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In this paper, we examine conditioning of the discretization of the Helmholtz problem. Although the discrete Helmholtz problem has been studied from different perspectives, to the best of our knowledge, there is no conditioning analysis for it. We aim to fill this gap in the literature. We propose a novel method in 1D to observe the near-zero eigenvalues of a symmetric indefinite matrix. Standard classification of ill-conditioning based on the matrix condition number is not true for the discrete Helmholtz problem. We relate the ill-conditioning of the discretization of the Helmholtz problem with the condition number of the matrix. We carry out analytical conditioning analysis in 1D and extend our observations to 2D with numerical observations. We examine several discretizations. We find different regions in which the condition number of the problem shows different characteristics. We also explain the general behavior of the solutions in these regions.
Quantum mechanical tunnelling describes transmission of matter waves through a barrier with height larger than the energy of the wave(1). Tunnelling becomes important when the de Broglie wavelength of the particle exceeds the barrier thickness; because wavelength increases with decreasing mass, lighter particles tunnel more efficiently than heavier ones. However, there exist examples in condensed-phase chemistry where increasing mass leads to increased tunnelling rates(2). In contrast to the textbook approach, which considers transitions between continuum states, condensed-phase reactions involve transitions between bound states of reactants and products. Here this conceptual distinction is highlighted by experimental measurements of isotopologue-specific tunnelling rates for CO rotational isomerization at an NaCl surface(3,4), showing nonmonotonic mass dependence. A quantum rate theory of isomerization is developed wherein transitions between sub-barrier reactant and product states occur through interaction with the environment. Tunnelling is fastest for specific pairs of states (gateways), the quantum mechanical details of which lead to enhanced cross-barrier coupling; the energies of these gateways arise nonsystematically, giving an erratic mass dependence. Gateways also accelerate ground-state isomerization, acting as leaky holes through the reaction barrier. This simple model provides a way to account for tunnelling in condensed-phase chemistry, and indicates that heavy-atom tunnelling may be more important than typically assumed.
The prevalence of obesity in the pediatric population has become a major public health issue. Indeed, the dramatic increase of this epidemic causes multiple and harmful consequences, Physical activity, particularly physical exercise, remains to be the cornerstone of interventions against childhood obesity. Given the conflicting findings with reference to the relevant literature addressing the effects of exercise on adiposity and physical fitness outcomes in obese children and adolescents, the effect of duration-matched concurrent training (CT) [50% resistance (RT) and 50% high-intensity-interval-training (HIIT)] on body composition and physical fitness in obese youth remains to be elucidated. Thus, the purpose of this study was to examine the effects of 9-weeks of CT compared to RT or HIIT alone, on body composition and selected physical fitness components in healthy sedentary obese youth. Out of 73 participants, only 37; [14 males and 23 females; age 13.4 ± 0.9 years; body-mass-index (BMI): 31.2 ± 4.8 kg·m-2] were eligible and randomized into three groups: HIIT (n = 12): 3-4 sets×12 runs at 80–110% peak velocity, with 10-s passive recovery between bouts; RT (n = 12): 6 exercises; 3–4 sets × 10 repetition maximum (RM) and CT (n = 13): 50% serial completion of RT and HIIT. CT promoted significant greater gains compared to HIIT and RT on body composition (p < 0.01, d = large), 6-min-walking test distance (6 MWT-distance) and on 6 MWT-VO2max (p < 0.03, d = large). In addition, CT showed substantially greater improvements than HIIT in the medicine ball throw test (20.2 vs. 13.6%, p < 0.04, d = large). On the other hand, RT exhibited significantly greater gains in relative hand grip strength (p < 0.03, d = large) and CMJ (p < 0.01, d = large) than HIIT and CT. CT promoted greater benefits for fat, body mass loss and cardiorespiratory fitness than HIIT or RT modalities. This study provides important information for practitioners and therapists on the application of effective exercise regimes with obese youth to induce significant and beneficial body composition changes. The applied CT program and the respective programming parameters in terms of exercise intensity and volume can be used by practitioners as an effective exercise treatment to fight the pandemic overweight and obesity in youth.
Compound inland flood events
(2022)
Several severe flood events hit Germany in recent years, with events in 2013 and 2016 being the most destructive ones, although dynamics and flood processes were very different. While the 2013 event was a slowly rising widespread fluvial flood accompanied by some severe dike breaches, the events in 2016 were fast-onset pluvial floods, which resulted in surface water flooding in some places due to limited capacities of the drainage systems and in destructive flash floods with high sediment loads and clogging in others, particularly in small steep catchments. Hence, different pathways, i.e. different routes that the water takes to reach (and potentially damage) receptors, in our case private households, can be identified in both events. They can thus be regarded as spatially compound flood events or compound inland floods. This paper analyses how differently affected residents coped with these different flood types (fluvial and pluvial) and their impacts while accounting for the different pathways (river flood, dike breach, surface water flooding and flash flood) within the compound events. The analyses are based on two data sets with 1652 (for the 2013 flood) and 601 (for the 2016 flood) affected residents who were surveyed around 9 months after each flood, revealing little socio-economic differences - except for income - between the two samples. The four pathways showed significant differences with regard to their hydraulic and financial impacts, recovery, warning processes, and coping and adaptive behaviour. There are just small differences with regard to perceived self-efficacy and responsibility, offering entry points for tailored risk communication and support to improve property-level adaptation.
Extreme habitats often harbor specific communities that differ substantially from non-extreme habitats. In many cases, these communities are characterized by archaea, bacteria and protists, whereas the number of species of metazoa and higher plants is relatively low. In extremely acidic habitats, mostly prokaryotes and protists thrive, and only very few metazoa thrive, for example, rotifers. Since many studies have investigated the physiology and ecology of individual species, there is still a gap in research on direct, trophic interactions among extremophiles. To fill this gap, we experimentally studied the trophic interactions between a predatory protist (Actinophrys sol, Heliozoa) and its prey, the rotifers Elosa woralli and Cephalodella sp., the ciliate Urosomoida sp. and the mixotrophic protist Chlamydomonas acidophila (a green phytoflagellate, Chlorophyta). We found substantial predation pressure on all animal prey. High densities of Chlamydomonas acidophila reduced the predation impact on the rotifers by interfering with the feeding behaviour of A. sol. These trophic relations represent a natural case of intraguild predation, with Chlamydomonas acidophila being the common prey and the rotifers/ciliate and A. sol being the intraguild prey and predator, respectively. We further studied this intraguild predation along a resource gradient using Cephalodella sp. as the intraguild prey. The interactions among the three species led to an increase in relative rotifer abundance with increasing resource (Chlamydomonas) densities. By applying a series of laboratory experiments, we revealed the complexity of trophic interactions within a natural extremophilic community.
Signaling trough p53is a major cellular stress response mechanism and increases upon nutrient stresses such as starvation. Here, we show in a human hepatoma cell line that starvation leads to robust nuclear p53 stabilization. Using BioID, we determine the cytoplasmic p53 interaction network within the immediate-early starvation response and show that p53 is dissociated from several metabolic enzymes and the kinase PAK2 for which direct binding with the p53 DNA-binding domain was confirmed with NMR studies. Furthermore, proteomics after p53 immunoprecipitation (RIME) uncovered the nuclear interactome under prolonged starvation, where we confirmed the novel p53 interactors SORBS1 (insulin receptor signaling) and UGP2 (glycogen synthesis). Finally, transcriptomics after p53 re-expression revealed a distinct starvation-specific transcriptome response and suggested previously unknown nutrient-dependent p53 target genes. Together, our complementary approaches delineate several nodes of the p53 signaling cascade upon starvation, shedding new light on the mechanisms of p53 as nutrient stress sensor. Given the central role of p53 in cancer biology and the beneficial effects of fasting in cancer treatment, the identified interaction partners and networks could pinpoint novel pharmacologic targets to fine-tune p53 activity.
Recently, glasses, a subset of amorphous solids, have gained attention in various fields, such as polymer chemistry, optical fibers, and pharmaceuticals. One of their characteristic features, the glass transition temperature (T-g) which is absent in 100% crystalline materials, influences several material properties, such as free volume, enthalpy, viscosity, thermodynamic transitions, molecular motions, physical stability, mechanical properties, etc. In addition to T-g, there may be several other temperaturedependent transitions known as sub-T-g transitions (or beta-, gamma-, and delta-relaxations) which are identified by specific analytical techniques. The study of T-g and sub-T-g transitions occurring in amorphous solids has gained much attention because of its importance in understanding molecular kinetics, and it requires the combination of conventional and novel characterization techniques. In the present study, three different analytical techniques [modulated differential scanning calorimetry (mDSC), dynamic mechanical analysis (DMA), and dielectric relaxation spectroscopy (DRS)] were used to perform comprehensive qualitative/quantitative characterization of molecular relaxations, miscibility, and molecular interactions present in an amorphous polymer (PVPVA), a model drug (indomethacin, IND), and IND/PVPVA-based amorphous solid dispersions (ASDs). This is the first ever reported DMA study on PVPVA in its powder form, which avoids the contribution of solvent to the mechanical properties when a selfstanding polymer film is used. A good correlation between the techniques in determining the T-g value of PVPVA, IND, and IND/ PVPVA-based ASDs is established, and the negligible difference (within 10 degrees C) is attributed to the different material properties assessed in each technique. However, the overall T-g behavior, the decrease in T-g with increase in drug loading in ASDs, is universally observed in all the above-mentioned techniques, which reveals their complementarity. DMA and DRS techniques are used to study the different sub-T-g transitions present in PVPVA, amorphous IND, and IND/PVPVA-based ASDs because these transitions are normally too weak or too broad for mDSC to detect. For IND/PVPVA-based ASDs, both techniques show a shift of sub-T-g transitions (or secondary relaxation peaks) toward the high-temperature region from -140 to -45 degrees C. Thus, this paper outlines the usage of different solid-state characterization techniques in understanding the different molecular dynamics present in the polymer, drug, and their interactions in ASDs with the integrated information obtained from individual techniques.
Sporadic E or Es is a transient phenomenon where thin layers of enhanced electron density appear in the ionospheric E region (90-120 km altitude). The neutral wind shear caused by atmospheric tides can lead ions to converge vertically at E-region heights and form the Es layer. This research aims to determine the role of atmospheric solar and lunar tides in Es occurrence. For this purpose, radio occultation data of FORMOSAT-3/COSMIC have been used, which provide complete global coverage of Es events. Moreover, GAIA model simulations have been employed to evaluate the vertical ion convergence induced by solar tides. The results show both migrating and non-migrating solar tidal signatures and the semidiurnal migrating lunar tidal signature mainly in low and mid-latitude Es occurrence. The seasonal variation of the migrating solar tidal components of Es is in good agreement with those in the vertical ion convergence derived from GAIA at higher altitudes. Furthermore, some non-migrating components of solar tides, including semidiurnal westward wavenumbers 1 and 3 and diurnal eastward wavenumbers 2 and 3, also significantly affect the Es occurrence rate.
Video is a widely used medium in teacher training for situating student teachers in classroom scenarios. Although the emerging technology of virtual reality (VR) provides similar, and arguably more powerful, capabilities for immersing teachers in lifelike situations, its benefits and risks relative to video formats have received little attention in the research to date. The current study used a randomized pretest-posttest experimental design to examine the influence of a video- versus VR-based task on changing situational interest and self-efficacy in classroom management. Results from 49 student teachers revealed that the VR simulation led to higher increments in self-reported triggered interest and self-efficacy in classroom management, but also invoked higher extraneous cognitive load than a video viewing task. We discussed the implications of these results for pre-service teacher education and the design of VR environments for professional training purposes. Practitioner notes What is already known about this topic Video is a popular teacher training medium given its ability to display classroom situations. Virtual reality (VR) also immerses users in lifelike situations and has gained popularity in recent years. Situational interest and self-efficacy in classroom management is vital for student teachers' professional development. What this paper adds VR outperforms video in promoting student teachers' triggered interest in classroom management. Student teachers felt more efficacious in classroom management after participating in VR. VR also invoked higher extraneous cognitive load than the video. Implications for practice and/or policy VR provides an authentic teacher training environment for classroom management. The design of the VR training environment needs to ensure a low extraneous cognitive load.
Here I present a comparison between two of the most widely used reduced-complexity models for the representation of sediment transport and deposition processes, namely the transport-limited (or TL) model and the under-capacity (or xi-q) model more recently developed by Davy and Lague (2009). Using both models, I investigate the behavior of a sedimentary continental system of length L fed by a fixed sedimentary flux from a catchment of size A(0) in a nearby active orogen through which sediments transit to a fixed base level representing a large river, a lake or an ocean. This comparison shows that the two models share the same steady-state solution, for which I derive a simple 1D analytical expression that reproduces the major features of such sedimentary systems: a steep fan that connects to a shallower alluvial plain. The resulting fan geometry obeys basic observational constraints on fan size and slope with respect to the upstream drainage area, A(0). The solution is strongly dependent on the size of the system, L, in comparison to a distance L-0, which is determined by the size of A(0), and gives rise to two fundamentally different types of sedimentary systems: a constrained system where L < L-0 and open systems where L > L-0. I derive simple expressions that show the dependence of the system response time on the system characteristics, such as its length, the size of the upstream catchment area, the amplitude of the incoming sedimentary flux and the respective rate parameters (diffusivity or erodibility) for each of the two models. I show that the xi-q model predicts longer response times. I demonstrate that although the manner in which signals propagates through the sedimentary system differs greatly between the two models, they both predict that perturbations that last longer than the response time of the system can be recorded in the stratigraphy of the sedimentary system and in particular of the fan. Interestingly, the xi-q model predicts that all perturbations in the incoming sedimentary flux will be transmitted through the system, whereas the TL model predicts that rapid perturbations cannot. I finally discuss why and under which conditions these differences are important and propose observational ways to determine which of the two models is most appropriate to represent natural systems.
Channel steepness index, k(s), is a metric derived from the stream power model that, under certain conditions, scales with relative rock uplift rate. Channel steepness index is a property of rivers, which can be relatively easily extracted from digital elevation models (DEMs). As DEM data sets are widely available for Earth and are becoming more readily available for other planetary bodies, channel steepness index represents a powerful tool for interpreting tectonic processes. However, multiple approaches to calculate channel steepness index exist. From this several important questions arise; does choice of approach change the values of channel steepness index, can values be so different that choice of approach can influence the findings of a study, and are certain approaches better than others? With the aid of a synthetic river profile and a case study from the Sierra Nevada, California, we show that values of channel steepness index vary over orders of magnitude according to the methodology used in the calculation. We explore the limitations, advantages and disadvantages of the key approaches to calculating channel steepness index, and find that choosing an appropriate approach relies on the context of a study. Given these observations, it is important that authors acknowledge the methodology used to calculate channel steepness index, to ensure that results can be contextualised and reproduced.
Supergenes are nonrecombining genomic regions ensuring the coinheritance of multiple, coadapted genes. Despite the importance of supergenes in adaptation, little is known on how they originate. A classic example of supergene is the S locus controlling heterostyly, a floral heteromorphism occurring in 28 angiosperm families. In Primula, heterostyly is characterized by the cooccurrence of two complementary, self-incompatible floral morphs and is controlled by five genes clustered in the hemizygous, ca. 300-kb S locus. Here, we present the first chromosome-scale genome assembly of any heterostylous species, that of Primula veris (cowslip). By leveraging the high contiguity of the P. veris assembly and comparative genomic analyses, we demonstrated that the S-locus evolved via multiple, asynchronous gene duplications and independent gene translocations. Furthermore, we discovered a new whole-genome duplication in Ericales that is specific to the Primula lineage. We also propose a mechanism for the origin of S-locus hemizygosity via nonhomologous recombination involving the newly discovered two pairs of CFB genes flanking the S locus. Finally, we detected only weak signatures of degeneration in the S locus, as predicted for hemizygous supergenes. The present study provides a useful resource for future research addressing key questions on the evolution of supergenes in general and the S locus in particular: How do supergenes arise? What is the role of genome architecture in the evolution of complex adaptations? Is the molecular architecture of heterostyly supergenes across angiosperms similar to that of Primula?
COMMIT
(2022)
Composition and functions of microbial communities affect important traits in diverse hosts, from crops to humans. Yet, mechanistic understanding of how metabolism of individual microbes is affected by the community composition and metabolite leakage is lacking. Here, we first show that the consensus of automatically generated metabolic reconstructions improves the quality of the draft reconstructions, measured by comparison to reference models. We then devise an approach for gap filling, termed COMMIT, that considers metabolites for secretion based on their permeability and the composition of the community. By applying COMMIT with two soil communities from the Arabidopsis thaliana culture collection, we could significantly reduce the gap-filling solution in comparison to filling gaps in individual reconstructions without affecting the genomic support. Inspection of the metabolic interactions in the soil communities allows us to identify microbes with community roles of helpers and beneficiaries. Therefore, COMMIT offers a versatile fully automated solution for large-scale modelling of microbial communities for diverse biotechnological applications. <br /> Author summaryMicrobial communities are important in ecology, human health, and crop productivity. However, detailed information on the interactions within natural microbial communities is hampered by the community size, lack of detailed information on the biochemistry of single organisms, and the complexity of interactions between community members. Metabolic models are comprised of biochemical reaction networks based on the genome annotation, and can provide mechanistic insights into community functions. Previous analyses of microbial community models have been performed with high-quality reference models or models generated using a single reconstruction pipeline. However, these models do not contain information on the composition of the community that determines the metabolites exchanged between the community members. In addition, the quality of metabolic models is affected by the reconstruction approach used, with direct consequences on the inferred interactions between community members. Here, we use fully automated consensus reconstructions from four approaches to arrive at functional models with improved genomic support while considering the community composition. We applied our pipeline to two soil communities from the Arabidopsis thaliana culture collection, providing only genome sequences. Finally, we show that the obtained models have 90% genomic support and demonstrate that the derived interactions are corroborated by independent computational predictions.
In the last years, electron density profile functions characterized by a linear dependence on the scale height showed good results when approximating the topside ionosphere. The performance above 800 km, however, is not yet well investigated.
This study investigates the capability of the semi-Epstein functions to represent electron density profiles from the peak height up to 20,000 km. Electron density observations recorded by the Van Allen Probes were used to resolve the scale height dependence in the plasmasphere.
It was found that the linear dependence of the scale height in the topside ionosphere cannot be directly used to extrapolate profiles above 800 km.
We find that the dependence of scale heights on altitude is quadratic in the plasmasphere. A statistical model of the scale heights is therefore proposed. After combining the topside ionosphere and plasmasphere by a unified model, we have obtained good estimations not only in the profile shapes, but also in the Total Electron Content magnitude and distributions when compared to actual measurements from 2013, 2014, 2016 and 2017.
Our investigation shows that Van Allen Probes can be merged to radio-occultation data to properly represent the upper ionosphere and plasmasphere by means of a semi-Epstein function.
Colloidal metal sulfide nanoparticles for high performance electrochemical energy storage systems
(2022)
Transition metal sulfides have emerged as excellent replacement candidates of traditional insertion electrode materials based on their conversion or alloying mechanisms, facilitating high specific capacity and rate ability. However, parasitic reactions such as massive volume change during the discharge/ charge processes, intermediate polysulfide dissolution, and passivating solid electrolyte interface formation have led to poor cyclability, hindering their feasibility and applicability in energy storage systems. Colloidal metal sulfide nanoparticles, a special class that integrates the intrinsic chemical properties of metal sulfides and their specified structural features, have fairly enlarged their contribution due to the synergistic effect. This review highlights the latest synthetic approaches based on colloidal process. Their corresponding electrochemical outcomes will also be discussed, which are thoroughly updated along with their insight scientific standpoints.
We consider a ring network of theta neurons with non-local homogeneous coupling. We analyse the corresponding continuum evolution equation, analytically describing all possible steady states and their stability. By considering a number of different parameter sets, we determine the typical bifurcation scenarios of the network, and put on a rigorous footing some previously observed numerical results.
We used structural topic modeling to analyze over 800,000 German tweets about COVID-19 to answer the questions: What patterns emerge in tweets as a response to a health crisis? And how do topics discussed change over time? The study leans on the goals associated with the health information seeking (GAINS) model, discerning whether a post aims at tackling and eliminating the problem (i.e., problem-focused) or managing the emotions (i.e., emotion-focused); whether it strives to maximize positive outcomes (promotion focus) or to minimize negative outcomes (prevention focus). The findings indicate four clusters salient in public reactions: 1) “Understanding” (problem-promotion); 2) “Action planning” (problem-prevention); 3) “Hope” (emotion-promotion) and 4) “Reassurance” (emotion-prevention). Public communication is volatile over time, and a shift is evidenced from self-centered to community-centered topics within 4.5 weeks. Our study illustrates social media text mining's potential to quickly and efficiently extract public opinions and reactions. Monitoring fears and trending topics enable policymakers to rapidly respond to deviant behavior, like resistive attitudes toward containment measures or deteriorating physical health. Healthcare workers can use the insights to provide mental health services for battling anxiety or extensive loneliness from staying home.
Recent observations have revealed remarkable insights into the gas reservoir in the circumgalactic medium (CGM) of galaxy haloes. In this paper, we characterise the gas in the vicinity of Milky Way and Andromeda analogues in the hestia (High resolution Environmental Simulations of The Immediate Area) suite of constrained Local Group (LG) simulations. The hestia suite comprise of a set of three high-resolution arepo-based simulations of the LG, run using the Auriga galaxy formation model.
For this paper, we focus only on the 𝑧 = 0 simulation datasets and generate mock skymaps along with a power spectrum analysis to show that the distributions of ions tracing low-temperature gas (H i and Si iii) are more clumpy in comparison to warmer gas tracers (O vi, O vii and O viii). We compare to the spectroscopic CGM observations of M31 and low-redshift galaxies.
hestia under-produces the column densities of the M31 observations, but the simulations are consistent with the observations of low-redshift galaxies. A possible explanation for these findings is that the spectroscopic observations of M31 are contaminated by gas residing in the CGM of the Milky Way.
Fram Strait in the northern North Atlantic is a key region for marine cold air outbreaks (MCAOs), southward discharges of polar air under northerly air flow, which have a strong impact on air-sea heat fluxes, boundary layer processes and severe weather. This study investigates climatologies and decadal trends of Fram Strait MCAOs of different intensity classes based on the ERA5 reanalysis product for 1979-2020. Among striking interannual variability, it is shown that the main MCAO season is December through March, when MCAOs occur around 2/3 of the time. We report on significant decadal MCAO decreases in December and January, and a significant increase in March. While the mid-winter decrease is mainly related to the different paces of warming between the surface and the lower atmosphere, the increase in March can be related to changes in synoptic circulation patterns. As an explanation for the latter, a possible feedback between retreating Barents Sea sea ice, enhanced cyclonic activity and Fram Strait MCAOs is postulated. Exemplifying the trend toward stronger MCAOs during March, the study details the recordbreaking MCAO season in early 2020, and an observational case study of an extreme MCAO event in March 2020 is conducted. Thereby, radiosonde observations are combined with kinematic air back-trajectories to provide rare observational evidence for the diabatic cooling and drying during the MCAO preconditioning phase.
Devolatilization of subducting lithologies liberates COH-fluids. These may become partially sequestered in peridotites in the slab and the overlying forearc mantle, affecting the cycling of volatiles and fluid mobile elements in subduction zones. Here we assess the magnitudes, timescales and mechanism of channelized injection of COH-fluids doped with Ca-aq(2+), Sr-aq(2+) and Ba-aq(2+) into the dry forearc mantle by performing piston cylinder experiments between 1-2.5 GPa and 600-700 degrees C. Cylindrical cores of natural spinel-bearing harzburgites were used as starting materials. Based on mineral assemblage and composition three reaction zones are distinguishable from the rim towards the core of primary olivine and orthopyroxene grains. Zone 1 contains carbonates + quartz +/- kyanite and zone 2 contains carbonates + talc +/- chlorite. Olivine is further replaced in zone 3 by either antigorite+ magnesite or magnesite +talc within or above antigorite stability, respectively. Orthopyroxene is replaced in zone 3 by talc + chlorite. Mineral assemblages and the compositions of secondary minerals depend on fluid composition and the replaced primary silicate. The extent of alteration depends on fluid CO2 content and fluid/rock-ratio, and is further promoted by fluid permeable reaction zones and reaction driven cracking. Our results show that COH-fluid induced metasomatism of the forearc mantle is self-perpetuating and efficient at sequestering Ca-aq(2+), Sr-aq(2+), Ba-aq(2+) and CO2aq into newly formed carbonates. This process is fast with 90% of the available C sequestered and nearly 50% of the initial minerals altered at 650 degrees C, 2 GPa within 55 h. The dissolution of primary silicates under high COH-fluid/rock-ratios, as in channelized fluid flow, enriches SiO2aq in the fluid, while CO2aq is sequestered into carbonates. In an open system, the remaining CO2-depleted, Si-enriched aqueous fluid may cause Si-metasomatism in the forearc further away from the injection of the COH-fluid into peridotite.
Maximizing the efficiency of nanocarrier-mediated co-delivery of genes for co-expression in the same cell is critical for many applications. Strategies to maximize co-delivery of nucleic acids (NA) focused largely on carrier systems, with little attention towards payload composition itself. Here, we investigated the effects of different payload designs: co-delivery of two individual "monocistronic" NAs versus a single bicistronic NA comprising two genes separated by a 2A self-cleavage site. Unexpectedly, co-delivery via the monocistronic design resulted in a higher percentage of co-expressing cells, while predictive co-expression via the bicistronic design remained elusive. Our results will aid the application-dependent selection of the optimal methodology for co-delivery of genes.
The highly structured nature of the educational sector demands effective policy mechanisms close to the needs of the field. That is why evidence-based policy making, endorsed by the European Commission under Erasmus+ Key Action 3, aims to make an alignment between the domains of policy and practice. Against this background, this article addresses two issues: First, that there is a vertical gap in the translation of higher-level policies to local strategies and regulations. Second, that there is a horizontal gap between educational domains regarding the policy awareness of individual players. This was analyzed in quantitative and qualitative studies with domain experts from the fields of virtual mobility and teacher training. From our findings, we argue that the combination of both gaps puts the academic bridge from secondary to tertiary education at risk, including the associated knowledge proficiency levels. We discuss the role of digitalization in the academic bridge by asking the question: which value does the involved stakeholders expect from educational policies? As a theoretical basis, we rely on the model of value co-creation for and by stakeholders. We describe the used instruments along with the obtained results and proposed benefits. Moreover, we reflect on the methodology applied, and we finally derive recommendations for future academic bridge policies.
Anomalous diffusion with a power-law time dependence vertical bar R vertical bar(2)(t) similar or equal to t(alpha i) of the mean squared displacement occurs quite ubiquitously in numerous complex systems. Often, this anomalous diffusion is characterised by crossovers between regimes with different anomalous diffusion exponents alpha(i). Here we consider the case when such a crossover occurs from a first regime with alpha(1) to a second regime with alpha(2) such that alpha(2) > alpha(1), i.e., accelerating anomalous diffusion. A widely used framework to describe such crossovers in a one-dimensional setting is the bi-fractional diffusion equation of the so-called modified type, involving two time-fractional derivatives defined in the Riemann-Liouville sense. We here generalise this bi-fractional diffusion equation to higher dimensions and derive its multidimensional propagator (Green's function) for the general case when also a space fractional derivative is present, taking into consideration long-ranged jumps (Levy flights). We derive the asymptotic behaviours for this propagator in both the short- and long-time as well the short- and long-distance regimes. Finally, we also calculate the mean squared displacement, skewness and kurtosis in all dimensions, demonstrating that in the general case the non-Gaussian shape of the probability density function changes.
Climatic and hydrological variability as a driver of the Lake Gościąż biota during the Younger Dryas
(2022)
The Younger Dryas (YD) is a roughly 1,100-year cold period marking the end of the last glaciation. Climate modelling for northern Europe indicates high summer temperatures and strong continentality. In eastern Europe, the scale of temperature variation and its influence on ecosystems is weakly recognised. Here, we present a multi-proxy reconstruction of YD conditions from Lake Gos ' ciaz (central Poland). The decadal-resolution analysis of its annually varved sediments indicates an initial decrease in Chironomidae-inferred mean July air temperature followed by steady warming. The pollen-inferred winter-to-summer temperature amplitude and annual precip-itation is highest at the Allerod/YD transition and the early YD (ca. 12.7-12.4 ky cal BP) and YD/Holocene (11.7-11.4 ka cal BP) transition. Temperature and precipitation were the main reasons for lake level fluctuations as reflected in the planktonic/littoral Cladocera ratio. The lake's diatom-inferred total phosphorus decreased with increasing summer temperature from about mid YD. Windy conditions in the early YD until ~12.3 ka cal BP caused water mixing and a short-lived/temporary increase in nutrient availability for phytoplankton. The Chironomidae-inferred summer temperature and pollen inferred summer temperature, winter temperature and annual precipitation herein are one of only a few in eastern Europe conducted with such high resolution.
Understanding the influence of climate change and population pressure on human conflict remains a critically important topic in the social sciences. Long-term records that evaluate these dynamics across multiple centuries and outside the range of modern climatic variation are especially capable of elucidating the relative effect of-and the interaction between-climate and demography. This is crucial given that climate change may structure population growth and carrying capacity, while both climate and population influence per capita resource availability. This study couples paleoclimatic and demographic data with osteological evaluations of lethal trauma from 149 directly accelerator mass spectrometry C-14-dated individuals from the Nasca highland region of Peru. Multiple local and supraregional precipitation proxies are combined with a summed probability distribution of 149 C-14 dates to estimate population dynamics during a 700-y study window. Counter to previous findings, our analysis reveals a precipitous increase in violent deaths associated with a period of productive and stable climate, but volatile population dynamics. We conclude that favorable local climate conditions fostered population growth that put pressure on the marginal and highly circumscribed resource base, resulting in violent resource competition that manifested in over 450 y of internecine warfare. These findings help support a general theory of intergroup violence, indicating that relative resource scarcity-whether driven by reduced resource abundance or increased competition-can lead to violence in subsistence societies when the outcome is lower per capita resource availability.
Climate Benefits of Cleaner Energy Transitions in East and South Asia Through Black Carbon Reduction
(2022)
The state of air pollution has historically been tightly linked to how we produce and use energy. Air pollutant emissions over Asia are now changing rapidly due to cleaner energy transitions; however, magnitudes of benefits for climate and air quality remain poorly quantified. The associated risks involve adverse health impacts, reduced agricultural yields, reduced freshwater availability, contributions to climate change, and economic costs. We focus particularly on climate benefits of energy transitions by making first-time use of two decades of high quality observations of atmospheric loading of light-absorbing black carbon (BC) over Kanpur (South Asia) and Beijing (East Asia) and relating these observations to changing energy, emissions, and economic trends in India and China. Our analysis reveals that absorption aerosol optical depth (AAOD) due to BC has decreased substantially, by 40% over Kanpur and 60% over Beijing between 2001 and 2017, and thus became decoupled from regional economic growth. Furthermore, the resultant decrease in BC emissions and BC AAOD over Asia is regionally coherent and occurs primarily due to transitions into cleaner energies (both renewables and fossil fuels) and not due to the decrease in primary energy supply or decrease in use of fossil use and biofuels and waste. Model simulations show that BC aerosols alone contribute about half of the surface temperature change (warming) of the total forcing due to greenhouse gases, natural and internal variability, and aerosols, thus clearly revealing the climate benefits due to a reduction in BC emissions, which would significantly reduce global warming. However, this modeling study excludes responses from natural variability, circulation, and sea ice responses, which cause relatively strong temperature fluctuations that may mask signals from BC aerosols. Our findings show additional benefits for climate (beyond benefits of CO2 reduction) and for several other issues of sustainability over South and East Asia, provide motivation for ongoing cleaner energy production, and consumption transitions, especially when they are associated with reduced emissions of air pollutants. Such an analysis connecting the trends in energy transitions and aerosol absorption loading, unavailable so far, is crucial for simulating the aerosol climate impacts over Asia which is quite uncertain.
The field of movement ecology has seen a rapid increase in high-resolution data in recent years, leading to the development of numerous statistical and numerical methods to analyse relocation trajectories. Data are often collected at the level of the individual and for long periods that may encompass a range of behaviours.
Here, we use the power spectral density (PSD) to characterise the random movement patterns of a black-winged kite (Elanus caeruleus) and a white stork (Ciconia ciconia). The tracks are first segmented and clustered into different behaviours (movement modes), and for each mode we measure the PSD and the ageing properties of the process.
For the foraging kite we find 1/f noise, previously reported in ecological systems mainly in the context of population dynamics, but not for movement data. We further suggest plausible models for each of the behavioural modes by comparing both the measured PSD exponents and the distribution of the single-trajectory PSD to known theoretical results and simulations.
Teachers frequently express stress associated with teaching in large classrooms. Despite the timehonored tradition in teacher stress research of treating class size as a job-related stressor, the underlying premise that class size directly impacts teachers' stress reactions remains untested. In this randomized controlled experiment targeted at preservice teachers, we utilized a standardized virtual reality (VR) classroom to examine whether class size (number of student avatars) directly affected physiological (heart rate) or psychological (subjective rating) stress reactions among 65 preservice teachers. Results from linear mixed-effects modeling (LMM) showed that class size significantly predicted both their physiological and psychological stress reactions in the simulated environment: Average heart rate and subjective stress ratings were both significantly higher in the large class size condition. Further investigations into the causes of this association has been proposed. These findings may contribute to a better understanding of the effects of classroom features on preservice teachers' emotional experiences and well-being.
Numerical magnitude information is assumed to be spatially represented in the form of a mental number line defined with respect to a body-centred, egocentric frame of reference. In this context, spatial language skills such as mastery of verbal descriptions of spatial position (e.g., in front of, behind, to the right/left) have been proposed to be relevant for grasping spatial relations between numerical magnitudes on the mental number line. We examined 4- to 5-year-old’s spatial language skills in tasks that allow responses in egocentric and allocentric frames of reference, as well as their relative understanding of numerical magnitude (assessed by a number word comparison task). In addition, we evaluated influences of children’s absolute understanding of numerical magnitude assessed by their number word comprehension (montring different numbers using their fingers) and of their knowledge on numerical sequences (determining predecessors and successors as well as identifying missing dice patterns of a series). Results indicated that when considering responses that corresponded to the egocentric perspective, children’s spatial language was associated significantly with their relative numerical magnitude understanding, even after controlling for covariates, such as children’s SES, mental rotation skills, and also absolute magnitude understanding or knowledge on numerical sequences. This suggests that the use of egocentric reference frames in spatial language may facilitate spatial representation of numbers along a mental number line and thus seem important for preschoolers’ relative understanding of numerical magnitude.
The process of number symbolization is assumed to be critically influenced by the acquisition of so-called verbal number skills (e.g., verbally reciting the number chain and naming Arabic numerals). For the acquisition of these verbal number skills, verbal and visuospatial skills are discussed as contributing factors. In this context, children’s verbal number skills have been found to be associated with their concurrent spatial language skills such as mastery of verbal descriptions of spatial position (e.g., in front of, behind). In a longitudinal study with three measurement times (T1, T2, T3) at an interval of about 6 months, we evaluated the predictive role of preschool children’s (mean age at T1: 3 years and 10 months) spatial language skills for the acquisition of verbal number skills. Children’s spatial language skills at T2 significantly predicted their verbal number skills at T3, when controlling for influences of important covariates such as vocabulary knowledge. In addition, further analyses replicated previous results indicating that children’s spatial language skills at T2 were associated with their verbal number skills at T2. Exploratory analyses further revealed that children’s verbal number skills at T1 predict their spatial language at T2. Results suggests that better spatial language skills at the age of 4 years facilitate the future acquisition of verbal number skills.
In vitro transcribed (IVT)-mRNA has been accepted as a promising therapeutic modality. Advances in facile and rapid production technologies make IVT-mRNA an appealing alternative to protein- or virus-based medicines.
Robust expression levels, lack of genotoxicity, and their manageable immunogenicity benefit its clinical applicability.
We postulated that innate immune responses of therapeutically relevant human cells can be tailored or abrogated by combinations of 5'-end and internal IVT-mRNA modifications.
Using primary human macrophages as targets, our data show the particular importance of uridine modifications for IVT-mRNA performance.
Among five nucleotide modification schemes tested, 5-methoxy-uridine outperformed other modifications up to 4-fold increased transgene expression, triggering moderate proinflammatory and non-detectable antiviral responses.
Macrophage responses against IVT-mRNAs exhibiting high immunogenicity (e.g., pseudouridine) could be minimized upon HPLC purification. Conversely, 5'-end modifications had only modest effects on mRNA expression and immune responses.
Our results revealed how the uptake of chemically modified IVT-mRNA impacts human macrophages, responding with distinct patterns of innate immune responses concomitant with increased transient transgene expression.
We anticipate our findings are instrumental to predictively address specific cell responses required for a wide range of therapeutic applications from eliciting controlled immunogenicity in mRNA vaccines to, e.g., completely abrogating cell activation in protein replacement therapies.
High pressure and high temperature experiments performed with laser-heated diamond anvil cells (LH-DAC) are being extensively used in geosciences to study matter at conditions prevailing in planetary interiors. Due to the size of the apparatus itself, the samples that are produced are extremely small, on the order of few tens of micrometers. There are several ways to analyze the samples and extract physical, chemical or structural information, using either in situ or ex situ methods. In this paper, we compare two nanoprobe techniques, namely nano-XRF and NanoSIMS, that can be used to analyze recovered samples synthetized in a LH-DAC. With these techniques, it is possible to extract the spatial distribution of chemical elements in the samples. We show the results for several standards and discuss the importance of proper calibration for the acquisition of quantifiable results. We used these two nanoprobe techniques to retrieve elemental ratios of dilute species (few tens of ppm) in quenched experimental molten samples relevant for the formation of the iron-rich core of the Earth. We finally discuss the applications of such probes to constrain the partitioning of trace elements between metal and silicate phases, with a focus on moderately siderophile elements, tungsten and molybdenum.
Improving nitrogen (N) status in European water bodies is a pressing issue. N levels depend not only on current but also past N inputs to the landscape, that have accumulated through time in legacy stores (e.g., soil, groundwater).
Catchment-scale N models, that are commonly used to investigate in-stream N levels, rarely examine the magnitude and dynamics of legacy components.
This study aims to gain a better understanding of the long-term fate of the N inputs and its uncertainties, using a legacy-driven N model (ELEMeNT) in Germany's largest national river basin (Weser; 38,450 km(2)) over the period 1960-2015.
We estimate the nine model parameters based on a progressive constraining strategy, to assess the value of different observational data sets.
We demonstrate that beyond in-stream N loading, soil N content and in-stream N concentration allow to reduce the equifinality in model parameterizations.
We find that more than 50% of the N surplus denitrifies (1480-2210 kg ha(-1)) and the stream export amounts to around 18% (410-640 kg ha(-1)), leaving behind as much as around 230-780 kg ha(-1) of N in the (soil) source zone and 10-105 kg ha(-1) in the subsurface.
A sensitivity analysis reveals the importance of different factors affecting the residual uncertainties in simulated N legacies, namely hydrologic travel time, denitrification rates, a coefficient characterizing the protection of organic N in source zone and N surplus input.
Our study calls for proper consideration of uncertainties in N legacy characterization, and discusses possible avenues to further reduce the equifinality in water quality modeling.
Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome.
The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular protein transport, immunoregulation, and several other crucial processes during hantavirus infection.
In this study, we generated fluorescently tagged N protein constructs derived from Puumalavirus (PUUV), the dominant hantavirus species in Central, Northern, and Eastern Europe.
We comprehensively characterized this protein in the rodent cell line CHO-K1, monitoring the dynamics of N protein complex formation and investigating co-localization with host proteins as well as the viral glycoproteins Gc and Gn.
We observed formation of large, fibrillar PUUV N protein aggregates, rapidly coalescing from early punctate and spike-like assemblies.
Moreover, we found significant spatial correlation of N with vimentin, actin, and P-bodies but not with microtubules. N constructs also co-localized with Gn and Gc albeit not as strongly as the glycoproteins associated with each other.
Finally, we assessed oligomerization of N constructs, observing efficient and concentration-dependent multimerization, with complexes comprising more than 10 individual proteins.
The strong chromospheric absorption lines Ca ii H & K are tightly connected to stellar surface magnetic fields. Only for the Sun, spectral activity indices can be related to evolving magnetic features on the solar disk. The Solar Disk-Integrated (SDI) telescope feeds the Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) of the Large Binocular Telescope (LBT) at Mt. Graham International Observatory, Arizona, U.S.A. We present high-resolution, high-fidelity spectra that were recorded on 184 & 82 days in 2018 & 2019 and derive the Ca ii H & K emission ratio, that is, the S-index. In addition, we compile excess brightness and area indices based on full-disk Ca ii K-line-core filtergrams of the Chromospheric Telescope (ChroTel) at Observatorio del Teide, Tenerife, Spain and full-disk ultraviolet (UV) 1600 angstrom images of the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). Thus, Sun-as-a-star spectral indices are related to their counterparts derived from resolved images of the solar chromosphere. All indices display signatures of rotational modulation, even during the very low magnetic activity in the minimum of Solar Cycle 24. Bringing together different types of activity indices has the potential to join disparate chromospheric datasets yielding a comprehensive description of chromospheric activity across many solar cycles.
Characterization of binding interactions of SARS-CoV-2 spike protein and DNA-peptide nanostructures
(2022)
Binding interactions of the spike proteins of the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) to a peptide fragment derived from the human angiotensin converting enzyme 2 (hACE2) receptor are investigated.
The peptide is employed as capture moiety in enzyme linked immunosorbent assays (ELISA) and quantitative binding interaction measurements that are based on fluorescence proximity sensing (switchSENSE).
In both techniques, the peptide is presented on an oligovalent DNA nanostructure, in order to assess the impact of mono- versus trivalent binding modes.
As the analyte, the spike protein and several of its subunits are tested as well as inactivated SARS-CoV-2 and pseudo viruses. While binding of the peptide to the full-length spike protein can be observed, the subunits RBD and S1 do not exhibit binding in the employed concentrations.
Variations of the amino acid sequence of the recombinant full-length spike proteins furthermore influence binding behavior. The peptide was coupled to DNA nanostructures that form a geometric complement to the trimeric structure of the spike protein binding sites.
An increase in binding strength for trimeric peptide presentation compared to single peptide presentation could be generally observed in ELISA and was quantified in switchSENSE measurements. Binding to inactivated wild type viruses could be shown as well as qualitatively different binding behavior of the Alpha and Beta variants compared to the wild type virus strain in pseudo virus models.
Nanostructured silicon and silicon-aluminum compounds are synthesized by a novel synthesis strategy based on spark plasma sintering (SPS) of silicon nanopowder, mesoporous silicon (pSi), and aluminum nanopowder. The interplay of metal-assisted crystallization and inherent porosity is exploited to largely suppress thermal conductivity. Morphology and temperature-dependent thermal conductivity studies allow us to elucidate the impact of porosity and nanostructure on the macroscopic heat transport. Analytic electron microscopy along with quantitative image analysis is applied to characterize the sample morphology in terms of domain size and interpore distance distributions. We demonstrate that nanostructured domains and high porosity can be maintained in densified mesoporous silicon samples. In contrast, strong grain growth is observed for sintered nanopowders under similar sintering conditions. We observe that aluminum agglomerations induce local grain growth, while aluminum diffusion is observed in porous silicon and dispersed nanoparticles. A detailed analysis of the measured thermal conductivity between 300 and 773 K allows us to distinguish the effect of reduced thermal conductivity caused by porosity from the reduction induced by phonon scattering at nanosized domains. With a modified Landauer/Lundstrom approach the relative thermal conductivity and the scattering length are extracted. The relative thermal conductivity confirms the applicability of Kirkpatrick's effective medium theory. The extracted scattering lengths are in excellent agreement with the harmonic mean of log-normal distributed domain sizes and the interpore distances combined by Matthiessen's rule.
Lithium-ion batteries have revolutionized battery technology. However, the scarcity of lithium in nature is driving the search for alternatives. For that reason, sodium-ion batteries have attracted increasing attention in recent years. The main obstacle to their development is the anode as, unlike for lithium-ion batteries, graphite cannot be used due to the inability to form stoichiometrically useful intercalation compounds with sodium. A promising candidate for sodium storage is hard carbon a form of nongraphitisable carbon, that can be synthesized from various precursor materials. Processing of hard carbons is often done by using mechanochemical treatments. Although it is generally accepted and often observed that they can influence the porosity of hard carbons, their effect on battery performance not well understood. Here, the changes in porosity occurring during ball milling are elucidated and related to the properties of hard carbons in sodium storage. Analysis by combined gas physisorption and small angle X-ray scattering shows that porosity changes during ball milling with a significant increase of the open porosity, unsuitable for reversible sodium storage, and decrease of the closed porosity, suitable for reversible sodium storage. While pristine hard carbon can store 58.5 mAh g(-1) in the closed pores, upon 5 h of mechanical treatment in a ball mill it can only store 35.5 mAh g(-1). The obtained results are furthermore pointing towards the disputed "intercalation-adsorption" mechanism.
INTRODUCTION:
We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort.
METHODS:
We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI).
RESULTS:
Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI <= 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile.
DISCUSSION:
Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.
Mathematical modelling and statistical inference provide a framework to evaluate different non-pharmaceutical and pharmaceutical interventions for the control of epidemics that has been widely used during the COVID-19 pandemic. In this paper, lessons learned from this and previous epidemics are used to highlight the challenges for future pandemic control. We consider the availability and use of data, as well as the need for correct parameterisation and calibration for different model frameworks. We discuss challenges that arise in describing and distinguishing between different interventions, within different modelling structures, and allowing both within and between host dynamics. We also highlight challenges in modelling the health economic and political aspects of interventions. Given the diversity of these challenges, a broad variety of interdisciplinary expertise is needed to address them, combining mathematical knowledge with biological and social insights, and including health economics and communication skills. Addressing these challenges for the future requires strong cross disciplinary collaboration together with close communication between scientists and policy makers.
CH2 + O-2
(2022)
The singlet and triplet potential surfaces for the title reaction were investigated using the CBS-QB3 level of theory. The wave functions for some species exhibited multireference character and required the CASPT2/6-31+G(d,p) and CASPT2/aug-cc-pVTZ levels of theory to obtain accurate relative energies. A Natural Bond Orbital Analysis showed that triplet (CH2OO)-C-3 (the simplest Criegee intermediate) and (CH2O2)-C-3 (dioxirane) have mostly polar biradical character, while singlet (CH2OO)-C-1 has some zwitterionic character and a planar structure. Canonical variational transition state theory (CVTST) and master equation simulations were used to analyze the reaction system. CVTST predicts that the rate constant for reaction of (CH2)-C-1 + O-3(2) is more than ten times as fast as the reaction of (CH2)-C-3 ((XB1)-B-3) + O-3(2) and the ratio remains almost independent of temperature from 900 K to 3000 K. The master equation simulations predict that at low pressures the (CH2O)-C-1 + O-3 product set is dominant at all temperatures and the primary yield of OH radicals is negligible below 600 K, due to competition with other primary reactions in this complex system.
Cell-free protein synthesis (CFPS) represents a versatile key technology for the production of toxic proteins. As a cell lysate, rather than viable cells, is used, the toxic effects on the host organism can be circumvented. The open nature of cell-free systems allows for the addition of supplements affecting protein concentration and folding. Here, we present the cell-free synthesis and functional characterization of two AB(5) toxins, namely the cholera toxin (Ctx) and the heat-labile enterotoxin (LT), using two eukaryotic cell-free systems based on Chinese hamster ovary (CHO) and Spodoptera frugiperda (Sf21) cells. Through an iterative optimization procedure, the synthesis of the individual AB(5) toxins was established, and the formation of multimeric structures could be shown by autoradiography. A functional analysis was performed using cell-based assays, thereby demonstrating that the LT complex induced the characteristic cell elongation of target cells after 24 h. The LT complex induced cell death at higher concentrations, starting at an initial concentration of 5 nM. The initial toxic effects of the Ctx multimer could already be detected at 4 nM. The detection and characterization of such AB(5) toxins is of utmost importance, and the monitoring of intracellular trafficking facilitates the further identification of the mechanism of action of these toxins. We showed that the B-subunit of LT (LTB) could be fluorescently labeled using an LTB-Strep fusion protein, which is a proof-of-concept for future Trojan horse applications. Further, we performed a mutational analysis of the CtxA subunit as its template was modified, and an amber stop codon was inserted into CtxA's active site. Subsequently, a non-canonical amino acid was site-specifically incorporated using bio-orthogonal systems. Finally, a fluorescently labeled CtxA protein was produced using copper-catalyzed click reactions as well as a Staudinger ligation. As expected, the modified Ctx multimer no longer induced toxic effects. In our study, we showed that CFPS could be used to study the active centers of toxins by inserting mutations. Additionally, this methodology can be applied for the design of Trojan horses and targeted toxins, as well as enabling the intracellular trafficking of toxins as a prerequisite for the analysis of the toxin's mechanism of action.
The investigation of protein structures, functions and interactions often requires modifications to adapt protein properties to the specific application. Among many possible methods to equip proteins with new chemical groups, the utilization of orthogonal aminoacyl-tRNA synthetase/tRNA pairs enables the site-specific incorporation of non-canonical amino acids at defined positions in the protein. The open nature of cell-free protein synthesis reactions provides an optimal environment, as the orthogonal components do not need to be transported across the cell membrane and the impact on cell viability is negligible. In the present work, it was shown that the expression of orthogonal aminoacyl-tRNA synthetases in CHO cells prior to cell disruption enhanced the modification of the pharmaceutically relevant adenosine A2a receptor. For this purpose, in complement to transient transfection of CHO cells, an approach based on CRISPR/Cas9 technology was selected to generate a translationally active cell lysate harboring endogenous orthogonal aminoacyl-tRNA synthetase.
We study theoretically the quantum dynamics and spectroscopy of rovibrational polaritons formed in a model system composed of a single rovibrating diatomic molecule, which interacts with two degenerate, orthogonally polarized modes of an optical Fabry-Perot cavity. We employ an effective rovibrational Pauli-Fierz Hamiltonian in length gauge representation and identify three-state vibro-polaritonic conical intersections (VPCIs) between singly excited vibro-polaritonic states in a two-dimensional angular coordinate branching space. The lower and upper vibrational polaritons are of mixed light-matter hybrid character, whereas the intermediate state is purely photonic in nature. The VPCIs provide effective population transfer channels between singly excited vibrational polaritons, which manifest in rich interference patterns in rotational densities. Spectroscopically, three bright singly excited states are identified when an external infrared laser field couples to both a molecular and a cavity mode. The non-trivial VPCI topology manifests as pronounced multi-peak progression in the spectral region of the upper vibrational polariton, which is traced back to the emergence of rovibro-polaritonic light-matter hybrid states. Experimentally, ubiquitous spontaneous emission from cavity modes induces a dissipative reduction of intensity and peak broadening, which mainly influences the purely photonic intermediate state peak as well as the rovibro-polaritonic progression. Published under an exclusive license by AIP Publishing.
It has been experimentally demonstrated that reaction rates for molecules embedded in microfluidic optical cavities are altered when compared to rates observed under "ordinary" reaction conditions. However, precise mechanisms of how strong coupling of an optical cavity mode to molecular vibrations affects the reactivity and how resonance behavior emerges are still under dispute. In the present work, we approach these mechanistic issues from the perspective of a thermal model reaction, the inversion of ammonia along the umbrella mode, in the presence of a single-cavity mode of varying frequency and coupling strength. A topological analysis of the related cavity Born-Oppenheimer potential energy surface in combination with quantum mechanical and transition state theory rate calculations reveals two quantum effects, leading to decelerated reaction rates in qualitative agreement with experiments: the stiffening of quantized modes perpendicular to the reaction path at the transition state, which reduces the number of thermally accessible reaction channels, and the broadening of the barrier region, which attenuates tunneling. We find these two effects to be very robust in a fluctuating environment, causing statistical variations of potential parameters, such as the barrier height. Furthermore, by solving the time-dependent Schrodinger equation in the vibrational strong coupling regime, we identify a resonance behavior, in qualitative agreement with experimental and earlier theoretical work. The latter manifests as reduced reaction probability when the cavity frequency omega(c) is tuned resonant to a molecular reactant frequency. We find this effect to be based on the dynamical localization of the vibro-polaritonic wavepacket in the reactant well.
Previous research demonstrated a close bidirectional relationship between spatial attention and the manual motor system. However, it is unclear whether an explicit hand movement is necessary for this relationship to appear. A novel method with high temporal resolution–bimanual grip force registration–sheds light on this issue. Participants held two grip force sensors while being presented with lateralized stimuli (exogenous attentional shifts, Experiment 1), left- or right-pointing central arrows (endogenous attentional shifts, Experiment 2), or the words "left" or "right" (endogenous attentional shifts, Experiment 3). There was an early interaction between the presentation side or arrow direction and grip force: lateralized objects and central arrows led to a larger increase of the ipsilateral force and a smaller increase of the contralateral force. Surprisingly, words led to the opposite pattern: larger force increase in the contralateral hand and smaller force increase in the ipsilateral hand. The effect was stronger and appeared earlier for lateralized objects (60 ms after stimulus presentation) than for arrows (100 ms) or words (250 ms). Thus, processing visuospatial information automatically activates the manual motor system, but the timing and direction of this effect vary depending on the type of stimulus.
Inter-brain synchronization is primarily investigated during social interactions but had not been examined during coupled muscle action between two persons until now. It was previously shown that mechanical muscle oscillations can develop coherent behavior between two isometrically interacting persons. This case study investigated if inter-brain synchronization appears thereby, and if differences of inter- and intrapersonal muscle and brain coherence exist regarding two different types of isometric muscle action. Electroencephalography (EEG) and mechanomyography/mechanotendography (MMG/MTG) of right elbow extensors were recorded during six fatiguing trials of two coupled isometrically interacting participants (70% MVIC). One partner performed holding and one pushing isometric muscle action (HIMA/PIMA; tasks changed). The wavelet coherence of all signals (EEG, MMG/MTG, force, ACC) were analyzed intra- and interpersonally. The five longest coherence patches in 8–15 Hz and their weighted frequency were compared between real vs. random pairs and between HIMA vs. PIMA. Real vs. random pairs showed significantly higher coherence for intra-muscle, intra-brain, and inter-muscle-brain activity (p < 0.001 to 0.019). Inter-brain coherence was significantly higher for real vs. random pairs for EEG of right and central areas and for sub-regions of EEG left (p = 0.002 to 0.025). Interpersonal muscle-brain synchronization was significantly higher than intrapersonal one, whereby it was significantly higher for HIMA vs. PIMA. These preliminary findings indicate that inter-brain synchronization can arise during muscular interaction. It is hypothesized both partners merge into one oscillating neuromuscular system. The results reinforce the hypothesis that HIMA is characterized by more complex control strategies than PIMA. The pilot study suggests investigating the topic further to verify these results on a larger sample size. Findings could contribute to the basic understanding of motor control and is relevant for functional diagnostics such as the manual muscle test which is applied in several disciplines, e.g., neurology, physiotherapy.
Aging is one of the major non-reversible risk factors for several chronic diseases, including cancer, type 2 diabetes, dementia, and cardiovascular diseases (CVD), and it is a key cause of multimorbidity, disability, and frailty (decreased physical activity, fatigue, and weight loss). The underlying cellular mechanisms are complex and consist of multifactorial processes, such as telomere shortening, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, accumulation of senescent cells, and reduced autophagy. In this review, we focused on the molecular mechanisms and translational aspects of cardiovascular aging-related inflammation, i.e., inflammaging.
The Arabidopsis knockout mutant lacking both the cytosolic disproportionating enzyme 2 (DPE2) and the plastidial phosphorylase (PHS1) had a dwarf-growth phenotype, a reduced and uneven distribution of starch within the plant rosettes, and a lower starch granule number per chloroplast under standard growth conditions. In contrast, a triple mutant impaired in starch degradation by its additional lack of the glucan, water dikinase (GWD) showed improved plant growth, a starch-excess phenotype, and a homogeneous starch distribution. Furthermore, the number of starch granules per chloroplast was increased and was similar to the wild type. We concluded that ongoing starch degradation is mainly responsible for the observed phenotype of dpe2/phs1. Next, we generated two further triple mutants lacking either the phosphoglucan, water dikinase (PWD), or the disproportionating enzyme 1 (DPE1) in the background of the double mutant. Analysis of the starch metabolism revealed that even minor ongoing starch degradation observed in dpe2/phs1/pwd maintained the double mutant phenotype. In contrast, an additional blockage in the glucose pathway of starch breakdown, as in dpe2/phs1/ dpe1, resulted in a nearly starch-free phenotype and massive chloroplast degradation. The characterized mutants were discussed in the context of starch granule formation.