Field-Dependent Reduced Ion Mobilities of Positive and Negative Ions in Air and Nitrogen in High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS)

In High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS), ions are formed in a reaction region and separated in a drift region, which is similar to classical drift tube ion mobility spectrometers (IMS) operated at ambient pressure. However, in contrast to the latter, the HiKE-IMS is operated at a decreased background pressure of 10–40 mbar and achieves high reduced electric field strengths of up to 120 Td in both the reaction and the drift region. Thus, the HiKE-IMS allows insights into the chemical kinetics of ion-bound water cluster systems at effective ion temperatures exceeding 1000 K, although it is operated at the low absolute temperature of 45 °C. In this work, a HiKE-IMS with a high resolving power of RP = 140 is used to study the dependence of reduced ion mobilities on the drift gas humidity and the effective ion temperature for the positive reactant ions H3O+(H2O)n, O2+(H2O)n, NO+(H2O)n, NO2+(H2O)n, and NH4+(H2O)n, as well as the negative reactant ions O2–(H2O)n, O3–(H2O)n, CO3–(H2O)n, HCO3–(H2O)n, and NO2–(H2O)n. By varying the reduced electric field strength in the drift region, cluster transitions are observed in the ion mobility spectra. This is demonstrated for the cluster systems H3O+(H2O)n and NO+(H2O)n

Inelastic Diffraction and Spectroscopy of Very Weakly Bound Clusters

We study the coherent inelastic diffraction of very weakly bound two body clusters from a material transmission grating. We show that internal transitions of the clusters can lead to new separate peaks in the diffraction pattern whose angular positions determine the excitation energies. Using a quantum mechanical approach to few body scattering theory we determine the relative peak intensities for the diffraction of the van der Waals dimers (D_2)_2 and H_2-D_2. Based on the results for these realistic examples we discuss the possible applications and experimental challenges of this coherent inelastic diffraction technique.Comment: 15 pages + 5 figures. J. Phys. B (in press

Positive Reactant Ion Formation in High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS)

In contrast to classical Ion Mobility Spectrometers (IMS) operating at ambient pressure, the High Kinetic Energy Ion Mobility Spectrometer (HiKE-IMS) is operated at reduced pressures of between 10 and 40 mbar and higher reduced electric field strengths of up to 120 Td. Thus, the ion–molecule reactions occurring in the HiKE-IMS can significantly differ from those in classical ambient pressure IMS. In order to predict the ionization pathways of specific analyte molecules, profound knowledge of the reactant ion species generated in HiKE-IMS and their dependence on the ionization conditions is essential. In this work, the formation of positive reactant ions in HiKE-IMS is investigated in detail. On the basis of kinetic and thermodynamic data from the literature, the ion–molecule reactions are kinetically modeled. To verify the model, we present measurements of the reactant ion population and its dependence on the reduced electric field strength, the operating pressure, and the water concentration in the sample gas. All of these parameters significantly affect the reactant ion population formed in HiKE-IMS

60 Years of Glacier Elevation and Mass Changes in the Maipo River Basin, Central Andes of Chile

Glaciers in the central Andes of Chile are fundamental freshwater sources for ecosystems and communities. Overall, glaciers in this region have shown continuous recession and down-wasting, but long-term glacier mass balance studies providing precise estimates of these changes are scarce. Here, we present the first long-term (1955–2013/2015), region-specific glacier elevation and mass change estimates for the Maipo River Basin, from which the densely populated metropolitan region of Chile obtains most of its freshwater supply. We calculated glacier elevation and mass changes using historical topographic maps, Shuttle Radar Topography Mission (SRTM), TerraSAR-X add-on for Digital Elevation Measurements (TanDEM-X), and airborne Light Detection and Ranging (LiDAR) digital elevation models. The results indicated a mean regional glacier mass balance of −0.12 ± 0.06 m w.e.a−1, with a total mass loss of 2.43 ± 0.26 Gt for the Maipo River Basin between 1955–2013. The most negative glacier mass balance was the Olivares sub-basin, with a mean value of −0.29 ± 0.07 m w.e.a−1. We observed spatially heterogeneous glacier elevation and mass changes between 1955 and 2000, and more negative values between 2000 and 2013, with an acceleration in ice thinning rates starting in 2010, which coincides with the severe drought. Our results provide key information to improve glaciological and hydrological projections in a region where water resources are under pressure

Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?

New synthetic opioids (NSOs) pose a public health concern since their emergence on the illicit drug market and are gaining increasing importance in forensic toxicology. Like many other new psychoactive substances, NSOs are consumed without any preclinical safety data or any knowledge on toxicokinetic (TK) data. Due to ethical reasons, controlled human TK studies cannot be performed for the assessment of these relevant data. As an alternative animal experimental approach, six pigs per drug received a single intravenous dose of 100 µg/kg body weight (BW) of U-47700 or 1000 µg/kg BW of tramadol to evaluate whether this species is suitable to assess the TK of NSOs. The drugs were determined in serum and whole blood using a fully validated method based on solid-phase extraction and LC–MS/MS. The concentration–time profiles and a population (pop) TK analysis revealed that a three-compartment model best described the TK data of both opioids. Central volumes of distribution were 0.94 L/kg for U-47700 and 1.25 L/kg for tramadol and central (metabolic) clearances were estimated at 1.57 L/h/kg and 1.85 L/h/kg for U-47700 and tramadol, respectively. The final popTK model parameters for pigs were upscaled via allometric scaling techniques. In comparison to published human data, concentration–time profiles for tramadol could successfully be predicted with single species allometric scaling. Furthermore, possible profiles for U-47700 in humans were simulated. The findings of this study indicate that unlike a multiple species scaling approach, pigs in conjunction with TK modeling are a suitable tool for the assessment of TK data of NSOs and the prediction of human TK data

Guideline adherence in the use of coronary angiography in patients presenting at the emergency department without myocardial infarction – results from the German ENLIGHT-KHK project

Background For patients with acute myocardial infarction (AMI), direct coronary angiography (CA) is recommended, while for non-AMI patients, the diagnostic work-up depends on clinical criteria. This analysis provides initial prospective German data for the degree of guideline-adherence (GL) in the use of CA on non-AMI patients presenting at the emergency department (ED) with suspected acute coronary syndrome (ACS) according to the 2015 ESC-ACS-GL. Furthermore the implications of the application of the 2020 ESC-ACS-GL recommendations were evaluated. Methods Patient symptoms were identified using a standardized questionnaire; medical history and diagnostic work-up were acquired from health records. In accordance with the 2015 ESC-ACS-GL, CA was considered GL-adherent if intermediate risk criteria (IRC) were present or non-invasive, image-guided testing (NIGT) was pathological. Results Between January 2019 and August 2021, 229 patients were recruited across seven centers. Patients presented with chest pain, dyspnea, and other symptoms in 66.7%, 16.2% and 17.1%, respectively, were in mean 66.3 ± 10.5 years old, and 36.3% were female. In accordance with the 2015 ESC-ACS-GL, the use of CA was GL-adherent for 64.0% of the patients. GL-adherent compared to non-adherent use of CA resulted in revascularization more often (44.5% vs. 17.1%, p < 0.001). Applying the 2020 ESC-ACS-GL, 20.4% of CA would remain GL-adherent. Conclusions In the majority of cases, the use of CA was adherent to the 2015 ESC-ACS-GL. With regard to the 2020 and 2023 ESC-ACS-GL, efforts to expand the utilization of NIGT are crucial, especially as GL-adherent use of CA is more likely to result in revascularization

A53T-alpha-synuclein-overexpression in the mouse nigrostriatal pathway leads to early increase of 14-3-3 epsilon and late increase of GFAP

Parkinson’s disease (PD) is a neurodegenerative disorder frequent at old age characterized by atrophy of the nigrostriatal projection. Overexpression and A53T-mutation of the presynaptic, vesicle-associated chaperone alpha-synuclein are known to cause early-onset autosomal dominant PD. We previously generated mice with transgenic overexpression of human A53T-alpha-synuclein (A53T-SNCA) in dopaminergic substantia nigra neurons as a model of early PD. To elucidate the early and late effects of A53T-alpha-synuclein on the proteome of dopaminergic nerve terminals in the striatum, we now investigated expression profiles of young and old mice using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and mass spectrometry. In total, 15 proteins were upregulated and 2 downregulated. Mice before the onset of motor anomalies showed an upregulation of the spot containing 14-3-3 proteins, in particular the epsilon isoform, as well as altered levels of chaperones, vesicle trafficking and bioenergetics proteins. In old mice, the persistent upregulation of 14-3-3 proteins was aggravated by an increase of glial fibrillary acidic protein (GFAP) suggesting astrogliosis due to initial neurodegeneration. Independent immunoblots corroborated GFAP upregulation and 14-3-3 upregulation for the epsilon isoform, and also detected significant eta and gamma changes. Only for 14-3-3 epsilon a corresponding mRNA increase was observed in midbrain, suggesting it is transcribed in dopaminergic perikarya and accumulates as protein in presynapses, together with A53T-SNCA. 14-3-3 proteins associate with alpha-synuclein in vitro and in pathognomonic Lewy bodies of PD brains. They act as chaperones in signaling, dopamine synthesis and stress response. Thus, their early dysregulation probably reflects a response to alpha-synuclein toxicity

Enhanced Odor Discrimination and Impaired Olfactory Memory by Spatially Controlled Switch of AMPA Receptors

Genetic perturbations of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are widely used to dissect molecular mechanisms of sensory coding, learning, and memory. In this study, we investigated the role of Ca(2+)-permeable AMPARs in olfactory behavior. AMPAR modification was obtained by depletion of the GluR-B subunit or expression of unedited GluR-B(Q), both leading to increased Ca(2+) permeability of AMPARs. Mice with this functional AMPAR switch, specifically in forebrain, showed enhanced olfactory discrimination and more rapid learning in a go/no-go operant conditioning task. Olfactory memory, however, was dramatically impaired. GluR-B depletion in forebrain was ectopically variable (“mosaic”) among individuals and strongly correlated with decreased olfactory memory in hippocampus and cortex. Accordingly, memory was rescued by transgenic GluR-B expression restricted to piriform cortex and hippocampus, while enhanced odor discrimination was independent of both GluR-B variability and transgenic GluR-B expression. Thus, correlated differences in behavior and levels of GluR-B expression allowed a mechanistic and spatial dissection of olfactory learning, discrimination, and memory capabilities

Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: Results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers ('average reader') was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI

Life and death in the Chicxulub impact crater: a record of the Paleocene–Eocene Thermal Maximum

latitudes, with sea surface temperatures at some localities exceeding the 35 ∘C at which marine organisms experience heat stress. Relatively few equivalent terrestrial sections have been identified, and the response of land plants to this extreme heat is still poorly understood. Here, we present a new record of the PETM from the peak ring of the Chicxulub impact crater that has been identified based on nannofossil biostratigraphy, an acme of the dinoflagellate genus Apectodinium, and a negative carbon isotope excursion. Geochemical and microfossil proxies show that the PETM is marked by elevated TEXH86-based sea surface temperatures (SSTs) averaging ∼37.8 ∘C, an increase in terrestrial input and surface productivity, salinity stratification, and bottom water anoxia, with biomarkers for green and purple sulfur bacteria indicative of photic zone euxinia in the early part of the event. Pollen and plants spores in this core provide the first PETM floral assemblage described from Mexico, Central America, and the northern Caribbean. The source area was a diverse coastal shrubby tropical forest with a remarkably high abundance of fungal spores, indicating humid conditions. Thus, while seafloor anoxia devastated the benthic marine biota and dinoflagellate assemblages were heat-stressed, the terrestrial plant ecosystem thrived