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Abstract The NASA Perseverance rover discovered light-toned float rocks scattered across the surface of Jezero crater that are particularly rich in alumina ( ~ 35 wt% Al2O3) and depleted in other major elements (except silica). These unique float rocks have heterogeneous mineralogy ranging from kaolinite/halloysite-bearing in hydrated samples, to spinel-bearing in dehydrated samples also containing a dehydrated Al-rich phase. Here we describe SuperCam and Mastcam-Z observations of the float rocks, including the first in situ identification of kaolinite or halloysite on another planet, and dehydrated phases including spinel and apparent partially dehydroxylated kaolinite. The presence of spinel in these samples is likely detrital in origin, surviving kaolinitization, pointing to an ultramafic origin. However, the association of low hydration with increased Al2O3 abundances suggests heating-induced dehydration which could have occurred during the lithification or impact excavation of these rocks. Given the orbital context of kaolinite-bearing megabreccia in the Jezero crater rim, we propose an origin for these rocks involving intense aqueous alteration of the parent material, followed by dehydration/lithification potentially through impact processes, and dispersion into Jezero crater through flood or impact-related processes.

Abstract Radio-frequency particle accelerators are engines of discovery, powering high-energy physics and photon science, but are also large and expensive due to their limited accelerating fields. Plasma-wakefield accelerators (PWFAs) provide orders-of-magnitude stronger fields in the charge-density wave behind a particle bunch travelling in a plasma, promising particle accelerators of greatly reduced size and cost. However, PWFAs can easily degrade the beam quality of the bunches they accelerate. Emittance, which determines how tightly beams can be focused, is a critical beam quality in for instance colliders and free-electron lasers, but is particularly prone to degradation. We demonstrate, for the first time, emittance preservation in a high-gradient and high-efficiency PWFA while simultaneously preserving charge and energy spread. This establishes that PWFAs can accelerate without degradation—an essential step toward energy boosters in photon science and multistage facilities for compact high-energy particle colliders.

Abstract Planetary exploration relies considerably on mineral characterization to advance our understanding of the solar system, the planets and their evolution. Thus, we must understand past and present processes that can alter materials exposed on the surface, affecting space mission data. Here, we analyze the first dataset monitoring the evolution of a known mineral target in situ on the Martian surface, brought there as a SuperCam calibration target onboard the Perseverance rover. We used Raman spectroscopy to monitor the crystalline state of a synthetic apatite sample over the first 950 Martian days (sols) of the Mars2020 mission. We note significant variations in the Raman spectra acquired on this target, specifically a decrease in the relative contribution of the Raman signal to the total signal. These observations are consistent with the results of a UV-irradiation test performed in the laboratory under conditions mimicking ambient Martian conditions. We conclude that the observed evolution reflects an alteration of the material, specifically the creation of electronic defects, due to its exposure to the Martian environment and, in particular, UV irradiation. This ongoing process of alteration of the Martian surface needs to be taken into account for mineralogical space mission data analysis.

Abstract Determination of the physical properties of subsurface geological bodies is essential for georesource management and geotechnical applications. In the absence of direct measurements, this usually passes via geophysical methods such as seismic and ground‐penetrating radar. These require conversion to physical properties, and measurements at different scales to test for consistency. This approach is non‐trivial in geobodies with heterogeneous patterns of properties. Tufa mounds—in‐situ terrestrial carbonate buildups precipitating from geothermal waters—are characterised by high contrasts in facies and petrophysical properties from microscale to macroscale, and are therefore ideally suited to test the ability of non‐invasive geophysical methods to estimate such contrasts, and to develop petrophysical models based on geophysical properties. Here, a laboratory‐based study of a Pleistocene tufa mound in Spain is presented that combines (1) petrography, (2) digital 2D pore network analysis, (3) gas porosity and permeability measurements, (4) acoustic velocity measurements and (5) electromagnetic wave velocity and porosity determination from ground‐penetrating radar, to develop empirical petrophysical models. These results show the consistency of petrophysical properties determined with different methods across various observational scales. Electromagnetically derived porosity positively correlates with gas porosity. Petrophysical properties depend on measurable rock fabric parameters and the degree of cementation, which provide predictive tools for subsurface geobodies. Strongly cemented peloidal‐thrombolitic fabrics with intergranular and intercrystalline pores, and a dominance of small complex pores best transmit acoustic waves. Weak cementation and a significant fraction of large simple pores (framework, vegetation moulds) increase porosity and permeability of shrubby fabrics, while causing lower acoustic velocity. This study demonstrates that ground‐penetrating radar models can be used in combination with direct measurements of physical subsurface properties to capture highly contrasting physical properties associated with different sedimentary facies that would not be achievable with other methods, thus improving the understanding of formational processes.

For plasma-wakefield accelerators to fulfill their potential for cost effectiveness, it is essential that their energy-transfer efficiency be maximized. A key aspect of this efficiency is the near-complete transfer of energy, or depletion, from the driver electrons to the plasma wake. Achieving full depletion is limited by the process of re-acceleration, which occurs when the driver electrons decelerate to nonrelativistic energies, slipping backward into the accelerating phase of the wakefield and being subsequently re-accelerated. Such re-acceleration is unambiguously observed here for the first time. At this re-acceleration limit, we measure a beam driver depositing (57 ± 3)% of its energy into a 195-mm-long plasma. This suggests that the energy-transfer efficiency of plasma accelerators could approach that of conventional accelerators.

Abstract We aimed to assess DPNCheck’s reliability for repeated sural nerve conduction (NC) parameters. This post hoc analysis used data from the randomized controlled ACUDPN trial assessing NC of the N. Suralis every eight weeks over a 6-month period in 62 patients receiving acupuncture against diabetic peripheral neuropathy (DPN) symptoms. The reliability of DPNCheck for nerve conduction velocity and amplitude was assessed using intraclass correlation coefficients (ICC) and was calculated using data from single time points and repeated measures design. The results of the NC measurements were correlated with the Total Neuropathy Score clinical (TNSc). Overall, for both nerve velocity and amplitude, the reliability at each measurement time point can be described as moderate to good and the reliability using repeated measures design can be described as moderate. Nerve velocity and amplitude showed weak correlation with TNSc. DPNCheck’s reliability results question its suitability for monitoring DPN’s progression. Given the limitation of our analysis, a long-term, pre-specified, fully crossed study should be carried out among patients with DPN to fully determine the suitability of the device for DPN progression monitoring. This was the first analysis assessing the reliability of the DPNCheck for DPN progression monitoring using data from multiple collection time points.

CRISPR-Cas induced HDR methods tend to have a low efficiency. Here the authors report an HDR improvement strategy, Recursive Editing, that selectively retargets undesired indel outcomes to create additional opportunities for HDR; they introduce REtarget, a tool for Recursive Editing experimental design.

Abstract We present a measurement of the cosmic-ray spectrum above 100 PeV using the part of the surface detector of the Pierre Auger Observatory that has a spacing of 750 m. An inflection of the spectrum is observed, confirming the presence of the so-called second-knee feature. The spectrum is then combined with that of the 1500 m array to produce a single measurement of the flux, linking this spectral feature with the three additional breaks at the highest energies. The combined spectrum, with an energy scale set calorimetrically via fluorescence telescopes and using a single detector type, results in the most statistically and systematically precise measurement of spectral breaks yet obtained. These measurements are critical for furthering our understanding of the highest energy cosmic rays.

Excitons in atomically thin crystals couple strongly with light. Here, the authors observe lattice polaritons in a tunable open optical cavity at room temperature, with an imprinted photonic lattice strongly coupled to excitons in a WS2 monolayer.

Abstract Background The rapid expansion of the CRISPR toolbox through tagging effector domains to either enzymatically inactive Cas9 (dCas9) or Cas9 nickase (nCas9) has led to several promising new gene editing strategies. Recent additions include CRISPR cytosine or adenine base editors (CBEs and ABEs) and the CRISPR prime editors (PEs), in which a deaminase or reverse transcriptase are fused to nCas9, respectively. These tools hold great promise to model and correct disease-causing mutations in animal and plant models. But so far, no widely-available tools exist to automate the design of both BE and PE reagents. Results We developed PnB Designer, a web-based application for the design of pegRNAs for PEs and guide RNAs for BEs. PnB Designer makes it easy to design targeting guide RNAs for single or multiple targets on a variant or reference genome from organisms spanning multiple kingdoms. With PnB Designer, we designed pegRNAs to model all known disease causing mutations available in ClinVar. Additionally, PnB Designer can be used to design guide RNAs to install or revert a SNV, scanning the genome with one CBE and seven different ABE PAM variants and returning the best BE to use. PnB Designer is publicly accessible at http://fgcz-shiny.uzh.ch/PnBDesigner/ Conclusion With PnB Designer we created a user-friendly design tool for CRISPR PE and BE reagents, which should simplify choosing editing strategy and avoiding design complications.

Abstract Background Acupuncture is used to treat patients with diabetic peripheral neuropathy; however, the evidence is unclear. We present the design and methodology of the ACUDPN (ACUpuncture in Diabetic Peripheral Neuropathy) trial, which investigates the effectiveness of acupuncture for the treatment of diabetic peripheral neuropathy (DPN) symptoms. The aim of this study is to investigate whether acupuncture is effective for the treatment of DPN symptoms. Methods This study is a two-armed, randomized, controlled, parallel group, open-label, confirmatory, multicenter trial (8-week intervention period plus 16 weeks of follow-up). Physicians in outpatient units in Germany who specialize in acupuncture treatment will treat 110 diabetes type II patients with clinical symptoms of peripheral neuropathy in the feet and legs with signs of neuropathy according to nerve conduction testing. The patients will be randomized in a 1:1 ratio to one of the following two groups: (a) semi-standardized acupuncture plus routine care or (b) routine care alone. Acupuncture will consist of 12 treatments per patient over 8 weeks. The primary outcome will be the overall DPN-related complaints in the extremities after 8 weeks as measured by the Visual Analog Scale (VAS). Further outcome measures will include DPN-related pain, the Neuropathic Pain Symptom Inventory (NPSI), Diabetic Peripheral Neuropathic Pain Impact (DPNPI) scores, and nerve conduction parameters of the sural nerve at weeks 8, 16, and 24. Discussion The results of this trial will be available in 2021 and will help clarify whether acupuncture can be considered effective for the treatment of DPN with regard to the subdimensions of the neuropathic clinical picture. Trial registration ClinicalTrials.gov NCT03755960 . Registered on 11 August 2018.

Controlled particle acceleration in plasmas requires precise measurements of the excited wakefield. Here the authors report and demonstrate a high-resolution method to measure the effective longitudinal electric field of a beam-driven plasma-wakefield accelerator.

Gallbladder cancer incidence shows characteristic geographic patterns. Here the authors perform a genomic analysis of gallbladder cancers in patients from countries with high incidence (South Korea, India and Chile) and identify ELF3 and other significantly mutated genes not previously associated with gallbladder cancer.

Abstract The hybrid design of the Pierre Auger Observatory allows for the measurement of the properties of extensive air showers initiated by ultra-high energy cosmic rays with unprecedented precision. By using an array of prototype underground muon detectors, we have performed the first direct measurement, by the Auger Collaboration, of the muon content of air showers between $$2\times 10^{17}$$ 2×1017 and $$2\times 10^{18}$$ 2×1018 eV. We have studied the energy evolution of the attenuation-corrected muon density, and compared it to predictions from air shower simulations. The observed densities are found to be larger than those predicted by models. We quantify this discrepancy by combining the measurements from the muon detector with those from the Auger fluorescence detector at $$10^{{17.5}}\, {\mathrm{eV}} $$ 1017.5eV and $$10^{{18}}\, {\mathrm{eV}} $$ 1018eV . We find that, for the models to explain the data, an increase in the muon density of $$38\%$$ 38% $$\pm 4\% (12\%)$$ ±4%(12%) $$\pm {}^{21\%}_{18\%}$$ ±18%21% for EPOS-LHC, and of $$50\% (53\%)$$ 50%(53%) $$\pm 4\% (13\%)$$ ±4%(13%) $$\pm {}^{23\%}_{20\%}$$ ±20%23% for QGSJetII-04, is respectively needed.

The Argentine-German Geodetic Observatory (AGGO) is one of the very few sites in the Southern Hemisphere equipped with comprehensive cutting-edge geodetic instrumentation. The employed observation techniques are used for a wide range of geophysical applications. The data set provides gravity time series and selected gravity models together with the hydrometeorological monitoring data of the observatory. These parameters are of great interest to the scientific community, e.g. for achieving accurate realization of terrestrial and celestial reference frames. Moreover, the availability of the hydrometeorological products is beneficial to inhabitants of the region as they allow for monitoring of environmental changes and natural hazards including extreme events. The hydrological data set is composed of time series of groundwater level, modelled and observed soil moisture content, soil temperature, and physical soil properties and aquifer properties. The meteorological time series include air temperature, humidity, pressure, wind speed, solar radiation, precipitation, and derived reference evapotranspiration. These data products are extended by gravity models of hydrological, oceanic, La Plata estuary, and atmospheric effects. The quality of the provided meteorological time series is tested via comparison to the two closest WMO (World Meteorological Organization) sites where data are available only in an inferior temporal resolution. The hydrological series are validated by comparing the respective forward-modelled gravity effects to independent gravity observations reduced up to a signal corresponding to local water storage variation. Most of the time series cover the time span between April 2016 and November 2018 with either no or only few missing data points. The data set is available at https://doi.org/10.5880/GFZ.5.4.2018.001 (Mikolaj et al., 2018).

The Niger River represents a challenging target for deriving discharge from spaceborne radar altimeter measurements, particularly since most terrestrial gauges ceased to provide data during the 2000s. Here, we propose deriving altimetric rating curves by “bridging” gaps between time series from gauge and altimeter measurements using hydrological model simulations. We show that classical pulse-limited altimetry (Jason-1 and Jason-2, Envisat, and SARAL/Altika) subsequently reproduces discharge well and enables continuing the gauge time series, albeit at a lower temporal resolution. Also, synthetic aperture radar (SAR) altimetry picks up the signal measured by earlier altimeters quite well and allows the building of extended time series of higher quality. However, radar retracking is necessary for pulse-limited altimetry and needs to be further investigated for SAR. Moreover, forcing data for calibrating and running the hydrological models must be chosen carefully. Furthermore, stage–discharge relations must be fitted empirically and may need to allow for break points.

Candida orthopsilosis is diploid asexual yeast that causes human disease. Most C. orthopsilosis isolates arose from at least four separate hybridizations between related, but not identical, parents. Here, we used population genomics data to correlate genotypic and phenotypic variation in 28 C. orthopsilosis isolates. We used cosine similarity scores to identify 65 variants with potential high-impact (deleterious effects) that correlated with specific phenotypes. Of these, 19 were Single Nucleotide Polymorphisms (SNPs) that changed stop or start codons, or splice sites. One variant resulted in a premature stop codon in both alleles of the gene ZCF29 in C. orthopsilosis isolate 185, which correlated with sensitivity to nystatin and caffeine. We used CRISPR-Cas9 editing to introduce this polymorphism into two resistant C. orthopsilosis isolates. Introducing the stop codon resulted in sensitivity to caffeine and to ketoconazole, but not to nystatin. Our analysis shows that it is possible to associate genomic variants with phenotype in asexual Candida species, but that only a small amount of genomic variation can be easily explored.

Personality traits describe dispositions influencing individuals' behavior and performance at work. However, in the context of personnel selection, the use of personality measures has continuously been questioned. To date, research in selection settings has focused uniquely on predicting task performance, missing the opportunity to exploit the potential of personality traits to predict non-task performance. Further, personality is often measured with self-report inventories, which are susceptible to self-distortion. Addressing these gaps, the planned study seeks to design new personality measures to be used in the selection context to predict a wide range of performance criteria. Specifically, we will develop a situational judgment test and a behavior description interview, both assessing Big Five personality traits and Honesty-Humility to systematically compare these new measures with traditional self-report inventories regarding their criterion-related validity to predict four performance criteria: task performance, adaptive performance, organizational citizenship behavior, and counterproductive work behavior. Data will be collected in a simulated selection procedure. Based on power analyses, we aim for 200 employed study participants, who will allow us to contact their supervisors to gather criterion data. The results of this study will shed light on the suitability of different personality measures (i.e., situational judgment tests and behavior description interviews) to predict an expanded range of performance criteria.

Summary: β-Hemoglobinopathies can trigger rapid production of red blood cells in a process known as stress erythropoiesis. Cellular stress prompts differentiating erythroid precursors to express high levels of fetal γ-globin. However, the mechanisms underlying γ-globin production during cellular stress are still poorly defined. Here, we use CRISPR-Cas genome editing to model the stress caused by reduced levels of adult β-globin. We find that decreased β-globin is sufficient to induce robust re-expression of γ-globin, and RNA sequencing (RNA-seq) of differentiating isogenic erythroid precursors implicates ATF4 as a causal regulator of this response. ATF4 binds within the HBS1L-MYB intergenic enhancer and regulates expression of MYB, a known γ-globin regulator. Overall, the reduction of ATF4 upon β-globin knockout decreases the levels of MYB and BCL11A. Identification of ATF4 as a key regulator of globin compensation adds mechanistic insight to the poorly understood phenomenon of stress-induced globin compensation and could inform strategies to treat hemoglobinopathies.

Abstract Elves are a class of transient luminous events, with a radial extent typically greater than 250 km, that occur in the lower ionosphere above strong electrical storms. We report the observation of 1,598 elves, from 2014 to 2016, recorded with unprecedented time resolution (100 ns) using the fluorescence detector (FD) of the Pierre Auger Cosmic‐Ray Observatory. The Auger Observatory is located in the Mendoza province of Argentina with a viewing footprint for elve observations of 3·106 km 2, reaching areas above the Pacific and Atlantic Oceans, as well as the Córdoba region, which is known for severe convective thunderstorms. Primarily designed for ultrahigh energy cosmic‐ray observations, the Auger FD turns out to be very sensitive to the ultraviolet emission in elves. The detector features modified Schmidt optics with large apertures resulting in a field of view that spans the horizon, and year‐round operation on dark nights with low moonlight background, when the local weather is favorable. The measured light profiles of 18% of the elve events have more than one peak, compatible with intracloud activity. Within the 3‐year sample, 72% of the elves correlate with the far‐field radiation measurements of the World Wide Lightning Location Network. The Auger Observatory plans to continue operations until at least 2025, including elve observations and analysis. To the best of our knowledge, this observatory is the only facility on Earth that measures elves with year‐round operation and full horizon coverage.

Vulvovaginal candidiasis (VVC) caused by Candida albicans is a common disease worldwide. A very important C. albicans virulence factor is its ability to form biofilms on epithelium and/or on intrauterine devices promoting VVC. It has been shown that VVC has a hormonal dependency and that progesterone affects virulence traits of C. albicans cells. To understand how the acidic environment (pH 4) and progesterone (either alone and in combination) modulate C. albicans response during formation of biofilm, a transcriptomic analysis was performed together with characterization of the biofilm properties. Compared to planktonic cells, acidic biofilm-cells exhibited major changes in their transcriptome, including modifications in the expression of 286 genes that were not previously associated with biofilm formation in C. albicans. The vast majority of the genes up-regulated in the acidic biofilm cells (including those uniquely identified in our study) are known targets of Sfl1, and consistently, Sfl1 deletion is herein shown to impair the formation of acidic biofilms (pH 4). Under the acidic conditions used, the presence of progesterone reduced C. albicans biofilm biomass and structural cohesion. Transcriptomic analysis of biofilms developed in the presence of progesterone led to the identification of 65 down-regulated genes including, among others, the regulator Tec1 and several of its target genes, suggesting that the function of this transcription factor is inhibited by the presence of the hormone. Additionally, progesterone reduced the susceptibility of biofilm cells to fluconazole, consistent with an up-regulation of efflux pumps. Overall, the results of this study show that progesterone modulates C. albicans biofilm formation and genomic expression under acidic conditions, which may have implications for C. albicans pathogenicity in the vaginal environment.

Water activity (aw) as an important parameter for self-preservation can help to control microbial growth in cosmetic formulations. However, high amounts of water-binding substances are required to lower the aw enough to affect microbial growth. Since consequences for the skin barrier have been poorly studied so far, we investigated the effect of aw-lowering agents on both the antimicrobial properties of o/w emulsions and skin physiological parameters. A combination of selected natural humectants (Sodium lactate, Propanediol, Erythritol, Betaine and Sodium PCA) with a total concentration of 28 wt% in an o/w emulsion was able to reduce its aw from 0.980 ± 0.003 to 0.865 ± 0.005. The challenge test results of the aw-lowered emulsion showed a convincing microbial count reduction in potentially pathogenic microorganisms. The addition of as little as 0.5% of the antimicrobial multifunctionals Glyceryl Caprylate and Magnolia Officinalis Bark Extract further enhanced the antimicrobial effect, resulting in adequate antimicrobial protection. Moreover, twice-daily application of the aw-lowered emulsion for a period of four weeks led to a skin barrier-enhancing effect: TEWL significantly decreased, and SC hydration significantly increased. Thus, we present an opportunity to replace conventional preservatives with a natural alternative preservation strategy that has been shown to offer benefits for the skin.

Within the framework of the global chemistry climate model ECHAM–HAMMOZ, a novel explicit coupling between the sectional aerosol model HAM-SALSA and the chemistry model MOZ was established to form isoprene-derived secondary organic aerosol (iSOA). Isoprene oxidation in the chemistry model MOZ is described by a semi-explicit scheme consisting of 147 reactions embedded in a detailed atmospheric chemical mechanism with a total of 779 reactions. Semi-volatile and low-volatile compounds produced during isoprene photooxidation are identified and explicitly partitioned by HAM-SALSA. A group contribution method was used to estimate their evaporation enthalpies and corresponding saturation vapor pressures, which are used by HAM-SALSA to calculate the saturation concentration of each iSOA precursor. With this method, every single precursor is tracked in terms of condensation and evaporation in each aerosol size bin. This approach led to the identification of dihydroxy dihydroperoxide (ISOP(OOH)2) as a main contributor to iSOA formation. Further, the reactive uptake of isoprene epoxydiols (IEPOXs) and isoprene-derived glyoxal were included as iSOA sources. The parameterization of IEPOX reactive uptake includes a dependency on aerosol pH value. This model framework connecting semi-explicit isoprene oxidation with explicit treatment of aerosol tracers leads to a global annual average isoprene SOA yield of 15 % relative to the primary oxidation of isoprene by OH, NO3 and ozone. With 445.1 Tg (392.1 Tg C) isoprene emitted, an iSOA source of 138.5 Tg (56.7 Tg C) is simulated. The major part of iSOA in ECHAM–HAMMOZ is produced by IEPOX at 42.4 Tg (21.0 Tg C) and ISOP(OOH)2 at 78.0 Tg (27.9 Tg C). The main sink process is particle wet deposition, which removes 133.6 (54.7 Tg C). The average iSOA burden reaches 1.4 Tg (0.6 Tg C) in the year 2012.

The chemistry–climate model ECHAM-HAMMOZ contains a detailed representation of tropospheric and stratospheric reactive chemistry and state-of-the-art parameterizations of aerosols using either a modal scheme (M7) or a bin scheme (SALSA). This article describes and evaluates the model version ECHAM6.3-HAM2.3-MOZ1.0 with a focus on the tropospheric gas-phase chemistry. A 10-year model simulation was performed to test the stability of the model and provide data for its evaluation. The comparison to observations concentrates on the year 2008 and includes total column observations of ozone and CO from IASI and OMI, Aura MLS observations of temperature, HNO3, ClO, and O3 for the evaluation of polar stratospheric processes, an ozonesonde climatology, surface ozone observations from the TOAR database, and surface CO data from the Global Atmosphere Watch network. Global budgets of ozone, OH, NOx, aerosols, clouds, and radiation are analyzed and compared to the literature. ECHAM-HAMMOZ performs well in many aspects. However, in the base simulation, lightning NOx emissions are very low, and the impact of the heterogeneous reaction of HNO3 on dust and sea salt aerosol is too strong. Sensitivity simulations with increased lightning NOx or modified heterogeneous chemistry deteriorate the comparison with observations and yield excessively large ozone budget terms and too much OH. We hypothesize that this is an impact of potential issues with tropical convection in the ECHAM model.

The impact of six heterogeneous gas–aerosol uptake reactions on tropospheric ozone and nitrogen species was studied using two chemical transport models, the Meteorological Synthesizing Centre-West of the European Monitoring and Evaluation Programme (EMEP MSC-W) and the European Centre Hamburg general circulation model combined with versions of the Hamburg Aerosol Model and Model for Ozone and Related chemical Tracers (ECHAM-HAMMOZ). Species undergoing heterogeneous reactions in both models include N2O5, NO3, NO2, O3, HNO3, and HO2. Since heterogeneous reactions take place at the aerosol surface area, the modelled surface area density (Sa) of both models was compared to a satellite product retrieving the surface area. This comparison shows a good agreement in global pattern and especially the capability of both models to capture the extreme aerosol loadings in east Asia. The impact of the heterogeneous reactions was evaluated by the simulation of a reference run containing all heterogeneous reactions and several sensitivity runs. One reaction was turned off in each sensitivity run to compare it with the reference run. The analysis of the sensitivity runs confirms that the globally most important heterogeneous reaction is the one of N2O5. Nevertheless, NO2, HNO3, and HO2 heterogeneous reactions gain relevance particularly in east Asia due to the presence of high NOx concentrations and high Sa in the same region. The heterogeneous reaction of O3 itself on dust is of minor relevance compared to the other heterogeneous reactions. The impacts of the N2O5 reactions show strong seasonal variations, with the biggest impacts on O3 in springtime when photochemical reactions are active and N2O5 levels still high. Evaluation of the models with northern hemispheric ozone surface observations yields a better agreement of the models with observations in terms of concentration levels, variability, and temporal correlations at most sites when the heterogeneous reactions are incorporated. Our results are loosely consistent with results from earlier studies, although the magnitude of changes induced by N2O5 reaction is at the low end of estimates, which seems to fit a trend, whereby the more recent the study the lower the impacts of these reactions.

Electron beams to be accelerated in beam-driven plasma wakes are commonly formed by a photocathode and externally injected into the wakefield of a preceding bunch. Alternatively, using the plasma itself as a cathode offers the possibility of generating ultrashort, low-emittance beams by trapping and accelerating electrons from the ambient plasma background. Here, we present a beam-driven plasma cathode realized via laser-triggered density-downramp injection, showing stable beam formation over more than a thousand consecutive events with an injection probability of 95%. The plasma cathode is highly tunable, resulting in the injection of electron bunches of tens of pC of charge, energies of up to 79 MeV, and relative energy spreads as low as a few percent. The stability of the injected beams was sufficiently high to experimentally determine their normalized emittance of 9.3 μm rms with a multishot method.

An overview of the multi-messenger capabilities of the Pierre Auger Observatory is presented. The techniques and performance of searching for Ultra-High Energy neutrinos, photons and neutrons are described. Some of the most relevant results are reviewed, such as stringent upper bounds that were placed to a flux of diffuse cosmogenic neutrinos and photons, bounds placed on neutrinos emitted from compact binary mergers that were detected by LIGO and Virgo during their first and second observing runs, as well as searches for high energy photons and neutrons from the Galactic center that constrain the properties of the putative Galactic PeVatron, observed by the H.E.S.S. collaboration. The observation of directional correlations between ultra-high energy cosmic rays and either high energy astrophysical neutrinos or specific source populations, weighted by their electromagnetic radiation, are also discussed. They constitute additional multi-messenger approaches aimed at identifying the sources of high energy cosmic rays.

A biogenic emission scheme based on the Model of Emissions of Gases and Aerosols from Nature (MEGAN) version 2.1 (Guenther et al., 2012) has been integrated into the ECHAM6-HAMMOZ chemistry climate model in order to calculate the emissions from terrestrial vegetation of 32 compounds. The estimated annual global total for the reference simulation is 634 Tg C yr−1 (simulation period 2000–2012). Isoprene is the main contributor to the average emission total, accounting for 66 % (417 Tg C yr−1), followed by several monoterpenes (12 %), methanol (7 %), acetone (3.6 %), and ethene (3.6 %). Regionally, most of the high annual emissions are found to be associated with tropical regions and tropical vegetation types. In order to evaluate the implementation of the biogenic model in ECHAM-HAMMOZ, global and regional biogenic volatile organic compound (BVOC) emissions of the reference simulation were compared to previous published experiment results with MEGAN. Several sensitivity simulations were performed to study the impact of different model input and parameters related to the vegetation cover and the ECHAM6 climate. BVOC emissions obtained here are within the range of previous published estimates. The large range of emission estimates can be attributed to the use of different input data and empirical coefficients within different setups of MEGAN. The biogenic model shows a high sensitivity to the changes in plant functional type (PFT) distributions and associated emission factors for most of the compounds. The global emission impact for isoprene is about −9 %, but reaches +75 % for α-pinene when switching from global emission factor maps to PFT-specific emission factor distributions. The highest sensitivity of isoprene emissions is calculated when considering soil moisture impact, with a global decrease of 12.5 % when the soil moisture activity factor is included in the model parameterization. Nudging ECHAM6 climate towards ERA-Interim reanalysis has an impact on the biogenic emissions, slightly lowering the global total emissions and their interannual variability.

To thrive in the acidic vaginal tract, Candida glabrata has to cope with high concentrations of acetic acid. The mechanisms underlying C. glabrata tolerance to acetic acid at low pH remain largely uncharacterized. In this work, the essential role of the CgHaa1 transcription factor (encoded by ORF CAGL0L09339g) in the response and tolerance of C. glabrata to acetic acid is demonstrated. Transcriptomic analysis showed that CgHaa1 regulates, directly or indirectly, the expression of about 75% of the genes activated under acetic acid stress. CgHaa1-activated targets are involved in multiple physiological functions including membrane transport, metabolism of carbohydrates and amino acids, regulation of the activity of the plasma membrane H+-ATPase, and adhesion. Under acetic acid stress, CgHaa1 increased the activity and the expression of the CgPma1 proton pump and contributed to increased colonization of vaginal epithelial cells by C. glabrata. CgHAA1, and two identified CgHaa1-activated targets, CgTPO3 and CgHSP30, are herein demonstrated to be determinants of C. glabrata tolerance to acetic acid. The protective effect of CgTpo3 and of CgHaa1 was linked to a role of these proteins in reducing the accumulation of acetic acid inside C. glabrata cells. In response to acetic acid stress, marked differences were found in the regulons controlled by CgHaa1 and by its S. cerevisiae ScHaa1 ortholog, demonstrating a clear divergent evolution of the two regulatory networks. The results gathered in this study significantly advance the understanding of the molecular mechanisms underlying the success of C. glabrata as a vaginal colonizer.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20676-1

Matching to small beta functions is required to preserve emittance in plasma accelerators. The plasma wake provides strong focusing fields, which typically require beta functions on the mm-scale, comparable to those found in the final focusing of a linear collider. Such beams can be time consuming to experimentally produce and diagnose. We present a simple, fast, and noninvasive method to measure Twiss parameters in a linac using two beam position monitors only, relying on the similarity of the beam phase space and the jitter phase space. By benchmarking against conventional quadrupole scans, the viability of this technique was experimentally demonstrated at the FLASHForward plasma-accelerator facility.

Purpose: We assessed the safety and efficacy of a technically advanced subretinal electronic implant, RETINA IMPLANT Alpha AMS, in end stage retinal degeneration in an interim analysis of two ongoing prospective clinical trials. The purpose of this article is to describe the interim functional results (efficacy).Methods: The subretinal visual prosthesis RETINA IMPLANT Alpha AMS (Retina Implant AG, Reutlingen, Germany) was implanted in 15 blind patients with hereditary retinal degenerations at four study sites with a follow-up period of 12 months (www.clinicaltrials.gov NCT01024803 and NCT02720640). Functional outcome measures included (1) screen-based standardized 2- or 4-alternative forced-choice (AFC) tests of light perception, light localization, grating detection (basic grating acuity (BaGA) test), and Landolt C-rings; (2) gray level discrimination; (3) performance during activities of daily living (ADL-table tasks).Results: Implant-mediated light perception was observed in 13/15 patients. During the observation period implant mediated localization of visual targets was possible in 13/15 patients. Correct grating detection was achieved for spatial frequencies of 0.1 cpd (cycles per degree) in 4/15; 0.33 cpd in 3/15; 0.66 cpd in 2/15; 1.0 cpd in 2/15 and 3.3 cpd in 1/15 patients. In two patients visual acuity (VA) assessed with Landolt C- rings was 20/546 and 20/1111. Of 6 possible gray levels on average 4.6 ± 0.8 (mean ± SD, n = 10) were discerned. Improvements (power ON vs. OFF) of ADL table tasks were measured in 13/15 patients. Overall, results were stable during the observation period. Serious adverse events (SAEs) were reported in 4 patients: 2 movements of the implant, readjusted in a second surgery; 4 conjunctival erosion/dehiscence, successfully treated; 1 pain event around the coil, successfully treated; 1 partial reduction of silicone oil tamponade leading to distorted vision (silicon oil successfully refilled). The majority of adverse events (AEs) were transient and mostly of mild to moderate intensity.Conclusions: Psychophysical and subjective data show that RETINA IMPLANT Alpha AMS is reliable, well tolerated and can restore limited visual functions in blind patients with degenerations of the outer retina. Compared with the previous implant Alpha IMS, longevity of the new implant Alpha AMS has been considerably improved. Alpha AMS has meanwhile been certified as a commercially available medical device, reimbursed in Germany by the public health system.

Mating between different species produces hybrids that are usually asexual and stuck as diploids, but can also lead to the formation of new species. Here, we report the genome sequences of 27 isolates of the pathogenic yeast Candida orthopsilosis. We find that most isolates are diploid hybrids, products of mating between two unknown parental species (A and B) that are 5% divergent in sequence. Isolates vary greatly in the extent of homogenization between A and B, making their genomes a mosaic of highly heterozygous regions interspersed with homozygous regions. Separate phylogenetic analyses of SNPs in the A- and B-derived portions of the genome produces almost identical trees of the isolates with four major clades. However, the presence of two mutually exclusive genotype combinations at the mating type locus, and recombinant mitochondrial genomes diagnostic of inter-clade mating, shows that the species C. orthopsilosis does not have a single evolutionary origin but was created at least four times by separate interspecies hybridizations between parents A and B. Older hybrids have lost more heterozygosity. We also identify two isolates with homozygous genomes derived exclusively from parent A, which are pure non-hybrid strains. The parallel emergence of the same hybrid species from multiple independent hybridization events is common in plant evolution, but is much less documented in pathogenic fungi.