Reconstructing historical trends of polycyclic aromatic hydrocarbon deposition in a remote area of Spain using herbarium moss material

Herbarium mosses from 1879-1881, 1973-1975 and 2006-2007 were used to investigate the historical changes of atmospheric deposition of polycyclic aromatic hydrocarbons (PAHs) at a remote site located in Northern Spain. Natural abundance of nitrogen and carbon isotopes was also measured in order to assess the evolution of emissions from anthropogenic sources. Nitrogen concentrations, 13C, 13N and PAH levels were significantly higher in 19th century samples with respect to the present century samples. Moreover, PAH distribution varied over the centuries, following a tendency of light PAH enrichment. The carbon, nitrogen and PAH levels measured in the mosses tally with the historic evolution of anthropogenic emissions in the area, mainly influenced by changes of economic activities, domestic heating and road traffic density. Mosses provided by herbaria seem to offer the possibility to study long-term temporal evolution of atmospheric PAH deposition

Ignition of solids exposed to transient irradiation

This work investigates the ignition of solid materials. Ignition is important for fire safety not only as the initiation of a fire event, but because it plays a critical role in all the phenomena of interest, such as fire growth and flame spread. Ignition is a multi-phase, complex phenomenon which requires the description of different, coupled, physical and chemical processes over a range of time and length scales. Consequently, most ignition models need to implement assumptions about the different mechanisms driving ignition to simplify the phenomena considered. Accordingly, the majority of ignition models neglect gas phase considerations and emphasise the heating and pyrolysis processes. There exist a breadth of models, of various levels of complexity, which seek to describe the pyrolysis processes of charring and non-charring materials. Within constrained experimental conditions, most of these models have performed well when compared to relevant experimental data. However, this thesis shows that the experimental data used to validate pyrolysis and ignition models does not reflect the entire range of heating scenarios. It is demonstrated that many scenarios of interest cannot be represented by assuming the irradiation is constant in time and, additionally, that a material exposed to a time dependent Incident Heat Flux will respond in a fundamentally different manner. This means that in previous studies, the effects of irradiation on the response of the solid have not been completely investigated. When a material is exposed to a constant Incident Heat Flux, the net or absorbed energy flux decreases with time. However, this is not the case when the material is exposed to time dependent Incident Heat Fluxes, since the net energy flux can increase with time. Given that the heating and the thermal degradation processes are driven by the energy absorption, these scenarios need to be investigated. It remains necessary to highlight that, even though the evolution of the absorbed energy flux differs, the fundamental process of interest (ignition) is still described by the attainment of a flammable mixture. This is important since it is necessary to predict the onset of ignition for solids that are exposed to thermal radiation during a fire. Data from flame spread and compartment fire experiments was compared and analysed to show that it is not possible to model the ignition of solids under these scenarios assuming a constant irradiation as the boundary condition for the ignition model. Hence, this thesis employs analytical, numerical and experimental investigations to address these limitations. Using analytical solutions, the thermal response of the inert solid was investigated. For constant irradiation, it is common for analytical ignition models (such as the classical ignition theory) to neglect the surface heat losses. It was shown that this is possible for a limited number of scenarios if a constant Incident Heat Flux is used but, it is not accurate for transient irradiation. A numerical model was used to investigate the assumption that surface heat losses are linearly dependent on temperature. This is implemented through the definition of a total heat transfer coefficient, hT. It was shown that this provides acceptable results, particularly for thermoplastic solids where the surface temperature is limited by the pyrolysis process. This is important since the use of hT eliminates the need to accurately describe the radiative properties of both the heat source and the sample. Piloted experiments with thermoplastic polymers and timber samples were completed. A novel approach to calculate the mass loss rate at ignition based on a linear regression for the time interval close to ignition was developed. It was found that for most materials, the mass loss rate at ignition is independent of the heating scenario. Consequently, the true ignition criterion remains unchanged from simple to complex heating. For PA6, large scatter reflected the influence of surface phenomena, particularly bubbling, on the processes driving ignition. A further study using in-depth temperature measurements showed that, even though this effect is large, it mainly affects the transport of gases to the pilot and not the heating of the solid. Gas phase measurements were completed to evaluate gas phase concentrations and investigate the flammability of the mixture. The data served to evaluate the delay between the onset of pyrolysis and the onset of ignition. Traditional ignition theory as well as the ignition temperature criterion are built on assuming this delay time is negligible. It was shown that this is not the case for samples exposed to transient irradiation. Finally, a new experimental methodology to investigate ignition was developed. The goal is to manipulate the material response. This is achieved by implementing an algorithm that monitors the thermal evolution of the solid and defines the irradiation instantaneously, depending on the difference between the desired response and the measured parameters. Conceptually, this represents an advancement in the use of transient irradiation, since the boundary condition becomes the means to manipulate the response of the solid and not the defining parameter of the study. It was shown that it is possible to manipulate the thermal degradation of the solid, but uncertainties associated to the measuring techniques limit the accuracy of the algorithm. This thesis advances the current knowledge on ignition of solids by: (i) investigating the implications of extending the analytical formulations of classical ignition theory for transient irradiation and showing that such an effort does not yield useful results for the advancement of ignition theory, (ii) analysing experimentally measured thermal radiation and showing the need to investigate the ignition of solids exposed to time-varying irradiation curves, (iii) addressing this need by creating a comprehensive data set of piloted ignition data of thermoplastic and charring solids exposed to transient irradiation, (iv) using these data to evaluate the applicability of common assumptions in ignition modelling, including the use of an ignition temperature criterion and (v) developing a novel experimental methodology that allows for the manipulation of the response of the material, which can be utilised to investigate the effect of surface and localised phenomena on the onset of ignition

Thickness dependent magnetic anisotropy of ultrathin LCMO epitaxial thin films

The magnetic properties of La0.7Ca0.3MnO3 (LCMO) manganite thin films were studied with magnetometry and ferromagnetic resonance as a function of film thickness. They maintain the colossal magnetoresistance behavior with a pronounced metal-insulator transition around 150-200 K, except for the very thinnest films studied (3 nm). Nevertheless, LCMO films as thin as 3 nm remain ferromagnetic, without a decrease in saturation magnetization, indicating an absence of dead-layers, although below approx. 6 nm the films remain insulating at low temperature. Magnetization hysteresis loops reveal that the magnetic easy axes lie in the plane of the film for thicknesses in the range of 4-15 nm. Ferromagnetic resonance studies confirm that the easy axes are in-plane, and find a biaxial symmetry in-plane with two, perpendicular easy axes. The directions of the easy axes with respect to the crystallographic directions of the cubic SrTiO3 substrate differ by 45 degrees in 4 nm and 15 nm thick LCMO films.Comment: Presented at Intermag conference (Madrid, 2008). Accepted for publication in IEEE Transactions on Magnetic

Immune checkpoint inhibitor-induced cholangitis—a three-case series

Over the last decade, immune checkpoint inhibitors (ICIs) have dramatically improved the systemic treatment of multiple solid tumour types. However, they can also induce inflammation in an extensive range of normal tissues types. The entity of ICI-induced cholangitis is rare and has not been widely described. We present three cases of ICI-induced cholangitis which illustrate the difficulties associated with its diagnosis and management. We also present associated radiological findings that include intrahepatic duct abnormalities consistent with sclerosing cholangitis-progressive worsening of intrahepatic duct dilatation and pericholecystic haziness suggesting inflammation characteristic of this rare, but severe, toxicity

Infection of liver sinusoidal endothelial cells with Muromegalovirus muridbeta1 involves binding to neuropilin-1 and is dynamin-dependent

Liver sinusoidal endothelial cells (LSEC) are scavenger cells with a remarkably high capacity for clearance of several blood-borne macromolecules and nanoparticles, including some viruses. Endocytosis in LSEC is mainly via the clathrin-coated pit mediated route, which is dynamin-dependent. LSEC can also be a site of infection and latency of betaherpesvirus, but mode of virus entry into these cells has not yet been described. In this study we have investigated the role of dynamin in the early stage of muromegalovirus muridbeta1 (MuHV-1, murid betaherpesvirus 1, murine cytomegalovirus) infection in mouse LSECs. LSEC cultures were freshly prepared from C57Bl/6JRj mouse liver. We first examined dose- and time-dependent effects of two dynamin-inhibitors, dynasore and MitMAB, on cell viability, morphology, and endocytosis of model ligands via different LSEC scavenger receptors to establish a protocol for dynamin-inhibition studies in these primary cells. LSECs were challenged with MuHV-1 (MOI 0.2) ± dynamin inhibitors for 1h, then without inhibitors and virus for 11h, and nuclear expression of MuHV-1 immediate early antigen (IE1) measured by immune fluorescence. MuHV-1 efficiently infected LSECs in vitro. Infection was significantly and independently inhibited by dynasore and MitMAB, which block dynamin function via different mechanisms, suggesting that initial steps of MuHV-1 infection is dynamin-dependent in LSECs. Infection was also reduced in the presence of monensin which inhibits acidification of endosomes. Furthermore, competitive binding studies with a neuropilin-1 antibody blocked LSEC infection. This suggests that MuHV-1 infection in mouse LSECs involves virus binding to neuropilin-1 and occurs via endocytosis

Towards few-shot reinforcement learning in particle accelerator control

This paper addresses the automation of particle accelerator control through reinforcement learning (RL). It highlights the potential to increase reliable performance, especially in light of new diagnostic tools and the increasingly complex variable schedules of specific accelerators. We focus on the physics simulation of the AWAKE electron line, an ideal platform for performing in-depth studies that allow a clear distinction between the problem and the performance of different algorithmic approaches for accurate analysis. The main challenges are the lack of realistic simulations and partially observable environments. We show how effective results can be achieved through meta-reinforcement learning, where an agent is trained to quickly adapt to specific real-world scenarios based on prior training in a simulated environment with variable unknowns. When suitable simulations are lacking or too costly, a model-based method using Gaussian processes is used for direct training in a few shots only. The work opens new avenues for implementing control automation in particle accelerators, significantly increasing their efficiency and adaptability

Dose- and time-dependent effects of triethylene glycol dimethacrylate on the proteome of human THP-1 monocytes

Triethylene glycol dimethacrylate (TEGDMA) is commonly used in polymer resin-based dental materials. This study investigated the molecular mechanisms of TEGDMA toxicity by identifying its time- and dose-dependent effects on the proteome of human THP-1 monocytes. The effects of different concentrations (0.07–5 mM) and exposure times (0–72 h) of TEGDMA on cell viability, proliferation, and morphology were determined using a real-time viability assay, automated cell counting, and electron microscopy, and laid the fundament for choice of exposure scenarios in the proteomic experiments. Solvents were not used, as TEGDMA is soluble in cell culture medium (determined by photon correlation spectroscopy). Cells were metabolically labeled [using the stable isotope labeled amino acids in cell culture (SILAC) strategy], and exposed to 0, 0.3 or 2.5 mM TEGDMA for 6 or 16 h before liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. Regulated proteins were analyzed in the STRING database. Cells exposed to 0.3 mM TEGDMA showed increased viability and time-dependent upregulation of proteins associated with stress/oxidative stress, autophagy, and cytoprotective functions. Cells exposed to 2.5 mM TEGDMA showed diminished viability and a protein expression profile associated with oxidative stress, DNA damage, mitochondrial dysfunction, and cell cycle inhibition. Altered expression of immune genes was observed in both groups. The study provides novel knowledge about TEGDMA toxicity at the proteomic level. Of note, even low doses of TEGDMA induced a substantial cellular response.publishedVersio

Changes in the proteome and secretome of rat liver sinusoidal endothelial cells during early primary culture and effects of dexamethasone

Introduction Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial cells involved in the elimination of modified plasma proteins and tissue turnover waste macromolecules from blood. LSECs also participate in liver immune responses. A challenge when studying LSEC biology is the rapid loss of the in vivo phenotype in culture. In this study, we have examined biological processes and pathways affected during early-stage primary culture of rat LSECs and checked for cell responses to the pro-inflammatory cytokine interleukin (IL)-1β and the anti-inflammatory drug dexamethasone. Methods LSECs from male Sprague Dawley rats were cultured on type I collagen in 5% oxygen atmosphere in DMEM with serum-free supplements for 2 and 24 h. Quantitative proteomics using tandem mass tag technology was used to examine proteins in cells and supernatants. Validation was done with qPCR, ELISA, multiplex immunoassay, and caspase 3/7 assay. Cell ultrastructure was examined by scanning electron microscopy, and scavenger function by quantitative endocytosis assays. Results LSECs cultured for 24 h showed a characteristic pro-inflammatory phenotype both in the presence and absence of IL-1β, with upregulation of cellular responses to cytokines and interferon-γ, cell-cell adhesion, and glycolysis, increased expression of fatty acid binding proteins (FABP4, FABP5), and downregulation of several membrane receptors (STAB1, STAB2, LYVE1, CLEC4G) and proteins in pyruvate metabolism, citric acid cycle, fatty acid elongation, amino acid metabolism, and oxidation-reduction processes. Dexamethasone inhibited apoptosis and improved LSEC viability in culture, repressed inflammatory and immune regulatory pathways and secretion of IL-1β and IL-6, and further upregulated FABP4 and FABP5 compared to time-matched controls. The LSEC porosity and endocytic activity were reduced at 24 h both with and without dexamethasone but the dexamethasone-treated cells showed a less stressed phenotype. Conclusion Rat LSECs become activated towards a pro-inflammatory phenotype during early culture. Dexamethasone represses LSEC activation, inhibits apoptosis, and improves cell viability

Active deep learning for nonlinear optics design of a vertical FFA accelerator

Vertical Fixed-Field Alternating Gradient (vFFA) accelerators exhibit particle orbits which move vertically during acceleration. This recently rediscovered circular accelerator type has several advantages over conventional ring accelerators, such as zero momentum compaction factor. At the same time, inherently non-planar orbits and a unique transverse coupling make controlling the beam dynamics a complex task. In general, betatron tune adjustment is crucial to avoid resonances, particularly when space charge effects are present. Due to highly nonlinear magnetic fields in the vFFA, it remains a challenging task to determine an optimal lattice design in terms of maximising the dynamic aperture. This contribution describes a deep learning based algorithm which strongly improves on regular grid scans and random search to find an optimal lattice: a surrogate model is built iteratively from simulations with varying lattice parameters to predict the dynamic aperture. The training of the model follows an active learning paradigm, which thus considerably reduces the number of samples needed from the computationally expensive simulations