116320 research outputs found
Sort by
Dynamic compression behaviour of innovative geopolymer-based lunar ultra-high performance concrete under ambient and cryogenic temperatures.
The rapid advancements in science and technology have accelerated efforts towards establishing sustainable extra-terrestrial habitats, with ultra-high performance concrete (UHPC) emerging as a promising candidate for constructing lunar bases due to its excellent mechanical and durability properties. This study employed a split Hopkinson pressure bar (SHPB) device to examine the dynamic compression behaviour of lunar regolith simulant-based UHPC (LUHPC), focusing on the effects of fibre type (steel and polyformaldehyde), fibre combinations (mono and hybrid), testing temperatures (20 °C ∼ -170 °C), and strain rates (50-200 s-1). The results revealed that cryogenic conditions markedly enhanced the static compressive strength (up to 20.6%) and elastic modulus (up to 13.7%) of steel fibre-reinforced LUHPC. Polyformaldehyde fibres yielded moderate improvements but attained a higher specific strength at -70 °C. Under dynamic loading, steel fibres exhibited pronounced strain-rate and temperature sensitivity, reaching a peak strength exceeding 280 MPa at -170 °C, achieving a dynamic increase factor from 1.137 to 1.630 as strain rates increased to 200 s-1, and improving impact energy absorption by up to 179.1%. In contrast, the polyformaldehyde fibres showed modest improvements and heightened brittleness at extreme temperatures. The failure patterns varied with strain rate and temperature, with steel and hybrid fibre reinforcements effectively mitigating fragmentation at sub-zero temperatures. The existing predictive models overestimated strain-rate effects at 20 °C, whereas the newly derived empirical equations accurately captured LUHPC behaviour under both ambient and cryogenic conditions. Future work will focus on evaluating the static and dynamic performance of LUHPC with lunar-derived reinforcement materials under extreme thermal cycles to further support its applications in extra-terrestrial infrastructure
From Lineage to Longevity: A Field Guide to the Key Players in Epigenetic Contribution to Offspring Health.
Epidemiological evidence firmly supports the rationale that chronic diseases demonstrate a heritability component. Notwithstanding recent advances in genomic technologies, in a significant proportion of heritable diseases, a candidate gene of interest that explains the entire picture of heritability remains to be identified. Further epidemiological evidence points to environmental risk factors contributing to chronic disease prevalence and severity. The Developmental Origins of Health and Disease hypothesis points to epigenetics as the mechanism modulating gene-environment interactions to elicit disease. Yet the primary effector of epigenetic inheritance remains to be elucidated. This review focuses on key contributors to mammalian development and the epigenetic changes measured therein, to draw attention towards potential molecular candidates underpinning chronic disease heritability
An immunoregulatory amphipathic peptide derived from Fasciola hepatica helminth defense molecule (FhHDM-1.C2) exhibits potent biotherapeutic activity in a murine model of multiple sclerosis.
The helminth defense molecules (HDM) are a family of immune regulatory peptides exclusively expressed by trematode worms. We have previously demonstrated that in vivo FhHDM-1, the archetypal member of the HDMs, regulated macrophage responses to inflammatory ligands, thereby ameliorating the progression of immune-mediated tissue damage in several murine models of inflammatory disease. Accordingly, we postulated that an understanding of the structure-function relationship of the HDMs would facilitate the identification of the minimal bioactive peptide, which would represent a more synthesizable, cost-effective, potent biotherapeutic. Thus, using a combination of bioinformatics, structural analyses, and cellular assays we discovered a 40 amino acid peptide derivative termed FhHDM-1.C2. This peptide contains a 12 amino acid motif at its N-terminus, which facilitates cellular interaction and uptake, and an amphipathic α-helix within the C-terminus, which is necessary for lysosomal vATPase inhibitory activity, with both regions linked by a short unstructured segment. The FhHDM-1.C2 peptide exhibits enhanced regulation of macrophage function, compared with the full-length FhHDM-1, and potent prevention of the progression of relapsing-remitting-experimental autoimmune encephalomyelitis (EAE) when administered prophylactically or therapeutically. The protective effect of FhHDM-1.C2 is not associated with global immune suppression, which places the HDMs peptides as an improved class of biotherapeutics for the treatment of inflammatory diseases. Comparing the HDMs from several zoonotic trematodes revealed a similar capacity for immune regulation. These important new advances into the structure-function relationship of the lead HDM peptide, FhHDM-1, encourage further prospecting and screening of the broader trematode family of peptides for the discovery of novel and potent immune-biotherapeutics
Varying Program Input to Assess Code Reading Skills
Explain-in-Plain-English (EiPE) questions are used by some researchers and educators to assess code reading skills. EiPE questions require students to briefly explain (in plain English) the purpose of a given piece of code, without restating what the code does line-by-line. The premise is that novices who can explain the purpose of a piece of code have higher code reading skills than those who can trace the code but cannot see its high-level purpose. However, using natural language in EiPE questions poses challenges. Students (especially those whose first language is not English) may struggle to convey their understanding of the code unambiguously. Also, grading responses written in natural language is time-consuming, requires the design of a rubric, and is difficult to automate. We propose a new code reading question type that addresses these issues with EiPE questions. Given a piece of code involving repetition (in the form of iteration or recursion), the student is asked to provide the output for a set of inputs, where the output for some of these inputs cannot be determined using code tracing alone and requires higher-level code comprehension. In empirical evaluations, using CS1 exams, think-Aloud interviews with students, and interviews with instructors, we found that assessments of code reading skills using the new question type are highly consistent with the assessments using EiPE questions, yet are more reliable. These results put forward the proposed question type as another way to assess high-level code reading skills without the issues associated with expressing in natural language or grading responses expressed in natural language
Bayesian adaptive trials for social policy
This article proposes Bayesian adaptive trials (BATs) as both an efficient method to conduct trials and a unifying framework for the evaluation of social policy interventions, addressing the limitations inherent in traditional methods, such as randomized controlled trials. Recognizing the crucial need for evidence-based approaches in public policy, the proposed approach aims to lower barriers to the adoption of evidence-based methods and to align evaluation processes more closely with the dynamic nature of policy cycles. BATs, grounded in decision theory, offer a dynamic, learning as we go approach, enabling the integration of diverse information types and facilitating a continuous, iterative process of policy evaluation. BATs' adaptive nature is particularly advantageous in policy settings, allowing for more timely and context-sensitive decisions. Moreover, BATs' ability to value potential future information sources positions it as an optimal strategy for sequential data acquisition during policy implementation. While acknowledging the assumptions and models intrinsic to BATs, such as prior distributions and likelihood functions, this article argues that these are advantageous for decision-makers in social policy, effectively merging the best features of various methodologies
Application of a Quantitative Real-Time PCR Assay for Early Detection of Salmonella enterica Serovar Enteritidis on Poultry Farms During an Outbreak in New South Wales, Australia (2018-2020).
Salmonella spp. are a significant cause of human foodborne illness globally, with ingestion of contaminated eggs a major vehicle for infection. Salmonella enterica serovar Enteritidis (S. Enteritidis, SE) is the serovar most linked to egg-related foodborne salmonellosis in most developed countries. Until 2018, the Australian egg industry was considered free of SE. This report documents the diagnostic testing performed on samples from egg layer farms across New South Wales (NSW), Australia, as part of a SE outbreak response between 2018 and 2020. Testing was undertaken following a cluster of cases of SE infection in humans traced to the consumption of eggs originating from a single contaminated poultry farm. Quantitative real-time polymerase chain reaction (qPCR) testing was used to screen environmental and animal samples (n = 2058) from 29 different properties identified through contact tracing. Confirmatory bacterial culture (n = 717) was performed on any SE qPCR-positive samples and a subset of qPCR-negative and qPCR-inconclusive samples. In total, 13/29 (45%) of egg layer farms were SE-positive by qPCR testing, with 12/13 (92%) of these farms confirmed SE-positive by bacterial culture and serotyping. Both environmental and animal samples produced SE-positive results, in particular surface swabs, boot covers, feces, and eggs. When qPCR testing and bacterial culture were performed side-by-side, qPCR testing to detect SE compared to bacterial culture had sensitivity of 100% (43/43) and specificity of 94.1% (238/253; 95% confidence interval[CI] 91.4-96.8). SE isolates obtained during the outbreak were predominantly phage type (PT)1b and PT12. Whole genome sequencing (WGS) of SE isolates from 9 of 12 culture-positive properties confirmed that they were all sequence type 11, Clade B, and derived from a single source. As a result of rapid qPCR detection of SE on contaminated farms, appropriate biosecurity responses were implemented, and NSW commercial layer farms were again considered SE-free in August 2020. This report highlights the utility of high-throughput molecular testing for SE in outbreak situations
Overcoming Barriers in Cancer Therapy with Oncolytic Adenoviruses: Engineering Strategies and Clinical Perspectives
Oncolytic adenoviruses (OADVs) have emerged as promising therapeutics for cancer treatment, offering tumour-selective replication and potent antitumor effects. These genetically engineered viruses infect and lyse cancer cells while simultaneously activating antitumor immunity. OADV can be engineered with therapeutic genes and tumour-specific promoters, further enhancing their specificity and efficacy. Various researchers have explored the use of OADV in cancer treatment, integrating direct oncolysis with immune activation, hence revealing promising therapeutic effects in preclinical studies. This review provides comprehensive insights into the mechanism of OADV engineering with tumor-specific promoters and therapeutic payloads, emphasizing advances in vector design that enhance specificity and efficacy. Key evidence from preclinical and clinical studies across lungs, pancreatic, hepatic, breast, renal, and brain cancers is highlighted, demonstrating the translational impact of OADV therapy. The synergistic potential of OADVs in combination regimens, including chemotherapy, immunotherapy, and gene therapy, is critically appraised. The review further examines central hurdles such as antiviral immunity, tumor microenvironment complexity, and delivery challenges, discussing innovative strategies like genetic modulation and nanoparticle carriers to overcome these barriers. Through integrating direct oncolysis and immune modulation, OADVs offer a multifaceted approach for the treatment of resistant and heterogeneous malignancies. The future of OADV therapy requires continued refinement in vector engineering, personalized delivery systems, and multidisciplinary research, positioning OADVs as pivotal agents for enhancing patient outcomes and quality of life in cancer care
Sliding-mode cement-based triboelectric nanogenerators in intelligent infrastructure for a new energy harvesting paradigm
Civil infrastructure with energy-harvesting capability is highly desirable because it can convert various ambient mechanical energy sources, such as vibrations, solar radiation, or thermal gradients into useable electrical energy. This study presented the first demonstration of a sliding-mode cement-based triboelectric nanogenerator (CBTENG), enabling energy harvesting directly from infrastructure surfaces. The results revealed the effects of sliding displacement, speed, applied force, surface scratches, and acid corrosion on the triboelectric performance. The triboelectric output is significantly influenced by sliding speed, followed by sliding displacement and applied load, achieving peak current and voltage outputs of approximately 0.6 μA and 7 V, respectively. Surface scratches, caused by pores, cracks, and protrusions on cement matrix surfaces, reduce effective contact area and degrade triboelectric performance. Exposure to sulphuric acid deteriorates the cement matrix, reducing triboelectric efficiency by increasing porosity, dissolving hydration products, and forming secondary phases such as gypsum and ettringite. Simple maintenance, such as re-polishing corroded cement matrix surfaces, can restore the CBTENGs’ triboelectric performance. Several practical application scenarios of the CBTENGs are demonstrated, including floor or wall surface cleaning and leaves sliding on pavements, highlighting the great potential of sliding-mode CBTENGs for enabling smart buildings and civil infrastructure solutions
Ultra-rapid start-up biological nitrification for nutrient recovery from source-separated urine.
Biological nitrification presents a sustainable approach for urine resource recovery. However, high salinity and ammonium concentrations in urine inhibit or even damage microorganisms, causing delayed start-up and unstable. This study first introduces betaine (150 mg·L⁻¹) to enhance urine nitrification by improving microbial salt tolerance and metabolic. Compared with the conventional typical process without betaine addition, introducing betaine shortened start-up time from 98 to 36 days, increased nitrification rate from 313.9 to 563.7 mg N·L⁻¹·d⁻¹, reduced nitrite accumulation, and improved resilience to water quality fluctuations. It also upregulated expression of nitrifying bacteria and related functional genes. Mechanistically, betaine stimulated extracellular polymeric substances production and regulated tryptophan and tyrosine metabolism genes, improving sludge aggregation and microbial stability. Betaine modulated genes for K⁺ uptake and Na⁺ extrusion to maintain initial osmotic balance. Subsequently, betaine promoted the uptake/synthesis of osmoprotectants (e.g., betaine and trehalose), upregulated electron transport chain genes and optimized energy metabolism. Notably, Betaine-induced multiple salt-tolerance mechanisms showed synergistic effects, with Rubrivivax sp., Paracoccus aminovorans, and Nitrobacter sp. identified as core salt-tolerant species. Even after betaine discontinuation (at day 40), high nitrification activity and salt tolerance persisted, though reduced amoABC gene abundance may constrain long-term performance. Furthermore, betaine-enhanced urine fertilizers demonstrated high nutrient recovery efficiency and reduced phytotoxicity, indicating strong potential for agricultural reuse. Overall, this study provides novel theoretical and practical insights, establishing betaine as an effective strategy for accelerating and stabilizing biological nitrification in high-salinity wastewater systems such as urine, with broad implications for sustainable treatment and resource recovery
Heliox: An advanced method for targeted drug delivery in respiratory airways
Background: Advancing treatment response in pulmonary diseases and health risk assessments requires a comprehensive understanding of the flow dynamics within the human respiratory tract. While current literature underscores high particle deposition in the Extrathoracic region during air inhalation, the significant impact of different inhalation gases such as heliox on particle transportation and deposition in the human lung airways remains an unexplored frontier. Methods: In the current study, a computational fluid dynamics-based discrete phase model is employed to analyze the flow of particles and two inhalation gases: air and heliox in a realistic tracheobronchial lung model. A realistic anatomical model of tracheobronchial airways, extending from the trachea to the fifth generation, is employed. Significant Findings: Lower pressure distribution and turbulent kinetic energy in the upper lung generations are reported during heliox inhalation. In case of breathing atmospheric air, comparatively higher deposition efficiencies of particles in the trachea and airway generations at multiple inlet flow rates have been found. In particular, the deposition percentages of inhaled particles from the trachea to generation 5 are 44.4 % for air inhalation and 37.12 % for heliox inhalation under resting condition. Knowledge of particle deposition hotspots in the tracheobronchial lung for air and heliox will lead to improved targeted drug delivery