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.

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.

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.

In this paper, using the two integers that describe the stationary 2-dimensional wave and the charge quantization along with the balance between the Lorentz force and electrical force, we succeed in deriving the fractional quantum Hall effect and the integer quantum Hall effect; we find that the latter exists as a special case of the former. Moreover, using the derived expression describing the fractional quantum Hall effect, a relationship between the plateau in the resistivity of the sample and the applied magnetic field is obtained. The findings of this model agree well with experimental measurements. Because the two integers that describe the stationary 2-dimensional wave and the charge quantization along with the force balance have concrete physical meanings in this work, we could provide a clear picture of the origin of both the integer quantum Hall effect and the fractional quantum Hall effect.

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.

The properties of the current-induced Hall effect are analysed, for which the static magnetic field, supplied by an external source in the traditional experiment, is created by the current itself. The special experimental setup, needed for its observation, is described. It is shown how, combined with the skin effect, it could give access to the concentration of conduction electrons in superconductors. Besides this experiment might permit to dodge shortcomings, ensueing from the Meissner effect and limiting severely the sensitivity of the conventional Hall voltage measurement.

The energy efficiency of existing buildings is a crucial factor in addressing Europe’s energy con-sumption challenges, accounting for nearly 40% of the total energy usage. The ongoing energy crisis, driven by the reliance on fossil fuels and increasing prices, has underscored the urgency of adopting sustainable and energy efficient practices especially to the existing building stock. Cyprus is par-ticularly vulnerable due to its heavy dependence on imported fuels for electricity generation and faces significant challenges in transforming its existing building stock into energy-efficient and sustainable structures. Extensive focus has been made by the government on the energy-efficient retrofit of non-residential public buildings. This study examines an existing cultural hall. The case study of the Cultural Hall represents the building stock before 2010 which is lacking thermal in-sulation, double glazing and any energy efficient element. It then offers an ideal case study to ex-plore sustainable solutions which can be easily adopted from the construction industry and from the building owners. The primary objective of this research is twofold: first, to develop a comprehensive retrofit plan to transform the cultural hall into a net-zero energy building; and second, to explore how this transformation can give value back to the local community. After running two simulation scenarios and providing two energy performance certificates, one with at the existing state and one with the intended retrofit measures, it is clear that the building can be a net zero energy consump-tion building. Some interesting results derived, present also how this building can provide value back to the community i.e. through solar carports for EV charging.

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.

More people around the world now have obesity than suffer from starvation thanks to our modern food system. Agriculture was transformed over the 20^th century by a variety of technological advancements that relied heavily on fossil fuels. In the United States of America, government policies and economic incentives led to surplus production of cheap inputs to processed food industries that produced a wide variety of heavily marketed, convenient, rewarding, timesaving, and relatively inexpensive ultra-processed foods. The energy available in the United States food supply increased much more than population needs, albeit with large inequities in food distribution and nutrition security. While most of the rise in per capita food availability during the late 20^th and early 21^st centuries in the United States resulted in increased food waste, a variety of mechanisms have been proposed by which changes in the increasingly ultra-processed food environment resulted in excess energy intake disproportionately in people genetically susceptible to obesity. As populations continue to grow, substantial investments in coordinated nutrition and agricultural research are needed to transform our current food system to one that relies less on fossil fuels, preserves biodiversity, ensures environmental health, and provides equitable access to affordable, safe, and nutritious food that reduces the prevalence of chronic diseases like obesity.

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.

This paper formulates the classic Monty Hall problem as a Bayesian game. Allowing Monty a small amount of freedom in his decisions facilitates a variety of solutions. The solution concept used is the Bayes Nash Equilibrium (BNE), and the set of BNE relies on Monty's motives and incentives. We endow Monty and the contestant with common prior probabilities (p) about the motives of Monty, and show that under certain conditions on p, the unique equilibrium is one where the contestant is indifferent between switching and not switching. This coincides and agrees with the typical responses and explanations by experimental subjects. Finally, we show that our formulation can explain the experimental results in Page (1998) [12]; that more people gradually choose switch as the number of doors in the problem increases.

Bovine respiratory disease (BRD) is a major health problem within the global cattle industry. This disease has a complex aetiology, with viruses playing an integral role. In this study, metagenomics was used to sequence viral nucleic acids in the nasal swabs of BRD affected cattle. Viruses detected included those well known for their association with BRD in Australia (bovine viral diarrhea virus 1), as well as viruses known to be present but not fully characterised (bovine coronavirus) and viruses that have not been reported in BRD affect cattle in Australia (bovine rhinitis, bovine influenza D, and bovine nidovirus). Nasal swabs from a case control study were subsequently tested for 10 viruses and the presence of at least one virus was found to be significantly associated with BRD. Some of the more recently detected viruses had inconsistent association with BRD. Full genome sequences for bovine coronavirus, a virus increasingly associated with BRD, and bovine nidovirus were complete. Both viruses belong to the Coronaviridae family, which are frequently associated with disease in mammals. This study has provided greater insights into the viral pathogens associated with BRD and highlighted the need for further studies to elucidate more precisely the roles viruses play in BRD.

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.

The building sector has a big potential to reduce the material resource demand needed for building construction and therefore, greenhouse gas (GHG) emissions. Digitalisation can help to make use of this potential and improve sustainability throughout the entire building’s life cycle. One way to address this potential is through the integration of Life-Cycle Assessment (LCA) into the building process by employing Building Information Modelling (BIM). BIM can reduce the effort needed to carry out an LCA and therefore facilitate the integration into the building process. A review of current industry practice and scientific literature shows two main approaches to address BIM-LCA integration. Either the LCA is performed in a simplified way at the beginning of the building process, or it is done at the very end when all the needed information is available, but it is too late for decision-making. One reason for this is the lack of methods, workflows and tools to implement BIM-LCA integration over the entire building process. Therefore, the main objective of this study is to develop an integrated BIM-LCA workflow implemented into a method for the whole building process using an existing structure for cost estimation. A tool is created and used in a case study in Switzerland to test the developed approach. The results of this study show that LCA can be performed continuously in each building phase over the entire building process using existing BIM modelling techniques. The main benefit of this approach is that the re-work caused by the need for re-entering data and the usage of many different software tools that characterise most of the current LCA practices is minimised. Furthermore, decision-making, both at the element and building levels, is supported.

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.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

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.

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.

The simultaneous breaking of time-reversal and inversion symmetry, in connection to superconductivity, leads to transport properties with disrupting scientific and technological potential. Indeed, the anomalous Josephson effect and the superconducting diode effect hold promises to enlarge the technological applications of superconductors and nanostructures in general. In this context, the system we theoretically analyze is a Josephson junction (JJ) with coupled reconstructed topological channels as a link; such channels are at the edges of a two-dimensional topological insulator (2DTI). We find a robust $\varphi_0$ Josephson effect without requiring the presence of external magnetic fields. Our results, which rely on a fully analytical analysis, are substantiated by means of symmetry arguments: Our system breaks both time-reversal symmetry and inversion symmetry. Moreover, the anomalous current increases as a function of temperature. We interpret this surprising temperature dependence by means of simple qualitative arguments based on Fermi's golden rule.

Teaching kinematic rotations is a daunting task for even some of the most advanced mathematical minds. However, envisioning and explaining the three-dimensional rotations can be highly simplified by changing the paradigm. This paradigm change allows for a high school student with a understanding of geometry to be able to not only develop the matrix but also explain the rotations at a collegiate level. The proposed method includes the assumption of a point (P) within the initial three-dimensional frame with axes (x ̂_i, y ̂_i, z ̂_i). It then utilizes a two-dimensional rotation view (2DRV) to measure how the coordinates of point P translate after the initial axis is rotated instead of using the established Euler's formula. The equations are used in matrix notation to develop a direction cosine matrix (DCM) for future equations. This method provides a high school student with an elementary and repeatable process to compose and explain kinematic rotations.

The interleukin 6 (IL-6) receptor blocking antibody tocilizumab was repurposed in the coronavirus pandemic with the intention of blocking the excess inflammatory activation associated with severe disease. We retrospectively evaluated the response to tocilizumab based on measured levels of IL-6 as well as other inflammatory markers. In the sample of 41 patients with measured levels, 16 received tocilizumab. In patients who received tocilizumab, there was a statistically significant relationship between both higher IL-6 levels and measured acute phase reactants with mortality, but not in those who did not. Additionally, an improved mortality after tocilizumab was suggested with those with higher IL-6 measurements, but not in those with lower levels, but this finding failed to achieve statistical significance (p=0.14). Though this study is limited by a small sample size and retrospective design, an association is suggested between higher IL-6 levels and improved mortality after tocilizumab.

Drones are increasingly becoming a ubiquitous feature of society. They are being used for a multiplicity of applications for military, leisure, economic, and academic purposes. Their application in the latter, especially as social science research tools has seen a sharp uptake in the last decade. This has been possible due, largely, to significant developments in computerization and miniaturization which have culminated in safer, cheaper, lighter, and thus more accessible drones for social scientists. Despite their increasingly widespread use, there has not been an adequate reflection on their use in the spatial social sciences. There is need a deeper reflection on their application in these fields of study. Should the drone even be considered a tool in the toolbox of the social scientist? In which fields is it most relevant? Should it be taught as a course in the universities much in the same way that geographic information system (GIS) became mainstream in geography? What are the ethical implications of its application in the spatial social science? This paper is a brief reflection on these questions. We contend that drones are a neutral tool which can be good and evil. They have actual and potential wide applications in academia but can be a tool through which breaches in ethics can be occasioned given their unique abilities to capture data from vantage perspectives. Researchers therefore need to be circumspect in how they deploy this powerful tool which is increasingly becoming mainstream in the social sciences.

Discrete, logic-based models are increasingly used to describe biological mechanisms. Initially introduced to study gene regulation, these models evolved to cover various molecular mechanisms, such as signalling, transcription factor cooperativity, and even metabolic processes. The abstract nature and amenability of discrete models to robust mathematical analyses make them appropriate for addressing a wide range of complex biological problems. Recent technological breakthroughs have generated a wealth of high throughput data. Novel, literature-based representations of biological processes and emerging algorithms offer new opportunities for model construction. Here, we review up-to-date efforts to address challenging biological questions by incorporating omic data into logic-based models, and discuss critical difficulties in constructing and analysing integrative, large-scale, logic-based models of biological mechanisms.

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.

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.

Recent advancements of computer and electronic systems have motivated the extensive use of intelligent systems for automation of agricultural industries. In this study, the temperature variation of the mushroom growing room is modeled through using a multi-layered perceptron (MLP) and radial basis function networks. Modeling has been done based on the independent parameters including ambient temperature, water temperature, fresh air and circulation air dampers, and water tap. According to the obtained results from the networks, the best network for MLP is found to be the second repetition with 12 neurons in the hidden layer and 20 neurons in the hidden layer for radial basis function networks. The obtained results from comparative parameters for two networks showed the highest correlation coefficient (0.966), the lowest root mean square error (RMSE) (0.787) and the lowest mean absolute error (MAE) (0.02746) for radial basis function. Therefore, the neural networks with radial basis function was selected as the optimal predictor for the behavior of the system.

LLMs are a compressed repository of a vast corpus of valuable information on which they are trained. Therefore, this work hypothesizes that LLMs such as Llama, Orca, Falcon, and Mistral can be used for misinformation detection by making them cross-check new information with the repository on which they are trained. Accordingly, this paper describes the findings from the investigation of the abilities of LLMs in detecting misinformation on multiple datasets. The results are interpreted using explainable AI techniques such as LIME, SHAP, and Integrated Gradients. The LLMs themselves are also asked to explain their classification. These complementary approaches aid in better understanding the inner workings of misinformation detection using LLMs and lead to conclusions about their effectiveness at the task.

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.

Poultry litter was converted to biochar by torrefaction and to hydrochar by hydrothermal carbonisation. Many parameters were measured for the resulting chars, to investigate the effect of production method and production temperature. SEM showed the presence of large quantities of crystalline material on the surface of the biochars. The elemental composition of some crystals was determined as 35% K and 31% Cl. This was confirmed as sylvite (KCl) crystals, which explains the high levels of water extractable potassium in the biochar and may also be important in germination inhibition. Biochars almost totally inhibited germination, whilst hydrochars decreased germination. Although germination occurred on hydrochar, root growth was severely inhibited. Consequently, germination index may be better to determine total phytotoxicity as it measures both effects and could be used as a bioassay for chars used as soil amendments. Washing removed germination inhibition in a low temperature char (3500C), possibly by removing KCl, however root toxicity remained. There were very low levels of heavy metals, suggesting they are not the source of toxicity. In biochars, pore mean size decreased with temperature from 3500C to 6000C, due to changes in pore size distribution. Mean pore size was measured directly using SEM. The merits of this method are discussed. Low temperature biochars seem best suited for fuel as they have high calorific value, high hydrophobicity, low ash content and high yield. Higher temperatures are better for soil amendment and sequestration applications with a smaller mean pore size, higher surface area, and higher pH.

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.

In magneto-photoluminescence (magneto-PL) spectra of quasi-two dimensional islands (quantum dots) having seven electrons and Wigner-Seitz radius rs~1.5, we revealed a suppression of magnetic field (B) dispersion, paramagnetic shifts and jumps of the energy of the emission components for filling factors >1 (B<10 T). Additionally, we observed B-hysteresis of the jumps and a dependence of all these anomalous features on rs. Using a theoretical description of the magneto-PL spectra and an analysis of the electronic structure of these dots based on the single-particle Fock-Darwin spectrum and many-particle configuration-interaction calculations, we show that these observations can be described by the rs-dependent formation of the anyon (magneto-electron) composites (ACs) involving single-particle states having non-zero angular momentum and that the anyon states observed involve Majorana modes (MMs), including zero-B modes having equal number of vortexes and anti-vortexes, which can be considered as Majorana anyons. We show that the paramagnetic shift corresponds to a destruction of the equilibrium self-formed ~5/2 AC by the external magnetic field and that the jumps and their hysteresis can be described in terms of Majorana qubit states controlled by B and rs. Our results show a critical role of quantum confinement in the formation of magneto-electrons and implies the liquid-crystal nature of fractional quantum Hall effect states, Majorana anyon origin of the states having even , i.e., composite fermions, which provide new opportunities for topological quantum computing.

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 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.

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.

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.

This study aims at an acoustic design of the classical concert hall and evaluation of the acoustic performance. In terms of three acoustic parameters (i.e., reverberation time (RT), clarity (C80), and lateral fraction (LF)), this study performed acoustic simulation modeling and site measurement with the K Art Hall located in South Korea as a case study. First, in order to meet the acoustic performance of the K Art Hall (target RT: 1.4~1.7 seconds, target C80: -2dB or more +2dB or less, and target LF: 10~35%), the finish materials and shape of the room as an interior acoustic design were determined. Second, the average values of the RT, C80, and LF using the acoustic simulation modeling were estimated at 1.4 second, 1.2~1.6 dB, and 29%, respectively. Third, the average values of the RT, C80, and LF through site measuring were measured at 1.5~1.64 second, 0.07~1.31dB, and 22.22~31.37%, respectively. Thus, the results of both the acoustic simulation modeling and site measuring were analyzed so as to satisfy the target acoustic performance. The results of this study will help the decision-makers (i.e., owner, construction managers, etc.) to plan the classical concert hall in terms of the RT, C80, and LF.

Low-frequency audible noise generated by the magnetostriction effect inherent to the operation of power transformers has become a major drawback, especially in cases where the electrical substation is located in urban areas subject to strict environmental regulations that imposes sound pressure limits, differing for day and night periods. Such regulations apply a +5 dB penalty if a tonal component of noise is present, which is clearly the case of magnetostriction noise, typically concentrated at twice the industrial frequency (50 Hz or 60 Hz, depending on the country). The strategy used to eliminate the tonal characteristics, therefore contributing to establish compliance with the applicable regulation and to alleviate the discomfort it causes to the human ear, consisted in superimposing to the substation noise a masking sound synthesized from “sounds of nature” with suitable intensities, to flatten the noise spectrum while enhancing the soundscape. The masking system (heavy-duty speakers powered by a microprocessor platform) was validated at an already judicialized urban scenario. Measurement results confirmed that the masking solution was capable of flattening the tonal frequencies, whose beneficial effect yielded the cancellation of the public civil action filed by the neighbors. The proposed solution is ready to be replicated to other scenarios.

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.

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).

Proton exchange membrane (PEM) fuel cells have emerged as a viable alternative energy production source for stationary and transportation applications. Reliable and sustainable fuel cell operation requires effective water management. Membrane water content can vary along the stack during transients which can lead to losses in fuel cell performance. To control these variations a model that predicts the internal humidity dynamics of the stack is needed. In this study, a control-oriented model for predicting membrane water content variation was developed and implemented in MATLAB/Simulink. A lumped parameter model was initially developed and then further discretized into smaller control volumes to track humidity distribution along the stack. To validate the model’s predictions, the predicted results were compared to computer simulation results from GT-Suite. The root mean square error (RMSE) between the model’s prediction and GT-Suite’s simulation results was found to be within 1.5 membrane water content for all cases, demonstrating the model’s capability to capture the variation of membrane water content along the stack. The developed model will be useful for real-time control of membrane water content variation in PEM fuel cells.

Glacial ripping is a newly recognized process sequence in which subglacial erosion is triggered by groundwater overpressure. Investigations in gneiss terrain in lowland Sweden indicate that ripping involves three stages of (i) hydraulic jacking, (ii) rock disruption under subglacial traction and (iii) glacial transport of rock blocks. Evidence for each stage includes, respectively, dilated fractures with sediment fills, disintegrated roches moutonnées and boulder spreads. Here we ask: can glacial ripping also occur in sedimentary rocks, and, if so, what are its effects? The case study area is in hard, thinly bedded, gently dipping Cambrian quartz-arenites at Loch Eriboll, NW Scotland. Field surveys reveal dilated, sediment filled, bedding-parallel fractures, open joints and brecciated zones, interpreted as markers for pervasive, shallow penetration of the quartz-arenite by water at over-pressure. Other features, including disintegrated rock surfaces, boulder spreads and monomict rubble tills, indicate glacial disruption and short distance subglacial transport. The field results, together with published cosmogenic isotope ages, indicate that glacial ripping operated with high impact close to the former ice margin at Loch Eriboll at 17.6-16.5 ka. Glacial ripping thus can operate effectively in bedded, hard sedimentary rocks and the accompanying brecciation is significant – if not dominant - in till formation. Candidate markers for glacial ripping are identified in other sedimentary terrains in former glaciated areas of the Northern Hemisphere.

Over-capacity flight scheduling by commercial airlines due to the surging demand in recent years creates congestion and significant delays at major airports. This maximizing throughput attitude calls for tactical flight rescheduling to comply with airports’ capacity limitations and distribute the peak hour demand over the course of a day. Such displacements of flights may cause significant problems and costs for airlines and some cancellations or missed connections for the passengers. This paper presents an optimization model for flight rescheduling at a schedule-coordinated airport to minimize congestion and flight delays. The optimization model is used to make better scheduling intervention decisions considering the airport resource constraints and safety of operation. We have also developed a simulation method to replicate arrival and departure processes in such an airport. The simulation adheres to a first come first served (FCFS) discipline and enforces runway capacity constraints and minimum turnaround times. We compare the delays caused by an ad hoc FCFS operation with those obtained by the optimization model. Computational results from a case study demonstrate that a reduction of 40.7% and 61.6% in total delay times for the arrival and departure flights can be achieved by the optimization model. It also facilitates implementing a collaborative decision-making system for better coordination with commercial airlines.

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.

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.

Scanning magnetic microscopy is a new tool that has recently been used to map magnetic fields with good spatial resolution and field sensitivity. This technology has great advantages over other instruments; for example, its operation does not require cryogenic technology, which reduces its operational cost and complexity. Here, we describe the construction of a customizing scanning magnetic microscope based on commercial Hall-effect sensors at room temperature that achieves a spatial resolution of 200 µm. Two scanning stages on the x- and y-axes of precision, consisting of two coupled actuators, control the position of the sample, and this microscope can operate inside or outside a magnetic shield. We obtained magnetic field sensitivities better than 521 nT_rms/√Hz between 1 and 10 Hz, which correspond to a magnetic momentum sensitivity of 9.20 × 10^–10 Am². In order to demonstrate the capability of the microscopy, polished thin sections of geological samples, samples containing microparticles and magnetic nanoparticles were measured. For the geological samples, a theoretical model was adapted from the magnetic maps obtained by the equipment. Vector field maps are valuable tools for the magnetic interpretation of samples with a high spatial variability of magnetization. These maps can provide comprehensive information regarding the spatial distribution of magnetic carriers. In addition, this model may be useful for characterizing isolated areas over samples or investigating the spatial magnetization distribution of bulk samples at the micro and millimeter scales. As an auxiliary technique, a magnetic sweep map was created using Raman spectroscopy; this map allowed the verification of different minerals in the samples. This equipment can be useful for many applications that require samples that need to be mapped without a magnetic field at room temperature, including rock magnetism, the nondestructive testing of steel materials and the testing of biological samples. The equipment can not only be used in cutting-edge research but also serve as a teaching tool to introduce undergraduate, master's and Ph.D. students to the measurement methods and processing techniques used in scanning magnetic microscopy.

Optimal use of Hierarchical Bayesian Model (HBM) assembled aerosol optical depth (AOD)-PM2.5 fused surfaces in epidemiologic studies requires homogeneous temporal and spatial fused surfaces. No analytical method is available to evaluate spatial heterogeneity. The temporal case-crossover design was modified to assess the spatial association between four experimental AOD-PM2.5 fused surfaces and four respiratory-cardiovascular hospital events in 12 km2 grids. The maximum number of adjacent lag grids with significant odds ratios (ORs) identified homogeneous spatial areas (HOSAs). The largest HOSA included 5 grids (lag grids 04; 720 km2) and the smallest HOSA contained 2 grids (lag grids 01; 288 km2). Emergency department asthma and inpatient asthma, myocardial infarction, and heart failure ORs were significantly higher in rural grids without air monitors than in urban grids with air monitors at lag grids 0, 1, and 01. Rural grids had higher AOD-PM2.5 concentration levels, population density, and poverty percent than urban grids. Warm season ORs were significantly higher than cold season ORs for all health outcomes at lag grids 0, 1, 01, and 04. The possibility of elevated fine and ultrafine PM and other demographic and environmental risk factors synergistically contributing to elevated respiratory-cardiovascular chronic diseases in persons residing in rural areas was discussed

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.

Climate and its fluctuations have wide-ranging impacts on the tourism industry. High temperatures, as a typical meteorological and climatic factor, influence tourists' travel intentions and spatial behavior. This study conducted a descriptive analysis and market trend analysis of Chinese tourism during periods of high temperatures, revealing several key findings. Firstly, tourists seeking respite from summer heat exhibit a preference for short-distance trips and resource-rich destinations. Secondly, heat-escape tourism products undergo changes over time, gradually shifting towards mountainous areas and waterfront locations. Furthermore, taking Shanghai Disneyland as a case study demonstrates that the holiday system holds greater significance than temperature constraints. Despite experiencing a significant decline in the quality of their tourist experience in high-temperature environments, long-distance travelers are not deterred from choosing pre-booked tourism products by sudden bouts of hot weather.

From the mid-19th century, Collegiate Gothic architecture gained prominence among American universities. Subsequently, through the efforts of American missionaries, the Collegiate Gothic style spread to Christian universities in Asia. Specifically, this study concentrates on the nuanced relationship between the transnational missionary routes and adopting the Collegiate Gothic style, primarily focusing on Anderson Hall at Soochow University, China. The investigation meticulously dissects the multifaceted factors influencing the choice of architectural styles, considering the perspectives of missionaries, architects, and other key stakeholders. Through an intricate analysis of Anderson Hall, this research illuminates the unique characteristics of Collegiate Gothic architecture. By unraveling the complex layers of East Asian campus heritage, this study enriches our comprehension of its origins. It establishes a robust foundation for guiding the preservation and revitalization of architectural styles within university campuses. This scholarly inquiry holds particular significance for experts in academic heritage conservation.

During the last decades the quantitative description of electrical and magnetotransport properties of solid-state materials has been a remarkable challenge in materials science. Recently, the discovery of a novel class of materials, the topological semimetals, has led to a growing interest for the full understanding of their magnetotransport properties. In this review, the strong interplay among topology, band structure and carrier mobility in recently discovered high carriers mobility topological semimetals is discussed and their effect on their magnetotransport properties is outlined. The huge magnetoresistance effect, especially in the Hall transverse configuration, and a new version of a three-dimensional quantum Hall effect observed in high-mobility Weyl and Dirac semimetals are reviewed. The design of novel quantum sensors based on solid-state semimetals is also encouraged.

The direct measurements of the magnetic flux density in steel blocks within Compact Muon Solenoid (CMS) magnet yoke are performed with 22 flux loops installed in selected regions of the yoke. The 10,000-ton CMS magnet flux return yoke encloses a 4 T superconducting solenoid with a 6-m-diameter by 12.5-m-length free bore and consists of five dodecagonal three-layered barrel wheels and four end-cap disks at each end. The yoke steel blocks, mostly up to 620 mm thick, serve as the absorber plates of the muon detection system. A TOSCA 3-D model of the CMS magnet has been developed to describe the magnetic field everywhere outside of the tracking volume which was measured with a field-mapping machine. In the present study, for the first time, the reliable reconstruction of the magnetic flux density in the steel blocks of the yoke is performed using the CMS magnet standard discharges from the operational magnet current of 18.164 kA. To provide this reconstruction, the voltages induced in the flux loops (with amplitudes of 20–250 mV) have been measured with six 16-bit DAQ modules and integrated offline over time. The results of the flux loop measurements during three magnet ramp downs are presented and discussed.

In this paper, we study the problem of controllability of impulsive neutral evolution integrodifferential equations with state dependent delay in Banach spaces. The main results are completely new and are obtained by using Sadovskii's fixed point theorem, theory of resolvent operators, and an abstract phase space. An example is given to illustrate the theory.

Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB₁R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB₁R and increases caloric intake during acute exposures. The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB₁R following acute Cannabis consumption reduces energy intake and storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

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.

The 2020 Elucidating the role of clouds-circulation coupling in climate - Ocean-Atmosphere (EUREC4A-OA) and Atlantic Tradewind Ocean-Atmosphere Mesoscale Interaction Campaign (ATOMIC) campaigns sought to improve the knowledge of the interaction between clouds, convection and circulation and their function in our changing climate. The campaign consisted of numerous research technologies, some of which are relatively novel to the scientific community. In this study we used a saildrone uncrewed surface vehicle to validate satellite and modelled sea surface salinity (SSS) products in the Western Tropical Atlantic. These products include the Soil Moisture Active Passive (SMAP) Jet Propulsion Laboratory (JPL), SMAP Remote Sensing Systems (RSS), and Hybrid Coordinate Ocean Model (HYCOM). In addition to the validation, we investigated a fresh tongue south east of Barbados. The saildrones accurately depicted the salinity conditions and all satellite and modelled products performed well in areas that lacked small-scale salinity variability. However, SMAP RSS 70 km outperformed its counterparts in areas with small submesoscale irregularities while RSS 40 km was better at identifying small irregularities in salinity such as a fresh tongue. These results will allow researchers to make informed decisions regarding the most ideal product for their application and aid in the improvement of mesoscale and submesoscale SSS products, which can lead to the refinement of numerical weather prediction (NWP) and climate models.

Extracorporeal membrane oxygenation (ECMO) can be a life-saving intervention in cases of potentially reversible refractory respiratory failure. One such indication can be bleomycin-induced lung injury. However, in some cases, the injury can be so severe that it becomes irreversible and creates complex medical decisions regarding life support and the continuation of care when no additional therapeutic options are feasible, particularly in cases of patients who were young and fully functional prior to an acute illness. In cases of full pulmonary replacement with mechanical support and the degree of functionality that can be attained utilizing modalities such as ECMO can obscure the true severity of illness and make end-of-life decisions significantly harder for families and caregivers.

Worldwide, millions of kilometres of sewers are constructed from concrete pipes. Unfortunately, concrete sewers are susceptible to corrosion from biogenic hydrogen sulphide, and though they may pass visual inspection, their ability to hold together under load may be degraded. This paper presents the design of a teleoperated robot with a protractible probe, that allows an operator to apply a localised load to selected points within a concrete sewer pipe. We report findings from laboratory and field trials of our prototype, with initial results suggesting that this approach has the potential to contribute useful information to sewer maintenance planning.

A hand-held laser-induced breakdown spectroscopy device was used to acquire spectral emission data from laser-induced plasmas created on the surface of cerium-gallium alloy samples with Ga concentrations ranging from 0 to 3 weight percent. Ionic and neutral emission lines of the two constituent elements were then extracted and used to generate calibration curves relating the emission line intensity ratios to the gallium concentration of the alloy. The Ga I 287.4 nm emission line was determined to be superior for the purposes of Ga detection and concentration determination.A limit of detection below 0.25% was achieved using a multivariate regression model of the Ga I287.4 nm line ratio versus two separate Ce II emission lines. This LOD is considered a conservative estimation of technique’s capability given the type of the calibration samples available and low power( 5 mJ per 1 ns pulse) and resolving power (λ/∆λ= 4000) of this handheld device. Nonetheless, the utility of the technique is demonstrated via a detailed mapping analysis of the surface Ga distribution of a Ce-Ga sample which reveals significant heterogeneity resulting from the sample production process.

We improved a magnetic scanning microscope for measuring the magnetic properties of minerals in thin sections of geological samples at submillimeter scales. The microscope is comprised of a 200 µm diameter Hall sensor that is 142 µm from the sample; an electromagnet capable of applying to the sample up to 500 mT dc magnetic fields over a 40 mm diameter region; a second Hall sensor arranged in a gradiometric configuration to cancel the background signal applied by the electromagnet and reduce overall noise in the system; a custom-designed electronics to bias the sensors and provide adjustment for background signal cancelation; and a scanning XY stage with micrometer resolution. Our system achieves a spatial resolution of 220 µm with noise at 6.0 Hz of »300 nT_rms/(Hz)^1/2 in an unshielded environment. The magnetic moment sensitivity is 1.3 × 10⁻¹¹ Am².^1/2 We successfully measured the representative magnetization of a geological sample using an alternative model that takes into account the sample geometry and identified different micrometric characteristics in the sample slice.

Type 1 diabetes (T1D) is associated with hyperglycaemia-induced hypoxia and inflammation. The study assessed the effects of a single high-intensity interval exercise (HIIE) on glycaemia (BG) and serum level of pro-inflammatory cytokines and an essential mediator of adaptive response to hypoxia in T1D patients. The macronutrients intake was also evaluated. Nine patients suffering from T1D for about 12 years and nine healthy individuals (CG) were enrolled and completed one session of HIIE at the intensity of 120% lactate threshold and duration of 4 x 5 min intermittent with 5 min rest after each bout of exercise. Capillary and venous blood was withdrawn at rest, immediately after and at the 24 h post-HIIE for analysis of BG, hypoxia-inducible factor alpha (HIF-1α), tumour necrosis factor alpha (TNF-α) and vascular-endothelial growth factor (VEGF). Pre-exercise BG was significantly higher in the T1D compared to the CG (p = 0.043). HIIE led to a significant decline in T1D patients’ BG (p = 0.027) and to a tendency for a lower BG at 24-h post-HIIE vs pre-HIIE. HIF-1α was significantly elevated in the T1D compared to CG and there was a trend for HIF-1α to decline, and VEGF, TNF-α to increase in response to HIIE in the T1D group. Both groups consumed higher and lower than recommended amounts of protein and fat, respectively. In T1D group, a tendency for a higher digestible carbohydrate intake and more frequent hyperglycaemic episodes on the day after HIIE were observed. HIIE was effective in reducing T1D patients’ glycaemia and improving the short-term glycaemic control. HIIE has the potential to improve adaptive response to hypoxia by elevating the serum level of VEGF. Patients’ diet and level of physical activity should be screened on a regular basis, and they should be educated on the glycaemic effects of digestible carbohydrates.

Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema (S) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has not been investigated. We recently reported that cyanobacterium Oscillatoria sp. LPS elicited classical and alternative activation of rat microglia in vitro [1]. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria S. javanicum or S. ocellatum LPS might stimulate classical and alternative activation with concomitant release of superoxide anion (O₂⁻), matrix metalloproteinase-9 (MMP-9) and cytokines and chemokines. Microglia were isolated from neonatal rats and treated in vitro with either S. javanicum LPS, S. ocellatum LPS, or E. coli LPS (positive control) in a concentration-dependent manner for 18 hours at 35.9 °C. We observed that treatment of microglia with either E. coli LPS, S. javanicum or S. ocellatum LPS generated statistically significant and concentration-dependent O₂⁻, MMP-9 and pro-inflammatory cytokines IL-6 and TNF-α, pro-inflammatory chemokines MIP-2/CXCL-2, CINC-1/CXCL-1 and MIP-1α/CCL3, and the anti-inflammatory cytokine IL-10. Thus, our results provide experimental support for our working hypothesis because both S. javanicum and S. ocellatum LPS elicited classical and alternative activation of microglia and concomitant release of O₂^-, MMP-9 and cytokines and chemokines in a concentration-dependent manner. To our knowledge this is the first report on the toxicity of cyanobacteria S. javanicum and S. ocellatum LPS to microglia, an immune cell type involved in neuroinflammation and neurotoxicity in the central nervous system.

Volumetric models are a crucial tool for forest management. The study aimed to adjust the mixed model by Schumacher and Hall for estimating commercial volume in a dense ombrophilous forest situated in Ferreira Gomes, Amapá, Brazil. Cubage data from 100 sample trees of 5 species were used to adjust the Schumacher and Hall model in fixed and mixed non-linear forms with the diameter class as a random effect. In addition, the same model was also adjusted for each class to verify whether good equations will be generated by stratifying by diameter class. After analysis, it was found that most of the equations by diameter class do not present all significant parameters. On the other hand, the mixed models using class as a random effect showed good results. Finally, it can be seen that mixed models are a much better alternative than stratification by diameter class for volume estimation.

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.

This review article aims to delve into several aspects of sweetpotatoes and their leaves, including their nutritional composition, health benefits, culinary uses, and potential future implications as a superfood. It suggests an in-depth exploration of sweet potatoes' history, status, and prospects, highlighting their significance and potential economic value. Sweetpotatoes, often referred to as a powerhouse of nutrients, have gained popularity recently due to their remarkable nutritional composition and versatile culinary uses. This starchy root vegetable comes from the Convolvulaceae family and is consumed worldwide, playing a significant role in diverse cultures and cuisines. Besides their vibrant colors ranging from orange to purple, sweetpotatoes offer many health benefits, making them an essential addition to a well-balanced diet. Its extraordinary nutritional profile and numerous health benefits make it a superfood. Incorporating it into the diet can improve digestion, strengthen immunity, and reduce the risk of chronic diseases. With their versatility in the kitchen, there is no deficiency of charming and healthy recipes to explore. So, make room for sweet potatoes on your plate and unlock their vast potential to enhance your overall health and well-being. Overall, the future of sweetpotatoes looks bright as research and innovation aim to improve their nutritional value, adapt them to changing climate conditions, develop new varieties and products, and promote sustainable production practices. These developments can contribute to food security, economic growth, and healthier diets. Future research should focus on nutritional composition, health benefits, sustainable farming practices, cultivar development, and industrial applications to ensure sustainable and efficient production. By prioritizing research in these areas, we can enhance the utilization of sweet potatoes in various fields and secure their future for the next century.

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.

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.

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.

We investigate emergent conductive phenomena triggered by collinear antiferromagnetic orderings. We show that an up-down-zero spin configuration in a triangle cluster leads to linear and nonlinear spin conductivities even without the relativistic spin–orbit coupling; the linear spin conductivity is characterized by the Drude-type one, while the nonlinear spin conductivity is characterized by the Hall-type one. We demonstrate the emergence of both spin conductivities in the breathing kagome system consisting of a triangle cluster. The nonlinear spin conductivity becomes larger than the linear one when the Fermi level lies near the region where a small partial band gap opens. Our results indicate that collinear antiferromagnets with the triangle geometry give rise to rich spin conductive phenomena.

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.

Face shields (also referred to as visors), goggles and safety glasses have been worn during the COVID-19 pandemic as one measure to control transmission of the virus. However, their effectiveness in controlling facial exposure to cough droplets is not well established and standard tests for evaluating eye protection for this application are limited. A method was developed to evaluate face shields, goggles and safety glasses as a control measure to protect the wearer against cough droplets. The method uses a semi-quantitative assessment of facial droplet deposition. A cough simulator was developed to generate droplets comparable to those from a human cough. The droplets consisted of a UV fluorescent marker (fluorescein) in water. Fourteen face shields, four pairs of goggles and one pair of safety glasses were evaluated by mounting them on two different sizes of breathing manikin head and challenging them with the simulated cough. The manikin head was positioned in seven orientations relative to the cough simulator to represent various potential occupational exposure scenarios, for example, a nurse standing over a patient. Droplet deposition in the eyes, nose and mouth regions were visualised following three ‘coughs’. Face shields, goggles and safety glasses reduced, but did not eliminate exposure to the wearer from droplets such as those produced by a human cough. The level of protection differed based on the design of the personal protective equipment and the relative orientation of the wearer to the cough. For example, face shields and goggles offered the greatest protection when a cough challenge was face on or from above and the least protection when a cough challenge was from below. Face shields were also evaluated as source control to protect others from the wearer. Results suggested that if a coughing person wears a face shield, it can provide some protection from cough droplets to those standing directly in front of the wearer.

A recent reanalysis of publicly available data claimed that the carbohydrate-insulin model was supported by results from a randomized crossover trial comparing low carbohydrate (LC) versus low fat (LF) diets. The reanalysis also claimed to have invalidated the primary outcome of the trial, namely the within-participant differences in ad libitum energy intake when they consumed LC vs LF diets. Here, we demonstrate that both claims are untrue. The reanalysis was fatally flawed in several respects, with the most egregious errors related to ignoring the within-participant, repeated-measures structure of the data and treating data timepoints as independent. This resulted in almost all statistical comparisons being incorrect and reporting wildly optimistic p-values. Furthermore, the authors failed to engage sufficiently with prior work on the same trail data and portrayed their reanalysis as being more novel than it was. The reanalysis also failed to disclose the possibility of bias and succumbed to common statistical errors that falsely led the authors to interpret the data as supporting the carbohydrate-insulin model of obesity.

Concrete condition assessing penetrometers need to be able to distinguish between making contact with a hard (concrete) surface as opposed to a semi-solid (corroded concrete) surface. If a hard surface is mistaken for a soft surface, concrete corrosion may be over-estimated, with the potential for triggering unnecessary remediation works. Unfortunately, the variably-angled surface of a concrete pipe can cause the tip of a force-sensing tactile penetrometer to slip and thus to make this mistake. We investigated whether different shaped tips of a cylindrical penetrometer were better than others at maintaining contact with concrete and not slipping. We designed a range of simple symmetric tip shapes, controlled by a single superellipse parameter. We performed a finite element analysis of these parametric models in SolidWorks before machining in stainless steel. We tested our penetrometer tips on a concrete paver cut to four angles at 20∘ increments. The results indicate that penetrometers with a squircle-shaped steel tip (a=b=1,n=4) have the least slip, in the context of concrete condition assessment.

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.

Sport centers are significant energy consumers. This article outlines the engineering design for a comprehensive energy performance upgrade of the indoor sport hall in Arkalochori, Greece, and presents the projected results. The indoor sport hall constitutes a major sport facility in the mainland of Crete, hosting a broad cluster of sport municipal activities and the official basketball games of the local team in the 2nd national category. Having being constructed in the mid ‘90s, the facility exhibits very low thermal performance, with considerably high U-factors for all constructive elements (from 4 to 5 W/m2∙K), still use of diesel oil for indoor space heating and domestic heat water production and ineffective, old lamps and luminaries covering the lighting needs of the facility. The energy performance upgrade of the indoor sport hall was holistically approached, through all possibly applicable passive and active measures: insulation of opaque surfaces and replacement of openings, installation of new stone wool panels, installation of heat pumps for indoor space conditioning, elimination of diesel oil for any final energy use, installation of a solar-combi system for domestic hot water production, upgrade of all indoor and outdoor lighting equipment, installation of solar tubes on the main sport hall roof for natural lighting and installation of a photovoltaic plant on the same roof for the compensation of the remaining electricity consumption. With the proposed measures, the indoor sport hall is upgraded to zero energy facility. The payback period of the investment was calculated at 26 years, on basis of the avoided energy resources procurement cost. This work has been funded by the Horizon 2020 project with the acronym “NESOI” and was awarded with the public award of the “Islands Gamechanger” competition of the NESOI project and the Clean Energy for EU Islands initiative.

This study examines HIV/AIDS-associated knowledge and attitudes towards treating disadvantaged communities among predoctoral dental students in U.S. dental schools who had not yet commenced their Community-Based Dental Education (CBDE) training. It also compares the difference in knowledge and attitudes between students with reported community engagement with PLWHA, and those without. Our study comprised 89 predoctoral dental students within their D1-D3 years of dental school who had not yet initiated their Community-Based Dental Education (referred to as pre-CBDE dental students). Responses were collected via an online survey. Participants were 68% females, 94% heterosexual, of mean age (years): 25.9 ± 3.5 SD. The majority (62%) were in their first (D1) and second (D2) years of dental education. Of the thirty knowledge questions, only five received a minimum of 90% correct responses. Similarly, we found no statistical differences in most of the knowledge/attitude sections, between those with and without prior PLWHA exposure. Encouragingly, 90% of our participants reported prior experience working with disadvantaged communities. Early community engagement fosters a sense of professional responsibility towards administering dental care to disadvantaged communities and we propose that it must be encouraged among aspiring dental school students.

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 World Health Organization (WHO) added Disease X to their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. During different virus outbreaks of the past, such as COVID-19, Influenza, Lyme Disease, and Zika virus, researchers from various disciplines utilized Google Trends to mine multimodal components of web behavior to study, investigate, and analyze the global awareness, preparedness, and response associated with these respective virus outbreaks. As the world prepares for Disease X, a dataset on web behavior related to Disease X would be crucial to contribute towards the timely advancement of research in this field. Furthermore, none of the prior works in this field have focused on the development of a dataset to compile relevant web behavior data, which would help to prepare for Disease X. To address these research challenges, this work presents a dataset of web behavior related to Disease X, which emerged from different geographic regions of the world, between February 2018 to August 2023. Specifically, this dataset presents the search interests related to Disease X from 94 geographic regions. These regions were chosen for data mining as these regions recorded significant search interests related to Disease X during this timeframe. The dataset was developed by collecting data using Google Trends. The relevant search interests for all these regions for each month in this time range are available in this dataset. This paper also discusses the compliance of this dataset with the FAIR principles of scientific data management. Finally, a brief analysis of specific features of this dataset is presented to uphold the applicability, relevance, and usefulness of this dataset for the investigation of different research questions in the interrelated fields of Big Data, Data Mining, Healthcare, Epidemiology, and Data Analysis.

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.

Recent studies have emphasized the influence of resettlement factors on the mental health of refugees resettling in developed countries. However, little research has addressed gender differences in the nature and influence of resettlement stressors and sources of resilience. We address this gap in knowledge by investigating how gender moderates and mediates the influence of several sources of distress and resilience among 259 Afghan refugees residing in northern California. Gender moderated the effects of four factors on levels of distress. Intimate and extended family ties have little correlation with men’s distress levels, but are strongly associated with lower distress for women. English ability is positively associated with lower distress for women, but not men. In terms of gender ideology, traditionally oriented women and egalitarian men have lower levels of distress. And experiencing greater dissonant acculturation increases distress for men, but not women. The influence of gender interaction terms is substantial and patterns may reflect difficulty adapting to a different gender order. Future studies of similar populations should investigate gender differences in sources of distress and resilience, and efforts to assist new arrivals might inform them of changes in gender roles they may experience, and facilitate opportunities to renegotiate gender roles.

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<0.01). Among those who were readmitted, hospitalizations for severe pneumonia had a longer length of stay (6.5 vs. 5.4 days, p<0.01) and higher daily cost ($3,246 vs. $2,679, p<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.

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.

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.

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.

The water and wastewater sectors are energy-intensive, and so a growing number of utility companies are seeking to identify opportunities to reduce energy use. Though England’s water sector is of international interest, in particular due to the early experience with privatisation, for the time being very little published data on energy usage exists. We analyse telemetry data from Thames Water Utilities Ltd. (TWUL), which is the largest water and wastewater company in the UK and serves one of the largest mega-cities in the world, London. In our analysis, we (1) break down sectoral energy use into their components, (2) present a statistical method to analyse the long-term trends in use, as well as the seasonality and irregular effects in the data, (3) derive energy-intensity (kWh m³) figures for the system, and (4) compare the energy-intensity of the network against other regions in the world. Our results show that electricity use grew during the period 2009 to 2014 due to capacity expansions to deal with growing water demand and storm water flooding. The energy-intensity of the system is within the range of reported figures for systems in other OECD countries. Plans to improve the efficiency of the system could yield benefits in lower the energy-intensity, but the overall energy saving would be temporary as external pressures from population and climate change are driving up water and energy use.

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.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV is a potent inducer of reactive oxygen species (ROS) which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an evolutionary conserved redox-responsive protein that helps to protect cells and whole organisms from oxidative stress and injury. The role of Nrf2 in the context of viral-mediated chronic lung injury is not known. Herein, we show that RSV experimental infection of adult Nrf2 deficient BALB/c mice (Nrf2-/-; Nrf2 KO) is characterized by enhanced disease, increased inflammatory cell recruitment to the bronchoalveolar compartment, and a more robust upregulation of innate and inflammatory genes and proteins, compared to wild type Nrf2+/+ competent mice (WT). These events that occur at very early time points, lead to increased peak RSV replication in Nrf2 KO compared to WT mice (day 5). To evaluate longitudinal changes of the lung architecture, mice were scanned weekly by high-resolution micro-computed tomography (micro-CT) imaging up to 28 days after initial viral inoculation. Based on micro-CT qualitative 2D imaging and quantitative reconstructed histogram-based analysis of lung volume and density, we found that RSV infected Nrf2 KO mice developed significantly greater and prolonged fibrosis compared to WT mice. Results of this study underscore the critical role of Nrf2-mediated protection from oxidative injury not only in acute pathogenesis of RSV infection, but also in its long-term consequences of chronic airway injury.

The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action – to uncover and develop anti-viral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analog prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of its mechanism of action, discovery, and the current studies exploring its clinical effectiveness.

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.

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.