A numerical benchmark for 2‐D variable‐density flow and solute transport in a freshwater lens is presented. The benchmark is based on results of laboratory experiments conducted by Stoeckl and Houben ...(2012) using a sand tank on the meter scale. This benchmark describes the formation and degradation of a freshwater lens over time as it can be found under real‐world islands. An error analysis gave the appropriate spatial and temporal discretization of 1 mm and 8.64 s, respectively. The calibrated parameter set was obtained using the parameter estimation tool PEST. Comparing density‐coupled and density‐uncoupled results showed that the freshwater‐saltwater interface position is strongly dependent on density differences. A benchmark that adequately represents saltwater intrusion and that includes realistic features of coastal aquifers or freshwater lenses was lacking. This new benchmark was thus developed and is demonstrated to be suitable to test variable‐density groundwater models applied to saltwater intrusion investigations.
Key Points:
This benchmark describes the formation and degradation of a freshwater lens
Comparable results are salinity distributions and angles of flow vectors
Sensitivity and convergence studies are included and worthiness is shown
The influence of the laser fluence on the quality of percussion-drilled holes was investigated both experimentally and by an analytical model. The study reveals that the edge quality of the drilled ...microholes depends on the laser fluence reaching the rear exit of the hole and changes with the number of pulses applied after breakthrough. The minimum fluence that must reach the hole’s exit in order to obtain high-quality microholes in stainless steel was experimentally found to be 2.8 times the ablation threshold.
The safety and efficacy of kratom (Mitragyna speciosa) for treatment of pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on ...just two of these, mitragynine and 7-hydroxymitragynine. Here, we profiled 53 commercial kratom products using untargeted LC-MS metabolomics, revealing two distinct chemotypes that contain different levels of the alkaloid speciofoline. Both chemotypes were confirmed with DNA barcoding to be M. speciosa. To evaluate the biological relevance of variable speciofoline levels in kratom, we compared the opioid receptor binding activity of speciofoline, mitragynine, and 7-hydroxymitragynine. Mitragynine and 7-hydroxymitragynine function as partial agonists of the human µ-opioid receptor, while speciofoline does not exhibit measurable binding affinity at the µ-, δ- or ƙ-opioid receptors. Importantly, mitragynine and 7-hydroxymitragynine demonstrate functional selectivity for G-protein signaling, with no measurable recruitment of β-arrestin. Overall, the study demonstrates the unique binding and functional profiles of the kratom alkaloids, suggesting potential utility for managing pain, but further studies are needed to follow up on these in vitro findings. All three kratom alkaloids tested inhibited select cytochrome P450 enzymes, suggesting a potential risk for adverse interactions when kratom is co-consumed with drugs metabolized by these enzymes.
Prone positioning in combination with the application of low tidal volume and adequate positive end-expiratory pressure (PEEP) improves survival in patients with moderate to severe acute respiratory ...distress syndrome (ARDS). However, the effects of PEEP on end-expiratory transpulmonary pressure (Ptp
) during prone positioning require clarification. For this purpose, the effects of three different PEEP titration strategies on Ptp
, respiratory mechanics, mechanical power, gas exchange, and hemodynamics were evaluated comparing supine and prone positioning.
In forty consecutive patients with moderate to severe ARDS protective ventilation with PEEP titrated according to three different titration strategies was evaluated during supine and prone positioning: (A) ARDS Network recommendations (PEEP
), (B) the lowest static elastance of the respiratory system (PEEP
), and (C) targeting a positive Ptp
(PEEP
). The primary endpoint was to analyze whether Ptp
differed significantly according to PEEP titration strategy during supine and prone positioning.
Ptp
increased progressively with prone positioning compared with supine positioning as well as with PEEP
and PEEP
compared with PEEP
(positioning effect p < 0.001, PEEP strategy effect p < 0.001). PEEP was lower during prone positioning with PEEP
and PEEP
(positioning effect p < 0.001, PEEP strategy effect p < 0.001). During supine positioning, mechanical power increased progressively with PEEP
and PEEP
compared with PEEP
, and prone positioning attenuated this effect (positioning effect p < 0.001, PEEP strategy effect p < 0.001). Prone compared with supine positioning significantly improved oxygenation (positioning effect p < 0.001, PEEP strategy effect p < 0.001) while hemodynamics remained stable in both positions.
Prone positioning increased transpulmonary pressures while improving oxygenation and hemodynamics in patients with moderate to severe ARDS when PEEP was titrated according to the ARDS Network lower PEEP table. This PEEP titration strategy minimized parameters associated with ventilator-induced lung injury induction, such as transpulmonary driving pressure and mechanical power. We propose that a lower PEEP strategy (PEEP
) in combination with prone positioning may be part of a lung protective ventilation strategy in patients with moderate to severe ARDS.
German Clinical Trials Register ( DRKS00017449 ). Registered June 27, 2019. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017449.
Abstract During pulmonary mucormycosis, inhaled sporangiospores adhere to, germinate, and invade airway epithelial cells to establish infection. We provide evidence that HIF1α plays dual roles in ...airway epithelial cells during Mucorales infection. We observed an increase in HIF1α protein accumulation and increased expression of many known HIF1α-responsive genes during in vitro infection, indicating that HIF1α signaling is activated by Mucorales infection. Inhibition of HIF1α signaling led to a substantial decrease in the ability of R. delemar to invade cultured airway epithelial cells. Transcriptome analysis revealed that R. delemar infection induces the expression of many pro-inflammatory genes whose expression was significantly reduced by HIF1α inhibition. Importantly, pharmacological inhibition of HIF1α increased survival in a mouse model of pulmonary mucormycosis without reducing fungal burden. These results suggest that HIF1α plays two opposing roles during mucormycosis: one that facilitates the ability of Mucorales to invade the host cells and one that facilitates the ability of the host to mount an innate immune response.
Luminophore stained micro- and nanobeads made from organic polymers like polystyrene (PS) are broadly used in the life and material sciences as luminescent reporters, for bead-based assays, sensor ...arrays, printable barcodes, security inks, and the calibration of fluorescence microscopes and flow cytometers. Initially mostly prepared with organic dyes, meanwhile luminescent core/shell nanoparticles (NPs) like spherical semiconductor quantum dots (QDs) are increasingly employed for bead encoding. This is related to their narrower emission spectra, tuneability of emission color, broad wavelength excitability, and better photostability. However, correlations between particle architecture, morphology, and photoluminescence (PL) of the luminescent nanocrystals used for encoding and the optical properties of the NP-stained beads have been rarely explored. This encouraged us to perform a screening study on the incorporation of different types of luminescent core/shell semiconductor nanocrystals into polymer microparticles (PMPs) by a radical-induced polymerization reaction. Nanocrystals explored include CdSe/CdS QDs of varying CdS shell thickness, a CdSe/ZnS core/shell QD, CdSe/CdS quantum rods (QRs), and CdSe/CdS nanoplatelets (NPLs). Thereby, we focused on the applicability of these NPs for the polymerization synthesis approach used and quantified the preservation of the initial NP luminescence. The spectroscopic characterization of the resulting PMPs revealed the successful staining of the PMPs with luminescent CdSe/CdS QDs and CdSe/CdS NPLs. In contrast, usage of CdSe/CdS QRs and CdSe QDs with a ZnS shell did not yield luminescent PMPs. The results of this study provide new insights into structure-property relationships between NP stained PMPs and the initial luminescent NPs applied for staining and underline the importance of such studies for the performance optimization of NP-stained beads.
Aspergillus fumigatus is an environmental fungus that can cause life-threatening pulmonary disease. Infections initiate when conidia are inhaled and land deep inside the small airways and alveoli of ...the lungs, where they interact with epithelial cells. These cells provide a physical barrier and secrete chemokines to attract innate immune cells to the site of infection. Melanin, a key constituent of the conidial cell wall, is required for the establishment of invasive infection due to its ability to inhibit the function of innate immune cells recruited to clear the infection. Here, we provide evidence for an additional mechanism by which A. fumigatus can alter host innate immune responses.
infection of a normal human small airway epithelial cell line (HSAEC1-KT) caused a decrease in extracellular protein levels of CXCL10 and CCL20, two proinflammatory chemokines that are required for the host defense against aspergillosis, despite a dramatic increase in the levels of each mRNA. A. fumigatus depleted recombinant human CXCL10 and CCL20 from medium in the absence of host cells, suggesting that the block in accumulation is downstream of protein translation and secretion. Melanin is both necessary and sufficient for this chemokine-depleting activity because a dihydroxynaphthalene (DHN)-melanin-deficient strain of A. fumigatus is defective in depleting chemokines and purified melanin ghosts retain potent depletion activity. We propose that A. fumigatus, through the action of melanin, depletes important chemokines, thereby dampening the innate immune response to promote infection.
Aspergillus fumigatus is the major airborne fungal pathogen that affects humans. In order to cause an invasive infection, inhaled spores must avoid killing by innate immune cells that are recruited to the site of infection. Understanding how A. fumigatus achieves immune evasion is important for the development of novel therapeutics. We provide evidence that melanin, a pigment contained in the spore cell wall, can remove certain chemokines from the extracellular space to suppress the host inflammatory response that is responsible for clearing fungal infection.
Efficient micromachining of glass with thicknesses of up to several millimeters can be enabled by using picosecond laser pulses with energies in the order of millijoules. In the experiments presented ...in this article, we investigated in-volume modifications in different thicknesses of borosilicate and soda lime glass using an axicon-generated Gaussian–Bessel beam. The main objective of the study was to demonstrate the separation of 8 mm thick soda lime glass within a single pass of the laser beam.
A
bstract
The Next-to-Minimal Supersymmetric Extension of the Standard Model (NMSSM) with a Higgs sector containing five neutral and two charged Higgs bosons allows for a rich phenomenology. In ...addition, the plethora of parameters provides many sources of CP violation. In contrast to the Minimal Supersymmetric Extension, CP violation in the Higgs sector is already possible at tree-level. For a reliable understanding and interpretation of the experimental results of the Higgs boson search, and for a proper distinction of Higgs sectors provided by the Standard Model or possible extensions, the Higgs boson masses have to be known as precisely as possible including higher-order corrections. In this paper we calculate the one-loop corrections to the neutral Higgs boson masses in the complex NMSSM in a Feynman diagrammatic approach adopting a mixed renormalization scheme based on on-shell and
conditions. We study various scenarios where we allow for tree-level CP-violating phases in the Higgs sector and where we also study radiatively induced CP violation due to a non-vanishing phase of the trilinear coupling
A
t
in the stop sector. The effects on the Higgs boson phenomenology are found to be significant. We furthermore estimate the theoretical error due to unknown higher-order corrections by both varying the renormalization scheme of the top and bottom quark masses and by adopting different renormalization scales. The residual theoretical error can be estimated to about 10%.
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