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Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.
Full text linkCOVID-19 has resulted in over 777 million confirmed cases and more than 7 million deaths globally. While vaccination offers protection for individuals with a functional immune system, immunocompromised populations will not generate sufficient responses, highlighting the critical need for new antiviral treatments. Here we evaluated four highly conserved anti-COVID siRNAs targeting the ORF1a-Nsp1, Membrane, and Nucleocapsid regions by identifying their antiviral efficacy in vitro and investigated the direct delivery of naked siRNAs to the respiratory tract of mice via intranasal instillation to provide proof-of-concept evidence of their in vivo antiviral activity. Dose-response analysis of siRNAs revealed a range of IC50 0.02 nM to 0.9 nM. Intranasal administration of naked anti-COVID siRNA-18 in a K18-hACE2 transgenic SARS-CoV-2 mouse model was capable of reducing viral mRNA levels and disease severity. While anti-COVID siRNA-30 induced modest interferon-stimulated gene expression in vitro and immune cell infiltration in vivo, these effects were markedly reduced by 2'-O-methyl-AS456 chemical modification, which preserved antiviral efficacy against SARS-CoV-2 while minimizing off-target immune activation. These results demonstrate the feasibility of direct respiratory siRNA administration for in vivo viral suppression and highlight the benefit of using conserved target sequences and chemical modification to enhance therapeutic safety and efficacy
Unplanned Interiors as Care
No full textWomen’s refuges rely on adaptable, unplanned interiors as a critical component of trauma-informed care for women and children escaping domestic and family violence. This essay examines the spatial dynamics of planned and unplanned interiors through a feminist lens, conceptualising the refuge not as a fixed design but as a living system co-created through acts of maintenance, adjustment, and relational care. By focusing on the spatial interior and challenging assumptions about design quality and spatial order, the study positions design as an everyday, collaborative process shaped by workers and residents. Drawing on feminist design theory, trauma-informed care, and feminist care ethics, the essay argues for greater recognition of workers’ spatial practices and the informal, often improvised transformations that respond to diverse cultural, emotional, and familial needs. Based on site visits to twenty-six refuges throughout New South Wales, Australia, and interviews with forty-eight workers, the research identifies strategies that support safety and recovery, including creating zones for retreat, softening institutional features, and introducing familiar domestic cues. Findings highlight the significance of unplanned interiors in enabling flexibility and choice, resisting prescriptive notions of safety, and accommodating evolving needs. The essay positions trauma-informed interior design as an adaptive, collaborative process that centres care, agency, and lived experience within spatial practice
Toward Plug-and-Play Asset Management: Spot-Based Visual Surveying in Untagged Industrial Spaces
No full textNeighborhood Environment Attributes are Associated With Disparities in Walking by Exercise Preference.
No full textBACKGROUND: We aimed to investigate the relationship between neighborhood environments and disparities in walking based on exercise preference. METHODS: This nationwide cross-sectional study included 40,423 Japanese adults (aged 20-98 y, male 50.5%) who responded to a web-based survey with stratified sampling in 2021. Neighborhood environment characteristics were assessed using the Japanese version of the International Physical Activity Questionnaire Environmental Module. Weekly time spent walking for leisure and utilitarian purposes was assessed by questionnaire. The Slope Index of Inequality was calculated using a multivariable logistic regression model and was used to examine the relationship between neighborhood environments and walking disparities by exercise preference. RESULTS: Almost half (45.2%) of the participants did not like exercise. Median total walking time was 180 minutes per week (utilitarian walking: 90 min/wk, leisure walking: 45 min/wk) for those who liked exercise and 100 minutes per week (utilitarian walking: 60 min/wk, leisure walking: 0 min/wk) for those who disliked it. Except for safety from traffic and crime, all walkability attributes were positively associated with walking, regardless of exercise preference. The association between access to shops and public transport and utilitarian walking was stronger among participants who disliked exercise, contributing to a disparity in walking by exercise preference. On the other hand, the presence of recreational facilities was more strongly associated with leisure walking among those who liked exercise, related to a greater disparity in leisure walking by exercise preference. CONCLUSIONS: Activity-friendly neighborhood environments may be associated with a smaller disparity in utilitarian walking between those who liked or disliked exercise
Osteoprotegerin Is Elevated in Pulmonary Fibrosis and Associates with Idiopathic Pulmonary Fibrosis Progression: A Pilot Study.
No full textINTRODUCTION: Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-κB ligand (RANKL), serves as a biomarker for liver fibrosis severity. Our recent findings show OPG production in fibrotic lung tissue, though its specific cellular source and role in pulmonary fibrosis are unknown. We hypothesized that OPG is produced by fibroblasts and serves as a marker for pulmonary fibrosis progression. METHODS: We examined OPG expression in human and mouse control and fibrotic lung tissue and used primary human lung fibroblasts and murine precision-cut lung slices to study OPG production. Serum from idiopathic pulmonary fibrosis (IPF) patients and controls was analyzed to investigate correlations between OPG levels and disease status, as measured by lung function. RESULTS: OPG-protein levels were significantly higher in murine and human fibrotic lung tissue compared to control. OPG-protein levels in fibrotic mouse lung tissue correlated positively with collagen deposition. OPG-mRNA and protein production increased in mouse lung slices upon TGFβ stimulation. Isolated lung fibroblasts from IPF patients produced more OPG-protein than controls. Serum OPG levels in IPF patients negatively correlated with diffusing capacity to carbon monoxide. Serum OPG levels above 1,243 pg/mL were linked to disease progression in IPF patients. CONCLUSION: OPG is produced by fibroblasts in lung tissue, associates with fibrosis, and may be a potential prognostic biomarker for IPF progression. Validation in a larger cohort is necessary to further explore OPG's role in pulmonary fibrosis and its potential for assessing fibrotic lung disease prognosis in individual patients
Chloride-Induced Corrosion Performance of ASR-Contaminated Concrete: Coupled Analysis Using Resistance Variation and NT Build 492 Method
Full text linkThis study examines how the Alkali–Silica Reaction (ASR) modifies chloride transport and chloride-induced corrosion (CIC) in reinforced concrete beams. Non-reactive and reactive concrete beams were cast with blue metal and dacite aggregates and subjected to a two-stage exposure: (i) alkali-rich immersion at 38 °C to induce ASR, and (ii) impressed-current CIC and NT BUILD 492 chloride migration testing. Microstructural changes were characterized using SEM–EDS and TGA. The reactive specimens developed extensive surface cracking, but after one year of ASR exposure, exhibited 47–53% lower non-steady-state migration coefficients (Dnssm: 7.03–8.02 × 10−12 m2/s) than the non-reactive beam (15.09 × 10−12 m2/s). After two years, Dnssm was reduced by approximately 37–56% (4.78–6.93 vs. 10.92 × 10−12 m2/s). Crack mapping confirmed higher crack density and width in reactive beams, while SEM–EDS and TGA evidenced Ca depletion and the formation of C–(N,K)–S–H gels, which fill cracks and refine the pore structure. Electrical resistance monitoring showed earlier corrosion initiation in ASR-damaged beams but less pronounced resistance loss during the propagation phase. Overall, the results indicate that ASR can initially accelerate corrosion initiation through microcracking and reduced resistivity, but long-term gel deposition can partially seal transport paths and lower chloride migration under the specific conditions of this study.</jats:p
Using modern measurement theory to test construct validity
No full textChapter 4 demonstrated the modified Delphi process of consensus formation that took place in Phase 2 of the study, which identified items that were deemed by expert participants to be essential, very desirable, somewhat desirable, or not relevant as an indicator of teacher quality in the current educational context. During a Delphi process an agreed cut score is established to use as the threshold for confidence levels between rounds as a kind of statistical threshold, which indicates the level of similarity chosen for indicator inclusion. This chapter describes how Rasch and Classical Test theories have been used to interrogate the findings emerging from the two iterative rounds of survey to measure the fit of indicators to the Teacher Quality Construct. Indicators that met the chosen level of agreement were retained in the second round of the survey used to support selection of indicators of teacher quality deemed essential for early career teachers. As a result of the synthesis of data collected in the first round, 7 indicators were deleted resulting in 30 indicators being used in round 2. The analysis of the results from round 2 using both Rasch and Classical Test Theories, provides further evidence to support the argument for the validity of the teacher quality construct
Application of spectral Galerkin method for consolidation analysis of multilayered soils
Full text linkPredicting sub-continental fuel hazard under future climate and rising atmospheric CO2 concentration
Full text linkBushfire fuel hazard is determined by the type, amount, density and three-dimensional distribution of plant biomass and litter. The fuel hazard represents a biological control on fire danger and may change in the future with plant growth patterns. Rising atmospheric CO2 concentration (Ca) stimulates plant productivity (‘fertilisation effect’) but also alters climate, leading to a ‘climatic effect’. Both effects have impacts on future vegetation and thus fuel hazard. Quantifying these effects is an important component of predicting future fire regimes and evaluating fire management options. Here, we combined a machine learning algorithm that incorporates the power of large fine spatial resolution (i.e. 90 m) datasets with a novel optimality model that accounts for the climatic and fertilisation effects on vegetation cover. We demonstrated the usefulness and practicality of this framework by predicting fuel hazard across the state of Victoria in Australia. We fitted and evaluated the models with long-term (i.e. 20 years), ground-based fuel observations. The models achieved strong agreement with observations across the fuel hazard range (accuracy >65%). We found fuel hazard increased more in dry environments due to future climate and Ca. The contribution of the ‘fertilisation effect’ to future fuel hazard varied spatially by up to 12%. The predictions of future fuel hazard are directly useful to inform fire mitigation policies and as a reference for climate model projections to account for fire impacts. Synthesis and applications: Climate change and rising Ca have profound impacts on vegetation and thus fuel load. Operational fire management and future fire risk forecasts will benefit from our realistic fuel load prediction framework that incorporates plant responses and fine soil and terrain attributes
Status of Micro/Nano-Plastic (MNP) Pollution in the Aquatic System
No full textOver the last few decades, due to the tremendous rise in plastic production, the contamination of micro/nano plastics (MNPs) has become widespread in aquatic systems around the globe. MNPs are tiny plastic particles with sizes < 5 mm/<100 nm. They are ubiquitous pollutants and can arrive in the aquatic environment from different sources. They persist in the environment for a long time. They can act as carriers for many organic pollutants, heavy metals, and pathogenic bacteria. They are an emerging environmental issue, and the scientific community is very much concerned about this issue. Raman spectroscopy, Fourier transform infrared spectroscopy, pyrolysis gas-chromatography mass-spectrometry, scanning electron microscopy, etc. are advanced instrumental techniques used to analyze MNPs. This chapter focuses on the occurrence, sources, and impact of MNP on the health of aquatic organisms. This chapter also describes the identification and detection techniques of MNPs and suggests some recommendations for the elimination of MNPs from the environment
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