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Hot Rocks Survey I: a possible shallow eclipse for LHS 1478 b
No full textM dwarf systems offer an opportunity to study terrestrial exoplanetary atmospheres due to their small size and cool temperatures. However, the extreme conditions imposed by these host stars raise question about whether their close-in rocky planets are able to retain any atmosphere at all. The Hot Rocks Survey aims to answer this question by targeting nine different M dwarf rocky planets. Of these, LHS 1478 b orbits an M3-type star, has an equilibrium temperature of T = 585 K and receives 21 times Earth's instellation. We observe two secondary eclipses using photometric imaging at 15m using the Mid-Infrared Instrument on the James Webb Space Telescope (JWST MIRI) to measure thermal emission from the dayside of the planet. We compare these values to atmospheric models to evaluate potential heat transport and CO absorption signatures. We find that a secondary eclipse depth of ppm at the expected time for a circular orbit is preferred over a null model at , a moderate detection, though dynamical models do favour a non-eccentric orbit for this planet. The second observation results in a non-detection due to significantly larger unexplained systematics. Based on the first observation alone, we can reject the null hypothesis of the dark (zero Bond albedo) no atmosphere bare rock model with a confidence level of 3.3, though for the significance decreases to . The tentative secondary eclipse depth is consistent with the majority of atmospheric scenarios we considered, spanning CO-rich atmospheres with surface pressures from 0.1 to 10 bar. However, we stress that the two observations from our program do not yield consistent results, and more observations are needed to verify our findings. The Hot Rocks Survey serves as a relevant primer for the Director's Discretionary Time (DDT) Rocky Worlds program
The mutation burden of narrowband ultraviolet B phototherapy (NB-UVB) in human skin; relevance to NB-UVB lifetime exposures and skin cancer surveillance
No full textBackground: ultraviolet radiation (UVR) is used as treatment for psoriasis and other skin diseases, but UVR can induce DNA mutations which may lead to skin cancer development. While skin cancers have been documented in patients treated with phototherapy, a limited number of epidemiological studies have examined skin cancer incidence in people receiving narrowband ultraviolet B (NB-UVB) treatment. Information on mutagenicity of NB-UVB would help inform about the potential skin cancer risks of this treatment.Objectives: to determine the mutation burden in human skin resulting from a NB-UVB treatment course and use this data to estimate the total number of NB-UVB exposures whereupon skin cancer surveillance should commence.Methods: biopsies of normal skin were obtained before and after a course of NB-UVB from 16 patients with psoriasis. Epidermal DNA was sequenced using nanorate sequencing (NanoSeq) to determine the mutational signatures and mutation burden from NB-UVB.Results: the NB-UVB treatment course increased the number of mutations in skin. Median increase in mutation burden was 0.55 substitutions/Mb in infrequently sun-exposed (buttock) and 0.89 substitutions/Mb in frequently sun-exposed (forearm) skin, P= 0.0001, n=14 patients and P=0.0098, n=10 patients respectively. Change in mutation burden due to NB-UVB ranged from 1.16 to 10.5-fold in buttock skin and 0.93 to 2.33-fold in forearm skin. This increase was mainly attributable to UVR-exposure linked mutational signatures, SBS7a and SBS7b, with some evidence that mutational burden related to genetic background of the individual. Modelling the change in mutation burden from NB-UVB relative to minimal erythema dose (MED) in comparison with average mutation burden in keratinocyte skin cancers allowed estimation of total lifetime exposures at which patients are likely to require skin cancer surveillance; for patients with MED equal to 2 standard erythemal doses (SEDs), skin cancer surveillance should be offered at 422, 165 and 58 NB-UVB exposures for those receiving low, typical, and high levels of sun exposure, respectively.Conclusions: a treatment course of NB-UVB causes UVR-induced mutations in normal skin of patients with psoriasis. Relating mutation burden to MED and sun behaviour habits allows estimation of when to commence skin cancer surveillance according to total lifetime NB-UVB exposures
The molecular basis of immunosuppression by soluble CD52 is defined by interactions of N-linked and O-linked glycans with HMGB1 box B
No full textHuman soluble CD52 is a short glycopeptide comprising 12 amino acids (GQNDTSQTSSPS) which functions as an immune regulator by sequestering the pro-inflammatory high mobility group box protein 1 (HMGB1) and suppressing immune responses. Recombinant CD52 has been shown to act as a broad anti-inflammatory agent, dampening both adaptive and innate immune responses. This short glycopeptide is heavily glycosylated, with a complex sialylated N-linked glycan at N3 and reported O-linked glycosylation possible on several serine and threonine residues. Previously we demonstrated that specific glycosylation features of CD52 are essential for its immunosuppressive function, with terminal α-2,3-linked sialic acids required for binding to the inhibitory SIGLEC-10 receptor leading to T-cell suppression. Using high resolution mass spectrometry, we have further characterized the N- and O-linked glycosylation of Expi293 recombinantly produced CD52 at a glycopeptide and released glycan level, accurately determining glycan heterogeneity of both N- and O-linked glycosylation, and localizing the site of O-glycosylation to T8 with high confidence and direct spectral evidence. This detailed knowledge of CD52 glycosylation informed the construction of a model system, which we analyzed by molecular dynamics simulations to understand the mechanism of recognition and define interactions between bioactive CD52, HMGB1 and the SIGLEC-10 receptor. Our results confirm the essential role of glycosylation, more specifically hyper-sialylation, in the function of CD52, and identify at the atomistic level specific interactions between CD52 glycans and the Box B domain of HMGB1 that determine recognition, and the stability of the CD52/HMGB1 complex. These insights will inform the development of synthetic CD52 as an immunotherapeutic agent.</p
Aircraft-level sensitivities of electric network component performance for (hybrid-) electric aircraft
No full textResearch on electric aviation energy networks tends to focus on either detailed studies of individual subsystems, or full-aircraft analyses that use highly simplified network (component) models. This paper aims to bridge that gap by performing sensitivity studies for various network parameters (HVDC cables, power converters, and motors), evaluating their effect on both the system and aircraft level. This is achieved through a combination of higher-fidelity explicit modeling of the network components and conceptual aircraft design software. This analysis is applied to a parallel-electric regional jet and a fully-electric commuter aircraft. The effects of parameter variations within literature-supported ranges are evaluated on component, network and aircraft mass for a given mission profile. Results show that the most influential parameters are the level of DC voltage in power transmission, the cable material, and the achievable mission-average efficiency of the electric motor. Individual component mass variations of over 100% can be observed within the investigated ranges; with variations of up to 10% of the aircraft mass for the parallel-electric jet. Aircraft mass variations for the fully-electric aircraft are up to 5%, with the required battery size due to component efficiency changes as driving factor. Results show that for large aircraft, the network is highly sensitive to power requirements. For small aircraft the network is more sensitive to mission energy requirements
Mechanistic evaluation of fatigue mitigation approaches to extend the fatigue lifetime of low-pressure steam turbine blades
No full textThe increasing use of renewable energy sources requires the energy output demand from fossil-fuel fired power plants to become increasingly sporadic. Thus, the Steam Turbines (ST) used in fossil fuel power plants are now subjected to a higher frequency of start-stop cycles and the use of ageing plant needs to be safely extended for the remaining proposed lifetime. ST blades are typically manufactured using martensitic stainless steel (MSS) due to the corrosion resistant properties and high achievable strength and fatigue resistance. This increase of loading frequency leads to premature end of predicted life compared to the original design, leading to more frequent maintenance cycles and potentially sooner than expected blade replacements. Also, due to an earlier than predicted decommissioning of power plants, the blades are too costly to replace hence an enhanced maintenance schedule was considered. The proposed maintenance process consists in grinding out of any observed fatigue short cracks in the fir tree notch root and shot peening. The process was evaluated by previous studies as potentially effective in increasing fatigue lifetimes in some MSS alloys, FV566 and FV448 namely. The focus of the current study is to evaluate the blade-to-blade variability effects of another MSS, FV520B, on shot-peening and its effects on a lifing model proposed to reduce the conservatism of fatigue lifetime prediction of ST blades. The current study focuses on FV520B, a stainless-steel alloy with a precipitation hardened martensitic microstructure. The delivered material was from ex-service blades, hence an initial analysis to verify the provided material matched expected FV520B features was conducted. Chemical and microstructural analysis confirmed the material to be FV520B. Mechanical and hardness testing was performed to analyse potential variability between blades. Results from microstructural and mechanical testing showed FV520B having scatter in fine microstructural features, mainly lath size, which correlated to hardness variations explaining scatter observed in both hardness and mechanical properties.Fatigue testing was performed to study the effect of the variation in properties and microstructural features on baseline fatigue properties and to compare FV520B with prior literature. Results showed consistency in stage II fatigue growth rates between FV520B samples from different blades, as well as consistency with FV566 performance. The threshold values from different blade of FV520B were found to be different and dependent on fine microstructural features like lath size. Crack tip opening displacement results indicated some effects from yield stress variation on fatigue crack opening effects4near threshold but in stage II the consistency between samples remained. Fracture surface observations between tested samples indicated a higher dependency of crack growth on laths at near threshold ΔK levels. The crack was observed to grow more tortuously at ΔKth levels progressively transitioning to smoother more transgranular growth as ΔK increased, the phenomena was observed consistently between blades.Short crack testing was performed on FV520B U-notched samples in 3-point bend under load control with two different surface conditions, polished and shot peened. The peening process was consistent with prior research on similar martensitic alloys from turbine blades. The residual compressive stresses after peening on FV520B were found to be consistent with the peening of FV566, indicating the peening process is equally effective on different blade alloys. Short fatigue crack growth testing was carried out at different strain ranges to evaluate the beneficial effects of peening, compared to polished unpeened samples, in terms of lifetimes and crack growth rates. Shot peening was found to increase fatigue lifetime in FV520B even at quite high local strain levels in a notch root under bending. Results also suggest FV520B was able to retain residual compressive stresses and have increased lifetimes at higher strain ranges when compared to FV566. Crack growth rate analysis in terms of ΔK showed strain range to have little effect on crack growth rate in polished samples, with growth rates being comparable to rates derived from long crack testing when characterised in terms of ΔK. The crack growth rate in peened samples showed a reduced growth rate at relatively low ΔK levels with some increase for higher ΔK compared to the unpeened case. Indicating residual compressive stresses retarded crack growth in the near-surface residual stress layer but had a decreased effect as they grow further into the depth. Paris law constants were also extrapolated from short crack tests and long crack tests.A mechanistic based lifetime prediction model originally proposed by Cunningham was applied with some modifications to FV520B. The model accounted for different phases of fatigue lifetimes, initiation, short crack growth and long crack growth. The number of cycles in each phase was either extrapolated from empirical data or iteratively calculated based on crack growth rate information gathered experimentally. The model was found to be conservative in lifetime prediction of fatigue in polished samples, but significantly overestimated lifetime for peened conditions. The conservative prediction for polished samples were attributed to the unaccounted-for arrested cracks and the assumptions on growth rate homogeneity. The overestimations in peened cases were likely due to the equally spaced initiation site assumption which strongly affects the expected coalescence phase, and given the greater number of initiation sites in the shot peened case this is likely to overestimate the onset of coalescence. Another factor to consider was the expected variations in crack growth rate through the residual compressive stress layer were not taken into account. Further data collection and analysis will be necessary to improve the model as well as highlighting the need to account for the spacing of initiation sites and the onset of coalescence as well as the varying crack growth rates in peened samples
Multispectral glasses and coatings for defence applications
No full textElectro-optical infrared (EO/IR) systems are integral to providing situational awareness and target detection in defence and various other applications. These systems employ both passive and active detection across a wide spectrum of wavelengths, ranging from ultraviolet (<0.4 µm) to long-wave infrared (>8 µm), thereby offering multiple detection methodologies even in conditions of low visibility. Presently, EO/IR systems utilise different optics that are specialised for transmitting specific wavelength bands. The introduction of a multispectral material capable of transmitting the entire wavelength range could potentially enable the use of a single optic, thus reducing the overall weight and size of the system. This enhancement could broaden the scope of EO/IR system applications, such as unmanned aerial vehicles typically constrained by weight limitations. Gallium lanthanum oxy-sulfide (GLS(O)) glasses emerge as a promising candidate for these applications, with 1 mm thick samples produced for this project transmitting from 0.53-9.6 µm. Oxide can be added to the base GLS(O) glass, but the base glass itself contains an amount of oxide (signified by the ‘(O)’ in the GLS(O) formula), this underlying oxide content was not, in general, quantified for this work. Other advantages include GLS(O) having a higher Vickers hardness (4.6 GPa) than ZnS (2.25 GPa), a contemporary material, while also being glass mouldable. Within this project, halide and nitride-based additives (CsCl, CsI, Si3N4, AlN) were incorporated into GLS(O) compositions to modify their optical and mechanical properties. Noteworthy findings include the addition of Si3N4 to 65Ga2S3:35La2S3:(O) glass, yielding a composition of 65Ga2S3:34.7La2S3:0.3Si3N4:(O), also containing oxide brought in by [O] contamination of Ga2S3 and La2S3 due to adventitious oxygen ingress during synthesis. This resulted in a blue shift from 530 nm to 500 nm for a 1 mm thick sample, accompanied by a minor blue shift of the multiphonon edge from 9.6 μm to 9.52 μm, and a slight increase in hardness from 4.67 to 4.75 GPa. Protective coatings were also deposited on GLS(O) via radio-frequency magnetron sputtering, including SixOyNz, AlxOyNz, and BxOyNz. In a notable example, a 1.8 μm-thick Al42O3N55 coating demonstrated a high hardness of 20.7 GPa, while maintaining transmittance (> 50 %) across the 0.375-10.6 μm range. This coating could be suitable for safeguarding GLS(O) on an EO/IR system against adverse defence and aerospace environments, including erosion from solid and liquid particles
Ten recommendations for scanning foraminifera by X-ray computed tomography
No full textMarine sediment cores uniquely provide a temporally high-resolution and well-preserved archive of foraminifera fossils, which are essential for understanding environmental, ecological, and evolutionary dynamics over geological timescales. Foraminifera preserve their entire ontogeny in their fossilized shells, and much of this life history remains hidden from view under a light microscope. X-ray microfocus computed tomography (μCT) imaging of individual foraminifera reveals internal chambers and pores that are traditionally hidden from view. Their volume, shape, and growth form foundations of oceanographic and environmental research.Here, we present a set of 10 recommendations for the preparation and scanning of individual fossilized foraminifera using glue-, gel-, and solvent-free methods. We focus on the primary X-ray parameters of μCT imaging that a researcher can optimize according to their throughput, signal-to-noise ratio, and cost requirements to generate three-dimensional (3D; volumetric) datasets. We showcase the effect of these parameters on image quality through repeated scans on a single planktonic foraminifer that varied the X-ray beam power and energy, detector binning, number of projections, and exposure times.In our case study, the highest beam power resulted in the widest contrast between the subject of interest and the background, allowing the easiest threshold-based segmentation of the object and aiding computers in automated feature extraction.The values of these parameters can exhibit significant variability across individuals, based on the specific needs of the study, the equipment used, and the unique attributes of the samples under consideration. Our motivation with this paper is to share our experience and offer a foundation for similar studies
Investigating a role for activity-regulated cytoskeleton-associated protein in the mast cell response to hydrogen peroxide and rhinovirus infection
No full textMast cells (MCs) are immune cells associated with mucosal surfaces where they are known as allergic and inflammatory effector cells. There is increased MC localisation to the airway epithelium of people with asthma, making them ideally located to respond to inhaled challenges that can trigger asthma exacerbations. A key example is rhinovirus (RV) infection, which is a major exacerbator of asthma. MCs are the only immune cell to support RV replication and release, and RV is the only respiratory virus known to replicate in MCs, but there is limited research showing the implications of this on RV-induced asthma exacerbations. Similarly, there is increased oxidative stress at the airway of people with asthma but the MC response to this oxidative stress is poorly understood. Activity-regulated cytoskeleton-associated protein (ARC) has a well-defined role in neuronal activity, but there is little research about a role for ARC outside of the brain. However, ARC is induced by oxidative stress and negatively regulates the heat shock response in HeLa cells, and ARC is associated with the neuronal and MC response to herpes simplex virus (HSV-1) and RV infection respectively. Therefore, ARC is a protein of interest in the investigation of the MC response to environmental challenges and I hypothesise that ARC plays a functional role in the MC response to both oxidative stress (H2O2 treatment) and RV infection.LAD2 MCs and HeLa cells were treated with H2O2 (2 mM, 1h treatment, 3h or 9h recovery respectively) or infected with RV16 (MOI 1) or a UV-irradiated control prior to quantification of ARC gene and protein expression by RT-qPCR and western blotting. Samples from H2O2-treated and RV16-infected LAD2 MCs were sequenced, and a transcriptomic analysis was used to explore the global response of MCs to these stimuli. Additionally, stable plasmid transfection was used to overexpress ARC in HeLa cells prior to RV infection or H2O2 exposure, using ARC-overexpressing HeLa cells as an initial model to investigate a role for ARC by transcriptomic analysis.To begin, conditions for H2O2 treatment and RV16 infection were optimised, and these data showed that ARC was induced by H2O2 treatment and RV16 infection of both LAD2 MCs and HeLa cells. Next, a HeLa cell line with stable ARC overexpression was produced and samples were generated for RNA-sequencing and subsequent investigation of a role for ARC in the cellular response to H2O2 and RV16. Transcriptomic data did not clearly indicate a role for ARC in the HeLa cells response to H2O2 treatment or RV16 infection, showing that future investigation of a role for ARC in MCs will require the use a MC model with altered ARC expression to gain further information. Transcriptomic analysis showed that H2O2 treatment upregulated the heat shock response and unfolded protein response in MCs, while ubiquitin proteasome system-mediated degradation was downregulated. This suggested that MCs favour protein refolding and autophagic degradation in their response to oxidative stress, contrasting the proteasomal degradation and upregulated the production of antioxidant systems that were associated with H2O2 treatment of HeLa cells. Transcriptomic data from RV16-infected MCs supported the hypothesis that RV is released from MCs via a non-lytic mechanism, in which RV assembly and maturation occurs at Golgi apparatus-derived membranes. Meanwhile, there was no enrichment of vesicle or Golgi apparatus-related pathways in RV16-infected HeLa cells where RV16 release is thought to occur by cell lysis. During this project, I generated datasets which provided transcriptomic profiles of the MC response to both H2O2 treatment and RV16 infection. These give novel information about changes in mediator expression, metabolic pathways and general pathways associated with MC responses that can be further investigated in the future to understand how MCs contribute to oxidative stress- or RV16-induced inflammation in the asthmatic airway. Although these data did not elucidate a role for ARC in the cellular response to stimuli, a set of genes were identified that may be expressed downstream of ARC which could link to the role of ARC in non-neuronal cells. <br/
Comparison results of range-based quantities in the classical risk models
No full textIn this paper, we investigate the range-based risk quantities in classical risk models. Specifically, we present some comparison results with respect to the stochastic ordering. We also propose some range-based VaR-type risk measures and study their properties, providing insights into their practical applications and implications for risk management.</p
A call for doubling the diagnostic rate of at-risk metabolic dysfunction-associated steatohepatitis
No full textMetabolic dysfunction-associated steatohepatitis (MASH) is an increasingly important contributor to morbidity and mortality. Little emphasis has been placed on its timely diagnosis and interventions to prevent adverse disease outcomes. The principal determinant of MASH outcomes is the liver fibrosis stage. The prevalence of MASH is higher among people living with obesity and/or type 2 diabetes, with MASH with moderate to advanced fibrosis affecting one in six adults. Delivering a paradigm shift in MASH diagnosis in the four countries studied will require an expansion of community-based diagnostic capability that will also foster prevention efforts and provide opportunities for treatment and care
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