Search

ABSTRACTThis work presents the integration of an elemental analyzer (EA) and an isotope ratio mass spectrometer (IRMS) into the 6 MV AMS system at the Institute for Nuclear Physics, University of Cologne. The AMS measurement of δ13C values for IAEA-C6 reference material resulted in –11.39(226)‰, compared to –10.28(32)‰ obtained by IRMS. The EA-IRMS system was also tested with IAEA-C3, IAEA-C5, and IAEA-C7 reference materials, yielding –24.79(9), –25.18(15), and –14.76(18)‰ respectively. Compared to the IAEA information values given as –24.91(49), –25.49(72) and –14.48(21)‰ respectively. To investigate an observed sample mass dependency, environmental samples from Spitzbergen were examined, showing δ13C values of –25.17(55), –25.80(31), and –26.17‰ in Cologne, while Hamburg recorded –24.8(1), –25.5(1), and –26.2(13)‰. In summary, this new setup could enable online analysis and quasi-simultaneous measurements of 14C, δ13C, and δ15N for ultra-small samples, utilizing precise δ13C values from IRMS for fractionation correction of the 14C/14C isotopic ratio.

Acetaminophen (APAP) is an analgesic and antipyretic drug used worldwide, which is safe at therapeutic doses. However, an overdose can induce liver injury and even liver failure. Mechanistic studies in mice beginning with the seminal papers published by B.B. Brodie’s group in the 1970s have resulted in important insight into the pathophysiology. Although the metabolic activation of APAP with generation of a reactive metabolite, glutathione depletion, and protein adduct formation are critical initiating events, more recently, mitochondria have come into focus as an important target and decision point of cell death. This review provides a comprehensive overview of the induction of mitochondrial superoxide and peroxynitrite formation and its propagation through a mitogen-activated protein kinase cascade, the mitochondrial permeability transition pore opening caused by iron-catalyzed protein nitration, and the mitochondria-dependent nuclear DNA fragmentation. In addition, the role of adaptive mechanisms that can modulate the pathophysiology, including autophagy, mitophagy, nuclear erythroid 2 p45-related factor 2 activation, and mitochondrial biogenesis, are discussed. Importantly, it is outlined how the mechanisms elucidated in mice translate to human hepatocytes and APAP overdose patients, and how this mechanistic insight explains the mechanism of action of the clinically approved antidote N-acetylcysteine and led to the recent discovery of a novel compound, fomepizole, which is currently under clinical development.

The Moon is considered a future destination for international space exploration. Transport costs to the Moon are enormous, requiring the use of available resources to build infrastructure. Lunar regolith, predominantly found in the form of dust, covers the entire Moon’s terrain. A promising approach to process regolith is laser-based additive manufacturing, which aims to melt it directly on the surface. This paper presents a finite element simulation model to investigate the effects of laser power and feed rate variation on the melting process, with the objective to predict experimentally unexplored parameter ranges. The focus of this study is the phase transition from solid to liquid, implemented by an enthalpy model. Validation is carried out using experimental melting tests with regolith simulants. Despite limited experimental data, the observed effects are consistent with the simulation results, confirming that sample thickness increases with laser power and decreases with feed rate.

The groundwater below the Red Hill Bulk Fuel Storage Facility (the facility) in Oʻahu, Hawaiʻi, contains fuel compounds from past spills. This study used carbon-14 analyses to distinguish fuel-derived carbon from background carbon, along with other biodegradation indicators, to address two goals: (1) determine the extent and migration direction of groundwater affected by residual fuel below the facility and (2) determine if residual fuel locations in the subsurface could be identified by analyzing soil gas at the surface above the facility. Groundwater from 19 wells was sampled between September 2022 and April 2023. Nonvolatile dissolved organic carbon (NVDOC) from a well presumed to be unaffected by past spills contained 38 percent ancient carbon indicating a natural source of ancient carbon in the subsurface. The NVDOC concentrations and ancient carbon percentages indicate fuel biodegradation products are likely present on the north and south of Red Hill with the greatest effects at well RHMW02 near the 2014 spill site. The NVDOC concentrations are almost three times higher than diesel range organic (DRO) concentrations in groundwater from the same sites. Major ion data indicate that iron reduction is an important biodegradation process. Soil probe samples and soil carbon traps were used to determine the carbon-14 content of soil carbon dioxide. Ancient carbon from fuel biodegradation was not detected at any soil probe or carbon trap site in contrast to a 2017 study which reported ancient carbon detections. A reanalysis of the 2017 results using a range of local values for background carbon-14 indicates that ancient carbon from fuel biodegradation was probably only detected in lower tunnel exhaust system samples and not in any soil carbon trap samples. Measurements of carbon dioxide efflux with a dynamic closed chamber were highly variable. The soil gas results indicate that soil gas measurements at land surface were not useful for detecting residual fuel at the facility. [ABSTRACT FROM AUTHOR]

Since the development of laser systems technology led to a significantly decreased energy input by pulsing, laser cutting became a noteworthy method for cutting fiber-reinforced polymers. Despite the occurrence of heat introduction and heat-affected zones (HAZ), there are advantages regarding processing speed and maneuverability. Within this work, the influence of two cutting parameters (low (A) and high heat introduction (B)) on the fatigue properties of carbon fiber–reinforced epoxy and polyamide 6 were investigated. At the same time, micro waterjet cut specimens were added as a reference. In doing so, laminates were cut to different specimen widths and orientations. Multiple amplitude tests were performed with strain and temperature measurements. The results show an influence of specimen width on fatigue lifetime for the epoxy system, but not in polyamide 6. The 45° specimens for both CFR-EP and CFR-PA6 showed a decreased lifetime when cut with parameters B. However, these findings do not apply to 0° specimens, since parameters Alead to a smaller lifetime for CFR-EP, and no influence was found for CFR-PA6. Furthermore, no clear HAZ could be identified for A. Since there is a decrease in lifetime for CFR-EP, the necessity of applying further methods for HAZ detection is described.

This article proposes a low-cost and practical alternative to vector network analyzers (VNAs) for characterizing dielectric materials using a calibrated frequency-modulated continuous wave (FMCW) radar measurement setup and a machine learning (ML) model. The calibrated FMCW radar measurement setup has the ability to accurately measure the $S$ -parameters of dielectric materials. In addition, an ML model is developed to extract material parameters such as thickness, dielectric constant, and loss tangent with high accuracy. $K$ -means clustering was additionally applied to significantly reduce the complexity of the neural network (NN). Additionally, a state-of-the-art open-set recognition (OSR) technique was adopted to simultaneously classify known classes and reject unknown classes. The developed model uses a modified version of the class anchor clustering (CAC) distance-based loss, which outperforms the conventional cross-entropy loss. The proposed model was evaluated on several dielectric materials and compared to reference measurements using a VNA and curve fitting. The results indicate that the proposed model is accurate and robust, and that the calibrated radar sensor provides a practical and cost-effective alternative to VNAs in characterizing dielectric materials, as long as the material parameters are within the defined limits.

Graphical abstract:

Hi Mark, The Winter issue of Health Science is a keeper. Al spotted the zucchini muffins and immediately requested a batch. The other recipes look equally appealing and appropriate for [...]

Issues of financial and intellectual conflict of interest in clinical practice guidelines have raised increasing concern. Professional organizations have responded by more rigorous regulation of conflict of interest. Nevertheless, tension remains between the competing goals of optimizing guideline quality by using the experience and insight of experts and ensuring that financial and intellectual conflicts of interest do not influence recommendations. The executive committee of the American College of Chest Physicians' Antithromboric Guidelines has developed a strategy comprising 3 innovative aspects to address this tension: First, place equal emphasis on intellectual and financial conflicts and provide explicit criteria for both; second, a methodologist without important conflicts of interest should have primary responsibility for each chapter; and third, experts with important financial or intellectual conflicts of interest can collect and interpret evidence, but only panel members without important conflicts can be involved in developing the recommendation for a specific question. These strategies may help to achieve the benefits of expert input without conflicts of interest influencing recommendations.

Addressing resistance to third-generation EGFR TKIs such as osimertinib via the EGFRC797Smutation remains a highly unmet need in EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we present the discovery of the allosteric EGFR inhibitor 57, a novel fourth-generation inhibitor to overcome EGFRC797S-mediated resistance in patients harboring the activating EGFRL858Rmutation. 57exhibits an improved potency compared to previous allosteric EGFR inhibitors. To our knowledge, 57is the first allosteric EGFR inhibitor that demonstrates robust tumor regression in a mutant EGFRL858R/C797Stumor model. Additionally, 57is active in an H1975 EGFRL858R/T790MNSCLC xenograft model and shows superior efficacy in combination with osimertinib compared to the single agents. Our data highlight the potential of 57as a single agent against EGFRL858R/C797Sand EGFRL858R/T790M/C797Sand as combination therapy for EGFRL858R- and EGFRL858R/T790M-driven NSCLC.

In my mind it is the soil-thanks to the coffee plant and with a little help from my coffee maker-that gets sublimated. Between a model and a metaphor for the systems and thought processes imbedded in architecture, Aleksandra Jaeschke looks at coffee, its production, and consumption. Like the energy generated from fossil fuels, the stimulation provided by coffee-by the way, it's all in your mind, coffee is not a source of free energy-leaves undesired traces and has ecological (and hence also mental) ramifications. It makes me think of how much work goes into transforming a coffee plant seedling into the beans I grind. [Extracted from the article]

Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of “trial-ineligible” and “potentially trial-eligible” patients.

Background: Understanding the risk factors for ventilator-associated pneumonia can help to assess prognosis and devise and test preventive strategies. Objective: To examine the baseline and time-dependent risk factors for ventilator-associated pneumonia and to determine the conditional probability and cumulative risk over the duration of stay in the intensive care unit. Design: Prospective cohort study. Setting: 16 intensive care units in Canada. Patients: 1014 mechanically ventilated patients. Measurements: Demographic and time-dependent variables reflecting illness severity, ventilation, nutrition, and drug exposure. Pneumonia was classified by using five methods: adjudication committee, bedside clinician's diagnosis, Centers for Disease Control and Prevention definition, Clinical Pulmonary Infection score, and positive culture from bronchoalveolar lavage or protected specimen brush. Results: 177 of 1014 patients (17.5%) developed ventilator-associated pneumonia 9.0 [+ or -] 5.9 days (median, 7 days [interquartile range, 5 to 10 days]) after admission to the intensive care unit. Although the cumulative risk increased over time, the daily hazard rate decreased after clay 5 (3.3% at day 5, 2.3% at day 10, and 1.3% at day 15). Independent predictors of ventilator-associated pneumonia in multivariable analysis were a primary admitting diagnosis of burns (risk ratio, 5.09 [95% Cl, 1.52 to 17.03]), trauma (risk ratio, 5.00 [Cl, 1.91 to 13.11]), central nervous system disease (risk ratio, 3.40 [Cl, 1.31 to 8.81]), respiratory disease (risk ratio, 2.79 [Cl, 1.04 to 7.51]), cardiac disease (risk ratio, 2.72 [Cl, 1.05 to 7.01]), mechanical ventilation in the previous 24 hours (risk ratio, 2.28 [Cl, 1.11 to 4.68]), witnessed aspiration (risk ratio, 3.25 [Cl, 1.62 to 6.50]), and paralytic agents (risk ratio, 1.57 [Cl, 1.03 to 2.39]). Exposure to antibiotics conferred protection (risk ratio, 0.37 [Cl, 0.27 to 0.51]). Independent risk factors were the same regardless of the pneumonia definition used. Conclusions: The daily risk for pneumonia decreases with increasing duration of stay in the intensive care unit. Witnessed aspiration and exposure to paralytic agents are potentially modifiable independent risk factors. Exposure to antibiotics was associated with low rates of early ventilator-associated pneumonia, but this effect attenuates over time., It may be possible to prevent ventilator-associated pneumonia in critically ill patients. Researchers analyzed the risk factors for ventilator-associated pneumonia in 1,014 patients on a ventilator, of whom 177 developed ventilator-associated pneumonia. The risk of developing ventilator-associated pneumonia was highest during the first few days after the patients were placed on the ventilator and subsequently decreased. Burns, trauma, diseases of the heart, lungs or central nervous system, exposure to paralytic drugs and aspiration were risk factors for developing ventilator-associated pneumonia.

Laser cutting of carbon fibre reinforced plastics (CFRP) has shown promising potential as an alternative to conventional manufacturing processes. Laser cutting has major benefits of contactless and therefore wear-free machining and high automation potential. The main challenge is to reduce the heat input into the material during the process. Excessive temperatures cause damage within the surrounding matrix material and could locally modify the structural properties of the CFRP. For industrial use it is necessary to be able to predict the resulting temperature fields. To gain knowledge of the temperature distribution during the process, a three-dimensional macroscopic finite element model is developed using ANSYS simulation software. Transient-thermal analyses are performed and the material removal process is implemented via the element-death technique. Simulations are run for a unidirectional composite structure and different cutting speeds. The resulting temperatures are compared to experimental data.

Laser transmission welding (LTW) is a known technique to join conventionally produced thermoplastic parts, e.g. injected molded parts. When using LTW for additively manufactured parts (usually prototypes, small series), this technique has to be evolved to overcome the difficulties in the part composition resulted in the additive manufacturing process itself.