Effects of wind-driven current and thermal dynamics in a temperate monomictic reservoir: Implications for manganese transport and treatment in water supply systems.

Increasing manganese (Mn) concentrations in source water contribute to aesthetic and health-related concerns in drinking water. The challenges with Mn in drinking water primarily arise from elevated Mn concentrations in the water supply reservoir, with the inefficacy of Mn treatment largely attributed to fluctuating Mn levels in the water source. A three-dimensional Mn cycle model in a temperate monomictic reservoir, Tarago Reservoir, and a decision support system reflecting Mn variations in the local water treatment plant have been established in previous research. This study aimed to examine Mn variations from the reservoir to raw water and treated water under the influence of wind conditions during different stages of thermal structure, and discover valuable recommendations for Mn treatment in the local water supply system. We crafted 12 scenarios to scrutinize the impact of varying intensities of offshore and onshore winds on hydrodynamic processes and Mn transport during strong thermal stratification, weak thermal stratification, and turnover. The scenario analysis revealed that, during the gradual weakening of thermal stratification, offshore wind induced a substantial amount of Mn to the upper layers near the water intake point. Conversely, onshore wind hindered the upward transport of Mn. The simulated Mn in the raw water under the 12 scenarios indicated that the timing of turnover in the Tarago Reservoir is the primary concern for Mn treatment in the water treatment plant. Additionally, close attention should be given to the frequency and intensity of offshore winds during the weakening of thermal stratification.

A Simple and Scalable Zebrafish Model of Sonic Hedgehog Medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor in children and is stratified into three major subgroups. The Sonic hedgehog (SHH) subgroup represents ~30% of all MB cases and has significant survival disparity depending upon TP53 status. Here, we describe the first zebrafish model of SHH MB using CRISPR to mutate ptch1, the primary genetic driver in human SHH MB. These tumors rapidly arise adjacent to the valvula cerebelli and resemble human SHH MB by histology and comparative genomics. In addition, ptch1-deficient MB tumors with loss of tp53 have aggressive tumor histology and significantly worse survival outcomes, comparable to human patients. The simplicity and scalability of the ptch1 MB model makes it highly amenable to CRISPR-based genome editing screens to identify genes required for SHH MB tumor formation in vivo, and here we identify the grk3 kinase as one such target.

Catching nano: Evaluating the fate and behaviour of nano-TiO2 in swimming pools through dynamic simulation modelling.

Engineered titanium dioxide nanoparticles (nano-TiO2) in consumer products such as sunscreens widely used by swimmers in aquatic settings have raised concerns about their potential adverse impact on ecosystems and human health due to their small size and unique physicochemical properties. Therefore, this research paper aims to investigate the fate and behaviour of nano-TiO2 from sunscreens in swimming pools using System Dynamics Modelling. The study developed a dynamic simulation model that considers various factors, including weather conditions, sunscreen and pool usage behaviour, filtration efficacy, pool maintenance, water chemistry, pool chemicals, and TiO2 concentration levels, which can affect exposure levels for different scenarios. The study considered non-linear interdependent relationships, feedback structures, and temporal changes and dealt with parameter uncertainties through Monte Carlo analyses. The results reveal that the regular use of sunscreen leads to nano-TiO2 concentrations ranging from 0.001 to 0.05 mg/L within a year, reflecting seasonal and pool usage variations. The study also found that changes in the weight percentage of TiO2 in the sunscreen formulation and the filtration duration per day are the most sensitive factors affecting TiO2 concentrations. Scenario analyses exploring different nano-TiO2 removal strategies suggested that one daily turnover is necessary for sufficient removal. Regular manual pool maintenance and monthly use of a pool clarifier are recommended for enhanced and accelerated removal without substantial additional costs. The study is novel in its integrated approach, combining empirical work with dynamic simulations, resulting in a novel approach to model the environmental fate and behaviour of nano-TiO2. The study makes important methodological contributions to the field and has initiated an interdisciplinary collaboration to create more accurate models. This study is of great significance as it presents a pioneering analysis of the impact of sunscreen properties, user behaviour, and environmental stressors on the fate and behaviour of nano-TiO2 in swimming pools.

GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade.

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. Here we show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous Hh pathway activation in the primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction. Reconstitution studies reveal that GRK2 phosphorylation enables active SMO to bind PKA-C directly. Lastly, the SMO-GRK2-PKA pathway underlies Hh signal transduction in a range of cellular and in vivo models. Thus, GRK2 phosphorylation of ciliary SMO, and the ensuing PKA-C binding and inactivation, are critical initiating events for the intracellular steps in Hh signaling. More broadly, our study suggests an expanded role for GRKs in enabling direct GPCR interactions with diverse intracellular effectors.

Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish.

Leptomeningeal disease occurs when cancer cells migrate into the ventricles of the brain and spinal cord and then colonize the meninges of the central nervous system. The triple-negative subtype of breast cancer often progresses toward leptomeningeal disease and has a poor prognosis because of limited treatment options. This is due, in part, to a lack of animal models with which to study leptomeningeal disease. Here, we developed a translucent zebrafish casper (roy-/-; nacre-/-) xenograft model of leptomeningeal disease in which fluorescent labeled MDA-MB-231 human triple-negative breast cancer cells are microinjected into the ventricles of zebrafish embryos and then tracked and measured using fluorescent microscopy and multimodal plate reader technology. We then used these techniques to measure tumor area, cell proliferation, and cell death in samples treated with the breast cancer drug doxorubicin and a vehicle control. We monitored MDA-MB-231 cell localization and tumor area, and showed that samples treated with doxorubicin exhibited decreased tumor area and proliferation and increased apoptosis compared to control samples.

Towards nutrient neutrality: A review of agricultural runoff mitigation strategies and the development of a decision-making framework.

Nutrient runoff from agriculture practices poses a significant risk to waterway health and can have long-lasting and complex implications for the environment, ecosystems, and the human population. Consequently, a systematic quantitative literature review (SQLR) was conducted to identify different nutrient runoff mitigation strategies (NRMS) that are currently used globally to prevent or remediate environmental damage from excessive agricultural fertilisation. Empirical data on the outcomes from various NRMS from the reviewed studies were used to evaluate the strategies based on environmental benefit, implementation cost, and practicality perspectives. An overall assessment of the feasibility of NRMS was determined, and a macro-level assessment of the reported barriers preventing the widespread implementation of NRMS was provided. Identified research gaps and issues included a dearth of literature covering nutrient runoff mitigation, scepticism from agricultural landowners to voluntarily adopt policy without substantial incentives, and a general lack of cost/benefit analyses, including an understanding of the uncertainty associated with NRMS that can inform decision-makers about effective and efficient strategies for different site situations. Synthesis of SQLR data facilitated the development of a comprehensive nutrient runoff decision-making framework which addresses present limitations and provides site-specific NRMS recommendations for policymakers to implement.

Investigating the characteristics of residential end uses of water: A worldwide review.

A detailed characterization of residential water consumption is essential for ensuring urban water systems' capability to cope with changing water resources availability and water demands induced by growing population, urbanization, and climate change. Several studies have been conducted in the last decades to investigate the characteristics of residential water consumption with data at a sufficiently fine temporal resolution for grasping individual end uses of water. In this paper, we systematically review 114 studies to provide a comprehensive overview of the state-of-the-art research about water consumption at the end-use level. Specifically, we contribute with: (1) an in-depth discussion of the most relevant findings of each study, highlighting which water end-use characteristics were so far prioritized for investigation in different case studies and water demand modelling and management studies from around the world; and (2) a multi-level analysis to qualitatively and quantitatively compare the most common results available in the literature, i.e. daily per capita end-use water consumption, end-use parameter average values and statistical distributions, end-use daily profiles, end-use determinants, and considerations about efficiency and diffusion of water-saving end uses. Our findings can support water utilities, consumers, and researchers (1) in understanding which key aspects of water end uses were primarily investigated in the last decades; and (2) in exploring their main features considering different geographical, cultural, and socio-economic regions of the world.

The scaffolding function of LSD1/KDM1A reinforces a negative feedback loop to repress stem cell gene expression during primitive hematopoiesis.

Lsd1/Kdm1a functions both as a histone demethylase enzyme and as a scaffold for assembling chromatin modifier and transcription factor complexes to regulate gene expression. The relative contributions of Lsd1's demethylase and scaffolding functions during embryogenesis are not known. Here, we analyze two independent zebrafish lsd1/kdm1a mutant lines and show Lsd1 is required to repress primitive hematopoietic stem cell gene expression. Lsd1 rescue constructs containing point mutations that selectively abrogate its demethylase or scaffolding capacity demonstrate the scaffolding function of Lsd1, not its demethylase activity, is required for repression of gene expression in vivo. Lsd1's SNAG-binding domain mediates its scaffolding function and reinforces a negative feedback loop to repress the expression of SNAG-domain-containing genes during embryogenesis, including gfi1 and snai1/2. Our findings reveal a model in which the SNAG-binding and scaffolding function of Lsd1, and its associated negative feedback loop, provide transient and reversible regulation of gene expression during hematopoietic development.

Integrated Environmental Assessment and Management.

Increasing demand for metals used in clean energy technologies, including electric vehicles, has led to an increased demand in certain metals such as Ni, Co, and Mn. This demand has in turn led to an expanding interest in deep-seabed mining (DSM) of polymetallic nodule deposits that contain these exact metals. The main concerns about DSM relate to the incomplete information available about the environmental risks associated with seabed mineral extraction. Key uncertainties need to be systematically addressed to refine environmental impact predictions and establish effective mitigation measures. Adaptive management is an iterative process for reducing the uncertainty that can be applied by both mining companies and regulatory bodies. This Special Series paper reviews the key opportunities and challenges to operationalizing adaptive management in DSM projects and highlights the need for a framework to move from theory to practice. The discussion proposes a systems approach to adaptive management, which could help to guide the environmental management of deep-sea mineral extraction. Integr Environ Assess Manag 2022;18:674-681. © 2021 SETAC.

Application of Eye Tracking Technology in Aviation, Maritime, and Construction Industries: A Systematic Review.

Most accidents in the aviation, maritime, and construction industries are caused by human error, which can be traced back to impaired mental performance and attention failure. In 1596, Du Laurens, a French anatomist and medical scientist, said that the eyes are the windows of the mind. Eye tracking research dates back almost 150 years and it has been widely used in different fields for several purposes. Overall, eye tracking technologies provide the means to capture in real time a variety of eye movements that reflect different human cognitive, emotional, and physiological states, which can be used to gain a wider understanding of the human mind in different scenarios. This systematic literature review explored the different applications of eye tracking research in three high-risk industries, namely aviation, maritime, and construction. The results of this research uncovered the demographic distribution and applications of eye tracking research, as well as the different technologies that have been integrated to study the visual, cognitive, and attentional aspects of human mental performance. Moreover, different research gaps and potential future research directions were highlighted in relation to the usage of additional technologies to support, validate, and enhance eye tracking research to better understand human mental performance.

Taxonomy and model for valuing the contribution of digital water meters to sustainability objectives.

Water security is an issue across the world as communities face ageing infrastructure, population increases and climate change. The application of digital water metering (DWM) to properties has had a demonstrable impact on water savings at the property and network levels, on efficiencies within water utilities, as well as on improvements to customer satisfaction scores. Gathering and processing near-real-time water usage data is very important for both end-users and utilities, as well as demand and supply management planning. The potential contribution of DWM to the three pillars of water sustainability (environmental, economic development and social equity) is often overlooked. In Australia and other jurisdictions water utilities are facing up to the challenge of climate change. However, business cases promoting DWM are often unsuccessful because the benefit side falls short of the cost side. This study sought to identify possible DWM benefits not previously considered through an extensive review of academic and industry literature, and then to view those benefits through the lens of sustainability. The 77 identified benefits of DWM were catalogued and a taxonomy was created. The study elicited the opinions of experts, before quantifying them, thus identifying two distinct contexts of benefit value; subsequently, it surveyed the views of customers and developed a stochastic model of benefit value. The model, named DWM360, was applied to the project data of a large metropolitan water utility in Australia to model their DWM proposal for cost savings, contribution to sustainability and uplift in customer satisfaction. This paper presents a novel focus on how the benefits of DWM assist water sustainability. It considers differing social norms that impact consumer acceptance of changes in metering and water charges. The study will be of interest to researchers as well as practitioners looking to identify sustainability aspects of DWM.

Dynamic modelling of Australian rooftop solar photovoltaic product stewardship transition.

As rooftop solar photovoltaic (PV) adoption in Australia is exponentially growing in the past decade, there is a need to promote effective product stewardship for PV panels reaching their end-of-life (EoL). This paper presents the development of a System Dynamics (SD) model for managing EoL rooftop PV panels based on the circular economy concept. Four stages of the SD modelling process include problem scoping and variable identification, model conceptualisation, SD model development, and scenario analysis. Stakeholder engagement is central to this research as the system under study is underpinned by high uncertainties and limited data availability. Four socio-technical transition pathways examined in this study include market-driven growth, conservative development, shared responsibility, and disruptive change. The simulation results indicated an improvement of collection and recovery performance when a stringent product stewardship scheme is enabled and improvement of installers' participation in the collection program. This study argued that a system of shared responsibility will be capable of balancing techno-economic motivations of stakeholders across the supply chain to participate in the recovery scheme, while being less disruptive to PV adoption. Under this scenario, a gradual change in regulatory requirements (e.g. recovery target and material recovery rate requirements) is introduced to allow a period of industry and market development.

Light-induced fluorescence quenching leads to errors in sensor measurements of phytoplankton chlorophyll and phycocyanin.

Optical sensors for fluorescence of chlorophyll a (f-Chl a) and phycocyanin (f-PC) are increasingly used as a proxy for biomass of algae and cyanobacteria, respectively. They provide measurements at high-frequency and modest cost. These sensors require site-specific calibration due to a range of interferences. Light intensity affects the fluorescence yield of cyanobacteria and algae through light harvesting regulation mechanisms, but is often neglected as a potential source of error for in-situ f-Chl a and f-PC measurements. We hypothesised that diel light variations would induce significant f-Chl a and f-PC suppression when compared to dark periods. We tested this hypothesis in a controlled experiment using three commercial fluorescence probes which continuously measured f-Chl a and f-PC from a culture of the cyanobacterium Dolichospermum variabilis as well as f-Chl a from a culture of the green alga Ankistrodesmus gracilis in a simulated natural light regime. Under light, all devices showed a significant (p<0.01) suppression of f-Chl a and f-PC compared to measurements in the dark. f-Chl a decreased by up to 79% and f-PC by up to 59% at maximum irradiance compared to dark-adapted periods. Suppression levels were higher during the second phase of the diel cycle (declining light), indicating that quenching is dependent on previous light exposure. Diel variations in light intensity must be considered as a significant source of bias for fluorescence probes used for algal monitoring. This is of high relevance as most monitoring activities take place during daytime and hence f-Chl a and f-PC are likely to be systematically underestimated under bright conditions. Compensation models, design modifications to fluorometers and sampling design are discussed as suitable alternatives to overcome light-induced fluorescence quenching.

Evaluating coral reef ecosystem services outcomes from climate change adaptation strategies using integrative system dynamics.

Coral reef ecosystems provide a broad spectrum of essential ecological, economic and cultural services for Small Island Developing State (SIDS) communities. However, coral reef communities are increasingly threatened by the adverse impacts of human activities at both global and local scales. This study aims to develop an integrated dynamic assessment framework to evaluate coral reef conditions under different adaptation and climate change scenarios, and their consequential economic impacts in the small island community of Port Resolution on Tanna Island in Vanuatu. Our assessment framework follows a sequential multilayered modelling approach that uses System Dynamics (SD) coupled with Bayesian Network (BN) modelling to deal with the complexity and dynamicity of socioeconomic and environmental systems, and impacts from trans-discipline variables. The BN incorporated existing data and expert knowledge to project the future conditions of coral reefs under different scenario settings, and to parametrise and quantify the SD model where the existing data and information was insufficient. The SD was then used to simulate the dynamic relationship between coral reef condition and the economic benefits derived from its ecosystem services under different climate change (i.e. RCPs) and management scenarios through to 2070. Our findings show that sustainable community-based conservation management strategies are key to preserving the flow of coral reef ecosystem services under RCP 2.6 and 6.0. Importantly, we demonstrate that the implementation of an integrated portfolio of management strategies better protects ecosystem services provided by coral reefs and maximises the total economic benefits achieved over the long-term despite a temporary and short-term economic loss due to high initial capital investments and income reduction due to fishing and tourism restrictions.

Exploring Macroporosity of Additively Manufactured Titanium Metamaterials for Bone Regeneration with Quality by Design: A Systematic Literature Review.

Additive manufacturing facilitates the design of porous metal implants with detailed internal architecture. A rationally designed porous structure can provide to biocompatible titanium alloys biomimetic mechanical and biological properties for bone regeneration. However, increased porosity results in decreased material strength. The porosity and pore sizes that are ideal for porous implants are still controversial in the literature, complicating the justification of a design decision. Recently, metallic porous biomaterials have been proposed for load-bearing applications beyond surface coatings. This recent science lacks standards, but the Quality by Design (QbD) system can assist the design process in a systematic way. This study used the QbD system to explore the Quality Target Product Profile and Ideal Quality Attributes of additively manufactured titanium porous scaffolds for bone regeneration with a biomimetic approach. For this purpose, a total of 807 experimental results extracted from 50 different studies were benchmarked against proposed target values based on bone properties, governmental regulations, and scientific research relevant to bone implants. The scaffold properties such as unit cell geometry, pore size, porosity, compressive strength, and fatigue strength were studied. The results of this study may help future research to effectively direct the design process under the QbD system.

Determining the relative importance of titania nanotubes characteristics on bone implant surface performance: A quality by design study with a fuzzy approach.

TiO2 nanotubes (TNTs) are a promising bone/dental implant surface modification strategy with enhanced bioactivity and local therapeutic functions. However, inconsistencies related to the understanding of the influence of various TNTs characteristics on Ti implant functions, and the multi-factorial inter-dependence of such characteristics, requires an in-depth Quality by Design (QbD) analysis towards optimizing TNTs-modified implants. To this end, an extensive systematic literature search was undertaken to identify the various TNTs characteristics that may influence implant performance. Subsequently, in order to facilitate a QbD analysis, an expert questionnaire survey was carried out to determine the perceived contribution of various TNTs characteristics on an implant's biological, physicochemical, and mechanical performance. To achieve this goal, the Quality Function Deployment method was employed using symmetrical triangular fuzzy numbers to translate qualitative expert opinion into meaningful quantitative information. The results show that pore diameter, inter-nanotube distance and wall thickness are the TNTs characteristics with the most influential effects on the overall implant performance. This pioneering study evaluates perceived importance of various parameters contributing to TNTs functionality, and represents a step forward in the implementation of QbD strategies towards optimizing nano-engineered Ti implants.

Pediatric Cancer Models in Zebrafish.

Pediatric cancer is a leading cause of death in children and adolescents. Improvements in pediatric cancer treatment that include the alleviation of long-term adverse effects require a deeper understanding of the genetic, epigenetic, and developmental factors driving these cancers. Here, we review how the unique attributes of the zebrafish model system in embryology, imaging, and scalability have been used to identify new mechanisms of tumor initiation, progression, and relapse and for drug discovery. We focus on zebrafish models of leukemias, neural tumors and sarcomas - the most common and difficult childhood cancers to treat.

Mapping long-term coral reef ecosystems regime shifts: A small island developing state case study.

Coral reefs are among the most fragile ecosystems that provide essential services to local Small Island Developing States (SIDS) communities. As such, exploring the characteristics and interactions shaping regime shifts of coral reefs is of paramount importance in managing system pressures; enhancing resilience; aiding their regeneration and recovery process; and restoring habitat complexity. However, understanding the dynamics of coral reef ecosystems regime shift requires employing an approach capable of dealing with systems being affected by multiple climatic and socio-economic non-climatic pressures as well as an effective treatment of systemic embedded uncertainties. This study applies Fuzzy Cognitive Mapping (FCM) in a participatory stepwise and systematic procedure to reflect dynamic casualties and temporal changes of coral reef ecosystem regime change over a long-time perspective. This mapping technique allows conceptualising dynamic models to represent causalities and modelling input values to simulate fluctuations within a complex temporal system. Port Resolution on Tanna Island in Vanuatu was selected as the case study region representative of Pacific-SIDS geography and human communities. As an initial outcome and an indicator of multidisciplinary of this study, twenty-seven principal influential factors and their corresponding causal relationships were identified. Subsequently, the coral reef regime shift was analysed under four main plausible scenarios representing major climatic and non-climatic trajectories. The results indicate that climate change factors play pivotal roles in the regime shift of the coral reef ecosystem globally. At the focal scale of this study, the tourism industry and coral fisheries are the most vulnerable services provided by coral reefs. As such, coupled local management interventions and global efforts in mitigating the adverse impacts of climate change is likely to yield better coral reef ecosystem services at a local community level.

Development of 18 Quality Control Gates for Additive Manufacturing of Error Free Patient-Specific Implants.

Unlike subtractive manufacturing technologies, additive manufacturing (AM) can fabricate complex shapes from the macro to the micro scale, thereby allowing the design of patient-specific implants following a biomimetic approach for the reconstruction of complex bone configurations. Nevertheless, factors such as high design variability and changeable customer needs are re-shaping current medical standards and quality control strategies in this sector. Such factors necessitate the urgent formulation of comprehensive AM quality control procedures. To address this need, this study explored and reported on a variety of aspects related to the production and the quality control of additively manufactured patient-specific implants in three different AM companies. The research goal was to develop an integrated quality control procedure based on the synthesis and the adaptation of the best quality control practices with the three examined companies and/or reported in literature. The study resulted in the development of an integrated quality control procedure consisting of 18 distinct gates based on the best identified industry practices and reported literature such as the Food and Drug Administration (FDA) guideline for AM medical devices and American Society for Testing and Materials (ASTM) standards, to name a few. This integrated quality control procedure for patient-specific implants seeks to prepare the AM industry for the inevitable future tightening in related medical regulations. Moreover, this study revealed some critical success factors for companies developing additively manufactured patient-specific implants, including ongoing research and development (R&D) investment, investment in advanced technologies for controlling quality, and fostering a quality improvement organizational culture.

Spatial Bayesian Network for predicting sea level rise induced coastal erosion in a small Pacific Island.

An integrated approach combining Bayesian Network with GIS was developed for making a probabilistic prediction of sea level rise induced coastal erosion and assessing the implications of adaptation measures. The Bayesian Network integrates extensive qualitative and quantitative information into a single probabilistic model while GIS explicitly deals with spatial data for inputting, storing, analysing and mapping. The integration of the Bayesian Network with GIS using a cell-by-cell comparison technique (aka map algebra) provides a new tool to perform the probabilistic spatial analysis. The spatial Bayesian Network was utilised for predicting coastal erosion scenarios at the case study location of Tanna Island, Vanuatu in the South Pacific. Based on the Bayesian Network model, a rate of the island shoreline change was predicted probabilistically for each shoreline segment, which was transferred into GIS for visualisation purposes. The spatial distribution of shoreline change prediction results for various sea level rise scenarios was mapped. The outcomes of this work support risk-based adaptation planning and will be further developed to enable the incorporation of high resolution coastal process models, thereby supporting localised land use planning decisions.