Abstract: Comparing outcrop data to laboratory results is important to verify and validate experiments of analogue and reservoir materials especially regarding conditions for deformation experiments. This is important better understand highly complex carbonate reservoir strata and their response to changes in subsurface conditions, reducing subsurface uncertainty. This study develops methods to allow for a more straightforward comparison of outcrop data (m-scale) with experimentally created fracture arrays developed in cylindrical samples (cm-scale). The main objective is to assess usefulness of experimentally-produced fracture networks as analogues for subsurface structures, typically at the meter and above scale by developing new techniques to use the lab deformation. It analyses key characteristics of laboratory-induced fracture networks by adapting scanline methods to use with x-ray tomography (XRT) images to allow for comparison with outcrop and field data. To test and verify these new methods two low permeability carbonate samples were used for deformation testing and analysis. Applying the different scanline methods we show that they can be used to analyse lab induced fractures (mm to cm-scale) identified in XRT images for comparison with outcrop data (m-scale). In addition, these methods also allow for quantification of fracture network attributes e.g. fracture spacing, fracture apertures, orientation. This new data bridges the gap between micro-scanlines using thin sections and outcrop scanlines.

As the era of omics continues to expand, omics-based experiments have become popular in industrial biotechnology. They promise deeper biological understanding, which may be leveraged to develop novel solutions to bioprocess optimization and cell line engineering strategies. Despite this expansion, naivety about what omic data offers and how to best handle such data can challenge the extraction of actionable value. However, the value of omic experiments in biotechnology research and development can be maximized with deliberate application of omic approaches and forethought about analysis techniques. Here we describe important considerations when designing and implementing omic-based experiments, and discuss how systems biology analysis strategies can enhance efforts to obtain actionable insights in biomanufacturing.

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n = 12) were fed either a standard (10% fat, n = 6) or high fat diet (HFD: 45% fat, n = 6) for 72 h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72 h induced rapid weight gain (c. 2.6%) and reduced serum NEFA with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and PPAR signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g. Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

This study explores the potential to reach a circular economy for post-consumer recycled polyethylene terephthalate (rPET) packaging and bottles by using it as a distributed recycling for additive manufacturing (DRAM) feedstock. Specifically, rPET is processed using only an open source toolchain with fused particle fabrication (FPF) or fused granular fabrication (FGF) processing. In this study, first the impact of granulation, sifting and heating (and their combination) is quantified on the shape and size distribution of the rPET flakes. Then feeding studies were performed to see if they could be printed through an external feeder or needed to be direct printed with a hopper using two Gigabot X machines, one with extended part cooling and one without. Print settings were optimized based on thermal characterization and for the latter which was shown to print rPET directly from shredded water bottles mechanical testing is performed. The results showed that geometry was important for extended feeding tubes and direct printed using a hopper. Further there is a wide disparity in the physical properties of rPET from water bottles depending on source and the history of the material. Future work is needed to enable water bottles to be used as a widespread DRAM feedstock.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Indonesia is among the countries developing the concept of smart city. The national government envisions Indonesia 2030 which shall implement the smart city towards sustainable development. Many regions in Indonesia have already implemented the concept of smart city, but still on the level of smart government and smart technology, lacking on the smart citizen component of a smart city. This paper aims to analyze the citizens behavior of using technology on Sleman smart citizen 2021 through the lapor sleman mobile application. This research uses mixed method of quantitative and qualitative approaches in examining the data. The authors distributed 100 questionares and conducted interviews to the government which is department of communication and information, Sleman and the several community that ever use the lapor sleman application. The result of the study reveals the following: firstly, performance expectancy, social influence, and behavioral intention are three independent variables which affect the users’ behavior. Secondly, the behavioral intention has the biggest significant effect on users’ behavior. Thirdly, the citizen behavior of using technology has affect the making a smart citizen. Therefore, using technology in term of lapor sleman mobile application can make the citizens as active participants in public life, in terms of social cooperation, freedom of expression and flexibility. However, there are still many problems in the use of lapor sleman mobile application such as the limited access to only android smartphones, lack of technical know-how, and people’s reluctance to use the lapor sleman mobile application.

Users with Autism Spectrum Disorder may find human-computer interaction (HCI) challenging due to a number of symptoms experienced, one of which is difficulty coping with change. Through capturing, comparing and statistically analysing the reactions of autistic and neurotypical users to seven individual design changes, it has been possible to identify the changes that cause significant difficulty in autistic users. These difficulty points were then used to form heuristics that can followed by HCI practitioners in the industry to reduce the negative impact of software interface design change on autistic users, hence making software updates more accessible.

Developmental modularity has long been viewed as a hierarchical organization that facilitates evolution over macro-evolutionary time through modification or co-option of preexisting modules. More recently, developmental modularity has been proposed as a micro-evolutionary mechanism capable of driving rapid evolution of novel color pattern phenotypes between closely related taxa. In this scenario, swapping allelic variants of modular cis-regulatory elements (CREs) via recombination generates novel phenotypes by shuffling preexisting color pattern modules into new arrangements. Recent evidence from Drosophila and butterflies, however, provides a series of examples in which pleiotropic CREs function in multiple developmental contexts. The potential prevalence of pleiotropy in CRE function is a major barrier to the proposed evolutionary role of CRE modules and encourages us to reconsider the relative importance of modularity for microevolutionary change. Here we first review the case for the apparent frequent exchange of modular color pattern phenotypes as a mechanism facilitating diversification. We then contrast this with recent evidence of CRE pleiotropy and argue that exchange of CRE modules should not be the default assumption, even when phenotypes look modular. Finally, we review experimental data on Heliconius butterfly wing patterns—which appear modular—and introduce the concept of evolutionary modularity as an alternative to developmental modularity. Evolutionary modularity reconciles the appearance of modularity in comparative genomic studies of Heliconius color patterns with experimental data supporting a non-modular architecture. We propose that evolutionary modularity provides a potentially important pathway for exchange of phenotypic elements between hybridizing taxa independent of the underlying developmental architecture.

Synthesis of natural products with complicated architecture often requires segments having the functional groups that can be structurally transformed with the desired stereogenic centers. Bicyclic ?-lactones have a great potential for a suitable segment for natural product synthesis. However, the stereoselective construction of such functionalized bicyclic ?-lactones is not as straightforward as one might expect. On the other hand, the Lewis acid template-mediated Diels-Alder reaction is one of the most powerful and versatile methods for providing bicyclic ?-lactones with high regioselectivity and stereoselectivity. In this reaction, the Lewis acid template activates the dienophile as well as linking the diene and dienophile by a temporary tether. Therefore, Diels-Alder reaction smoothly proceeds in a stereocontrolled manner, allowing a simple access to bicyclic ?-lactone as a valuable building block for the synthesis of complicated natural products. In this review, some highlights of the Lewis acid-mediated Diels-Alder reaction, along with its application to the synthesis of biologically active compounds are discussed.

This article draws on empirical research seeking to develop more nuanced understandings of child prostitution, previously theorised on the basis of children’s rights, feminist, and structure/agency debates, largely ignoring children’s own understandings of their involvement in prostitution. Conducted in Malawi, one of the economically poorest countries in the world, the study goes to the heart of questions of inequality and child protection. With careful attention to ethical considerations, a participatory approach was used to enable 19 girls and young women, whose involvement in prostitution began in childhood, to convey their own experiences and understandings of involvement. Data were collected using a range of methods, chosen by participants to match their abilities and interests. Data analysis and interpretation were aided by reference to the capability approach focussing on questions of human rights and social justice for women and girls. Generating rare insights into participants’ worlds, the research demonstrates how the persistence of deeply embedded cultural values in contexts of extreme poverty serves to sustain gender inequalities, constraining choices for girls and denying them opportunities to lead valued lives. The article ends by considering the theoretical and methodological implications of the study, policy and practice recommendations and opportunities for further research.

It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis Lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After the treatment of 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damage when compared to treatment with particles only and radiation alone. This radio-sensitization was further translated into a reduction in cell survival demonstrated by clonogenicity. This work indicates that GNPs of both sizes induce DNA damage in LLC cells at the tested concentrations, whereas the 37.4 nm particle size treatment group demonstrated greater significance in vitro. The presented data aids in the evaluation of the radiobiological response of Lewis Lung carcinoma cells treated with gold nanoparticles.

This paper presents a new engagement model for climate change education (CCE) as a result of analysing interactive digital narratives (IDNs) created during the You and CO2 Climate Change Education Programme. Young people aged 13-15 from two schools in Wales participated in three workshops, which culminated in students producing IDNs about climate change using Twine storytelling software. An inductive, grounded-theory approach informed by Bourdieusien principles of habitus and value was used to explore students’ responses to the Programme. Stage 1 coding identified ‘Core Themes’ and located student responses along tri-axial continua showing engagement, agency, and power. Stage 2 coding combined ‘Core Themes’ to build upon Cantell’s 2019 Bicycle Model of Climate Change Education to create a new ‘Holistic Engagement Model for Climate Change Education and Action’ (HEMCCEA), where learners’ journeys towards full engagement with and understanding of CCE and action could be traced. Barriers to students’ engagement with and understanding of CCE were identified through Bourdieusien analysis of responses. Results show that engagement was related to children’s views on their capacity to effect change on individual, local and governmental level. The HEMCCEA provides a model for adjusting CCE curricula to accommodate young people’s varying cultures and views.

Mechanical forces and mechanical energy are prevalent in living cells. This may be because mechanical forces and mechanical energy preceded chemical energy at life’s origins. Mechanical energy is more readily available in non-living systems than the various forms of chemical energy used by living systems. Two possible prebiotic environments that might have provided mechanical energy are hot pools that experience wet/dry cycles and mica sheets as they move, open and shut, as heat pumps or in response to water movements.

Cells execute biological functions to support phenotypes such as growth, migration, and secretion. Complementarily, each function of a cell has resource costs that constrain phenotype. Resource allocation by a cell allows it to manage these costs and optimize their phenotypes. In fact, the management of resource constraints (e.g., nutrient availability, bioenergetic capacity, and macromolecular machinery production) shape activity and ultimately impact phenotype. In mammalian systems, quantification of resource allocation provides important insights into higher-order multicellular functions; it shapes intercellular interactions and relays environmental cues for tissues to coordinate individual cells to overcome resource constraints and achieve population-level behavior. Furthermore, these constraints, objectives, and phenotypes are context-dependent, with cells adapting their behavior according to their microenvironment, resulting in distinct steady-states. This review will highlight the biological insights gained from probing resource allocation in mammalian cells and tissues.

Dielectric elastomer actuators (DEAs) offer robust, high energy density solutions for soft robotics. The proposed end effector consists of three spring roll configuration DEAs, each acting as a robotic finger, using a 3M VHB-F9473PC adhesive membrane. The lateral force, bending angle and response time of the actuator are measured experimentally and compared with the predictions of an analytical model. The cylindrical actuator measures 70 mm in length and 15 mm in diameter and achieved a lateral force of 30 mN, a bending angle of 6.8 ° and a response time of ≈ 1 s. Spring roll configuration DEAs are shown to reduce the effects of viscoelasticity seen in the membrane, making the actuator more controllable at higher voltages. The dielectric constant of the membrane is shown to be a limiting factor of actuation, with a decrease in dielectric constant resulting in larger actuation. The end effector successfully gripped numerous light objects for extended periods, showing the applicability of spring roll DEAs for soft end effectors.

Data relating to the rate at which pesticide active substances dissipate on or within various plant matrices are important for a range of different risk assessments; however, despite the importance of this data, dissipation rates are not included in the most common online data resources. Databases have been collated in the past, but these tend not to be maintained or regularly updated. The purpose of the exercise described herein was to collate a new database in a format compatible with the main online pesticide database resource (the Pesticide Properties Database, PPDB), to validate this database in line with the Pesticide Properties Database protocols and thus ensure that the data is maintained and updated in future. Data was collated using a systematic review approach using several scientific databases. Collated literature was subjected to a quality assessment, and then data was extracted into an MS Excel spreadsheet. The outcome of the study is a database based on data collated from 1390 published articles covering over 400 pesticides and over 200 crops across a wide variety of different matrices (leaves, fruits, seeds etc.) for pesticide residues on the crop surface, as well as residues absorbed within the plant material. This data is now fully incorporated into the PPDB.

Economists have long been interested in examining inflation-growth nexus. Nevertheless, the nature of their relationship and the optimal level of inflation threshold for economic growth have still remained controversial in both theoretical and empirical works. Accordingly, this study investigates the existence of threshold effects of inflation on economic growth in Ethiopia over the period 1975-2018 using a Two-regime Threshold Auto-regressive (TAR) model. The study mainly departs from previous works since it estimates sector-specific inflation threshold level in food and non-food sectors. Our preliminary analyses clearly reveal that inflation in food sector has become more volatile, less-persistent and key contributor to the general inflation as compared to its non-food counterpart. Further, The TAR model results and robustness checks indicate the existence of inflation threshold in a range of 9-10%. In particular, the threshold level for food inflation is 10% and 8% for non-food inflation. In all cases, our results robustly confirm growth-detrimental effects of inflation after the threshold levels. After all, this study suggests the need for considering specific behaviors of food and non-food prices, and implementing appropriate fiscal and monetary policies to bring inflation down to a single-digit level.

Simulated crime scene investigation is an essential component of forensic science education, but its implementation poses challenges relating to cost, accessibility and breadth of experience. Virtual reality (VR) is an emerging technology which offers exciting prospects for teaching and learning, especially for imparting practical skills. We document here a multidisciplinary experimental study in which a bespoke VR crime scene app was designed and implemented, after which it was tested by both undergraduate student and staff/postgraduate student cohorts. Through both qualitative and quantitative analyses, we demonstrate that VR applications support learning of practical crime scene processing skills. VR-based practical sessions have the potential to add value to forensic science courses through offering cost-effective practical experience and the ability to work in isolation, in a variety of different scenarios. Both user groups reported high levels of satisfaction with the process and reports of adverse effects (motion sickness) were minimal. With reference to user feedback, we proceed to evaluate the scalability and development challenges associated with large-scale implementation of VR as an adjunct to forensic science education.

Intracellular potassium concentrations, [K+], are high in all types of living cells, but the origins of this K+ are unknown. The simplest hypothesis is that life emerged in an environment that was high in K+. One such environment is the spaces between the sheets of the clay mineral, mica. The best mica for life’s origins is the black mica, biotite, because it has a high content of Mg++ and it has iron in various oxidation states. Life also has many of the characteristics of the environment between mica sheets, giving further support for the possibility that mica was the substrate on and within which life emerged.

This paper presents a hypothesis about the origins of life in a clay mineral, starting with the earliest molecules, continuing through the increasing complexity of the development, in neighboring clay niches, of “Metabolism First,” “RNA World,” and other necessary components of life, to the encapsulation by membranes of the components in the niches, to the interaction and fusion of these membrane-bound protocells, resulting finally in a living cell, capable of reproduction and evolution. Biotite (black mica) in micaceous clay is the proposed site for this origin of life. Mechanical energy of moving biotite sheets provides one endless source of energy. Potassium ions between biotite sheets would be the source of the high intracellular potassium ion concentrations in all living cells.

Digital health research is an emerging discipline that requires easy-to-understand theoretical frameworks and implementation models for digital health providers in health and social care settings. The COVID-19 pandemic has heightened demand for digital health discipline-specific instruction on ‘how to’ manage evidence-based digital health transformation. Access to the use of these models guarantees that digital health providers can investigate phenomena using safe and suitable approaches and methods to conduct research and identify answers to challenges and problems that arise in health and social care settings. The COMPASS theory is designed to aid transformation of health and social care environments. A navigational rose of primary quadrants is divided by four main compass points, with person-centred care being central to the philosophy. Two axes produce Cartesian planes that intersect to form a box plot, which can be used to discover human and physical resource weightings to augment digital health research design and implementation. A third continuum highlights stakeholders' capabilities, critical for any multidisciplinary study. The COMPASS mnemonic guides end-users through the process of design, development, implementation, evaluation, and communication of digital health transformations. The theory's foundations are presented and explained in context of the 'new normal' of health and social care delivery.

The temperature effect plays an important role for an accurate determination of the polar free energy, polar thermodynamic parameters, and enthalpic and entropic Lewis’s acid base properties of oxides, polymers and composites polymers/oxides. The adsorption of polymers on other solid surfaces is crucial in many industrial applications, coatings, paints, catalysis, colloids and adhesion processes. (1) Background: Inverse gas chromatography at infinite was used for the physico-chemical characterization of solid substrates by determining the thermodynamic parameters of adsorption of model organic solvents on solid surfaces such as polymers, metallic oxides, carbon fibers, pharmaceutical or 3D/4D printing substrates. (2) Methods: A new method based on the London dispersion equation was applied with a new parameter associating the deformation po-larizability and the harmonic mean of the ionization energies of solvent. More accurate values of the dispersive and polar interaction energies of the various organic solvents adsorbed on PMMA in bulk phase and PMMA/silica at different recovery fractions were obtained as well as the Lewis acid-base parameters and the transition temperatures of the different composites. (3) Results: This new methodology gave very interesting results on the behavior of PMMA adsorbed on silica. An important effect of the temperature and the recovery fraction on the various physicochemical and thermodynamic properties was highlighted. The variations of all interaction parameters showed the presence of three transition temperatures for the different PMMA adsorbed on silica with the various coverage rates with a shift of these temperatures for a recovery fraction of 31% (4) Con-clusions: An important variation of the polar enthalpy and entropy of adsorption, the Lewis ac-id-base parameters and the intermolecular separation distance as a function of the temperature and the recovery fraction of PMMA on silica.

There is a continuous interest in cannabinoids like Δ9-tetrahydro cannabinol (Δ9-THC) and cannabidiol (CBD). A patent of Webster et al., described the conversion of CBD to either D8-THC or D9-THC, depending on the acid catalyst applied. The use of para-toluene sulfonic acid (pTSA) led to the formation of D8-THC, while boron trifluoride etherate (BF3·Et2O) yielded mainly D9-THC. The enormous difference in product selectivity between these two catalysts was investigated with Molecular Modeling. It was found that pTSA leads to fast isomerization of Δ9-CBD to Δ8-CBD and subsequent ring closure to Δ8-THC. BF3·Et2O catalysis leads to the formation of tertiary carbenium ions in the Transition States which yield D9-THC and some iso D8-THC. Under dry conditions in refluxing toluene, it was found that pTSA is predominantly present as a dimer, and only a small fraction is available as monomeric catalyst. Applying the computationally derived activation barriers in Transition State theory yielded reaction rates predicting amounts of cannabinoids that are in close agreement with the experimental findings.

Passive dynamics is an aspect of locomotion which is entirely dependent on the mechanical configuration and linkages of adjacent body segments. Tension distribution along mechanical linkages enables execution of movement patterns with reduced need for complex neurological pathways and may play a role in reestablishing postural stability following external disturbances. Here we demonstrate a uni-directional mechanical relationship between the equine forelimb, head and neck, which may have implications for balance and forelimb loading in the horse. These observations suggest that forelimb, head and neck movement coordination (observed in the horse during unrestrained locomotion) is largely controlled by the mechanical linkages between body segments, rather than being entirely dependent on neurological input as previously thought. This highlights the potential significance of research directed at investigating passively induced movements in understanding common locomotory patterns. Additionally, it suggests a mode of postural control which may provide instantaneous adjustments to postural disturbances, thus promoting rapid and efficient locomotion.

Tumor heterogeneity is a major obstacle in cancer therapy. We offer a novel perspective on tumor heterogeneity, informed by expanding upon the current view on tumor evolution. It is commonly known that in cancer, it is the advantageous genes and mutations that drive tumor capacities and the progression. We recognize an earlier, often overlooked, but necessary thus crucial step preceding the activation of advantageous genes functionality, namely, cellular response. We suggest that cancer is driven by an adaptive action taken by any organism when confronted with adversity - a cellular response to generate specific cancer capacities demanded to overcome survival threat - the responses that prompt the utilization of the functionality of advantageous genetic mutations and genes to attain these capacities and drive the disease. The ongoing development of cancer capabilities, as cells endeavor to obtain a competitive advantage, results in increased molecular chaos, observed as tumor heterogeneity. When the evolutionary drive for survival is impeded by therapeutic inhibition of critical genes, cell death occurs, a phenomenon thus termed oncogene addiction. We summarize the implications of this new framework for understanding tumor evolution and anti-cancer drug discovery, as well as understanding of basic cancer biology.

Phagocytosis (and endocytosis) is an unusual cellular process which results in the formation of a novel subcellular organelle, the phagosome. This phagosome contains not only the internalised target of phagocytosis, but also the external medium, creating a new border between extracellular and intracellular environments. The boundary at the plasma membrane is, of course, tightly controlled and exploited in ionic cell signalling events. Although there has been much work on the control of phagocytosis by ions, notable Ca2+ ions influxing across the plasma membrane, increasing our understanding of the mechanism enormously, very little work has been done exploring the phagosome/cytosol boundary. In this paper, we have explored the changes in the intra-phagosomal Ca2+ ion content which occur during phagocytosis and phagosome formation in human neutrophils. Measuring Ca2+ ion concentration in the phagosome is potentially prone to artefacts as the intra-phagosomal environment experiences changes in pH and oxidation. However, by excluding such artefacts, we conclude that there are open Ca2+ channels on the phagosome, which allow Ca2+ ions to ‘drain’ into the surrounding cytosol. This conclusion was confirmed by monitoring the translocation of intracellularly expressed YFP-tagged C2 domain of PKC-γ. This approach marked regions of membrane at which Ca2+ influx occurred, the earliest being the phagocytic cup, and then the whole cell. This paper therefore presents data which has novel implications for understanding phagocytic Ca2+ signalling events, such as peri-phagosomal Ca2+ hotspots, and other phenomena.

This study evaluated the antimicrobial activity of Leptospermum scoparium (Mānuka) and Cryptomeria japonica (Sugi) essential oils and assessed the effect of seasonal chemical variation on the oils’ antimicrobial efficacies. Plate based assays were conducted to elucidate the oils’ spectrum of in vitro antimicrobial activity and to determine the oils’ minimum inhibitory concentrations (MIC) as a measure of antimicrobial efficacy. Gas chromatography – mass spectrometry was adopted to chemically profile oils distilled in different seasons. The resultant compositional information in conjunction with MIC data was used to evaluate the effect of seasonal variation on the oils’ antimicrobial efficacy. Both Mānuka and Sugi essential oils were active against all classes of target microorganisms. However, limited activity was observed against Gram-negative bacteria. The oils displayed consistent chemotypic characteristics regardless of the time of distillation. Nonetheless, there were quantitative differences in compound abundance in both essential oils. Significant differences in the MIC of Sugi essential oil was observed against target microorganisms as a result of seasonal variation in constituent abundances while Mānuka essential oil’s antimicrobial efficacy was unaffected. This study demonstrates that seasonal chemical variation is an important quality assurance parameter to consider for future application of essential oils as antimicrobial agents in consumer products.

There is less attention to use an environmental perspective in economic valuation and individuals' willingness to pay for recreational sites. Therefore, the aim of this study is to use contingent valuation methods to estimate the recreational value and willingness to pay of visitors to the protected area of Helen forest, considering the scale of the new environmental paradigm (NEP). To achieve this, the sample size for survey was determined using the Cochran method, and then economic valuation and environmental perspective questions were designed and completed through the completion of a dual-dimensional questionnaire and NEP scale. To determine the factors influencing individuals' willingness to pay, the logistic regression model was employed. In this study, two modeling approaches were used. The first utilized a base model containing socio-economic variables, while the second model integrated a NEP into the base, and subsequent estimations were conducted. The results indicated that 83.04% of visitors are willing to pay an amount for the recreational use of the study area. The estimated model results demonstrated that variables such as the proposed amount, frequency of visits, environmental statement, age, gender, education, individual monthly income, residency, and the NEP are among the most influential factors affecting the likelihood of accepting the proposed amount by tourists. The strong and positive correlation between the NEP and willingness to pay indicates that individuals with a favorable environmental perspective tend to exhibit a higher willingness to pay. In this study, the average willingness to pay per household per visit was 199,793 Rials, and the annual recreational value for the entire Helen forest area was 23746832564 Rials. Furthermore, the survey results regarding visitors' perspective on the NEP revealed that the average NEP score for visitors to Helen forest was 36.57, with the statement 'plants and animals have similar rights to humans' receiving the highest average score of 28.4. The result of this study shows the importance of environmental perspective for sustainable management of a recreational site to balance economic development with environmental conservation and social well-being.

With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes. Our study is the first to investigate the combinatorial effects of low physiologically achievable concentrations of WA and SFN on breast cancer cell proliferation, histone deacetylase1 (HDAC1) and DNA methyltransferases (DNMTs). No adverse effects were observed on control cells at optimal concentrations. There was synergistic inhibition of cellular viability in MCF-7 cells and a greater induction of apoptosis with the combinatorial approach than with either compound administered alone in both MDA-MB-231 and MCF-7 cells. HDAC expression was down-regulated at multiple levels. Lastly, we determined the combined effects of these bioactive compounds on the pro-apoptotic BAX and anti-apoptotic BCL-2 and found decreases in BCL-2 and increases in BAX. Taken together, our findings demonstrate the ability of low concentrations of combinatorial WA and SFN to promote cancer cell death and regulate key epigenetic modifiers in human breast cancer cells.

Inverse gas chromatography at infinite dilution was used to determine the surface thermodynamic properties of silica particles and PMMA adsorbed on silica, and more particularly, to quantify the London dispersive energy γsd, the Lewis acid γs+ and base γs- polar surface energies of PMMA/silica composites as a function of the temperature and the recovery fraction θ of PMMA. The polar acid–base surface energy γsAB and the total surface energy of the different composites were then deduced as a function of the temperature. In this paper, the Hamieh thermal model was used to quantify the surface thermodynamic energy of poly methyl methacrylate (PMMA) adsorbed on silica particles at different recovery fractions. A comparison of the new results was carried out with those obtained by applying other molecular models of the surface areas of organic molecules adsorbed on the different solid substrates. An important deviation of these molecular models from the thermal model was proved. The determination of γsd, γs+, γs-, and γsAB of PMMA in both bulk and adsorbed phases showed an important non-linearity variation of these surface parameters as a function of the temperature. The presence of maxima in the curves of γsd(T) highlighted the second order transition temperatures in PMMA showing beta-relaxation, glass transition and liquid-liquid temperatures. These three transition temperatures depended on the adsorption rate of PMMA on silica. The proposed method gave a new relation between the recovery fraction of PMMA and its London dispersive energy showing an important effect of the temperature on the surface energy parameters of adsorption of PMMA on silica. A universal equation relating γsd(T,θ) of the systems PMMA/silica to the recovery fraction and the temperature was proposed.

This research was devoted to study the effect of the tacticity of PMMA on the surface physicochemical properties such as the London dispersive component of the surface energy of the polymer, the polar and dispersive free energies, the Lewis’s acid-base surface parameters, and the Lewis acid and base surface energies of atactic, isotactic and syndiotactic PMMAs as a function of the temperature. Inverse gas chromatography (IGC) at infinite dilution was used to determine the surface thermodynamic properties of PMMA at different tacticities. The experimental values of the net retention time and volume of model organic molecules adsorbed on the atactic, isotactic and syndiotactic PMMAs, were obtained by IGC technique at infinite dilution. The London dispersion interaction energy was used for the separation of the polar and dispersive energy of the different n-alkanes and polar solvents adsorbed on the different PMMA surfaces. The London dispersive surface energy γ_s^d (T) of PMMAs was determined by applying the Hamieh thermal model that took into account the effect of the temperature on the surface area of adsorbed molecules. The obtained results showed non-linear variations of γ_s^d (T) of atactic, isotactic, and syndiotactic PMMAs with three maxima characterizing the three transition temperatures of PMMAs, T_g, T_g and T_(liq-liq) with a shift of these temperatures with the isotactic and syndiotactic PMMAs. It was showed that the polar interaction free energy ∆G_a^p (T) also showed the presence of the three above transition temperatures of the polymers. The study showed an important non-linearity variation of the different acid-base parameters in the various polymer surfaces proving the highest effect of the temperature and the tacticity on these parameters. The determination of the enthalpic and entropic Lewis’s acid-base parameters showed an amphoteric character for the different PMMAs. The basicity of the atactic PMMA was about four times larger than its acidity outside the neighborhood of the transition temperatures of the polymer. Whereas, the isotactic PMMA was about 2 to 2.5 times more basic than acid, while the syndiotactic PMMA exhibited the highest basicity by showing a surface 5 to 8 times more basic than acid. However, the Lewis acid-base parameters strongly depended on the temperature and sudden variations of these surface parameters were observed around the transition temperatures largely depending on the PMMA tacticity. The determination of the polar acid and base surface energies of the three PMMAs led to the same previous transition temperatures with an important effect of the tacticity of PMMA on the values of these acid-base surface energies.

MP2/aug-cc-pVTZ calculations were carried out for the ZFH₃-B complexes (Z = C, Si, Ge, Sn and Pb; B = C₂H₂, C₂H₄, C₆H₆ and C₅H₅^-; relativistic effects were taken into account for Ge, Sn and Pb elements). These calculations are supported by other approaches; the decomposition of the energy of interaction, Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbital (NBO) method. The results show that tetrel bonds with π-electrons as Lewis bases are classified as Z…C links between single centers (C is an atom of the π-electron system) or as Z…π interactions where F-Z bond is directed to the mid-point (or nearly so) of the CC bond of the Lewis base. The analogues systems with Z…C/π interactions were found in the Cambridge Structural Database (CSD). It was found that the strength of interaction increases with the increase of the atomic number of the tetrel element and that for heavier tetrel elements the ZFH₃ tetrahedral structure is more deformed towards the structure with the planar ZH₃ fragment. The results of calculations show that the tetrel bond is sometimes accompanied by the Z-H…C hydrogen bond or even sometimes the ZFH₃-B complexes are linked only by the hydrogen bond interaction.

Natural vegetation restoration can take decades to achieve and requires information on species composition and trend to inform management strategies. Here we demonstrate the potential and portability of drone, dove and Sentinel-2 imagery for species level classification and trajectory monitoring using three study sites with different revegetation histories. Drone imagery (4 cm) was classified using random forests. Dove (3 m) and Sentinel-2 (10 m) images were acquired close to the anniversary of the drone flights and converted into fractional cover maps showing the proportion of exotics, natives and other land covers using ordinary least squares (OLS) and geographically weighted regression (GWR). The time series of fractional cover maps were converted into positive and negative slope and second-order curvature and summarised as one RGB composite to illustrate trend and observe exotic expansion. Drone classification accuracies ranged from 73%-76% when applied to the full plant species list and between 93% and 97% when grouped into natives, exotics, and other land covers. GWR outperformed OLS for all fractional cover mapping and GWR with dove imagery was more accurate than with Sentinel imagery. The combination of very high-resolution drone acquired imagery with the versatility of dove acquired imagery arms land managers with highly accurate species composition and their spatio-temporal dynamics to promote timely intervention.

This paper examines the interplay between media and the “social side of soils” whereby climate change action implicates individual and collective capacity to adapt, participate in groups or organizations, networks, and respond to challenges and opportunities across a system. The context examined here is Canadian agriculture, and soil health initiatives in the province of Ontario. Our review of relevant literature points to a knowledge gap on the role of the media in enabling climate action in the Canadian agricultural sector with a focus on soil management practices. This study conducted a media content analysis of 100 English-language news articles published between 2022 and 2024 and conducted 31 surveys with media professionals. Approximately one-quarter of the screened news articles contained any relevant coverage of soil health-related climate change mitigation issues. Journalist surveys identified the resource constraints on soil health media coverage with a wide range of traditional and Internet-based journalism on climate change issues, motivated particularly by crisis communication and one-off “parachute reporting”. Going forward, the engagement of key stakeholders of soil health in Canada such as farmers for media and communication about climate change mitigation needs attention. Key policy structures at the federal and provincial levels can help to make this happen.

In this paper we compare using computational fluid dynamics the aerothermal performance of two candidate casing manifolds for supplying an impingement-actuated active tip clearance control system for an aero-engine high-pressure turbine. The two geometries are (a) single-entry: an annular manifold fed at one circumferential location; (b) multiple-entry: a casing manifold split into four annular sectors, each sector supplied separately from an annular ring main. Both the single-entry and multiple-entry systems analysed in this paper are idealised version of active clearance control systems in current production engines. Aerothermal performance is quantitatively assessed on the basis of the heat transfer coefficient distribution, driving temperature difference for heat transfer between the jet and casing wall, and total pressure loss within the high-pressure turbine active clearance control system. We predict that the mean heat transfer coefficient (defined with respect to the inlet temperature and local wall temperature) of the single-entry active clearance control system is 77% greater than the multiple-entry system; primarily because the coolant in the multiple-entry case picks up approximately 40 K of temperature from the ring main walls, and secondarily because the average jet Reynolds number of impingement holes in the single entry system is 1.2 times greater than in the multiple entry system. The multiple-entry system exhibits many local hot and cold spots, depending on the position of the transfer boxes, while the single-entry case has a more predictable aerothermal field across the system. The multiple-entry feed system uses an average of 20% of the total available pressure drop, while the feed system for the single-entry geometry uses only 2% of the total available pressure drop. From the aerothermal results of this computational study, and in consideration of holistic aero-engine design factors, we conclude that a single-entry system is closer to an optimal solution than a multiple-entry system.

Biodiesel, a potent replacement for petroleum diesel, is derived from fatty acids in biomass through transesterification, which is renewable, non-toxic, and biodegradable and is a powerful replacement for petroleum diesel. Lewis acid has been proven effective for esterification and transesterification. The Lewis base enhances the electrophilic and nucleophilic properties of the molecules that bind to it, leading to the remarkable versatility in the Lewis base catalytic reaction. Many studies have shown that Lewis acid/base catalyzed in-situ transesterification is a fast and environmentally friendly method for producing biodiesel. The utilization of Lewis acid-base sites to catalyze transesterification has been shown to enhance their efficiency and utilization of ac-id-base active sites. This review explores biodiesel production by different catalysts using Lewis acid-base sites, the conditions for catalytic transesterification, the effects of different reaction parameters on biodiesel production, and biodiesel production process.

This case study explores the transformative effects of emergent digital technologies, particularly augmented reality (AR), on literacy engagement and reading for pleasure. The United Arab Emirates Ministry of Education implemented the UAE Storytime programme, utilising AR to create an interactive literacy experience for young learners. The programme incorporated bilingual episodes, featuring stories based on local and global contexts, with 3D objects and interactive games to enhance understanding. The results indicate a positive correlation between the use of AR and literacy engagement. A high proportion of learners scanned the QR codes to access the AR objects, which enhanced their engagement and understanding of the stories. The programme fostered a learner agency, engaged family members in the learning process, and established a sense of global community. The study recommends the integration of similar initiatives into the curriculum to promote collaboration, creativity, and holistic learning experiences.

Active contour models present a robust segmentation approach which make efficient use of specific information about objects in the input data rather than processing all the data. They have been widely used in many applications including image segmentation, object boundary localisation, motion tracking, shape modelling, stereo matching and object reconstruction. In this paper, we investigate the potential of active contour models in extracting roads from Mobile Laser Scanning (MLS) data. The categorisation of active contours based on their mathematical representation and implementation are discussed in detail. We discuss an integrated version in which active contour models are combined to overcome their limitations. We review various active contour based methodologies which have been developed to extract roads and other features from LiDAR and digital imaging datasets. We present a small case study in which an integrated version of active contour models is applied to automatically extract road edges from MLS dataset. An accurate extraction of left and right edges from the tested road section validates the use of active contour models. The present study provides a valuable insight on the potential of active contours for extracting roads and other infrastructures from 3D LiDAR point cloud data.

The neural-crest derived enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal (GI) tract and controls all gut functions, including motility. Lack of ENS neurons causes various ENS disorders such as Hirschsprung Disease. One treatment option for ENS dis-orders includes the activation of resident stem cells to regenerate ENS neurons. Regeneration in the ENS has mainly been studied in mammalian species using surgical or chemically-induced injury methods. These mammalian studies showed a variety of regenerative responses with generally limited regeneration of ENS neurons, but (partial) regrowth and functional recovery of nerve fibers. Several aspects might contribute to the variety in regenerative responses, including observation time after injury, species, and gut region targeted. Zebrafish have recently emerged as a promising model system to study ENS regeneration as larvae possess the ability to generate new neurons after ablation. As the next steps in ENS regeneration research, we need a detailed under-standing of how regeneration is regulated on a cellular and molecular level both in animal models with high and low regenerative capacity. Understanding the regulatory programs necessary for robust ENS regeneration will pave the way for using neural regeneration as a therapeutic approach to treating ENS disorders.

Despite continued efforts by educators, UN declarations and numerous international agreements, progress is still limited in handling major global challenges such as ecosystem collapse, accelerating climate change, poverty and inequity. The capacity to collaborate globally on addressing these issues remains weak. This systematic review of research on global learning for sustainable development (GLSD) aims to clarify the diverse directions research on GLSD has taken, to present the historical development of the research area, and highlight emerging research issues. The review summarises key findings of the English language literature in the period 1994-2020 identified with the search terms “global learning” and “sustainable development”, sustainability or GLSD, respectively. The review documented a gradually growing knowledge base, mostly authored by scholars located in the global North. Conclusions point to what we might achieve if we could learn from one another in new ways, moving beyond Northern-centric paradigms. It is also time to re-evaluate core assumptions that underlie education for sustainable development more generally, such as a narrow focus on formal learning institutions. The review provides a benchmark for future reviews of research on GLSD, reveals the emerging transformative structure of this transdisciplinary field, and offers reference points for further research

Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult heart. Therefore, cardioprotective strategies for adults need to be tested in immature heart. We have recently shown that simultaneous activation of PKA and EPAC confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibra-tion period with activators of PKA and/or EPAC. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 minutes preceding ischaemia of injury- matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and EPAC, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced ten-dency to MPTP opening following reperfusion. Further, simultaneous stimulation of PKA & EPAC causes cardioprotection which is additive to the innate resistance.

PTK6, a Non-Receptor–Tyrosine-Kinase, modulates the pathogenesis of breast and prostate cancers, and is recognized as a biomarker of breast cancer prognosis. There are over 30 known substrates of PTK6, including signal transducers, transcription factors and RNA binding proteins. Many of these substrates are known drivers of other cancer types such as colorectal cancer. Colon and rectal tumours also express higher levels of PTK6 than the normal intestine suggesting a potential role in tumorigenesis. However, the importance of PTK6 in colorectal cancer remains unclear. PTK6 inhibitors such as XMU-MP-2 and Tilfrinib have demonstrated potency and selectivity in breast cancer cells when used in combination with chemotherapy, indicating the potential for PTK6 targeted therapy in cancer. However, most of these inhibitors are yet to be tested in other cancer types. Here, we discuss the current understanding of the function of PTK6 in normal intestinal cells compared with colorectal cancer cells. We review existing PTK6 targeting therapeutics and explore the possibility of PTK6 inhibitory therapy for colorectal cancer.

Laser scanning systems make use of Light Detection and Ranging (LiDAR) technology to acquire accurately georeferenced sets of dense 3D point cloud data. The information acquired using these systems produces better knowledge about the terrain objects which are inherently 3D in nature. The LiDAR data acquired from mobile, airborne or terrestrial platforms provides several benefit over conventional sources of data acquisition in terms of accuracy, resolution and attributes. However, the large volume and scale of LiDAR data have inhibited the development of automated feature extraction algorithms due to the extensive computational cost involved in it. Moreover, the heterogeneously distributed point cloud, which represents objects with varying size, point density, holes and complicated structures pose a great challenge for data processing. Currently, geospatial database systems do not provide a robust solution for efficient storage and accessibility of raw data in a way that data processing could be applied based on optimal spatial extent. In this paper, we present Global LiDAR and Imagery Mobile Processing Spatial Environment (GLIMPSE) system that provides a framework for storage, management and integration of 3D LiDAR data acquired from multiple platforms. The system facilitates an efficient accessibility to the raw dataset, which is hierarchically represented in a geographically meaningful way. We utilise the GLIMPSE system to automatically extract road median from Airborne Laser Scanning (ALS) point cloud. In the first part of this paper, we detail an approach to efficiently retrieve the point cloud data from the GLIMPSE system for a particular geographic area based on user requirements. In the second part, we present an algorithm to automatically extract road median from the retrieved LiDAR data. The developed road median extraction algorithm utilises the LiDAR elevation and intensity attributes to distinguish the median from the road surface. We successfully tested our algorithms on two road sections consisting of distinct road median types based on concrete and grass-hedge barriers. The use of GLIMPSE improved the efficiency of the road median extraction in terms of fast accessibility to ALS point cloud data for the required road sections. The developed system and its associated algorithms provide a comprehensive solution to the user's requirement for an efficient storage, integration, retrieval and processing of large volumes of LiDAR point cloud data. These findings and knowledge contribute to a more rapid, cost-effective and comprehensive approach to surveying road networks.

Lifestyle health has been recognized as an evidence-based innovation that defines how daily habits and practices impact both the prevention and treatment of disease and provides an important adjunctive component to overall health. Specifically, an approach with small changes over time can have a dramatic impact on the health and well-being of individuals not only, in general, but also can be applied to skin health. However, lifestyle health factors to improve skin well-being have not been discussed extensively and/or well promulgated. The narrative for this overview focuses on providing a summary for topic background information, but more importantly, presents four lifestyle factors that can improve dermal health [i.e., factor 1: nutrition - diet; factor 2: rest (sleep); factor 3: movement/physical exercise, and factor 4: social and community associations]. This was accomplished by identifying previous journal articles and reviews with emphasis over the last five years (from January 2018 through July 2023; 156 out of 190 references cited or 82 %) using scientific search databases. The main conclusions of this overview encourage the concept that lifestyle health factors such as nutrition/diet, rest/sleep, movement/physical exercise, and community/social interactions support enhanced skin health and well-being with aging. Plus, social media interventions that aim to promote dietary, sleep and physical activity changes might be an application to improve skin health in the future.

This paper is devoted to an accurate determination of the London dispersive and polar free energy of adsorption, the two Lewis acid γs+ and base γs- components of polar surface energy γsAB of 2D single-crystalline and polycrystalline covalent organic frameworks such as TAPPy-TPA-COFs. Inverse gas chromatography (IGC) at infinite dilution was used to quantify the different surface parameters of the different materials. From IGC measurements, one determined the net retention time of the adsorption of n-alkanes and several polar solvents on single-crystalline and polycrystalline covalent organic frameworks. The free surface Gibbs energy of adsorption was obtained for the various organic molecules at different temperatures from their net retention volume values. The separation between the London dispersive energy and the polar energy of adsorbed molecules was carried out by using a new thermodynamic parameter PSX chosen as new indicator variable and taken into account the deformation polarizability and the harmonic mean of the ionization energies of solvents and solid materials, derived from London dispersion equation. The obtained results are very promising for the accurate determination of the surface thermodynamic parameters of adsorption of organic solvents on solid surfaces.

Work has begun in earnest to formulate a post-2020 Global Biodiversity Framework which will outline the vision and targets for the next decade of biodiversity conservation and beyond. However, the performance of the 2011-2020 Strategic Plan for Biodiversity suggests that even a meaningful target can fail to deliver if not accompanied by fit-for-purpose indicators. Here we provide a review of how ‘protected area’ effectiveness was addressed in the 2011-2020 plan and based on this, provide recommendations for fit-for-purpose indicators that will measure how such efforts contribute to the conservation of biodiversity. Indicators need to be built on quantitative data from site-level biodiversity monitoring of species and ecosystems combined with measurements of the state of nature in near-time, informed by remote-sensed products and other technologies. Additionally, indicators need to capture whether the essential elements of good management are in place including the identification of ecological values, threats, and objectives, equitable governance, and sufficient management resources and capacity. These fit-for-purpose indicators will require multilateral collaboration to galvanize support for, and resources to develop, the necessary infrastructure to collate and store information from countries.

This paper presents a comparison of the predictive capability of three hydrological models in a heavily influenced catchment in Peninsula India. In catchments where there is a high dependence on both streamflow and groundwater to meet demands, it is of importance to capture the catchment processes correctly. This study highlights the performance evaluation of a multi-model ensemble consisting of GWAVA (Global Water AVailability Assessment) model, SWAT (Soil Water Assessment Tool) and VIC (Variable Infiltration Capacity) model for comparative purposes and the key catchment hydrological processes. The three models were compared in several sub-catchments in the upstream reaches of the Cauvery river catchment. Model performances for monthly streamflow simulations from 1983 – 2005 were analysed for five catchments in the Upper Cauvery. The analysis was undertaken using Nash- Sutcliffe Efficiency, Kling- Gupta Efficiency and percent bias. Additionally, a mean ensemble is presented. The application of a multi-model ensemble approach can be useful in overcoming the uncertainties associated with individual models. The ensemble mean has a better predictive ability in catchments with reservoirs than the individual models. Utilising multiple models could be a suitable methodology to offset uncertainty in input data and poor reservoir operation functionality within individual models. This study has highlighted the importance of an accurate spatial representation of precipitation for input into hydrological models and comprehensive reservoir functionality is paramount to obtaining good results in this region.

Scholars of the English Literature unanimously say that J.R.R. Tolkien and C.S. Lewis influenced each other writings. For the first time we have investigated this issue mathematically by using an original multi–dimensional analysis of linguistic parameters, based on surface deep–language variables and linguistic channels. To set our investigation in the framework of the English Liter-ature, we have considered some novels written by earlier authors, such as C. Dickens, G. Mac-Donald and others. The deep–language variables and the linguistic channels, discussed in the paper, are likely due to writers’ unconscious design and have revealed connections between texts far beyond writers’ awareness. In summary, the capacity of the extended short–term memory required to readers, the universal readability index of texts, the geometrical representation of texts and the fine tuning of linguistic channels within texts – all tools largely discussed in the paper – have revealed strong connections between The Lord of the Rings (Tolkien), The Chronicles of Narnia, The Space Trilogy (Lewis) and novels by MacDonald, therefore in agreement with what scholars of the English Literature say.

Blockchain technology (BCT) has the potential for sustainable development, enhancing business efficiency, reducing costs, and strengthening data security. Despite its potential, adoption among small and medium-sized enterprises (SMEs) is low due to the need for significant changes in technology infrastructure and the challenge of interoperability. A cross-sectional survey was done with 226 Hong Kong SMEs. The PLS-SEM results highlighted favorable transformation conditions as the most critical factor for SMEs considering the adoption of BCT. These conditions address both internal and external readiness for adopting the disruptive strategy. Other contributing factors to BCT adoption include trust in BCT developers, perceived usefulness and ease of use, government support, and perceived security. The research results contributed to the literature on disruptive technology acceptance, adoption, transformation conditions, technology readiness, and SMEs’ technology adoption. Government-supported policies and initiatives can promote BCT adoption, including educational programs, case studies, and resources for readiness. Financial support and regulatory frameworks can further encourage adoption. BCT developers can demonstrate the value of their systems, effectively communicate potential ROI and cost savings, and provide user-friendly interfaces to increase SMEs’ intention to adopt BCT.

The Rosetta software suite for macromolecular modeling, docking, and design is widely used in pharmaceutical, industrial, academic, non-profit, and government laboratories. Considering its broad modeling capabilities, Rosetta consistently ranks highly when compared to other leading methods created for highly specialized protein modeling and design tasks. Developed for over two decades by a global community of scientists at more than 60 institutions, Rosetta has undergone multiple refactorings, and now comprises over three million lines of code. Here we discuss the methods developed in the last five years, involving the latest protocols for structure prediction, protein–protein and protein–small molecule docking, protein structure and interface design, loop modeling, the incorporation of various types of experimental data, and modeling of peptides, antibodies and other proteins in the immune system, nucleic acids, non-standard amino acids, carbohydrates, and membrane proteins. We briefly discuss improvements to the energy function, user interfaces, and usability of the ­­software. Rosetta is available at www.rosettacommons.org.

Lewis Carroll, both logician and writer, suggested a logical paradox containing furthermore two connotations (connotations or metaphors are inherent in literature rather than in mathematics or logics). The paradox itself refers to implication demonstrating that an intermediate implication can be always inserted in an implication therefore postponing its ultimate conclusion for the next step and those insertions can be iteratively and indefinitely added ad lib, as if ad infinitum. Both connotations clear up links due to the shared formal structure with other well-known mathematical observations: (1) the paradox of Achilles and the Turtle; (2) the transitivity of the relation of equality. Analogically to (1), one can juxtapose the paradox of the Liar (for Lewis Carroll’s paradox) and that of the arrow (for “Achilles and the Turtle”), i.e. a logical paradox, on the one hand, and an aporia of motion, on the other hand, suggesting a shared formal structure of both, which can be called “ontological”, on which basis “motion” studied by physics and “conclusion” studied by logic can be unified being able to bridge logic and physics philosophically in a Hegelian manner: even more, the bridge can be continued to mathematics in virtue of (2), which forces the equality (for its property of transitivity) of any two quantities to be postponed analogically ad lib and ad infinitum. The paper shows that Hilbert arithmetic underlies naturally Lewis Carroll’s paradox admitting at least three interpretations linked to each other by it: mathematical, physical and logical. Thus, it can be considered as both generalization and solution of his paradox therefore naturally unifying the completeness of quantum mechanics (i.e. the absence of hidden variables) and eventual completeness of mathematics as the same and isomorphic to the completeness of propositional logic in relation to set theory as a first-order logic (in the sense of Gödel (1930)’s completeness theorems).

In this article we shed light on the position of Finland in conversations on the movement of unprovenanced cultural objects, within the national, the Nordic and the global contexts. Finland’s geopolitical position, as a ‘hard border’ of the European Union neighbouring the Russian Federation, and its current legislative provisions which do not include import regulation, mean that nonetheless has the potential to be significant in understanding the movement of cultural property at transnational levels. In particular, we outline a recent initiative started at the University of Helsinki to kick-start a national debate on ethical working with cultural object and manuscripts. We analyse exploratory research on current awareness and opinion within Finland, and summarize our current work to produce robust research ethics to guide scholars working in Finland. Although Finland has a small population and is usually absent from international discussions on the illicit movement of cultural property (save a few exceptions), we argue that it is still possible — and important — to affect policy and attitudes concerning art crime, provenance, and the role of stakeholders such as decision-makers, traders and the academy.

In recent years, compound glass microsphere resonator devices have attracted increasing interest and have been widely used in sensing, microsphere lasers, and nonlinear optics. Compared with traditional silica resonators, compound glass microsphere resonators have many significant and attractive properties, such as high-Q factor, an ability to achieve high rare earth ion, wide infrared transmittance and low phonon energy. This review provides a summary and a critical assessment of the fabrication and the optical characterization of compound glasses and the related fabrication and applications of compound glass microsphere resonators.

We interviewed 48 people including local communities, ex hunters and protected area management professionals. The purpose of the interviews was to understand the motivations for, and the nature of, illegal hunting of prey species of iconic predators - tigers and leopards - in the northern section of Bardia National Park. Participants reported that hunting of prey species occurs mostly in spring and autumn and is less common during the summer. In the past, hunting was primarily for the purposes of obtaining meat for household consumption. Since the introduction of a road network in the region, opportunities to sell wild meat at ad-hoc ‘highway markets’ have developed. The purported medicinal properties of wild meat was also cited as a driver for illegal hunting. Mostly, locally hand-made guns are used for hunting and the use of dogs in hunting was often reported. Protected area managers informed that illegal hunting problems in the study area are associated with a lack of presence of park authorities, remoteness and underdevelopment and poverty of the community. Our study suggested that skills development training for local community members might reduce dependency on wild meat for household consumption and earning thereby reducing illegal hunting.

The objective of this pilot study was to compare glucose concentrations in capillary blood (CB) samples analysed in a laboratory by a validated method and glucose concentrations measured in the interstitial fluid (ISF) by continuous glucose monitoring under different physical activity levels in a postprandial state in healthy and active subjects without diabetes. Ten healthy, active subjects (26±4 years, 67±11 kg bodyweight (BW), 11±3 h) were included in the study. Within 14 days, they underwent six tests consisting of a) resting fasted (R/Fast), b) resting after intake of 1 g glucose/kg BW (R/Glc) and c) running for 60 minutes at moderate (65/Glc) and d) high (85/Glc) intensity after intake of 1 g glucose/kg BW. Data were collected in the morning, following a standardised dinner before test day. Sensor-based glucose concentrations were compared to simultaneous capillary blood glucose concentrations. Pearson’s r correlation coefficient was highest for R/Glc (.92, p<.001) compared to R/Fast (.45, p<.001), 65/Glc (.60, p<.001) and 85/Glc (.70, p<.001). Mean absolute relative deviation (MARD) and standard deviation (SD) was smallest for resting fasted and similar between all other conditions (R/Fast: 8±6%, R/Glc: 17±12%, 65/Glc: 22 ± 24%, 85/Glc: 18±17%). However, Bland-Altman plot analysis showed a higher range between lower and upper limits of agreement (95% confidence interval) of paired data under exercising compared to resting conditions. Under resting fasted conditions, both methods produce similar outcomes. Under resting postprandial and exercising conditions, respectively, there are differences between both methods. However, further data in healthy subjects need to be gathered considering physical activity and nutrition status.

Adventurous play, defined as exciting, thrilling play where children are able to take age-appropriate risks has been associated with a wide range of positive outcomes. Despite this, it remains unclear what factors might aid or hinder schools in offering adventurous play opportu-nities. The purpose of this systematic review is to synthesise findings from qualitative studies on the perceived barriers and facilitators of adventurous play in schools. A total of nine studies were included in the final synthesis. The review used two synthesis strategies: a meta-aggregative syn-thesis and narrative synthesis. Findings were similar across the two syntheses, highlighting that key barriers and facilitators were: adults’ perceptions of children; adults’ attitudes and beliefs about adventurous play and concerns pertaining to health; and, safety and concerns about legis-lation. Based on the findings of the review, recommendations for policy and practice as provided to support adventurous play in schools.

The use of bioethanol in cooking is not new, but until recently its application has been confined exclusively to small scale projects. However, a new bioethanol cooking utility in Kenya has now reached mass market adoption, serving more than 950,000 households with cooking fuel since launching in late 2019. Its success was made possible by a significant investment in technology to facilitate safe, convenient and affordable fuel distribution. It is funded by climate finance which is based on bioethanol fuel replacing charcoal used for cooking, a leading cause of African defor-estation. This development has been so recent that it has not widely been discussed in the academic literature. More broadly, the health, environmental and economic impacts of bioethanol for cooking have not been systematically assembled in one place. This article details what is known about the impact of bioethanol for cooking, how and why bioethanol for cooking was able to suddenly reach commercially viable scale in spite of the challenges it faced. It also discusses implications for further scaling of clean cooking fuel solutions.

Non-alcoholic fatty liver disease (NAFLD), a frequent complication of metabolic syndrome and visceral obesity, is characterized by marked accumulation of lipids in hepatocytes, accompanied by oxidant stress. In a substantial minority of cases, this progresses to steatohepatitis, which in turn can lead to life-threatening hepatic fibrosis and/or hepatocarcinogenesis. This essay analyzes the molecular biology underlying fat accumulation and oxidant stress in NAFLD, and identifies targets that can be addressed by nutraceutical or dietary measures. Nutraceuticals with potential for prevention or control of NAFLD – as suggested on theoretical grounds, and borne out by experience in rodent studies and/or clinical trials - include ferulic acid, melatonin, methylnicotinamide, tetrahydrocurcumin, nicotinamide riboside, carnosic acid, urolithin A, quercetin, high-dose biotin, citrulline, astaxanthin, long-chain omega-3 fatty acids, berberine, lipoic acid, silibinin, N-acetylcysteine, taurine, capsaicin, spermidine, spirulina, and carnitine. Some of these agents can also address the NLRP3 inflammasome activation and transforming growth factor-β signaling that play a role in driving the transition to steatohepatitis and fibrosis. In addition, soy isoflavones, via estrogen receptor-beta agonism, have anti-fibrotic potential, and supplemental glycine may blunt the contribution of Kupffer cells to the progression of NAFLD. Whole-food plant-based diets of modest protein content, owing to their impact on hormones such as fibroblast growth factor 21 and adiponectin, as well as on the obesity and metabolic syndrome underlying NAFLD, may also be protective in this syndrome. There is considerable potential for complex medical foods or nutraceutical supplementation regimens of rational design to aid prevention and control of NAFLD.

The purpose of this research was two-fold: (a) to observe whether highly trained adolescent swimmers abide to vitamin D supplement recommendations; and (b) to monitor changes in circulating 25-hydroxyvitamin D (25(OH)D) that occur between the autumn and winter months. Twenty swimmers (age: 17 ± 2 years) from a UK high-performance swimming club volunteered to complete two blood spot cards to determine 25(OH)D concentration: the first in an autumn training phase (October) and the second during winter training (January). All swimmers were advised to consume vitamin D3 supplements across the assessment period; however, only 50% of swimmers adhered to this recommendation. Resultantly, a winter decline in 25(OH)D was observed in non-supplementing swimmers (79.6 ± 25.2 to 52.6 ± 15.1 nmol·L-1, p = 0.005), with swimmers either displaying an ‘insufficient’ (60%) or ‘deficient’ (40%) vitamin D status. In comparison, greater maintenance of 25(OH)D occurred in supplementing swimmers (92.0 ± 25.5 to 97.2 ± 38.3 nmol·L-1, p = 0.544), although variable outcomes occurred at the individual level (four increased, three maintained, three declined). These findings highlight possible risks of vitamin D insufficiency during the winter for swimmers in the UK, possibly requiring standardised supplement practices. Moreover, alternative educational strategies may be required for swimmers to transfer knowledge to practice in order to improve supplement adherence in future.

A remarkable feature of US federal investments in human genetics has been the availability of parallel funding for studies examining ethical, legal and social implications (ELSI). This funding has allowed ELSI researchers to develop new strategies to understand genetics, evaluate the benefits of genetic testing, and propose health policy that maximize the promise while minimizing harms. Despite successes, a consequence of this investment is the preoccupation with what is arguably the least actionable system of biomolecules, human DNA. In contrast, the most actionable system of biomolecules, the metabolome, is grossly understudied, despite its often more alarming ELSI.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017/2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four parameter logistic) curves. The NHANES cohort (n=2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs 44 [25, 61] µmol/L, p&lt;0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs 53 [24, 104] mg/d, p=0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst the those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had lower a BMI than the NHANES cohort (26 [24, 28] kg/m2 vs 29 [25, 34] kg/m2, respectively). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes have 1.4- to 1.6-fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes.

Background: To inform global health policies and resources planning, this paper analyzes evolving trends in physical rehabilitation needs, using data on Years Lived with Disability (YLDs) from the Global Burden of Disease Study (GBD) 2017. Methods: Secondary analysis of how YLDs from conditions amenable to physical rehabilitation have evolved from 1990 to 2017, for the world and across countries of varying income levels. Linear regression analyses were used. Results: A 66.2% growth was found in estimated YLD Counts amenable to physical rehabilitation: a significant and linear growth of more than 5.1 billion YLDs per year (99%CI: 4.8–5.4; r² = 0.99). Low-income countries more than doubled (111.5% growth) their YLD Counts amenable to physical rehabilitation since 1990. YLD Rates per 100,000 people and the percentage of YLDs amenable to physical rehabilitation also grew significantly over time, across locations (all p > 0.05). Finally, only in high-income countries Age-standardized YLD Rates significantly decreased (p < 0.01; r² = 0.86). Conclusions: Physical rehabilitation needs have been growing significantly in absolute, per-capita and in percentage of total YLDs, globally and across countries of varying income level. In absolute terms, growths were higher in lower income countries, wherein rehabilitation is under-resourced.

The effects of four cycles of recurrent selection on simple sequence repeat (SSR) marker allele frequencies and population structure were examined in the Maksimir 3 Synthetic (M3S) maize population (Zea mays L.). Genotyping of 32 plants from each cycle of selection at 38 SSR loci revealed that the mean number of alleles per locus and the mean expected heterozygosity were preserved over cycles of selection, indicating maintenance of sufficient genetic variability in the population needed for future genetic gain. Waples test of selective neutrality revealed that genetic drift was the main force in changing allele frequencies in the population. The proportion of selectively nonneutral loci in single cycles of selection varied between 16% and 37%. Some nonneutral loci shared the same genomic locations with previously published QTLs controlling important agronomic traits. Between 5% and 29% of loci were found to be in significant Hardy-Weinberg (HW) disequilibrium with the majority showing an excess of homozygosity. Excess of homozygosity at several loci was highly consistent across cycle populations suggesting positive assortative mating as the possible cause of the observed HW disequilibrium. Linkage disequilibrium (LD) tests revealed that the M3S population was essentially in linkage equilibrium. The proportion of pairs of loci in significant LD varied across cycles of selection between 0.1% and 1.8% probably due to the effects of genetic drift and epistatic selection.

COVID-19, caused by SARS-CoV-2, was first identified in China in 2019. The exact origin of the disease remains uncertain, with theories suggesting it may have emerged from animals or accidentally leaked from a research laboratory. If the hypothesis that COVID-19 originated from a research laboratory is accurate, it is crucial to investigate potential pathways for pathogens to escape from biocontainment research animal facilities (BRAFs). We examine key biosafety issues associated with BRAFs, including inadequate decontamination procedures for water and experimental samples, handling high biosafety level pathogens in lower level laboratories, risks of animal bites and sharps injuries, contamination of bedding and enrichment materials, and improper management and transportation of biohazard samples. Additionally, we discuss the role of veterinarians in African research animal facilities and the challenges they encounter in maintaining biocontainment standards. We emphasize the importance of routine monitoring of effluent water to detect possible disease outbreaks. We recommend a thorough investigation of the COVID-19 pandemic to identify potential sources of pathogen release from BRAFs, which could serve as hotspots for future disease outbreaks. Findings from such investigations will inform the development of policies aimed at safeguarding human populations from future pandemics and preventing BRAFs from becoming sources of infectious disease outbreaks.

If given the correct remotely sensed information, machine learning can accurately describe soil moisture conditions in a heterogeneous region at the large scale based on soil moisture readings at the small scale through rule transference across scale. This paper reviews an approach to increase soil moisture resolution over a sample region over Australia using the Soil Moisture Active Passive (SMAP) sensor and Landsat 8 only and a validation experiment using Sentinal-2 and the Advanced Microwave Scanning Radiometer (AMSR-E) over Nevada. This approach uses an inductive localized approach, replacing the need to obtain a deterministic model in favor of a learning model. This model is adaptable to heterogeneous conditions within a single scene unlike traditional polynomial fitting models and has fixed variables unlike most learning models. For the purposes of this analysis, the SMAP 36 km soil moisture product is considered fully valid and accurate. Landsat bands coinciding in collection date with a SMAP capture are down sampled to match the resolution of the SMAP product. A series of indices describing the Soil-Vegetation-Atmosphere Triangle (SVAT) relationship are then produced, including two novel variables, using the down sampled Landsat bands. These indices are then related to the local coincident SMAP values to identify a series of rules or trees to identify the local rules defining the relationship between soil moisture and the indices. The defined rules are then applied to the Landsat image in the native Landsat resolution to determine local soil moisture. Ground truth comparison is done via a series of grids using point soil moisture samples and air-borne L-band Multibeam Radiometer (PLMR) observations done under the SMAPEx-5 campaign. This paper uses a random forest due to its highly accurate learning against local ground truth data yet easily understandable rules. The predictive power of the inferred learning soil moisture algorithm did well with a mean absolute error of 0.054 over an airborne L-band retrieved surface over the same region.

The Great Barrier Reef (GBR) is currently experiencing widespread crown of thorns starfish (CoTS) outbreaks as part of the fourth wave of outbreaks since 1962. It is believed that outbreaks have become more frequent on the GBR and elsewhere in the Indo-Pacific associated with anthropogenic causes. The two widely accepted potential causes are (1) anthropogenic nutrient enrichment leading to increased biomass of phytoplankton, the food of the planktonic stage of larval CoTS; and (2) overfishing of predators on the juvenile to adult stages of CoTS, for example, commercial fished species such as coral trout. In this study, we show the evidence for the nutrient enrichment causation hypothesis is strong based on a large number of recent studies in the GBR. We also hypothesise that secondary outbreaks in the region between Cairns and Townsville can also be enhanced by nutrient enriched conditions associated with the annual nutrient discharge from Wet Tropics rivers.

Pneumonia is the leading cause of hospitalization in pediatric patients. Disease severity greatly influences pneumonia progression and adverse health outcomes such as hospital readmission. Hospital readmissions have become a measure of healthcare quality to reduce excess expenditures. The aim of this study was to examine 30-day all-cause readmission rates and evaluate the association between pneumonia severity and readmission among pediatric pneumonia hospitalizations. Using 2018 Nationwide Readmissions Database (NRD), we conducted a cross-sectional study of pediatric hospitalizations for pneumonia. Pneumonia severity was defined by the presence of respiratory failure, sepsis, mechanical ventilation, dependence on long-term supplemental oxygen, and/or respiratory intubation. Outcomes of interest were 30-day all-cause readmission, length of stay, and cost. The rate of 30-day readmission for the total sample was 5.9%, 4.7% for non-severe pneumonia, and 8.7% for severe pneumonia (p&lt;0.01). Among those who were readmitted, hospitalizations for severe pneumonia had a longer length of stay (6.5 vs. 5.4 days, p&lt;0.01) and higher daily cost ($3,246 vs. $2,679, p&lt;0.01) than admissions for non-severe pneumonia. Factors associated with 30-day readmission were pneumonia severity, immunosuppressive conditions, length of stay, and hospital case volume. To reduce potentially preventable readmissions, clinical interventions to improve the disease course and hospital system interventions are necessary.

The enormous increase in the volume of Earth Observations (EOs) has provided the scientific community with unprecedented temporal, spatial, and spectral information. However, this increase in the volume of EOs has not yet resulted in proportional progress with our ability to forecast agricultural systems.This study examines the applicability of EOs obtained from Sentinel2 and Landsat8 for constraining the APSIM-Maize model parameters. We leveraged leaf area index (LAI) retrieved from Sentinel2 and Landsat8 NDVI to constrain a series of APSIM-Maize model parameters in three different Bayesian multi-criteria optimization frameworks across 13 different sites across the U.S Midwest. A time variant sensitivity analysis was performed to identify the most influential parameters driving the LAI estimates in APSIM-Maize model. Then surrogate models were develop using random samples taken from the parameter space using Latin hypercube sampling to emulate APSIM’s behavior in simulating NDVI and LAI at all sites. Site-level, global and hierarchical Bayesian optimization models were then developed using the site-level emulators to simultaneously constrain all parameters and estimate the site to site variability in crop parameters. For within sample predictions, site-level optimization showed the largest predictive uncertainty around LAI and crop yield, whereas the global optimization showed the most constraint predictions for these variables. Lowest RMSE for within sample yield prediction was found for hierarchical optimization scheme (1423 Kg ha−1) while the largest RMSE was found for site-level (1494 Kg ha−1). In out-of-sample predictions within the spatio-temporal extent of the training sites, global optimization showed lower RMSE (1627 Kg ha−1) compared to the hierarchical approach (1822 Kg ha−1) across 90 independent sites in the U.S Midwest. On comparison between these two optimization schemes across another 242 independent sites outside the spatio-temporal extent of the training sites, global optimization also showed substantially lower RMSE (1554 Kg ha−1) as compared to the hierarchical approach (2532 Kg ha−1). Overall, EOs demonstrated their real use case for constraining process-based crop models and showed comparable results to model calibration exercises using only field measurements.

Background:Almost the entire country of Burkina Faso was endemic to onchocerciasis. Onchocerciasis control efforts thus brought the prevalence of O. volvulus to a level where the disease was no longer a public health problem and a national onchocerciasis control program was set up in 1991 to ensure surveillance and maintain the gains made. A resurgence of onchocerciasis cases has been observed in two regions (Comoé, South West) located around several river basins in the 2010-2011. In accordance with WHO guidelines, for the management of resurgent cases, CDTI was implemented in the affected areas of Comoé and Sud-Ouest regions. Methodology: We conducted an extensive analysis to determine the effects of CDTI on parasitological indices of onchocerciasis in these two areas and we also analyzed the data in relation to the location of the village in relation to the river to see if this was a factor in the decrease in prevalence. Results: A total of 43 villages in 6 health districts, i.e., 100% of the villages that participated in the epidemiological surveys before and after the implementation of CDTI in the Southwest and Cascade regions were included in the study. The key findings were that standardized microfilaria prevalence and CMFL decreased significantly after the implementation of CDTI in both regions. For the average of the two regions, the results for standardized microfilaria prevalence were -5.91 with a 95% confidence interval of (-9.67; -2.16) and for CMFL were -0.29 with a 95% confidence interval of (-0.57; -0.01). Our results showed also a decline in standardized microfilaria prevalence and CMFL in all villages involved in the study. Moreover, the drop in the trajectory of the curve representing the predicted standardized microfilaria prevalence of villages located within 5 km of the streams was greater than that of villages located more than 5 km from the streams. Conclusion: Our results thus show that the implementation of effective CDTI could stop the transmission of O. volvulus in these two regions. The main challenge for stopping transmission could be the migration of populations to neighboring countries and migration of the vector from one country to another, as Burkina Faso shares some river basins with neighboring countries.

A method for generating fluoroscopic (time-varying) volumetric images using patient-specific motion models derived from 4-dimensional cone-beam CT (4D-CBCT) images is developed. 4D-CBCT images acquired immediately prior to treatment have the potential to accurately represent patient anatomy and respiration during treatment. Fluoroscopic 3D image estimation is done in two steps: 1) deriving motion models and 2) optimization. To derive motion models, every phase in a 4D-CBCT set is registered to a reference phase chosen from the same set using deformable image registration (DIR). Principal components analysis (PCA) is used to reduce the dimensionality of the displacement vector fields (DVFs) resulting from DIR into a few vectors representing organ motion found in the DVFs. The PCA motion models are optimized iteratively by comparing a cone-beam CT (CBCT) projection to a simulated projection computed from both the motion model and a reference 4D-CBCT phase, resulting in a sequence of fluoroscopic 3D images. Patient datasets were used to evaluate the method by estimating the tumor location in the generated images compared to manually defined ground truth positions. Experimental results showed that the average tumor mean absolute error (MAE) along the superior-inferior (SI) direction and the 95th percentile in two patient datasets were (2.29 mm and 5.79 mm) for patient 1 and (1.89 mm and 4.82 mm) for patient 2. This study has demonstrated the feasibility of deriving 4D-CBCT-based PCA motion models that have the potential to account for the 3D non-rigid patient motion and localize tumors and other patient anatomical structures on the day of treatment.

Polyethylene terephthalate (PET) pollution poses significant environmental consequences, and thus new degradation methods must be explored to mitigate this problem. We previously demonstrated that a consortium of three Pseudomonas and two Bacillus species can synergistically degrade PET in culture. The consortium more readily consumes Bis(2-Hydroxyethyl) terephthalate (BHET), a byproduct made in PET depolymerization, compared to PET, and can fully convert BHET into metabolically usable monomers terephthalic acid (TPA) and ethylene glycol (EG). Because of its crystalline structure, the main limitation of the biodegradation of post-consumer PET is the initial transesterification from PET to BHET, depicting the need for the transesterification step in the degradation process. Additionally, there have been numerous studies done on the depolymerization reaction of PET to BHET, yet few have tested the biocompatibility of that product with a bacterial consortium. In this report, a two-step process was implemented for sustainable PET biodegradation, where PET is first depolymerized to form BHET using an Orange Peel Ash (OPA) catalyzed glycolysis reaction, followed by complete degradation of the BHET glycolysis product by the bacterial consortium. Results show that OPA-catalyzed glycolysis reactions can fully depolymerize PET, with an average BHET yield of 92% (w/w) and that the reaction product is biocompatible with the bacterial consortium. After inoculation with the consortium, 19% degradation of the glycolysis product was observed in 2 weeks, for a total degradation percentage of 17% when taking both steps into account. Furthermore, the 10-week total BHET degradation rate was 35%, demonstrating that the glycolysis products are biocompatible with the consortium for longer periods of time, for a total two-step degradation rate of 33% over 10 weeks. While we predict complete degradation is achievable using this method, further experimentation with the consortium can allow for a circular recycling process, where TPA can be recovered from culture media and reused to create new materials.

Lipidomics provides comprehensive study of all lipid components in cells, serum, plasma or tissues of organisms, aiming to the discovery of diagnostic, prognostic and predictive biomarkers of diseases such as malignancies. This systematic review evaluates studies, where lipidomics applies to the diagnosis, prognosis, prediction of ovarian cancer (OC) and the discrimination between malignant and benign ovarian masses. Literature search was conducted in PubMed, Science Direct and SciFinder. Only publications written in English language after 2012 were included. From the reference lists of primary included studies, relevant citations were identified and were also added in our list. All studies included referred to the application of lipidomics in serum/plasma samples of human cases with OC, whereby few of them included also tumor tissue samples. In some of the included studies metabolomic analysis was also involved where other metabolites besides lipids were identified. Qualitative data were assessed and risk of bias was determined using the ROBINS-I tool. In total, 29 studies were included, 15 of which applied non-targeted, 7 targeted lipidomics and 7 were reviews relevant to our aim. Most studies concerned the possible application of lipidomics in OC diagnosis, exhibiting phospholipids and sphingolipids as the most significantly altered during development of the disease. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management.

The Lewis basicity of selected organic bases, modeled by the enthalpies of adduct formation between gaseous BF3 and the bases in dichloromethane (DCM) solution, is critically examined. Although experimental enthalpies for a large number of molecules have been reported in the literature, it may be desirable to estimate missing or uncertain data for important Lewis bases. We have decided to use high-level ab initio procedures, combined with a polarized continuum solvation model, in which the solvated species are the clusters formed by specific hydrogen bonding of DCM with the Lewis base and the Lewis base/BF3 adduct. This mode of interaction with DCM corresponds to a specific solvation model (SSM). The results actually show that the enthalpy of BF3 adduct formation in DCM solution is clearly influenced by specific interactions, DCM acting as hydrogen-bonding donor (HBD) molecule in two ways: base/DCM and adduct/DCM, confirming that specific solvation is an important contribution to experimentally determined Lewis basicity scales. This analysis allows us to conclude that there are reasons to suspect some gas-phase values to be in error by more than the stated experimental uncertainty. Some experimental values in DCM solution that were uncertain because of identified reasons can be complemented by the computed values.

Recently, there has been renewed interest in the performance, functionality, and sustainability of traditional small-scale storage interventions (check dams, farm bunds and tanks) used across India for the improvement of local water security. The Central Groundwater Board of India is en-couraging the construction of such interventions for the alleviation of water scarcity. It is of critical importance to understand the hydrological effect of these interventions at basin scales to maximise their effectiveness. The quantification of small-scale interventions in hydrological modelling is often neglected, especially in large-scale modelling exercises. A bespoke version of the GWAVA model was developed to assess the impact of interventions on the water balance of the Cauvery Basin and two smaller sub-catchments. Model results demonstrate that farm bunds appear to have a negligible effect on the estimated average annual simulated streamflow at the outlets of the two sub-catchments and the basin whereas tanks and check dams have a more significant effect. In-terventions generally were found to increase evaporation losses across the catchment. The model adaption used in this study provides a step-change in the conceptualisation and quantification of the consequences of small-scale storage interventions in large- or basin-scale hydrological models.

(1) Background: There is robust evidence of an attention bias-anxiety relationship in children, but lack of appropriate methods has limited the number of studies with children younger than 8 years old. This study used eye-tracking as a measure of overt attention in young children. The aim of this study was to assess anxiety related attention bias in children aged 4 to 8 years. Age was considered as a moderator and the influence of effortful control was investigated. (2) Method: A community sample of 104 children were shown pairs of happy-neutral and angry-neutral faces. Growth curve analyses were used to examine patterns of gaze over time. (3) Results: Analyses revealed moderation by age and anxiety, with distinct patterns of anxiety-related biases seen in different age groups in the angry-neutral face trials. Effortful control did not account for age related effects. (4) Conclusions: Results support a moderation model of the development of anxiety in children.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or “PEM”), and by fatigue whose severity and associated requirement for rest are excessive and disproportionate to the fatigue-inducing activity. There is no definitive molecular marker or known underlying pathological mechanism for the condition. Increasing evidence for aberrant energy metabolism suggests a role for mitochondrial dysfunction in ME/CFS. Our objective was therefore to measure mitochondrial function and cellular stress sensing in actively metabolising patient blood cells. We immortalized lymphoblasts isolated from 51 ME/CFS patients diagnosed according to the Canadian Consensus Criteria and an age- and gender-matched control group. Parameters of mitochondrial function and energy stress sensing were assessed by Seahorse extracellular flux analysis, proteomics, and an array of additional biochemical assays. As a proportion of the basal oxygen consumption rate (OCR), the rate of ATP synthesis by Complex V was significantly reduced in ME/CFS lymphoblasts, while significant elevations were observed in Complex I OCR, maximum OCR, spare respiratory capacity, nonmitochondrial OCR and “proton leak” as a proportion of the basal OCR. This was accompanied by a reduction of mitochondrial membrane potential, chronically hyperactivated TOR Complex I stress signalling and upregulated expression of mitochondrial respiratory complexes, fatty acid transporters and enzymes of the β-oxidation and TCA cycles. By contrast, mitochondrial mass and genome copy number, as well as glycolytic rates and steady state ATP levels were unchanged. Our results suggest a model in which ME/CFS lymphoblasts have a Complex V defect accompanied by compensatory upregulation of their respiratory capacity that includes the mitochondrial respiratory complexes, membrane transporters and enzymes involved in fatty acid β-oxidation. This homeostatically returns ATP synthesis and steady state levels to “normal” in the resting cells, but may leave them unable to adequately respond to acute increases in energy demand as the relevant homeostatic pathways are already activated.

Cytochrome P450s (CYP450s) are a versatile superfamily of enzymes known to undergo rapid evolution. They have important roles across growth and development pathways in crustaceans, although it is difficult to characterise orthologs between species due to their sequence diversity. Conserved CYP450s enzymes in crustaceans are those associated with ecdysteroidogenesis; synthesising and breaking down the active moult hormone, 20-hydroxyecdysone. The complex life-cycle of the ornate spiny lobster, Panulirus ornatus, relies on moulting in order to grow and develop. Many of these diverse life stages have been analysed to establish a comprehensive transcriptomic database for this species. The transcripts putatively encoding for CYP450s were mapped using transcriptomic analysis and identified across growth and development stages. With the aid phylogeny, 28 transcripts of 42 putative P. ornatus CYP450s were annotated, including the well conserved Halloween genes, which are involved in ecdysteroidogenesis. Expression patterns across the life-stages determined that only a subset of the CYP450s can be detected in each life-stage or tissue. Four Shed transcripts show overlapping expression between metamorphosis and adult tissues, suggesting pleotropic functions of the multiple Shed orthologs within P. ornatus.

The aim of this study was to observe the nutritional supplement practices of highly trained swimmers on a national talent pathway, since it is often reported that swimmers engage in widespread supplement use at the elite level. Thus, this study conducted short interviews based on a validated supplement intake questionnaire with forty-four swimmers from a high-performance swimming club, which had three distinct talent stages: development (aged 11–14 years, n = 20), age-group (aged 13 – 17 years, n = 13), and national level (aged ≥16 years, n = 11). Ninety-eight percent of the interviewed swimmers reported using at least one supplement, with performance (34%) and recovery (19%) cited as the primary reasons. National swimmers used more total supplements (8.1 ± 3.4 supplements) compared to age-group (4.8 ± 2.0 supplements, p = 0.003, g = 1.17) and development (3.9 ± 1.7 supplements, p <0.001, g = 1.69) swimmers, mostly because of a greater intake of ergogenic aids (2.4 ± 1.4 supplements vs. age-group: 0.5 ± 0.5 sup-plements, p <0.001, g = 1.12; vs. development: 0.1 ± 0.2 supplements, p <0.001, g = 1.81). Par-ents/guardians were the primary supplement informants of development swimmers (74%, p <0.001, V = 0.50), whereas performance nutritionists informed ~50% of supplements used by age-group and national swimmers (p <0.001, V = 0.51). Based on these results, supplement edu-cation and greater focus on basic sport nutrition practices may be required for parents/guardians at the development level. Moreover, further research is needed to support the high number of ergogenic aids used by national swimmers, with the efficacy of these supplements currently equivocal in the applied setting.

The double burden of malnutrition (DBM) is escalating in low- and middle-income countries (LMICs), including in Rwanda, most notably in urbanizing areas. The 2019-2020 Rwanda Demographic Health Survey (DHS) revealed 33% of children under 5 are stunted while 42% of women in urban areas are overweight or obese. This coexistence has contributed to a surge in non-communicable diseases (NCDs), particularly in secondary cities. Using the World Health Organization’s (WHOs) “double-duty action” (DDA) concept, this study aims to identify and evaluate interventions with double-duty potential in Rwanda, focusing on the districts of Rusizi and Rubavu. Guided by Hawkes et al.’s conceptual framework for identifying DDA entry points, a desk review of national policies pinpointed 4 programs with DDA potential: early childhood development (ECD) centers, the school feeding program, farmer field schools (FFS), and the provision of nutrition-sensitive direct support. In-person interviews with key stakeholders assessed their implementation and a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis informed context-specific recommendations for their improvement. Recommendations include targeting beliefs surrounding nutrition, improving trainings for community educators, enhancing parent – particularly father – involvement, and close follow-up. These findings offer actionable strategies for governments and nutrition stakeholders and may benefit similar interventions in other rapidly urbanizing LMICs.

Radiomics involves the extraction of information from medical images not visible to the human eye. There is evidence these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations namely Matlab toolkit and Pyradiomics when applied on independent datasets of CT scans of patients i) the open access RIDER dataset containing a set of repeat CT scans taken 15 minutes apart for 31 patients (RIDER Scan 1 and Scan 2 respectively) treated for lung cancer and ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV) manually outlined by an experienced observer available on both datasets was used. 43 common radiomics features available on Matlab and Pyradiomics were calculated using 2 intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters and the Spearman’s rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset and vice versa. 29 out of 43 reported stable features were found to be highly reproducible between Matlab and Pyradiomics implementations, having consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs &gt; 0.8). 18/43 reported features were common in RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Background: Developing patient-centric baseline standards that enable the detection of clinically significant outlier gene products on a genome-scale remains an unaddressed challenge required for advancing personalized medicine beyond the small pools of subjects implied by “precision medicine”. This manuscript proposes a novel approach for reference standard development to evaluate the accuracy of single-subject analyses of metabolomes, proteomes, or transcriptomes. Since distributional assumptions of statistical testing may inadequately model genome dynamics of gene products, the so-called significant results of previous studies may artefactually conflate with real signals. Model confirmation biases escalate when studies use the same analytical methods in the discovery sets and reference standards, as corroboration of results leads to an evaluation of reproducibility confounded with replicated biases rather than a measure of accuracy. We hypothesized that developing method-agnostic reference standards using effect-size and expression-level filtering of results, obtained from multiple discovery methods that are distinct from the one evaluated, would maximize the evaluation of clinical-transcriptomic signals and minimize statistical artefactual biases. We developed and released an R package “referenceNof1” to facilitate the construction of robust reference standards. Results: Since RNA-Seq data analysis methods often rely on binomial and negative binomial assumptions to non-parametric analyses, the differences create statistical noise and make the reference standards method dependent. In our experimental design, the accuracy of 30 distinct combinations of fold changes (FC) and expression levels (EL) were determined for five types of RNA analyses in two different datasets. This design was applied to two distinct datasets: breast cancer cell lines and a yeast study with isogenic biological replicates in two experimental conditions. In addition, the reference standard (RS) comprised all RNA analytical methods with the exception of the method testing accuracy. To mitigate for biased optimization of the RS parameters towards a specific analytical method, similarity between observed results of distinct analytical methods were calculated across all methods (Jaccard Concordance Index). The greatest differences were observed across diametric extremes. For example, filtering out differentially expressed genes (DEGs) using a fold change < 1.2 leads to a 50% increase in concordance between techniques when compared to results with FC > 1.2. Combining this FC cutoff with genes with mean expressions > 30 counts leads to a 65% increase in concordance in comparison to genes with expression levels < 30 counts and with FC < 1.2. Conclusions: We have demonstrated that comparing accuracies of different single-subject analysis methods for clinical optimization requires a new evaluation framework. Reliable and robust reference standards, independent of the evaluated method, can be obtained under a limited number of parameter combinations: fold change (FC) ranges thresholds, expression level cutoffs, and exclusion of the tested method from the RS development process. When applying anticonservative reference standard frameworks (e.g., using the same method for RS development and for prediction), a majority of the concordant signal between prediction and Gold Standard (GS) cannot be confirmed by other methods, which we conclude as biased results. Statistical tests to determine DEGs from a single-subject study generate many biased results that require subsequent filtering for increasing their reliability. Conventional single-subject studies pertain to one or a few measures in one patient over time [1]and need a substantial conceptual framework extension in order to address the tens of thousands of measures in genome-wide analyses of gene products. The proposed referenceNof1 framework addresses some of the inherent challenges in improving transcriptome scale single-subject analyses by providing a robust approach to constructing reference standards. Github: https://github.com/SamirRachidZaim/referenceNof1

Integrated assessment modelling (IAM) has been successfully used in the development of international agreements to reduce transboundary pollution in Europe, based on the GAINS model of IIASA. At a national level in the UK a similar approach has been taken with the UK Integrated Assessment Model, UKIAM, superimposing pollution abatement measures and behavioural change on energy projections designed to meet targets set for reduction of greenhouse gas emissions, and allowing for natural and imported contributions from other countries and shipping. This paper describes how UKIAM has been used in development of proposed targets for reduction of fine particulate PM2.5 in the Environment Act, exploring scenarios encompassing different levels of ambition up to 2050 with associated health and other environmental benefits. There are two PM2.5 targets, an annual mean concentration target setting a maximum concentration to be reached by a future year, and a population exposure reduction target with benefits for health across the whole population. The work goes further, to also demonstrate links to social deprivation. There is a strong connection between climate measures aimed at reducing net GHG emissions to zero by 2050 and future air quality, which may be positive or negative, as illustrated by sectoral studies for road transport where electrification of the fleet needs to match the evolution of energy production, and for domestic heating where use of wood for heating is an air quality issue. UKIAM has been validated against air pollution measurements and other modelling, but there are many uncertainties including future energy projections. New work is beginning to link UKIAM directly with the TIMES model addressing future energy projections, to explore different uptake scenarios for hydrogen production and use with respect to air quality.

Drivers of L3 automated vehicles (AVs) are not required to continuously monitor the AV system. However, they must be prepared to take over when requested. Therefore, it is necessary to design an in-vehicle environment that allows drivers to adapt their levels of preparedness to the likelihood of control transition. This study evaluates ambient in-vehicle lighting that continuously communicates the current level of AV reliability, specifically on how it could influence drivers' take-over performance and mental workload (MW). We conducted an experiment in a driving simulator with 42 participants who experienced 10 take-over requests (TORs). The experimental group experienced a four-stage ambient light display that communicated the current level of AV reliability, which was not provided to the control group. The experimental group demonstrated better take-over performance, based on lower vehicle jerks. Notably, perceived MW did not differ between the groups, and the EEG indices of MW (frontal theta power, parietal alpha power, Task-Load Index) did not differ between the groups. These findings suggest that communicating the current level of reliability using ambient light might help drivers be better prepared for TORs and perform better without increasing their MW.

Raman Spectroscopy has long been anticipated to augment clinical decision making, such as classifying oncological samples. Unfortunately, the complexity of Raman data has thus far inhibited its routine use in clinical settings. Traditional machine learning models have been used to help exploit this information, but recent advances in deep learning have the potential to improve the field. However, there are a number of potential pitfalls with both traditional and deep learning models. We conduct a literature review to ascertain the recent machine learning methods used to classify cancers using Raman spectral data. We find that while deep learning models are popular, and ostensibly outperform traditional learning models, there are many methodological considerations which may be leading to an over-estimation of performance: primarily, small sample sizes which compound upon sub-optimal choices regarding sampling and validation strategies. Amongst several recommendations is a call to collate large benchmark Raman datasets, similar to those that have helped transform digital pathology, which researchers can use to develop and refine deep learning models.

Fagonia indica is a perennial plant grown in arid climates and utilised in traditional medicine as a treatment for cancer. Previous research has highlighted potential antineoplastic effects of Fagonia indica against breast cancer cell lines. Despite this, there has been little research demonstrating the potential of an aqueous extract of Fagonia indica against colon cancer. Colon cancer is a leading cause of cancer-related mortality, with drug resistance remaining a barrier to treatment. The aim of the present study was to investigate the cytotoxic mechanisms of Fagonia indica in colon cancer cells, including pathways related to proliferation, angiogenesis and inflammation, and ABC membrane transporters. Treatment with Fagonia indica caused a reduction in cell viability in wild-type and chemotherapy resistant colon cancer. Results indicated a role for Akt/ MAPK signalling as a mechanism of Fagonia indica induced cell death, alongside a reduction in the expression of VEG-F, NK-κB and ICAM-1. RT-PCR demonstrated a reduction in expression of ABCG2/ABCC4 in resistant colon cancers, after treatment with Fagonia indica extract. Further research is required to isolate bioactive compounds of Fagonia indica for use against colon cancer.

The purpose of this paper is to highlight the main themes and insights from the Journal of Orthopedic Research (JOR)/JOR Spine Workshop during the Orthopedic Research Society 2022 Annual Meeting in Tampa Bay, Florida. This workshop, organized by JOR Editor-in-Chief Dr. Linda Sandell, focused on communication strategies (particularly using social media) to broadcast published work in orthopedic research. In this manuscript, we summarize data that support the beneficial impacts of amplifying scholarly works on social media and outline a linearized workflow for constructing a Twitter posts, which can be generalized to other social media platforms, to share academic research. Finally, we identify resources to alleviate barriers to social media use and help promote professionalism and success online in the orthopedic research community. As early career scientists in orthopedics, we see immense value in using social media, particularly Twitter, to communicate our research findings and build our scholarly networks. We hope this information will be persuasive to those in the orthopedic field and be broadly applicable to others in related scientific fields who wish to disseminate findings and engage a public audience on social media. For the orthopedic research society and journal of orthopedic research, social media can assist in accomplishing our mission of creating a world without musculoskeletal limitations via the timely dissemination of orthopedic research findings and news.

Over recent decades, therapeutic proteins have had widespread success in treating a myriad of diseases. Glycosylation, a near universal feature of this class of drugs, is a critical quality attribute that significantly influences the physical properties, safety profile and biological activity of therapeutic proteins. Optimizing protein glycosylation, therefore, offers an important avenue to developing more efficacious therapies. In this review, we discuss specific examples of how variations in glycan structure and glycoengineering impacts the stability, safety, and clinical efficacy of protein-based drugs that are already in the market as well as those that are still in preclinical development. We also highlight the impact of glycosylation on next generation biologics such as T cell-based cancer therapy and gene therapy.

Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signaling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.

Mediterranean coastal lagoons and their peripheral areas often provide a collection of habitats for many species, and they often face significant threats from anthropogenic activities. Diverse human activities in such areas directly affect the spatio-temporal dynamic of surface water and its ecological characteristics. Monitoring the surface water dynamic, and understanding the impact of human activities are of great significance for coastal lagoon conservation. The Regional Natural Park of Narbonne includes a typical Mediterranean lagoon complex where surface water dynamic and its potential link with local diverse human activities has not yet been studied. In this context, based on all the available Landsat images covering the study area during 2002-2016, this study identified the water and non-water classes for each satellite observation by comparing three widely used water indices (i.e., NDVI, NDWI and MNDWI) and using the Otsu method. The yearly water frequency index was then computed to present the spatio-temporal dynamic of surface water for each year, and three water dynamic scenarios were also identified for each year: permanent water (PW), non-permanent water (NPW) and non-water (NW). The spatial and inter-annual variation in the patterns of the three water scenarios were characterized by computing the landscape metrics at scenario-level quantifying area/edge, shape, aggregation and fragmentation. Finally, the quantitative link between different land use and land cover (LULC) types derived from the LULC maps of 2003, 2012 and 2015 and the surface water dynamic scenarios was established in each of the 300 m x 300 m grid cells covering the study area to determine the potential impact of human activities on the surface water dynamic. In terms of the inter-annual variation during 2002-2016, PW presented an overall stability, and NPW occupied only a small part of the water surface in each year and presented an inter-annual fluctuation. NPW had a smaller patch size, with lower connectivity degree and higher fragmentation degree. In terms of spatial variation during 2002-2016, NPW often occurred around PW, and its configurational features varied from place to place. Moreover, PW mostly corresponded to natural lagoon, and salt marsh (as a part of lagoons), and NPW had a strong link with arable land (agricultural irrigation) and salt marsh (salt production), sand beach/dune, coastal wetlands and lagoon for the LULC maps of 2003, 2012 and 2015. However, more in-depth analysis is required for understanding the impact of sand beach/dune, coastal wetlands and lagoon on surface water dynamics. This study covers the long-term variations of surface water patterns in a Mediterranean lagoon complex having intense and diverse human activities, and the potential link between LULC types and the water dynamic scenarios was investigated on different dates. The results of the study should be useful for environmental management and protection of coastal lagoons.

Intertidal seagrass plays a vital role in estimating the overall health and dynamics of coastal environments due to its interaction with tidal changes. However, most seagrass habitats around the globe have been in steady decline due to human impacts, disturbing the already delicate balance in environmental conditions that sustain seagrass. Miniaturization of multi-spectral sensors has facilitated very high resolution mapping of seagrass meadows, which significantly improve the potential for ecologists to monitor changes. In this study, two analytical approaches used for classifying intertidal seagrass habitats are compared: Object-based Image Analysis (OBIA) and Fully Convolutional Neural Networks (FCNNs). Both methods produce pixel-wise classifications in order to create segmented maps, however FCNNs are an emerging set of algorithms within Deep Learning with sparse application towards seagrass mapping. Conversely, OBIA has been a prominent solution within this field, with many studies leveraging in-situ data and multiscale segmentation to create habitat maps. This work demonstrates the utility of FCNNs in a semi-supervised setting to map seagrass and other coastal features from an optical drone survey conducted at Budle Bay, Northumberland, England. Semi-supervision is also an emerging field within Deep Learning that has practical benefits of achieving state of the art results using only subsets of labelled data. This is especially beneficial for remote sensing applications where in-situ data is an expensive commodity. For our results, we show that FCNNs have comparable performance with standard OBIA method used by ecologists, while also noting an increase in performance for mapping ecological features that are sparsely labelled across the study site.

Background: Changes in body weight are associated with the regulation of DNA methylation (DNAm). In this study, we investigated the associations between maternal gestational weight gain-related DNAm and foetal and neonatal body composition. Methods: Brazilian pregnant women from the Araraquara Cohort Study were followed up during pregnancy, delivery, and after hospital discharge. Women with normal pre-pregnancy BMI were allocated to two groups: adequate gestational weight gain (AGWG, n=45) and excessive gestational weight gain (EGWG, n=30). Foetal and neonatal body composition was evaluated by ultrasound and plethysmography, respectively. DNAm was assessed in maternal blood using Illumina Infinium MethylationEPIC BeadChip arrays. Linear regression models were used to explore the associations between DNAm and foetal and neonatal body composition. Results: Maternal weight, GWG, neonatal weight, and fat mass were higher in the EGWG group. Analysis of DNAm identified 46 differentially methyl-ated positions and 11 differentially methylated regions (DMRs) between the EGWG and AGWG groups. Nine human phenotypes were enriched for these 11 DMRs located in 13 genes (EMILIN1, HOXA5, CPT1B, CLDN9, ZFP57, BRCA1, POU5F1, ANKRD33, HLA-B, RANBP17, ZMYND11, DIP2C, TMEM232), highlighting the terms insulin resistance, and hyperglycaemia. Maternal DNAm was associated with foetal total thigh and arm tissues and subcutaneous thigh and arm fat, as well as with neonatal fat mass percentage and fat mass. Conclusion: The methylation pat-tern in the EGWG group indicated a risk for developing chronic diseases and involvement of ma-ternal DNAm in foetal lean and fat mass and in neonatal fat mass.

This paper investigates the adaptability of four state-of-the-art Artificial Intelligence (AI) models to the Australian mammographic context through transfer learning, explores the impact of image enhancement on model performance and analyses the relationship between AI outputs and histopathological features for clinical relevance and accuracy assessment. A total of 1712 screening mammograms (n=856 cancer cases and n=856 matched normal cases) were used in this study. The 856 cases with cancer lesions were annotated by two expert radiologists and the level of concordance between their annotations was used to establish image subsets. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of Globally aware Multiple Instance Classifier (GMIC), Global-Local Activation Maps (GLAM), I&amp;H and End2End AI models, both in the pre-trained and transfer learning modes, with and without applying the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm. The four AI models with and without transfer learning in the high-concordance subset outperformed those in the entire dataset. Applying the CLAHE algorithm to mammograms improved the performance of the AI models. In the high-concordance subset with transfer learning and CLAHE algorithm applied, the AUC of the GMIC model was highest (0.912), followed by GLAM model (0.909), I&amp;H (0.893) and End2End (0.875). There were significant differences (P&lt;0.05) in the performances of the four AI models between high-concordance subset and entire dataset. The AI models demonstrated significant differences in malignancy probability concerning different tumour size categories in mammograms. The performance of AI models was affected by several factors such as concordance classification, image enhancement and transfer learning. Mammograms with strong concordance of radiologists’ annotations, applying image enhancement and transfer learning could enhance the accuracy of AI models.

Hydroponic farming systems play an increasingly important role in the sustainable production of nutrient-rich foods. The contamination of surfaces in hydroponic fresh produce production poses risks to the food safety of crops, potentially endangering public health and causing economic losses in the industry. While sanitizers are widely used in commercial hydroponic farms, their effectiveness against human pathogens on surfaces, and their impact on plant health and quality are not known. In this study, we evaluated the efficacy of chemical sanitizers in eliminating Salmonella Typhimurium from inanimate surfaces in commercial hydroponic Nutrient Film Technique (NFT) systems. Further, we assessed the impact of sanitizers on the yield, quality, and nutritional value of lettuce and basil. Sanitizers (Virkon, LanXess; Sanitate 12.0, Bi-oSafe Systems; Kleen Grow, Pace Chemical Ltd.; Green Shield, United Labs Inc.; Zerotol, BioSafe Systems; Bleach, Pure Bright), were tested against Salmonella Typhimurium inoculated on NFT surfaces (nutrient reservoirs, growing channels, top covers, drain lines). The effective treatments were then tested for their impact on lettuce and basil in a split-plot experiment conducted in commercial NFT units. Crop yield, color, and nutrient content were measured throughout the crop life cycle. While all quaternary ammonium compounds (QAC), SaniDate 12.0 (200ppm), Zorotol (5%), and Virkon (1%) eliminated Salmonella Typhimurium from commercial NFT surfaces, chlorine-based sanitizer treatments were statistically similar to water treatments on most surfaces. All chemical sanitizers impacted the yield, color, and nutritional value of lettuce and basil. SaniDate 12.0 (200ppm) was the least detrimental to crops and was identified as a potential candidate for further validation in commercial hydroponic settings. The findings of this study will be translated into recommendations for the industry and will contribute to the development of future food safety guidelines and policies.

Red beetroot, is a well-recognized and established source of bioactives (e.g., betalains and polyphenols) with anti-inflammatory and antimicrobial properties. It is proposed as a potential alternative to zinc oxide, with a focus on gut microbiota modulation and metabolite production. In this study, weaned pigs aged 28-days were fed either a control diet, diet supplemented with zinc oxide (3,000 mg/kg), or 2% and 4% pulverized whole red beetroot (CON, ZNO, RB2 and RB4; respectively) for 14 days. After the pigs were euthanized, blood and digesta samples were collected for microbial composition and metabolite analyses. Results showed, red beetroot supplemented diet at 2% improved the gut microbial richness relative to other diets, but marginally influenced the caecal microbial diversity compared to zinc oxide supplemented diet. Further increase in red beetroot levels (4% -RB4) lead to loss of caecal diversity, decreased short chain fatty acids and secondary bile acid concentrations. An increased Proteobacteria abundance, presumably due to increased lactate/lactic acid producing bacteria was also observed. Summarily, red beetroot contains several components conceived to improve the gut microbiota and metabolite output of weaned pigs. Future studies investigating individual components in red beetroot will better elucidate their contributions to gut microbiota modulation and pig health.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme and one of the causes of tumor resistance to topoisomerase 1 inhibitors such as topotecan. Inhibitors of this Tdp1 in combination with topotecan may improve the effectiveness of therapy. In this work, we synthesized usnic acid derivatives, which are hybrids of its known derivatives - tumor sensitizers to topotecan. New compounds inhibit Tdp1 in the micromolar and submicromolar concentration range; some of them enhance the effect of topotecan on the metabolic activity of cells of various lines according to the MTT test. One of the new compounds (compound 7) not only sensitizes Krebs-2 and Lewis carcinomas of mice to the action of topotecan, but also normalizes the state of the peripheral blood of mice, which is disturbed in the presence of a tumor. Thus, the synthesized substances may be the prototype of a new class of additional therapy for cancer.

Background: Recent work has investigated significant force transmission between the compo-nents of myofascial chains. Misalignments in the body due to fascial thickening and shortening can therefore lead to complex compensatory patterns. For the treatment of such nonlinear cause-effect pathology, a comprehensive neuro-musculoskeletal therapy such as the Rolf Meth-od of Structural Integration (SI) could be targeted. Methods: A total of 727 subjects were retro-spectively screened from the medical records of an SI practice over a 23-year period. 383 subjects who had completed 10 basic SI sessions met eligibility criteria and were assessed for active range of motion (AROM) of the shoulder and hip before and after SI treatment. Results: Shoulder flex-ion, external and internal rotation, and hip flexion improved significantly (all p < 0.0001) after 10 SI sessions. Left shoulder flexion and external rotation of both shoulders increased more in men than in women (p < 0.0001), but were not affected by age. Conclusions: SI intervention produces multiple changes in the components of myofascial chains that could help maintain upright pos-ture in humans and reduce inadequate compensatory patterns. SI affects differently the outcome of some AROM parameters in women and men.

Freezing of gait (FOG), a debilitating symptom of Parkinson’s disease (PD), can be safely studied using the stepping in place (SIP) task. However, clinical, visual identification of FOG during SIP is subjective and time consuming, and automatic FOG detection during SIP currently requires measuring center of pressure on dual force plates. This study examines whether FOG elicited during SIP in 10 individuals with PD could be reliably detected using kinematic data measured from wearable inertial measurement unit sensors (IMUs). A general, logistic regression model (AUC = 0.81) determined that three gait parameters together were overall the most robust predictors of FOG during SIP: arrhythmicity, swing time coefficient of variation, and swing angular range. Participant-specific models revealed varying sets of gait parameters that best predicted FOG for each participant, highlighting variable FOG behaviors, and demonstrated equal or better performance for 6 out of the 10 participants, suggesting the opportunity for model personalization. The results of this study demonstrated that gait parameters measured from wearable IMUs reliably detected FOG during SIP, and the general and participant-specific gait parameters allude to variable FOG behaviors that could inform more personalized approaches for treatment of FOG and gait impairment in PD.

The prevalence of Noncommunicable Diseases (NCDs) in South Africa is increasing annually, with the burden projected to escalate by 2030. Devastatingly, factors such as lifestyle changes, urbani- sation, and an aging population significantly contribute to a rising burden of Cardiovascular disease (CVDs), diabetes, and cancer which directly impact the mortality and morbidity rates seen in South Africa. Recognising this, the South African government has seen the need for emphasis on developing policies and interventions tar- geting physical inactivity to prevent and manage NCD, particularly cost-free and easy to administer training protocols. However, phys- ical inactivity remains a significant issue, leading to various health concerns in rural communities, including injuries and Fetal Alcohol Spectrum Disorders (FASD). Despite effort to promote physical ac- tivity, the prevalence of NCDs continues to rise, necessitating target- ed interventions to ensure equitable healthcare among South African citizens. On the Contrast, preservation and promotion of traditional games is vital as they offer indigenous populations accessible and culturally relevant means to maintain health and wellness. In this regard, it is important to recognize the importance of preserving and promoting traditional games as they potentially serve as a method for indigenous people to maintain their health and wellness in a way that is accessible and culturally relevant to them. These games have gained popularity in South Africa, with initiatives underway to show- case them globally fostering cultural exchange. Further, revitalizing and conserving these games can cultivate a culture of health and wellbeing in South Africa.

Background and aims: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional –and that cohort research– have reported several risk factors associated with the prevalence and incidence of this condition. However, alterations of body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. Methods: This is a secondary analysis in older adults (≥60 years old) derived from the study “Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)” a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. Results: The cohort included 241 subjects. Average age was 75.6±7.8 years; 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in subjects with excess fat mass index, even after adjusting for several covariates. RM was also more likely to occur in subjects with low total lean tissue index, according to both an unadjusted model and after adjusting for the corresponding variables. Regarding the association between RM and gait speed, RM was also more likely to occur in subjects with low gait speed according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. Conclusion: The risk of malnutrition diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, but possibility was significantly higher in those with low total lean tissue and low gait speed after 4.1 years of follow-up in community-dwelling older adults. These results highlight that excess fat mass, low total lean tissue, and low gait speed are first than risk of malnutrition and not vice versa.