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The latest operational National Air Quality Forecast Capability (NAQFC) has been advanced to use the Community Multiscale Air Quality (CMAQ) model (version 5.3.1) with the CB6r3 (Carbon Bond 6 revision 3) AERO7 (version 7 of the aerosol module) chemical mechanism and is driven by the Finite-Volume Cubed-Sphere (FV3) Global Forecast System, version 16 (GFSv16). This update has been accomplished via the development of the meteorological preprocessor, NOAA-EPA Atmosphere–Chemistry Coupler (NACC), adapted from the existing Meteorology–Chemistry Interface Processor (MCIP). Differing from the typically used Weather Research and Forecasting (WRF) CMAQ system in the air quality research community, the interpolation-based NACC can use various meteorological outputs to drive the CMAQ model (e.g., FV3-GFSv16), even though they are on different grids. In this study, we compare and evaluate GFSv16-CMAQ and WRFv4.0.3-CMAQ using observations over the contiguous United States (CONUS) in summer 2019 that have been verified with surface meteorological and AIRNow observations. During this period, the Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) field campaign was performed, and we compare the two models with airborne measurements from the NASA DC-8 aircraft. The GFS-CMAQ and WRF-CMAQ systems show similar performance overall with some differences for certain events, species and regions. The GFSv16 meteorology tends to have a stronger diurnal variability in the planetary boundary layer height (higher during daytime and lower at night) than WRF over the US Pacific coast, and it also predicted lower nighttime 10 m winds. In summer 2019, the GFS-CMAQ system showed better surface ozone (O3) than WRF-CMAQ at night over the CONUS domain; however, the models' fine particulate matter (PM2.5) predictions showed mixed verification results: GFS-CMAQ yielded better mean biases but poorer correlations over the Pacific coast. These results indicate that using global GFSv16 meteorology with NACC to directly drive CMAQ via interpolation is feasible and yields reasonable results compared to the commonly used WRF approach.

Seasonal variability of non-refractory PM1 (NR-PM1) was studied at a rural background site (National Atmospheric Observatory Košetice – NAOK) in the Czech Republic to investigate the effect of regional and long-range atmospheric transport in central Europe. NR-PM1 measurements were performed by compact time-of-flight aerosol mass spectrometry (C-ToF-AMS), and the chemically speciated mass size distributions, density, shape, and origin were discussed. Average PM1 concentrations, calculated as the sum of the NR-PM1 and the equivalent black carbon (eBC) concentrations measured by an aethalometer (AE), were 8.58 ± 3.70 µg m−3 in summer and 10.08 ± 8.04 µg m−3 in winter. Organics were dominant during both campaigns (summer/winter: 4.97 ± 2.92/4.55 ± 4.40 µg m−3), followed by SO42-in summer (1.68 ± 0.81/1.36 ± 1.38 µg m−3) and NO3- in winter (0.67 ± 0.38/2.03 ± 1.71 µg m−3). The accumulation mode dominated the average mass size distribution during both seasons, with larger particles of all species measured in winter (mode diameters: Org: 334/413 nm, NO3-: 377/501 nm, SO42-: 400/547 nm, and NH4+: 489/515 nm) indicating regional and long-range transport. However, since the winter aerosols were less oxidized than the summer aerosols (comparing fragments f44 and f43), the importance of local sources in the cold part of the year was still enough to be considered. Although aged continental air masses from the south-east (SE) were rare in summer (7 %), they were related to the highest concentrations of PM1, eBC, and all NR-PM1 species, especially SO42- and NH4+. In winter, slow continental air masses from the south-west (SW) (44 %) were linked to inversion conditions over central Europe and were associated with the highest concentrations among all NR-PM1 species as well as PM1 and eBC. Average PM1 material density (ρm) corresponded to higher inorganic contents in both seasons (summer: ∼ 1.30 g cm−3 and winter: ∼ 1.40 g cm−3). During episodes of higher mass concentrations ρm ranged from 1.30–1.40 g cm−3 in summer and from 1.30–1.50 g cm−3 in winter. The dynamic shape factors (χ) decreased slightly with particle mobility diameter (Dm) in both seasons. This study provides insights into the seasonal effects and air mass variability on aerosol particles, focusing on episodes of high mass and number concentrations measured at a central European rural background site.

Abstract Background Cost-effective methods to facilitate practical medical education are in high demand and the “mixed-reality” (MR) technology seems suitable to provide students with instructions when learning a new practical task. To evaluate a step-by-step mixed reality (MR) guidance system for instructing a practical medical procedure, we conducted a randomized, single-blinded prospective trial on medical students learning bladder catheter placement. Methods We enrolled 164 medical students. Students were randomized into 2 groups and received instructions on how to perform bladder catheter placement on a male catheterization training model. One group (107 students) were given their instructions by an instructor, while the other group (57 students) were instructed via an MR guidance system using a Microsoft HoloLens. Both groups did hands on training. A standardized questionnaire covering previous knowledge, interest in modern technologies and a self-evaluation was filled out. In addition, students were asked to evaluate the system’s usability. We assessed both groups’s learning outcome via a standardized OSCE (objective structured clinical examination). Results Our evaluation of the learning outcome revealed an average point value of 19.96 ± 2,42 for the control group and 21.49 ± 2.27 for the MR group - the MR group’s result was significantly better (p = 0.00). The self-evaluations revealed no difference between groups, however, the control group gave higher ratings when evaluating the quality of instructions. The MR system’s assessment showed less usability, with a cumulative SUS (system usability scale) score of 56.6 (lower half) as well as a cumulative score of 24.2 ± 7.3 (n = 52) out of 100 in the NASA task load index. Conclusions MR is a promising tool for instructing practical skills, and has the potential to enable superior learning outcomes. Advances in MR technology are necessary to improve the usability of current systems. Trial registration German Clinical Trial Register ID: DRKS00013186

Droughts are multidimensional hazards that can lead to substantial environmental and societal impacts. To understand causes and impacts, multiple perspectives need to be considered. Many studies have identified past drought events and investigated drought propagation from meteorological droughts via soil moisture to hydrological droughts, and some studies have included the impacts of these different types of drought. However, it is not certain whether the increased frequency and severity of drought events in the past decade is unprecedented in recent history. Therefore, we analyze different droughts and their impacts in a regional context using a multidisciplinary approach. We compile a comprehensive and long-term dataset to investigate possible temporal patterns in drought occurrence and place recent drought events into a historical context. We assembled a dataset of drought indices and recorded impacts over the last 218 years in southwestern Germany. Meteorological and river-flow indices were used to assess the natural drought dynamics. In addition, tree-ring data and recorded impacts were utilized to investigate drought events from an ecological and social perspective. Since 1801, 20 extreme droughts have been identified as common extreme events when applying the different indices. All events were associated with societal impacts. Our multi-dataset approach provides insights into similarities but also the unique aspects of different drought indices.

To the present day, a Francisella infection is diagnosed by a mandatory combination of two methods: a screening Enzyme-linked Immunosorbent Assay (ELISA) and a confirmatory Western Blot (WB), both based on the use of Francisella tularensis subsp. holarctica lipopolysaccharides (LPS) as a capture antigen. The purpose of the present work was to obtain and assess three recombinant proteins (FTT1696, FTT0077, FTT0975) as antigens in an indirect ELISA (iELISA) with the final goal to replace the confirmatory WB. Cloning strategy in vector pASG103, expression in E. coli and purification of proteins using Strep-system are described in detail in this report. Sera with confirmed antibody titers against F. tularensis reacted with all three antigens, which make them suitable for the serological detection of F. tularensis in swine and humans.

A study of the stable carbon isotope ratios (δ13C) of total carbon (TC) and the nitrogen isotope ratios (δ15N) of total nitrogen (TN) was carried out for fine aerosol particles (PM1) and was undertaken every 2 days with a 24 h sampling period at a rural background site in Košetice (Central Europe) from 27 September 2013 to 9 August 2014 (n=146). We found a seasonal pattern for both δ13C and δ15N. The seasonal variation in δ15N was characterized by lower values (average of 13.1±4.5 ‰) in winter and higher values (25.0±1.6 ‰) in summer. Autumn and spring were transition periods when the isotopic composition gradually changed due to the changing sources and ambient temperature. The seasonal variation in δ13C was less pronounced but more depleted in 13C in summer (-27.8±0.4 ‰) as compared to winter (-26.7±0.5 ‰). A comparative analysis with water-soluble ions, organic carbon, elemental carbon, trace gases and meteorological parameters (mainly ambient temperature) has shown major associations with the isotopic compositions, which has provided greater knowledge and understanding of the corresponding processes. A comparison of δ15N with NO3-, NH4+ and organic nitrogen (OrgN) revealed that although a higher content of NO3- was associated with a decrease in the δ15N of TN, NH4+ and OrgN caused increases. The highest concentrations of nitrate, mainly represented by NH4NO3 related to the emissions from biomass burning leading to an average δ15N of TN (13.3 ‰) in winter. During spring, the percentage of NO3- in PM1 decreased. An enrichment of 15N was probably driven by the equilibrium exchange between the gas and aerosol phases (NH3(g) ↔ NH4+(p)), which is supported by the increased ambient temperature. This equilibrium was suppressed in early summer when the molar ratios of NH4+/SO42- reached 2, and the nitrate partitioning in aerosol was negligible due to the increased ambient temperature. Summertime δ15N values were among the highest, suggesting the aging of ammonium sulfate and OrgN aerosols. Such aged aerosols can be coated by organics in which 13C enrichment takes place by the photooxidation process. This result was supported by a positive correlation of δ13C with ambient temperature and ozone, as observed in the summer season. During winter, we observed an event with the lowest δ15N and highest δ13C values. The winter event occurred in prevailing southeast air masses. Although the higher δ13C values probably originated from biomass-burning particles, the lowest δ15N values were probably associated with agriculture emissions of NH3 under low-temperature conditions (∘C).

Similarities and differences in the submicron atmospheric aerosol chemical composition are analyzed from a unique set of measurements performed at 21 sites across Europe for at least one year. These sites are located between 35 and 62°N and 10° W – 26°E, and represent various types of settings (remote, coastal, rural, industrial, urban). Measurements were all carried out on-line with a 30-min time resolution using mass spectroscopy based instruments known as Aerosol Chemical Speciation Monitors (ACSM) and Aerosol Mass Spectrometers (AMS) and following common measurement guidelines. Data regarding organics, sulfate, nitrate and ammonium concentrations, as well as the sum of them called non-refractory submicron aerosol mass concentration ([NR-PM1]) are discussed. NR-PM1 concentrations generally increase from remote to urban sites. They are mostly larger in the mid-latitude band than in southern and northern Europe. On average, organics account for the major part (36–64%) of NR-PM1 followed by sulfate (12–44%) and nitrate (6–35%). The annual mean chemical composition of NR-PM1 at rural (or regional background) sites and urban background sites are very similar. Considering rural and regional background sites only, nitrate contribution is higher and sulfate contribution is lower in mid-latitude Europe compared to northern and southern Europe. Large seasonal variations in concentrations (μg/m³) of one or more components of NR-PM1 can be observed at all sites, as well as in the chemical composition of NR-PM1 (%) at most sites. Significant diel cycles in the contribution to [NR-PM1] of organics, sulfate, and nitrate can be observed at a majority of sites both in winter and summer. Early morning minima in organics in concomitance with maxima in nitrate are common features at regional and urban background sites. Daily variations are much smaller at a number of coastal and rural sites. Looking at NR-PM1 chemical composition as a function of NR-PM1 mass concentration reveals that although organics account for the major fraction of NR-PM1 at all concentration levels at most sites, nitrate contribution generally increases with NR-PM1 mass concentration and predominates when NR-PM1 mass concentrations exceed 40 μg/m³ at half of the sites.

Global Navigation Satellite System (GNSS) radio occultation (RO) observations are highly accurate, long-term stable data sets and are globally available as a continuous record from 2001. Essential climate variables for the thermodynamic state of the free atmosphere – such as pressure, temperature, and tropospheric water vapor profiles (involving background information) – can be derived from these records, which therefore have the potential to serve as climate benchmark data. However, to exploit this potential, atmospheric profile retrievals need to be very accurate and the remaining uncertainties quantified and traced throughout the retrieval chain from raw observations to essential climate variables. The new Reference Occultation Processing System (rOPS) at the Wegener Center aims to deliver such an accurate RO retrieval chain with integrated uncertainty propagation. Here we introduce and demonstrate the algorithms implemented in the rOPS for uncertainty propagation from excess phase to atmospheric bending angle profiles, for estimated systematic and random uncertainties, including vertical error correlations and resolution estimates. We estimated systematic uncertainty profiles with the same operators as used for the basic state profiles retrieval. The random uncertainty is traced through covariance propagation and validated using Monte Carlo ensemble methods. The algorithm performance is demonstrated using test day ensembles of simulated data as well as real RO event data from the satellite missions CHAllenging Minisatellite Payload (CHAMP); Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC); and Meteorological Operational Satellite A (MetOp). The results of the Monte Carlo validation show that our covariance propagation delivers correct uncertainty quantification from excess phase to bending angle profiles. The results from the real RO event ensembles demonstrate that the new uncertainty estimation chain performs robustly. Together with the other parts of the rOPS processing chain this part is thus ready to provide integrated uncertainty propagation through the whole RO retrieval chain for the benefit of climate monitoring and other applications.

Laser-generated ion acceleration has received increasing attention due to recent progress in super-intense lasers. Here the authors demonstrate the role of the self-generated magnetic field on the ion acceleration and limitations on the energy scaling with laser intensity.

Abstract To what extent and how post-transcriptional dysregulation affects aging proteome remains unclear. Here, we provide proteomic data of whole-tissue lysates (WTL) and low-solubility protein-enriched fractions (LSF) of major tissues collected from mice of 6, 15, 24, and 30 months of age. Low-solubility proteins are preferentially affected by age and the analysis of LSF doubles the number of proteins identified to be differentially expressed with age. Simultaneous analysis of proteome and transcriptome using the same tissue homogenates reveals the features of age-related post-transcriptional dysregulation. Post-transcriptional dysregulation becomes evident especially after 24 months of age and age-related post-transcriptional dysregulation leads to accumulation of core matrisome proteins and reduction of mitochondrial membrane proteins in multiple tissues. Based on our in-depth proteomic data and sample-matched transcriptome data of adult, middle-aged, old, and geriatric mice, we construct the Mouse aging proteomic atlas ( https://aging-proteomics.info/ ), which provides a thorough and integrative view of age-related gene expression changes.

Long-lasting research infrastructures covering the research areas of atmospheric chemistry, meteorology and climatology are of highest importance. The Atmospheric Station (AS) Křešín u Pacova, central Czech Republic, is focused on monitoring of the occurence and long-range transport of greenhouse gases, atmospheric aerosols, selected gaseous atmospheric pollutants and basic meteorological characteristics. The AS and its 250 m tall tower was built according to the recommendations of the Integrated Carbon Observation System (ICOS) and cooperates with numerous national and international projects and monitoring programmes. First measurements conducted at ground started in 2012, vertical profile measurements were added in 2013. A seasonal variability with slightly higher autumn and winter concentrations of elemental and organic carbon was revealed. The suitability of the doubly left-censored Weibull distribution for modelling and interpretation of elemental carbon concentrations, which are often lower than instrumental quantification limits, was verified. Initial data analysis also suggests that in summer, the tower top at 250 m is frequently above the nocturnal surface inversions, thus being decoupled from local influences.

A comparison exercise on thermal-optical elemental carbon/organic carbon (ECOC) analysers was carried out among 17 European laboratories. Contrary to previous comparison exercises, the 17 participants made use of an identical instrument set-up, after correcting for temperature offsets with the application of a recently developed temperature calibration kit (Sunset Laboratory Inc, OR, US). Temperature offsets reported by participants ranged from −93 to +100 °C per temperature step. Five filter samples and two sucrose solutions were analysed with both the EUSAAR2 and NIOSH870 thermal protocols. z scores were calculated for total carbon (TC); nine outliers and three stragglers were identified. Three outliers and eight stragglers were found for EC. Overall, the participants provided results between the warning levels with the exception of two laboratories that showed poor performance, the causes of which were identified and corrected through the course of the comparison exercise. The TC repeatability and reproducibility (expressed as relative standard deviations) were 11 and 15% for EUSAAR2 and 9.2 and 12% for NIOSH870; the standard deviations for EC were 15 and 20% for EUSAAR2 and 20 and 26% for NIOSH870. TC was in good agreement between the two protocols, TCNIOSH870 = 0.98 × TCEUSAAR2 (R2 = 1.00, robust means). Transmittance (TOT) calculated EC for NIOSH870 was found to be 20% lower than for EUSAAR2, ECNIOSH870 = 0.80 × ECEUSAAR2 (R2 = 0.96, robust means). The thermograms and laser signal values were compared and similar peak patterns were observed per sample and protocol for most participants. Notable deviations from the typical patterns indicated either the absence or inaccurate application of the temperature calibration procedure and/or pre-oxidation during the inert phase of the analysis. Low or zero pyrolytic organic carbon (POC), as reported by a few participants, is suggested as an indicator of an instrument-specific pre-oxidation. A sample-specific pre-oxidation effect was observed for filter G, for all participants and both thermal protocols, indicating the presence of oxygen donors on the suspended particulate matter. POC (TOT) levels were lower for NIOSH870 than for EUSAAR2, which is related to the heating profile differences of the two thermal protocols.

Abstract Objective Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non‐invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE‐ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non‐demented older adults. Methods Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid β1‐42 and p‐Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow‐up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed‐effects model for each tract. Results AD pathology, APOE‐ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE‐ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. Interpretation Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.

Summary: Background: DNA methylation integrates environmental signals with transcriptional programs. COVID-19 infection induces changes in the host methylome. While post-acute sequelae of COVID-19 (PASC) is a long-term complication of acute illness, its association with DNA methylation is unknown. No universal blood marker of PASC, superseding single organ dysfunctions, has yet been identified. Methods: In this single centre prospective cohort study, PASC, post-COVID without PASC, and healthy participants were enrolled to investigate their symptoms association with peripheral blood DNA methylation data generated with state-of-the-art whole genome sequencing. PASC-induced quality-of-life deterioration was scored with a validated instrument, SF-36. Analyses were conducted to identify potential functional roles of differentially methylated loci, and machine learning algorithms were used to resolve PASC severity. Findings: 103 patients with PASC (22.3% male, 77.7% female), 15 patients with previous COVID-19 infection but no PASC (40.0% male, 60.0% female), and 27 healthy volunteers (48.1% male, 51.9% female) were enrolled. Whole genome methylation sequencing revealed 39 differentially methylated regions (DMRs) specific to PASC, each harbouring an average of 15 consecutive positions, that differentiate patients with PASC from the two control groups. Motif analyses of PASC-regulated DMRs identify binding domains for transcription factors regulating circadian rhythm and others. Some DMRs annotated to protein coding genes were associated with changes of RNA expression. Machine learning support vector algorithm and random forest hierarchical clustering reveal 28 unique differentially methylated positions (DMPs) in the genome discriminating patients with better and worse quality of life. Interpretation: Blood DNA methylation levels identify PASC, stratify PASC severity, and suggest that DNA motifs are targeted by circadian rhythm-regulating pathways in PASC. Funding: This project has been funded by the following agencies: NIH-AI173035 (A. Jaitovich and R. Alisch); and NIH-AG066179 (R. Alisch).

Soot, which is produced from biomass burning and the incomplete combustion of fossil and biomass fuels, has been linked to regional and global climate change and to negative health problems. Scientists measure the properties of soot using a variety of methods in order to quantify source emissions and understand its atmospheric chemistry, reactivity under emission conditions, interaction with solar radiation, influence on clouds, and health impacts. A major obstacle currently limiting progress is the absence of established standards or reference materials for calibrating the many instruments used to measure the various properties of soot. The current state of availability and practicability of soot standard reference materials (SRMs) was reviewed by a group of 50 international experts during a workshop in June of 2011. The workshop was convened to summarize the current knowledge on soot measurement techniques, identify the measurement uncertainties and limitations related to the lack of soot SRMs, and identify attributes of SRMs that, if developed, would reduce measurement uncertainties. The workshop established that suitable SRMs are available for calibrating some, but not all, measurement methods. The community of users of the single-particle soot-photometer (SP2), an instrument using laser-induced incandescence, identified a suitable SRM, fullerene soot, but users of instruments that measure light absorption by soot collected on filters did not. Similarly, those who use thermal optical analysis (TOA) to analyze the organic and elemental carbon components of soot were not satisfied with current SRMs. The workshop, and subsequent, interactive discussions, produced a number of recommendations for the development of new SRMs, and their implementation, that would be suitable for the different soot measurement methods.

In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.

Flow velocity is generally presumed to influence flood damage. However, this influence is hardly quantified and virtually no damage models take it into account. Therefore, the influences of flow velocity, water depth and combinations of these two impact parameters on various types of flood damage were investigated in five communities affected by the Elbe catchment flood in Germany in 2002. 2-D hydraulic models with high to medium spatial resolutions were used to calculate the impact parameters at the sites in which damage occurred. A significant influence of flow velocity on structural damage, particularly on roads, could be shown in contrast to a minor influence on monetary losses and business interruption. Forecasts of structural damage to road infrastructure should be based on flow velocity alone. The energy head is suggested as a suitable flood impact parameter for reliable forecasting of structural damage to residential buildings above a critical impact level of 2 m of energy head or water depth. However, general consideration of flow velocity in flood damage modelling, particularly for estimating monetary loss, cannot be recommended.

Sulfonamides are consumed as pharmaceutical antibiotics and reach agricultural soils with excreta used as fertilizer. Subsequently, nonextractable residues rapidly form in soil, which has been researched in a couple of studies. To further elucidate conditions, strength, and mechanisms of the fixation to soil humic substances, three selected sulfonamides were investigated using the biochemical oligomerization of substituted phenols as a model for the humification process. Catechol, guaiacol, and vanillin were enzymatically reacted using laccase from Trametes versicolor. In the presence of the substituted phenols alone, the concentration of sulfonamides decreased. This decrease was even more pronounced when additional laccase was present. Upon the enzymatic oligomerization of the substituted phenols to a humic-like structure the sulfonamides were sorbed, transformed, sequestered, and nonextractable bound. Sulfonamides were transformed depending on their molecular properties. Fractions of different bonding strength were determined using a sequential extraction procedure. Isolated nonextractable products were analyzed by chromatographic, spectroscopic, and calorimetric methods to identify coupling and bonding mechanisms of the sulfonamides. Differential scanning calorimetry measurements suggested cross-linking of such incorporated sulfonamides in humic oligomers. Nuclear magnetic resonance spectroscopy measurements showed clear differences between the vanillin-sulfapyridine oligomer and the parent sulfapyridine indicating bound residue formation through covalent binding.

A Berner low pressure impactor was used to collect size-segregated aerosol samples at Finokalia, located on the north-eastern coast of Crete, Greece during July 2000 and January 2001. Several samples were also collected during the summer campaign aboard the research vessel "AEGAIEO" in the Aegean Sea. Gravimetric analysis and inversion techniques yielded daily PM1 and PM10 mass concentrations. The samples were also analysed by PIXE giving the elemental size distributions of Al, Si, K, Ca, Ti, Mn, Fe, Sr, S, Cl, Ni, V, Cu, Cr, Zn, and Pb. The crustal elements and sea-salt had a unimodal supermicron size distribution. Sulphur was found predominantly in submicron fractions. K, V, and Ni exhibited a bimodal distribution with a submicron mode produced by forest fires and oil combustion. The anthropogenic elements had broad and not well-defined distributions. The time series for PM1 and PM10 mass and elemental concentrations showed both daily and seasonal variation. Higher mass concentrations were observed during two incursions of Saharan dust, whilst higher concentrations of S, Cu, Zn, and Pb were encountered in samples collected in air masses arriving from northern Greece or the western coast of Turkey. Elevated concentrations of chlorine were found in samples with air masses either originating above the Atlantic Ocean and arriving at Finokalia via western Europe or recirculating over the western coast of the Black Sea.

Vor etwa 35 000-40 000 Jahren schuf eine Episode neotektonischer Aktivität an der Indus-Sutur bei Lamayuru (Ladakh) einen See, von dem eine über 105 m mächtige Abfolge fluviolakustriner Ablagerungen erhalten ist. Die zwischen Ton/Silt/Sand eingelagerten lakustrinen Horizonte (Kalkschlämme) und karbonatreichen Schichten haben Süßwasser-Ostrakoden, Gastropoden und Charophyten geliefert. Insgesamt wurden 9 Fossilhorizonte angetroffen. Die hauptsächlichen Ostrakodentaxa sind llyocypris (l. gibba und I. bradyi), Eucypris und Candona. Bei den Gastropoden dominieren Lymnaea, Succinea und Gyraulus. Die Charophyten werden durch Chara globularis vertreten. Die paläoökologische Interpretation basiert auf den charakteristischen Faunen- und Florenelementen und auf der Natur der Sedimente. Es wird vermutet, daß der See während seiner ganzen Existenz ziemlich flach war und kaltes, extrem salzarmes, langsam fließendes, pflanzenreiches Wasser führte. Als ein offenes Becken mag er einen kontinuierlichen Abfluß während seiner ganzen Existenz gehabt haben. Die Entleerung des Sees wurde verursacht durch eine strukturelle Zerrüttung des Seebodens und die Ausfüllung durch riesige, durch einen weiteren Impuls tektonischer Aktivität ausgelöste Schuttmassen.

Abstract The Mitochondrial Complex I Assembly (MCIA) complex is essential for the biogenesis of respiratory Complex I (CI), the first enzyme in the respiratory chain, which has been linked to Alzheimer’s disease (AD) pathogenesis. However, how MCIA facilitates CI assembly, and how it is linked with AD pathogenesis, is poorly understood. Here we report the structural basis of the complex formation between the MCIA subunits ECSIT and ACAD9. ECSIT binding induces a major conformational change in the FAD-binding loop of ACAD9, releasing the FAD cofactor and converting ACAD9 from a fatty acid β-oxidation (FAO) enzyme to a CI assembly factor. We provide evidence that ECSIT phosphorylation downregulates its association with ACAD9 and is reduced in neuronal cells upon exposure to amyloid-β (Aβ) oligomers. These findings advance our understanding of the MCIA complex assembly and suggest a possible role for ECSIT in the reprogramming of bioenergetic pathways linked to Aβ toxicity, a hallmark of AD.

We have developed conceptual designs of two petawatt-class pulsed-power accelerators: Z 300 and Z 800. The designs are based on an accelerator architecture that is founded on two concepts: single-stage electrical-pulse compression and impedance matching [Phys. Rev. ST Accel. Beams 10, 030401 (2007)]. The prime power source of each machine consists of 90 linear-transformer-driver (LTD) modules. Each module comprises LTD cavities connected electrically in series, each of which is powered by 5-GW LTD bricks connected electrically in parallel. (A brick comprises a single switch and two capacitors in series.) Six water-insulated radial-transmission-line impedance transformers transport the power generated by the modules to a six-level vacuum-insulator stack. The stack serves as the accelerator’s water-vacuum interface. The stack is connected to six conical outer magnetically insulated vacuum transmission lines (MITLs), which are joined in parallel at a 10-cm radius by a triple-post-hole vacuum convolute. The convolute sums the electrical currents at the outputs of the six outer MITLs, and delivers the combined current to a single short inner MITL. The inner MITL transmits the combined current to the accelerator’s physics-package load. Z 300 is 35 m in diameter and stores 48 MJ of electrical energy in its LTD capacitors. The accelerator generates 320 TW of electrical power at the output of the LTD system, and delivers 48 MA in 154 ns to a magnetized-liner inertial-fusion (MagLIF) target [Phys. Plasmas 17, 056303 (2010)]. The peak electrical power at the MagLIF target is 870 TW, which is the highest power throughout the accelerator. Power amplification is accomplished by the centrally located vacuum section, which serves as an intermediate inductive-energy-storage device. The principal goal of Z 300 is to achieve thermonuclear ignition; i.e., a fusion yield that exceeds the energy transmitted by the accelerator to the liner. 2D magnetohydrodynamic (MHD) simulations suggest Z 300 will deliver 4.3 MJ to the liner, and achieve a yield on the order of 18 MJ. Z 800 is 52 m in diameter and stores 130 MJ. This accelerator generates 890 TW at the output of its LTD system, and delivers 65 MA in 113 ns to a MagLIF target. The peak electrical power at the MagLIF liner is 2500 TW. The principal goal of Z 800 is to achieve high-yield thermonuclear fusion; i.e., a yield that exceeds the energy initially stored by the accelerator’s capacitors. 2D MHD simulations suggest Z 800 will deliver 8.0 MJ to the liner, and achieve a yield on the order of 440 MJ. Z 300 and Z 800, or variations of these accelerators, will allow the international high-energy-density-physics community to conduct advanced inertial-confinement-fusion, radiation-physics, material-physics, and laboratory-astrophysics experiments over heretofore-inaccessible parameter regimes.

Summary: Background: Multiple organ dysfunction syndrome (MODS) disproportionately drives morbidity and mortality among critically ill patients. However, we lack a comprehensive understanding of its pathobiology. Identification of genes associated with a persistent MODS trajectory may shed light on underlying biology and allow for accurate prediction of those at-risk. Methods: Secondary analyses of publicly available gene-expression datasets. Supervised machine learning (ML) was used to identify a parsimonious set of genes associated with a persistent MODS trajectory in a training set of pediatric septic shock. We optimized model parameters and tested risk-prediction capabilities in independent validation and test datasets, respectively. We compared model performance relative to an established gene-set predictive of sepsis mortality. Findings: Patients with a persistent MODS trajectory had 568 differentially expressed genes and characterized by a dysregulated innate immune response. Supervised ML identified 111 genes associated with the outcome of interest on repeated cross-validation, with an AUROC of 0.87 (95% CI: 0.85–0.88) in the training set. The optimized model, limited to 20 genes, achieved AUROCs ranging from 0.74 to 0.79 in the validation and test sets to predict those with persistent MODS, regardless of host age and cause of organ dysfunction. Our classifier demonstrated reproducibility in identifying those with persistent MODS in comparison with a published gene-set predictive of sepsis mortality. Interpretation: We demonstrate the utility of supervised ML driven identification of the genes associated with persistent MODS. Pending validation in enriched cohorts with a high burden of organ dysfunction, such an approach may inform targeted delivery of interventions among at-risk patients. Funding: H.R.W.′s NIH R35GM126943 award supported the work detailed in this manuscript. Upon his death, the award was transferred to M.N.A. M.R.A., N.S.P, and R.K were supported by NIH R21GM151703. R.K. was supported by R01GM139967.