign, the product specification must include related targets that are reachable and challenging. To do so, this article presents a stepwise approach for combining benchmarking information and component impact, out of life cycle assessment (LCA) scaling. This approach requires allocating environmental impacts to each subsystem, which is not commonly done for some life cycle phases in LCAs, most particularly for use phases. This article includes a methodology for allocating such impacts. The underlying criterion is avoiding complex calculations, to make the method more agile. This methodology is presented in a full case study of a complex product: a knuckle boom crane. The case study results in the percentage of impact reduction needed to meet the market average or best competitors. In particular, the results show that the cylinders of the crane have a high contribution to environmental impact, not only because of their weight, but also because of the active power consumed to activate them. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper, a digital filter for the generation/correlation of binary Golay pairs of sequences of length 2 N · 10 M · 26 P ( N, M and P are non-negative integers) is proposed. It is carried out by means of a novel Golay kernel 26 decomposition, also introduced in this paper, combined with building blocks of Golay kernels 2 and 10, presented in previous works. The proposed filter has a similar architecture to the digital filter for the generation/correlation of Golay multilevel pairs of sequences, where the parameters at intermediate stages have to be adjusted to obtain Golay binary pairs of sequences in the final stage. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Many authors have agreed on the interest of considering environmental concerns in the early stages of product development. However, most eco-design tools are based on life cycle assessment principles and require a model to give information about the product's environmental performance. This modeling can have negative effects on team performance and on the potential for innovation, not to mention on the project's duration. Additionally, the model requires information that is not available in the early design stages. This article analyzes the potential of inferring conclusions about the life cycle stages with the highest impact by using similar products. From a database of previous products, environmental profile estimations are carried out, that is, the assessments of the contribution of each life cycle stage to the total impact and the variability of this measure. It is then possible to discard-or ensure consideration of-life cycle stages. Furthermore, the level of the conclusions is assessed on a five-point scale. The proposed approach is applied to four case studies with different levels of abstraction and the relevance of the conclusions is assessed. The article resolves the problems regarding potential for estimating the distribution of the environmental impacts along the life cycle. [ABSTRACT FROM AUTHOR]

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the regulation of coagulation and inflammation. In addition to inhibiting the fibrinolytic system, TAFI may also regulate the bradykinin and complement systems. We hypothesized that TAFI also plays a role in defense mechanisms of the gastric mucosa during Helicobacter pylori infection. This study comprised 65 patients with gastroduodenal disorders: 41 patients with H. pylori infection, 13 without, and 11 patients with cured H. pylori infection. The gastric intramucosal concentrations of TAFI were measured by enzyme immunoassay. The gastric levels of TAFI and plasminogen activator inhibitor-1 were significantly increased in patients with H. pylori compared to those without infection or cured H. pylori. The presence of TAFI was detected in gastric mucosal epithelial cells. The concentration of TAFI was correlated with the degree of gastric mucosal atrophy, inflammation, and disease activity. These results show that TAFI is present in the gastric mucosa and that it may play a role in the pathogenesis of H. pylori infection-associated gastroduodenal disorders. [ABSTRACT FROM AUTHOR]

The local geometry of the parameter space of a quantum system is described by the quantum metric tensor and the Berry curvature, which are two fundamental objects that play a crucial role in understanding geometrical aspects of condensed matter physics. Classical integrable systems are considered and a new approach is reported to obtain the classical analogs of the quantum metric tensor and the Berry curvature. An advantage of this approach is that it can be applied to a wide variety of classical systems corresponding to quantum systems with bosonic and fermionic degrees of freedom. The approach used arises from the semiclassical approximation of the Berry curvature and the quantum metric tensor in the Lagrangian formalism. This semiclassical approximation is exploited to establish, for the first time, the relation between the quantum metric tensor and its classical counterpart. The approach described is illustrated and validated by applying it to five systems: the generalized harmonic oscillator, the symmetric and linearly coupled harmonic oscillators, the singular Euclidean oscillator, and a spin‐half particle in a magnetic field. Finally, some potential applications of this approach and possible generalizations that can be of interest in the field of condensed matter physics are mentioned. [ABSTRACT FROM AUTHOR]