This paper proposes an optimal trading algorithm based on a novel application of the conventional Control Engineering (CE). We consider a fundamental CE concept, namely, the feedback control and apply it to the Algorithmic Trading (AT). The concrete feedback control strategy is designed in a form of the celebrated Proportional-Integral-Derivative (PID) model. The highly fluctuating nature of the modern financial markets has led to the adoption of a model-free realisation of the generic PID framework. The control theoretical methodology we propose is combined with the advanced statistics for the historical market data. We obtain a specific log-normal probability distribution function (pdf) associated with the specific quantities associated with the available stock data. The empirical log-normal pdf mentioned above makes it possible the necessary PID gains optimization. For this aim, we apply the data-driven optimization approaches and consider the corresponding Monte Carlo solution procedure. The optimized PID trading algorithm we propose is also studied in the Fourier analysis framework. This equivalent frequency domain representation involves a new concept in the financial engineering, namely, the "stock market energy" concept. For the evaluation, we implement the proposed PID optimal trading algorithm and develop a Python based prototype software. We finally apply the corresponding prototype software to a dataset from the Binance BTC / USDT stock market. The experimental result illustrates the implementability of the proposed optimal PID trading scheme and also shows the effectiveness of the proposed CE methods in the modern AT.

Fast Field-Cycling (FFC) Nuclear Magnetic Resonance (NMR) relaxometry is a powerful non-destructive magnetic resonance technique that enables, among other things, the investigation of slow molecular dynamics at low magnetic field intensities. FFC-NMR relaxometry measurements provide insight into molecular motion across various timescales within a single experiment. This study focuses on a \textit{model-free} approach, representing the NMRD profile $R_1$ as a linear combination of Lorentzian functions, thereby addressing the challenges of fitting data within an ill-conditioned linear least-squares framework. Tackling this problem, we present a comprehensive review and experimental validation of three regularization approaches to implement the model-free approach to analysing NMRD profiles. These include: (1) \nameUpe, utilizing locally adapted $L_2$ regularization; (2) \nameL, based on $L_1$ penalties; and (3) a hybrid approach combining locally adapted $L_2$ and global $L_1$ penalties. Each method's regularization parameters are determined automatically, according to the Balancing and Uniform Penalty principles. % Our contributions include the implementation and experimental validation of the \nameUpe{} and \nameUp{} algorithms, and the development of a "dispersion analysis" technique to assess the existence range of the estimated parameters. The objective of this work is to delineate the variance in fit quality and correlation time distribution yielded by each algorithm, thus broadening the set of software tools for the analysis of sample structures in FFC-NMR studies. The findings underline the efficacy and applicability of these algorithms in the analysis of NMRD profiles from samples representing different potential scenarios. 1

Explaining the emergence of behavior and understanding on the basis of neuronal mechanisms is still elusive. One renowned proposal is the Free Energy Principle (FEP), which uses an information-theoretic framework derived from thermodynamic considerations to describe how behavior and understanding would emerge. FEP starts from a whole organism approach, based on mental states and phenomena, mapping them into the neuronal substrate. An alternative approach, the Energy Homeostasis Principle (EHP), initiates a similar explanatory effort, but starting from single neuron phenomena and building up to the whole organism’s behavior and understanding. In this work, we develop the EHP as an alternative but complementary vision to FEP and try to explain how behavior and understanding would emerge from the local requirements of the neurons. Based on EHP and a strict naturalist approach that sees living beings as physical and deterministic systems, we explain scenarios where learning would emerge without the need for volition or goals. Given these starting points, we state several considerations of how we see the nervous system, particularly the role of function, purpose, and the conception of goal-oriented behaviors. We problematize these conceptions, giving an alternative teleology-free framework in which behavior and, ultimately, understanding would still emerge. We reinterpret neural processing explaining basic learning situations up to simple anticipatory behavior. Finally, we end the work with an evolutionary perspective of how this non-goal-oriented behavior appears. We acknowledge that in the current form of our proposal, we are still far from explaining the emergence of understanding. Still, we set the ground for an alternative neuron-based framework to ultimately explain understanding.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Integral atmospheric dispersion models are used widely for flammable hazard and its risk analysis. There is a widespread belief that flammable distances from these models are conservative when flammable ranges are calculated using the 0.5 lower flammability limits (LFL) concentration threshold. This is erroneous. This paper traces through the development of these models and the research that led to the Birch Guidance. It shows that the 0.5 LFL is a necessary factor to transform the results of dispersion models designed for environmental assessment to applications to flammable hazard assessment in quiescent conditions. Current applications do not take account of turbulence due to wind, large and small obstructions, etc. A set of simple guidance is given in the paper to manage flammable hazards based on results from atmospheric dispersion models, including topics for future research.

The discovery of a growing number of exoplanets and even extrasolar systems supports the scientific consensus that it is possible to find other signs of life in the universe. The present work proposes for the first time, an explicit mechanism inspired by the dynamics of biological dispersion, widely used in ecology and epidemiology, to study the dispersion of biogenic units, interpreted as complex organic molecules, between rocky or water exoplanets (habitats) located inside star clusters. The results of the dynamic simulation suggest that for clusters with populations lower than 4 M+/ly³ it is not possible to obtain biogenic worlds after 5 Gyr. Above this population size, biogenic dispersion seems to follow a power law, the larger the density of worlds lesser will be the impact rate (β ) value to obtain at least one viable biogenic Carrier habitat after 5 Gyr. Finally, when we investigate scenarios by varying β, a well-defined set of density intervals can be defined in accordance to its characteristic β value, suggesting that biogenic dispersion has a behavior of “minimal infective dose” of “minimal biogenic effective” events by interval i.e. once this dose has been achieved, doesn’t matter if additional biogenic impact events occur on the habitat.

The properties of rubber are strongly influenced by the distribution of filler within the polymer matrix. Here we introduce a Monte Carlo-based morphology generator. The basic elements of our model are cubic cells, which, in the current version, can be either silica filler particles or rubber volume elements in adjustable proportion. The model allows the assignment of surface free energies to the particles according to whether a surface represents, for instance, 'naked' silica or silanised silica. The amount of silanisation is variable. We use a nearest-neighbour site-exchange Monte Carlo algorithm to generate filler morphologies, mimicking flocculation. Transmission electron micrographs (TEM) as well as small angle scattering (SAS) intensities can be calculated along the Monte Carlo trajectory. In this work we demonstrate the application of our morphology generator in terms of selected examples. We illustrate its potential as a tool for screening studies, relating interface tensions between the components to filler network structure as characterized by TEM and SAS.

This study employs the FLACS code to analyze hydrogen leakage, vapor dispersion, and subsequent explosions. Utilizing pseudo-source models, a liquid pool model, and a hybrid model combining both, we investigate dispersion processes for varying leak mass flow rates (0.225 kg/s and 0.73 kg/s) in a large open space. We also evaluate explosion hazards based on overpressure and impulse effects on humans. The computational results, compared with experimental data, demonstrated reasonable hydrogen vapor cloud concentration predictions, especially aligned with the wind direction. For higher mass flow rate of 0.73 kg/s, the pseudo-source model and hybrid model proved appropriate, while the liquid pool model was more suitable for lower mass flow rate of 0.225 kg/s. Regarding explosion analyses using overpressure-impulse diagram, higher mass flow rates leaded to potentially fatal overpressure and impulse effects on humans. However, lower mass flow rates may cause severe eardrum damage at the maximum overpressure point.

The application of warm-mixing technology brings considerable economical and environment benefits by decreasing the mixing temperature during warm asphalt mixture(WMA) production. However, the possible water residue also generates concerns in moisture susceptibility. For deep investigation on the influencing factors and mechanism of the moisture susceptibility of WMA, surface free energy(SFE) test and laboratory tests are applied in this research. A novel indicator based on SFE namely effective adhesion work is proposed to assess the asphalt-aggregate adhesion with different moisture contents. Then, given the mixing procedure of dry mixing method, an advanced three-phase model as form of asphalt-aggregate-warm mixing additive is introduced improving from the conventional two-phase asphalt-aggregate model for better reflecting the separate addition of warm mixing additive during mixing. Afterwards, the influence of aggregate types, asphalt type, aggregate moisture contents, warm-mixing agent types and warm-mixing process on the moisture susceptibility of WMA is analyzed utilizing the models and indicators proposed. Finally, the validity of the SFE indicator is verified by comparing the calculation of effective adhesion work with freeze-thaw splitting test result. The results show that all of the above factors impact the moisture susceptibility of WMA by influencing the interfacial adhesion, with the effect of moisture content being the most significant. Meanwhile, effective adhesion work and the three-phase model brought out in this research are proven to be feasible to characterize the adhesion properties of WMA, offering theoretical support to the research on warm mixing technology.

In Lagrangian dynamics, the detection of coherent clusters can help understand the organization of transport by identifying regions with coherent trajectory patterns. Many clustering algorithms, however, rely on user-input parameters, requiring a priori knowledge about the flow and making the outcome subjective. Building on the conventional spectral clustering method of Hadjighasem et al (2016), a new parameter-free spectral clustering approach is developed that automatically identifies parameters and does not require any user-input choices. A noise-based metric for quantifying the coherence of the resulting coherent clusters is also introduced. The parameter-free spectral clustering is applied to two benchmark analytical flows, the Bickley Jet and the asymmetric Duffing oscillator, and to a realistic, numerically-generated oceanic coastal flow. In the latter case, the identified model-based clusters are tested using observed trajectories of real drifters. In all examples, our approach succeeded in performing the partition of the domain into coherent clusters with minimal inter-cluster similarity and maximum intra-cluster similarity. For the coastal flow, the resulting coherent clusters are qualitatively similar over the same phase of the tide on different days and even different years, whereas coherent clusters for the opposite tidal phase are qualitatively different.

Tight gas, a category of Deep Green Energy Resources, rely on advanced intelligent monitoring methods for their extraction. Conventional logging for reservoir evaluation relies on logging data and the manual setting of evaluation criteria to classify reservoirs. However, the complexity and heterogeneity of tight reservoirs pose challenges in accurately identifying target layers by using traditional well-logging techniques. Machine learning may hold the key to solving this problem, as it enables computers to learn without being explicitly programmed and manually added rules. Therefore, it is possible to make reservoir evaluation via using machine learning methods. In this paper, the reservoir quality index (RQI) and porous geometric parameters obtained from the optimized inversion of the spherical-tubular model are adopted to evaluate the reservoir. Then, three different machine learning approaches, the random forest (RF) algorithm, support vector machine (SVM) algorithm, and extreme gradient boosting (XGB) algorithm, are utilized for reservoir classification. The selected dataset covers more than 7,000 samples from five wells. The data from four wells are arranged as the training dataset, and the data of the remaining one well is designed as the testing dataset to calculate the prediction accuracies of different machine learning algorithms. Among them, accuracies of RF, SVM, and XGB are all higher than 90%, and XGB owns the highest result by reaching 97%. Machine learning based approaches can greatly assist reservoir prediction by implementing the well-logging data. The research highlights the application of reservoir classification with a higher prediction accuracy by combining machine learning algorithms with NMR logging based pore structure characterization, which can provide a guideline for sweet spot identification within the tight formation. This not only optimizes resource extraction but also aligns with the global shift towards clean and renewable energy sources, promoting sustainability and reducing the carbon footprint associated with conventional energy production. In summary, the fusion of machine learning and NMR logging based reservoir evaluation plays a crucial role in advancing both energy efficiency and the transition to cleaner energy sources.

This paper deals with a non-contact method to identify the aerodynamic propeller parameters of the Parrot AR.Drone quadrotor. The experimental set consists in a camera recording the vehicle flights, the audio signal is extracted and is used a spectrogram analysis to estimates the propeller velocity. First, the aerial vehicle takes off and starts a hovering maneuver. The experiment is repeated with different additional masses attached to its rigid body. If the weight over the UAV increases/decreases, then the propeller must rotates faster/slower to produce a higher/lower thrust, and consequently, the sound frequency increases/decreases. Finally, this proposition is validated experimentally, and the estimated velocity is used to identify the quadrotor thrust parameters.

Twenty-four extensively-reared Iberian pigs were used to study the influence of fattening period length (30, 60 or 90 days) on the fatty acid profiles of intramuscular and subcutaneous fat and the relationships between both profiles. Regarding fatty acid (FA) percentage, PUFA was greater in backfat and MUFA was greater in intramuscular fat (IMF), regardless fattening period length. The longer fattening period increased MUFA content in backfat (which had a more marked change in oleic acid) and decreased PUFA content in backfat and IMF, but it did not affect SFA content. Within the 3-layers subcutaneous backfat, SFA content was greater in the inner layer, MUFA was greater in the outer layer and PUFA was greater in both of these layers. The few differences in FA composition between both adipose tissues suggest that the changes due to the feeding regime are slow and, therefore, although the length of the fattening phase was increased, the fatty acid profile did not change substantially. The strong relationship between the FA profiles of IMF and backfat might be used to predict one profile from the other one when this latter was more readily available for sampling or analytical reasons.

Cancer stem cells play a crucial role in tumor initiation, metastasis and therapy resistance. Cellular heterogeneity and plasticity challenge the isolation of cancer stem cells. The impact of intratumoral cellular heterogeneity in the context of treatment resistance using a label-free approach remains understudied. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three cell subpopulations sorted by SdFFF exhibits cancer stem cell traits, including high tumorigenicity in vivo, and a higher frequency of tumor-initiating cells compared to the other subpopulations. In vitro two- and three-dimensional chemosensitivity assays emphasize the therapeutic relevance of this cancer stem cell-like subpopulation due to its chemoresistance. Therefore, our findings highlight a label-free cell sorting approach to reveal intratumoral cellular heterogeneity and its implication in therapy resistance. This approach enables the study of the individualized response of each sorted cell subpopulation by breaking down the tumor, thus offering new perspectives for personalized therapy.

The exact dynamics of emergence remains one of the most prominent outstanding questions for the field of complexity science. I first discuss various perspectives on emergence in various contexts, then offer a different perspective on understanding emergence in a graph-theoretic representation. From the discussion, an observer’s choice in state space seems to have an effect for that observer to detect emergent behavior. To test these ideas, I analyze the dynamics of all possible spatial state spaces near the critical temperature in an Ising model. As a result, state space topologies that appear more deterministic flip more bits than topologies that appear more random, which is contrary to our intuitions about randomness. In addition, the size of different state spaces constrain a system’s ability to explore various states within the same time frame. These results are important to understanding emergent phenomena in biological systems, which are layered with various state spaces and observational perspectives.

Postgraduate research is a massive stumbling block to students who had never had an opportunity of exposure to research methods. A study conducted by the researcher (Costa, 2018) revealed challenges in postgraduate supervision—one of these challenges was lack of exposure to research language by students. Qualitative research and its complexities due to a variety of approaches including rigour determination pose a plethora of challenges to novice researchers. This document presents C.O.S.T.A model as a tool suitable for use by academics and students, with a panoramic view of steps to be taken first to understand foundational concepts and the language of research and secondly to make informed choices on the research methods and design strategy options available for the prospective researcher. Conclusions drawn on the reliability of the model are based on empirical evidence of application of the model observed over a period of 12 months, with some students testifying to have passed their research projects satisfactorily at their respective leading universities in South Africa. Secondary research also provides voluminous sources of success of similar research supervision programmes both in South Africa and abroad.

In a context of increasingly necessary energy transition, precise modelling of profiles for low-voltage (LV) network consumers is crucial to enhance hosting capacity. Typically, load curves for these consumers are estimated through measurement campaigns conducted by Distribution System Operators (DSO) for a representative subset of customers or through the aggregation of load curves from household appliances within a residence. With the instrumentation of smart meters becoming more common, a new approach to modelling profiles for residential customers is proposed to make the most of the measurements from these meters. The disaggregation model estimates the load profile of customers on a low-voltage network by disaggregating the load curve measured at the secondary substation level. By utilizing only the maximum power measured by Linky smart meters, along with the load curve of the secondary substation, this model can estimate the daily profile of customers. For 48 secondary substations in our dataset, the model obtained an average symmetric mean average percentage error (SMAPE) error of 4.91% in reconstructing the load curve of the secondary substation from the curves disaggregated by the model. This methodology can allow the estimation of the daily consumption behaviors of the low-voltage customers. In this way, we can safely envision solutions that enhance the grid hosting capacity.

Fitts' law predicts the human movement response time for a specific task by a simple linear formulation, in which the intercept and the slope are estimated from the task's empirical data. This research was motivated by our pilot study, which found that the linear regression's essential assumptions are not satisfied in the literature. Furthermore, the keystone hypothesis in Fitts' law, that the movement time per response will be directly proportional to the minimum average amount of information per response demanded by the particular amplitude and target width, has never been formally tested. Therefore, this study developed an optional formulation derived from fusing the findings in psychology, physics, and physiology for fulfilling the statistical assumptions. An experiment was designed to test the hypothesis in Fitts' law and validate the proposed model. To conclude, our results indicated that movement time could be related to the index of difficulty underlying the same constant amplitude. The optional formulation accompanies the index of difficulty in Shannon form robustly performs the prediction better than the traditional model across studies. Finally, a new approach to modeling movement time prediction is deduced from our research results

The thermal properties of a building envelope are key indicators of the energy performance of the building. Therefore, methods are needed to determine quantities like U-values or heat capacitance in a fast, reliable way and with as little impact on the use of the building as possible. In this paper a technique is proposed that relies on a simplified electrical analogical model of building envelope components which can cover their dynamic thermal behavior. The parameters of this model are optimized to produce the best fit between simulated and measured outside surface temperatures. As the temperatures can be measured remotely with an infrared camera this approach requires significantly less installation effort and intrusion in the building than other methods. At the same time, a single measurement provides data for a large range of locations on a facade or a roof. The paper describes the method and a first experimental implementation of it. The experiment indicates that this method has the potential to produce results which have an accuracy that is comparable to standardized reference methods.

Air pollution poses a significant risk to public health and ecosystems. The use of sophisticated models to simulate the transformation and dispersion of pollutants in the atmosphere is a recognized method to assess air pollution levels and its sources and inform policy decisions for effective mitigation strategies in urban and industrial environments. The reliability of models depends, in part, on the sensitivity to the variance of input parameters, which can introduce uncertainty into the model's predictions. This uncertainty is especially challenging when the input parameters exhibit inherent variability. In this study, we analyse the uncertainty of an integrated emission/dispersion model by evaluating the relationship between input parameters and model outcomes. We uncover new aspects of this relationship while clarifying some previously known dependencies. Wind speed was found to have the most significant effect on calculated concentrations, with small differences leading to substantial concentration variations. The time of day, which reflects prevailing vertical turbulence conditions, was also found to have a notable impact on concentrations, whereas ambient temperature can also significantly influence model’s results. Based on these findings, we offer specific recommendations for regulators and scientists involved in environmental impact assessment to improve the accuracy and reliability of air pollution modelling.

Enterprises that seek for sustainable development should align economic interests with environmental and social requirements. It is not enough to take into account just these basics components. Technology plays a significant role in company activity. The aim of this article is to highlight the relationship between the dimensions characterising sustainability and to take a deeper look at the structure of the concept of sustainability so that to understand in more detail the completeness of the dimensions of sustainability. For achieving this aim is necessary through the analysis of researchers’ opinions to apply the logical assessment, systematisation, and comparison of information, selects the most important information describing the sustainability of technology, highlights the relationships between the technological aspect of sustainability and other sustainability dimensions, evaluates the technological processes of the corporate product in terms of sustainability, clarifies and presents arguments highlighting the importance of the technological aspect in sustainable business activity, rejects inappropriate arguments, identifies links between the arguments, and, basing on the information, proves and/or formulates anew some logical considerations to justify the full competency of the technological dimension in the sustainable development framework.

In an increasingly complex world there is a real, urgent need for methodologies to enable engineers to model complex sociotechnical systems, as these now seem to describe the majority of systems in use today. This is of course exacerbated by the increasing involvement and augmentation with “black box” AI contributions. Hollnagel produced a methodology, (FRAM) which did allow the analyst in-sights into these systems’ behaviour, but the model-based system engineering applications demand numbers and a quantitative ap-proach. In the last 10 years, this original approach developed to model systems as sets of interactive, interdependent “functions”, (abstracted from agent or component details), has been further developed to the point where it can take the basic data and structures from the current component focussed system engineering “models”, and can pull it all together into dynamic models, (as opposed to static, fixed System Theoretic Process Accimaps), from which analysts can discern how they really work in practice, and predict the emergent behaviours characteristic of complex systems. This paper describes how the FRAM methodology has now been extended to provide these extra, essential attributes. It also describes its implementation using an open-source software, freely available for use and verification on the GitHub site.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

Modern medicine adopted four presumptions when it evolved from ancient experienced-based mind-body medicine. To understand its failure in finding cures for chronic diseases, we examined four presumptions, and found that statistical population of health properties does not exist for most research purposes, mathematical models are misused to model intensive properties, synthetic drugs are inherently more dangerous than nature-made medicines under their respective application conditions, and reductionist treatments are inferior and inherently dangerous. We found that clinical trials are valid only for research where treatment effect is much stronger than the total effects of all interfering or co-causal factors or errors introduced by misused mathematical models can be tolerated. In all other situations, clinical trials introduce excessive errors and fail to detect treatment effects, or produce biased, incorrect or wrong results. We further found that chronic diseases are manifestation of small departures in multiple process attributes in distinctive personal biological pathways networks, that modern medicine lacks required accuracy for accurately characterizing chronic diseases, and that reductionist treatments are good at controlling symptoms and safe for short term uses. For all stated reasons, as long as modern medicine continues relying on the flawed presumptions, it can never find predictable cures for chronic diseases. By implication, predictable cures to chronic diseases are adjustments to lifestyle, dietary, emotional, and environmental factors to slowly correct departures in process attributes responsible for chronic diseases.

There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.

Process mining offers significant services in the development of digital threads and digital twin applications for healthcare. One of the sub-emerging case studies is the use of patients’ location data in process mining analyses. While the streamlining of published works is focused on introducing process discovery algorithms, there is a necessity to address challenges beyond that. Literature analysis indicates that explainability, reasoning, and characterizing the root causes of process drifts in healthcare processes is an important but overlooked challenge. In addition, incorporating domain-specific knowledge into process discovery could be a significant contribution to process mining literature. To address this, we present the DIAG approach that consists of a meta-model and an algorithm that enables diagnosing in process mining through an ontology-driven approach. With DIAG, we modeled the healthcare semantics in a process mining application and diagnosed the causes of drifts in patients’ pathways. We performed an experiment in a hospital living lab to examine the effectiveness of the DIAG approach.

Oscillating Sequential Universes Model (OSUM), an innovative cosmological model describing the universe's evolution through the interplay of dark energy and dark matter is presented in this study. The model proposes a series of expansions and contractions driven by dark energy and dark matter interactions, challenging the conventional view of a singular Big Bang event followed by continuous expansion. The necessity for model refinements, incorporating new observational constraints, reassessing dark energy-dark matter interaction assumptions, and investigating alternative mathematical formulations for the oscillation mechanism have been discussed in this study. The OSUM offers a comprehensive framework for future research and potential discoveries in astrophysics, cosmology, and fundamental physics, raising new questions and challenging prevailing assumptions about the cosmos.

We propose that the coexistence of gapless Fermi arcs with the metal-insulator crossover of in-plane resistivity in strongly underdoped cuprates can be explained by the FL* fractionalized Fermi liquid nature of these systems and it is not due simply to disorder effects. The particle excitations of this FL* system derived from variants of the t-J model are: the gapless holon carrying charge with small Fermi momentum proportional to the doping, the gapful spinon carrying spin 1/2, gauge fluctuations coupling them and the hole as a spinon-holon bound state or resonance due to gauge binding with a Fermi surface respecting the topological Luttinger theorem. In our proposal Fermi arcs are determined by the hole resonance, whereas the metal-insulator crossover is dominated by spinon-spinon (with subleading holon-holon) gauge interactions and this dichotomy is able to explain their coexistence.

A formula for the turbulent Prandtl number is derived in terms of local variables available from two-equations turbulence models. The derivation is a direct consequence of the expected square additivity of the molecular and turbulent parameters defining the effective viscosity and the effective conductivity. The formula does not degenerate and leads to a Kays like formulation if approximated. Its utility and its limitation are discussed.

Long-term continuous time series of SO2 emissions are considered critical elements of both volcano monitoring and basic research into processes within magmatic systems. One highly successful framework for computing these fluxes involves reconstructing a representative time-averaged SO2 plume from which to estimate the SO2 source flux. Previous methods within this framework have used ancillary wind datasets from reanalysis or numerical weather prediction (NWP) to construct the mean plume and then again as a constrained parameter in the fitting. Additionally, traditional SO2 datasets from ultraviolet (UV) sensors lack altitude information which must be assumed to correctly calibrate the SO2 data and to capture the appropriate NWP wind level which can be a significant source of error. We have made novel modifications to this framework which do not rely on prior knowledge of the winds and therefore do not inherit errors associated with NWP winds. To perform the plume rotation, we modify a rudimentary computer vision algorithm designed for object detection in medical imaging to detect plume-like objects in gridded SO2 data. We then fit a solution to the general time-averaged dispersion of SO2 from a point source. We demonstrate these techniques using SO2 data generated by a newly developed probabilistic layer height and column loading algorithm designed for the Cross-track Infrared Sounder (CrIS), a hyperspectral infrared sensor aboard the Joint Polar Satellite System’s Suomi-NPP and NOAA-20 satellites. This SO2 data source is best suited to flux estimates at high-latitude volcanoes and at low-latitude, but high-altitude volcanoes. Of particular importance, IR SO2 data can fill an important data gap in the UV-based record: estimating SO2 emissions from high-latitude volcanoes through the polar winters when there is insufficient solar backscatter for UV sensors to be used.

Introduction. The use of probiotics demonstrate efficacy against obesity and metabolic syndrome (MetS). Detection effective probiotic strains for hyperglycemia and immunity associated with is important task. The aim of the study was to evaluate an influence of Lactobacillus casei IMV B-7280 separately and composition L. casei IMV B-7280 / Bifidobacterium animalis VKB / B. animalis VKL on the levels of blood glucose and immunity in obese mice. Meterials and methods. Obesity was induced by fat-enriched diet (FED) in male BALB/c mice. Obese mice were transferred to standard diet and received per os probiotic strains daily during 10 days. We measured tumor necrosis factor-a (TNF-a) in blood serum using enzyme-linked immunosorbent assay and functional activity of peritoneal exudate macrophages (PEMs). Glucose levels in blood was defined with glucometer. Results. We ascertained that all probiotic strains induced reducing mice weight and visceral fat, normalization of TNF-a production and functional activity of PEMs. Treatment with L. casei IMV B-7280 was associated with decreasing blood glucose levels. No normalization of glucose and TNF-a levels in obese mice, transferred to standard diet without probiotic treatment, although we revealed decreasing their weight and visceral fat and partial recover of functional activity of PEMs. Conclusions. Probiotic strain L. casei IMV B-7280 (separately) and composition L. casei IMV B-7280 / B. animalis VKB / B. animalis VKL can re-equilibrate metabolic and inflammation indices in mouse obesity model. L. casei IMV B-7280 alone was more efficient in decreasing glucose levels than composition of strains.

The perception in pair trading is to recognize two stocks that move together, and their prices will converge to a mean value in future. However, finding the mean-reverted point at which the value of the pair will converge, and optimal boundaries of the trade is not easy. As uncertainty and model misspecifications may lead to losses. To cater for the problems, this study employs the novel entropic approach that utilizes entropy as penalty function for the misspecification of the model. The use of entropy as a measure of risk in pair trading is a nascent idea and this study utilizes daily data for 64 companies listed on PSX for the years 2017, 2018, and 2019, respectively to compute the returns based on the entropic approach. These companies cover the major sectors including Cement, Chemical, Automobile Assembler, Food and Personal Care Products, Oil and Gas Marketing Companies, Oil and Gas Exploration Companies Ltd, Power Generation and Distribution, Refinery and Pharmaceuticals. The returns to these stocks are then evaluated and compared with the Buy and Hold strategy. The results show positive and significant returns from pair trading using an entropic approach.

A study on the selection of hyperelastic constitutive model for polymeric materials is performed using a hybrid experimental-computational approach. Bis-GMA polymer is used as a case study of hyperelastic material to describe the polymer characteristics by determining its Poisson’s ratio and its valid range of the hyperelastic stress-strain curves. These two parameters are then used to determine the hyperelastic constitutive model by using the hybrid approach. Several uniaxial compression tests along with their finite element simulations are implemented in a systematic way, to identify the polymer behavior under the compressive loading conditions. Nano-indentation experiments are conducted to verify the hyperelastic behavior of the polymer. The experimental and computational evidences confirm that the Poisson’s ratio of Bis-GMA is 0.40 and the appropriate hyperelastic constitutive model for this polymer is of a second order polynomial. It is shown that, the results can be used to determine the true stress-strain curve of hyperelastic materials.

Shelter-in-place policies and the closure of non-essential workplaces intended to disrupt transmission of the SARS-COV-2 virus are effective approaches to combating COVID-19. They have, however, caused record levels of unemployment in the United States, raising questions of whether mitigation is more societally damaging than the disease. Here we use a coupled epidemiological-economic model to estimate the impact on employment of an unmitigated, business-as-usual approach to the pandemic. We compared unemployment between March-August 2020 in ten Californian socio-economic systems (SESs) to unemployment forecast by a model of industrial sector inter-dependencies subjected to unmitigated outbreaks of COVID-19. We found that economic losses are unavoidable because disease-driven losses propagate economically through SESs, amplifying losses to the disease. While model forecasts are generally lower than actual unemployment, jobs savings would come at the cost of greatly increased worker mortality. The costs would also be disproportionately greater among smaller and inland SESs.

As the global aging trend continues to intensify, there will inevitably be more complex and diverse aging problems in the future. There is no doubt that designers have the responsibility to explore the possibilities of the future and solve the problems that will be faced in the future. Based on the Future Cone, the Double Diamond Model and the IDEO Method Cards, this study proposes a new model to guide the design practice of future aging issues in the context of aging. With the aim of validating and refining the framework, an ageing designer workshop was held where participants were asked to imagine, explore and express ideas about future ageing issues. The workshop was used to refine the proposed model. More specifically, the model includes a future concept, a design guidance process based on the Double Diamond Model, and tools that can be applied at all stages of design, which can help designers generate ideas and solutions for future aging problems, and collectively lead society to a more desirable future. Moreover, this study also explores broader directions for the development of the model and provides a reference for continued research on this topic in the future.

The aim of this study was to investigate the effect of discoursal approach on Iranian intermediate EFL learners’ reading comprehension ability. Quick Placement Test (QPT) was used to select 60 intermediate EFL learners as the participants of this study. Then, they were randomly divided into experimental and control groups. Each consisted of 30 learners. Prior to the treatment, the participants of both groups were given a pretest to ensure their reading comprehension. The experimental group was exposed to the Hymes’ model. In the control group the researcher used placebo for teaching reading skill. Then a posttest was administered to both groups. An Independent samples t-test between posttests of the study and a paired-samples t-test between the pretest and posttest of the groups of the study were run. The results of the study revealed and emphasized that the Hymes’ model improved the learners’ reading comprehension.

The main aim of this study is to predict whether the type of breast cancer is “benign” or “malignant” by classical generalized linear model (GLM) approach and an extended family of GLM called generalized linear mixed model (GLMM) approach for binomially distributed response variable with binary link functions. In this study, an advanced statistical modeling approach based on the GLMM to the traditional statistical modeling approach based on the GLM for binomially distributed response variable with various binary link functions is proposed to investigate the relationships between the “malignant or benign diagnosis of the BC in patients” and “nine attributes” of 699 BC diagnosed patients. This study also focuses on the statistical significance of the accurate classification of the BC diagnosed patients in cancer studies in medicine in “benign” or “malignant” type based on the WBC dataset. In this study, the superiority of the GLMM approach over the GLM approach for the binary response variable especially belonging to the WBC dataset is emphasized in the field of cancer diagnosis in medicine. Also the importance and the power of the IC and performance metrics as the goodness-of-fit test statistics are strongly emphasized for accurate statistical inferences from the “best” fitted model. In this study, from the main findings, the best fitted model among the GLM and GLMM approaches for the binary response variable is determined as the GLMM under “logit” link function with “id” random effect with the most statistically significant odds of the occurance of the BC being “malignant” as 7.9104, 5.6888, 5.6643, 4.9842, 4.1212, 2.0679, 1.8755, and 1.3970 times more than being “benign” for every one-unit increase in the quantities of “clump thickness”, “bland chromatin”, “mitoses”, “bare nuclei”, “cell shape”, “marginal adhesion”, “epithelial cell size”, and “cell size”, respectively.

A controlled ammonia (NH₃) release experiment was performed at a grassland site to quantify the effect of dry deposition, at the field scale between the source and the receptors (NH₃ measurement locations), on the estimates of emission rates by means of inverse dispersion modelling. NH₃ was released for 3 hours at a constant rate of Q = 6.29 mg s⁻¹ from a grid of 36 orifices spread over an area of 250 m². The increase in line-integrated NH₃ concentration was measured with open-path optical miniDOAS devices at different locations downwind of the artificial source. Using a backward Lagrangian stochastic (bLS) dispersion model (bLSmodelR), the fraction of the modelled release rate to the emitted NH₃ (Q_bLS/Q) was calculated from the measurements of the individual instruments. Q_bLS/Q was found to be systematically lower than 1, on average between 0.69 and 0.91, depending on the location of the receptor. We hypothesized that NH₃ dry deposition to grass and soil surfaces was the main factor responsible for the observed depletion of NH₃ between source and receptor. A dry deposition algorithm based on a deposition velocity approach was included in the bLS modelling. Model deposition velocities were evaluated from a ‘big‑leaf’ canopy resistance analogy. Canopy resistances (generally termed Rc) that provided Q_bLS/Q = 1 ranged from 75 to 290 s m⁻¹, showing that surface removal of NH₃ by dry deposition can plausibly explain the original underestimation of Q_bLS/Q. The inclusion of a dry deposition process in dispersion modelling is crucial for emission estimates, which are based on concentration measurements of depositing tracers downwind of homogeneous area sources or heterogeneously distributed hot spots, such as e.g. urine patches on pastures in the case of NH₃.

To cope with a projected global population increase from 7.2 bn to 9.6 bn by 2050, many more cities must be built. Although there are great benefits to modern urban living, there also great costs, such as the seemingly unstoppable rise in Type 2 diabetes, obesity, coronary issues and various cancers. The new towns should be designed to contain or constrain the epidemic of those ‘Western Lifestyle Diseases’ that currently plagues today’s cities. But how might this be achieved? It is suggested here that a greater understanding of human evolution combined with the potency of the ‘Palaeolithic genome’ holds the key to our future urban wellbeing. Consequently, a new paradigm is suggested that underpins positive forward thinking on townplanning and city lifestyles to create healthier urban environments. This builds directly on the ‘Evolutionary Determinants of Health’ programme initiated at University College London (UCL). A four-stage model is proposed that integrates and develops both evolutionary-concordant personal and institutional health behaviours with appropriately reconfigured town-planning and building regulations. When integrated, these strands could deliver a healthier urban culture within greened, active townscapes by proactively constraining or eliminating some of the key underlying causes of the so-called ‘Western Lifestyle Diseases’.

The genetic engineering of plants often relies on the use of antibiotic or herbicide resistance genes for initial selection of primary transgenic events. Nevertheless, the commercial release of genetically modified crops containing any marker gene encounters several challenges stemming from the lack of consumer acceptance. Development of strategies enabled the generation of marker-free transgenic plants is a possible alternative to deal with public concerns over the safety of biotech crops. Leveraging the high in vitro regeneration and transformation capabilities of potato, this study examined the factors associated with the development of transgenic plants without presence of selective substances in medium. To compare the antibiotic-assisted with the antibiotic-free transformation, nodal explants from five highly regenerative potato cultivars were inoculated with the Agrobacterium strain AGL0 carrying the pBIN-mGFP5-ER (35SGFP/nosNPTII) plasmid. The efficiency of transient expression and the formation of chimeric and completely transgenic shoots were assessed through vital GFP observations. Under non selective conditions, the regeneration efficiency of stable non-chimeric transgenic shoots varied from 0.9 (‘Chicago’) to 2.7% (#12-36-42). In order to streamline transformation protocol, a specific timeline for collecting transgenic plantlets was established for each analyzed cultivar. This timeline strategy was implemented to generate transgenic potato plants, which demonstrated the suppression of homologous SteIF4Es family genes as a result of the successful introduction of the marker-free hpRNAi construct.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

Over the years, machine learning has emerged as a tool for automated translation and has been studied relentlessly for decades. RBMT, SMT, and NMT models have been used to achieve machine translation and the results have drastically improved from when research in this field first began. Although a few general-purpose translators such as Google Translate or Microsoft Translator have accurate translations compared to that of a human translator, many pieces of text containing highly technical terms or homonyms are often mistranslated completely. When considering the necessity and importance of translating technical patents from different domains, accuracy in translation is not something that can be compromised. This motivates the need to improve the performance of machine translation further. The scope of this paper covers three open-source machine translation models for the purpose of patent documentation translation from English to Japanese, evaluates their performance on patent data, and proposes a methodology that enabled us to improve one of the model’s BLEU score by 41.22%, achieving a BLEU score of 46.18.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p<0.05; p<0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p<0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

The paper examines the various uncertainties encountered in high-frequency trading (HFT) environments and delves into the multiple challenges faced by HFT firms in navigating the Dodd-Frank Wall Street Reform and Consumer Protection Act (referred to as the "Dodd-Frank Act"), particularly during the initial stages of its enactment. These challenges include the ambiguity surrounding the definition of HFT, the lack of clarity regarding regulatory requirements and boundaries, inconsistencies in enforcement resulting from deviations in understanding the content, and the absence of detailed descriptions of the Act’s provisions. These hurdles significantly impact not only the daily operations of HFT firms but also pose higher demands on their long-term strategic planning and risk management. Drawing upon the Data, Information, Knowledge, Wisdom, and Purpose (DIKWP) model, this study employs an innovative analytical framework. Through the comprehensive application of conceptual space, cognitive space, and semantic space, it provides a systematic methodology for identifying and analyzing the aforementioned issues. This approach not only aids firms in better comprehending and adhering to complex regulatory requirements but also enables them to explore new business opportunities and competitive advantages while ensuring compliance.

The stick-free flight stability is an old-fashioned and non-progressive issue; nevertheless, it is still existent, and of significant importance to the design of aircraft whose control system is reversible. The problem’s existence necessitates a deep assessment of stick-free flight stability throughout the aircraft design. Up to now, this problem has been addressed using either analytical approaches, which are only related to the static stability evaluation, or performing flight tests. In this study, the problem is handled in its entirety, from static and dynamic flight stability assessment to design criteria with a comprehensive perspective. Moreover, it is also exhibited that contrary to what has been generally proposed in the literature, limiting the problem of stick-free flight stability through static stability assessment is far from the main challenge. As a brief scope, the derivation of the control surface dynamics, a stick-free trim algorithm, and assessment rationale of the stick-free static and dynamic flight stability using a simulation approach are proposed. As a consequence, the aim is to set a broad understanding for designers related to this phenomenon and add adjunct design criteria in the design optimization process by approaching it in terms of modeling, simulation, and flight test perspective.

An imbalance in any metabolic system can be traced to its homeostasis. When homeostatic environment is not attainable then there will be a response from the body. A new shift has emerged, “the negative feedback effect of high fructose consumption;” more pain than gain. The human metabolic system daily combat fructose sugar metabolism which emanates from high consumption. This inadvently lead to a chronological series of complications arising from the feedback. These feedbacks play pivotal roles in skeletal muscle damage and other body frameworks, it also fosters toxic advanced glycation end products (AGEs), factors that impose and inflict damaging effects to the body`s energy currency and serious threat to health. These damages are missed or overlooked because of early nonspecific physiological symptoms. High level of fructose has both long- and short-term effects on human metabolic processes. These effects which are majorly through the production of reactive oxygen species (ROS) and other free radicals, are felt in the disruption of biomolecules such as causing DNA mutation, lipid peroxidation etc. these effects in turn lead to various diseases such as cancer, diabetes, atherosclerosis, and other health issues. In this review, we will focus on the damaging effects this sugar has on human health and the present solutions being applied. We will also look at the next step in combatting and controlling these negative feedbacks.

Modern organic synthesis is majorly focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-Mass spectroscopy. Major highlights of the reported work include: atom economical process, extremely milder reaction conditions, operational simplicity, high isolated yields, and excellent catalyst turnover number. The molecular docking studies suggest that the compound 4n has the hydrogen bonding, hydrophobic and π-pair interactions with the active site of active sites of CXT M 15 receptor.

Software engineers from all over the world solve independently a lot of similar problems. In this condition the problem of code or even better architecture reusing becomes an issue of the day. In this paper two phase approach to determining the functional and structural likenesses of software projects is proposed. This approach combines two methods of artificial intelligence: natural language processing techniques with a novel method for comparing software projects based on ontological representation of their architecture automatically obtained from the projects source code. Additionally several similarity metrics are proposed to estimate similarity between projects.

Volcanic emissions (ash, gas, aerosols) dispersed in the atmosphere during explosive eruptions generate hazards affecting aviation, human health, air quality and the environment. We document for the first time the contamination of airspace by very fine volcanic ash due to sequences of tran-sient ash plumes from Mount Etna. The atmospheric dispersal of sub-10 μm (PM10) ash is mod-elled using the WRF-Chem model coupled online with meteorology and aerosols and offline with Mass Eruption Rates (MER) derived from near-vent Doppler radar measurements and inferred plume altitudes. We analyse two sequences of paroxysms with widely varied volcanological conditions and contrasted meteorological synoptic patterns in October–December 2013 and on 3-5 December 2015. We analyse the PM10 ash dispersal simulation maps in terms of time-averaged columnar ash density, concentration at specified flight levels averaged over the entire sequence interval, and daily average concentration during selected paroxysm days at these flight levels. The very fine ash from such eruption sequences is shown to easily contaminate the airspace around the volcano within a radius of about 1000 km in a matter of a few days. Synoptic patterns with relatively weak tropospheric currents lead to the accumulation of PM10 ash at a re-gional scale all around Etna. In this context, closely interspersed paroxysms tend to accumulate very fine ash more diffusively in the lower troposphere and in stretched ash clouds higher up in the troposphere. Low-pressure, high-winds weather systems tend to stretch ash clouds into ~100 km-wide clouds forming large-scale vortices 800-1600 km in diameter. Daily average PM10 ash concentrations commonly exceed the aviation hazard threshold up to 1000 km downwind from the volcano and up to the upper troposphere for intense paroxysms. Vertical distributions show ash cloud thicknesses in the range 0.7–3 km, and PM10 sometimes stagnating at ground level, represent a potential health hazard.

The three-dimensional Ising model on the m$\times$n$\times$l cubic lattice with the screw boundary condition along the ${\bf X}$ direction and the periodic boundary conditions along both ${\bf Y}$ and ${\bf Z}$ directions is exactly solved by using the $2^{mn}$-dimensional representation of the rotation group in $2mn$-dimensions, similar to the Kaufman's spinor approach in two dimensions. The exact partition function is obtained from two sets of $2^{mn-1}$ eigenvalues of the $2^{mn}$-dimensional transfer matrix {\bf V} corresponding to the even and odd eigenvectors, respectively. Such the eigenvalues are determined by the angles of the 2mn-dimensional rotation associated with {\bf V}.

Cervical cancer is the fourth most common malignancy in women worldwide, although it is preventable with prophylactic HPV vaccination. HPV transmission-dynamic models can predict the potential for global elimination of cervical cancer. The random network model is a new approach that allows individuals to be followed, and to implement a given vaccination policy according to their clinical records. We developed an HPV transmission dynamics model on a lifetime sexual partners network based on individual contacts, also accounting for the sexual behavior of men who have sex with men (MSM). We analyzed the decline in the prevalence of HPV infection in a scenario of 75% and 90% coverage for both sexes. An important herd immunity effect for men and women was observed in the heterosexual network, even with 75% coverage. However, HPV in-fections are persistent in the MSM population, with sustained circulation of the virus among un-vaccinated individuals. Coverage around 75% of both sexes would be necessary to eradicate HPV-related conditions in women within five decades. Nevertheless, the variation in the decline in infection in the long term between vaccination coverage of 75% and 90% is relatively small, suggesting that reaching coverage of around 70-75% in the heterosexual network may be enough to confer high protection. Nevertheless, HPV eradication maybe achieved if men’s coverage is strictly controlled. This accurate representation of HPV transmission demonstrates the need to maintain high HPV vaccination coverage, especially in men, for whom the cost-effectiveness of vaccination is questioned.

Development of methods and algorithms to predict the effect of mutations on protein stability, protein-protein, and protein-DNA/RNA binding is necessitated by the needs of protein engineering and for understanding the molecular mechanism of disease-causing variants. The vast majority of the leading methods are either methods with adjustable parameters or machine learning algorithms, both requiring a database of experimentally measured folding and binding free energy changes. These databases are collections of experimental data taken from scientific investigations typically aimed at probing the role of particular residue on the above-mentioned thermodynamics characteristics, i.e., the mutations are not introduced at random and do not necessarily represent mutations originating from single nucleotide variant (SNV). Thus, the reported performance of the leading algorithms assessed on these databases or other limited cases, may not be applicable for predicting the effect of SNVs seen in the human population. Indeed, we demonstrate that the SNVs and non-SNVs are not equally presented in the corresponding databases and the distribution of the free energy changes are not the same. Furthermore, the Pearson correlation coefficients (PCCs) obtained on cases involving SNVs are less impressive than for non-SNVs, indicating that caution should be used in applying them to reveal the effect of human SNVs. All methods are found to underestimate the energy changes by roughly a factor of 2.

In Model-Driven Development (MDD), the models, their generation, and imposing changes on them (model transformation) are used for the development of software. Models provide a framework to start from the imagination and abstraction to create and accomplish the final system. Models create a slow and steady transition from whatness to howness, i.e. from the natural path of the generation of software. For supporting this path, the Logic and Functionality of software must be changeable during its evolution. Here we provide a brief introduction to the concept of Model Driven Development.

Rollover prevention of partially-filled tank trucks is an industry teaser, with the core challenge being real-time perception and observation of the liquid state inside the tank. In order realize re-liable observation of sloshing liquid, this article firstly proposes a sloshing modeling method based on multi-degree-of-freedom pendulum model, and derives the double mass trammel pendulum model (DMTP, 2DOF) accordingly, which accurately reflects the sloshing dynamics under more pervasive working conditions. Secondly, a free surface fluctuation sensor is designed based on magnetostriction, capable of measuring the inclination and height of the liquid level inside tanks filled with hazardous chemical. Finally, the unscented Kalman filter (UKF) is utilized to synthesize the information of the two, establishing a credible real-time observation of the sloshing liquid. Verified through vehicle-fluid coupled co-simulation, under condition of con-secutive double lane change, observation error of the proposed method is only 25.9% that of the open-loop calculation, providing a secure guarantee for the observation of the state variables of the single pendulum model (SP) used for most kinds of anti-rollover controller.

Diets that restrict the amount of carbohydrates positively affect markers related to metabolic syndrome (MS). However, completely carbohydrate-free diets have been studied in lesser extent, being their effect on biochemical and morphometric parameters in a rat model of MS the main objective of this study. MS was induced by a high-glucose diet for 20 weeks in male Wistar rats with a subsequent exposition to an essentially carbohydrate-free diet (CFD) for 20 weeks. Daily measurements of food consumption and monthly measurements of body weight were made. At week 40, glucose, insulin, lipid profile, ketone bodies, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, liver and muscle glycogen, and serum, hepatic, renal and pancreatic malondialdehyde (MDA) were assessed. Exposition to CFD showed decrease in caloric intake and body weight. Likewise, the group showed normalization in liver and serum MDA parameters, insulin, lipid profile, ALT, liver glycogen, and creatinine. The CFD decreased glucose concentration and the inflammatory state, also, increased the concentration of ketone bodies and urea. The change towards CFD reverses the metabolic alterations generated with MS except for glycemia and uremia, probably due to the high rate of gluconeogenesis generated by the high protein content in the diet.

Peripheral nerve injury remains a medical challenge with no easy resolution. Over the last few decades, significant advances have been achieved in promoting peripheral nerve regeneration, and new assessment tools have been developed, both functional and imaging, to quantify the proportion and quality of nerve recovery. The exploration of new animal models, larger, more complex and with more similarities to humans, has made it possible to reduce the gap between the results obtained in classic animal models such as rodents and the application of new therapies in humans and animals of clinical interest. Ultrasonography is an imaging technique recurrently used in clinical practice to assess the peripheral nerves, allowing its anatomical and topographic characterization, and aiding in the administration of anesthesia and in the performance of nerve blocks. The use of this technique in animal models is scarce, but it could be a useful tool in monitoring the progression of nerve regeneration after the induction of controlled experimental lesions. In this work, sheep, a promising animal model in the area of peripheral nerve regeneration, were subjected to an ultrasonographic study of three peripheral nerves of the hind limb, the common peroneal, tibial and sciatic nerves, in order to establish values of dimensions and ultrasound appearance in healthy nerves and also landmarks for their identification. At the same time, an echographic evaluation of the cranial tibial muscle, an effector muscle of the common peroneal nerve, was also carried out, establishing normal values for the echographic aspect and dimensions. The results obtained will allow the use of these data as control values in future work exploring new therapeutic options for nerve regeneration after induction of common peroneal nerve injuries in sheep.

To understand forest dynamics under today’s changing environmental conditions, it is important to analyze the state of forests at large scales. Forest inventories are not available for all regions, so it is important to use other additional sources of information, e.g. remote sensing observations. Increasingly, remotely sensed data based on optical instruments and airborne LIDAR are becoming widely available for forests. There is great potential in analyzing these measurements and gaining an understanding of forests state. In this work, we combine the new generation radiative transfer model mScope with the individual-based forest model FORMIND to generate reflectance spectra for forests. Combining the two models allows us to account for species diversity at different height layers in the forest. We compare the generated reflectances for forest stands in Finland, in the region of North Karelia, with Sentinel-2 measurements. We investigate which level of forest representation gives the best results. For the majority of the forest stands, we generated good reflectances with all levels forest representation compared to the measured reflectance. Good correlations were also found for the vegetation indices (especially NDVI with R²=0.62). This work provides a forward modelling tool for relating forest reflectance to forest characteristics. With this tool it is possible to generate a large set of forest stands with corresponding reflectances. This opens the possibility to understand how reflectance is related to succession and different forest conditions.

For more than half a century, Manfred Deistler has been contributing to the construction of the rigorous theoretical foundations of the statistical analysis of time series and more general stochastic processes. Half a century of unremitting activity is not easily summarized in a few pages. In this short note, we chose to concentrate on a relatively little-known aspect of Manfred's contribution which nevertheless had quite an impact on the development of one of the most powerful tools of contemporary time series and econometrics: dynamic factor models.

This study investigates the application of regression neural networks, in particular the fitrnet model, in predicting the hardness of steels. The experiments involve extensive tuning of hyperparameters using Bayesian optimization and employ 5-fold and 10-fold cross-validation schemes. The trained models are rigorously evaluated, and their performances are compared using various metrics such as mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE), and coefficient of determination (R2). The results provide valuable insights into the effectiveness of the models and their ability to generalize to unseen data. In particular, Model 4208 (8-85-141-1) emerges as the top performer with an impressive RMSE of 1.0790 and an R² of 0.9900. The research paper contains an illustrative example that demonstrates the practical application of the developed model in determining the hardenability band for a specific steel grade and shows the effectiveness of the model in predicting and optimizing heat treatment results.

In his Cynefin classification of system behaviours, Snowden (2007), posits that his Simple (Clear ) and even Complicated system categories are sufficiently understandable to be amenable to the traditional methods of system analysis and modelling. Here, relationships between entities in the system are clear and unambiguous and they behave predictably. So, we can build mathematical “models” to describe how the system is expected to function in different situations. Leaving aside his fourth category, Chaotic, as too hard for the moment, this paper focusses on the third category, Complex systems. Yaneer Bar-Yam [1998] defined "complex systems" as systems that "have multiple interacting components, whose collective behaviour cannot be simply inferred from the behaviour of components." So, the traditional system modelling approach of decomposition into components and attempting to build up a picture of system performance from individual pieces, alone, is no longer appropriate for this class. The problem is that most of the methods we currently employ, and particularly the methods that attempt to make the case that these systems are safe, (such as Fault trees, FMEA. and Root Cause Analysis), rely on this decomposition into components and attempt to make the parts more reliable individually. Even the more systemic approaches, such as Reason’s (1990) Swiss Cheese Model, and Leveson’s System Theoretic Analysis (STPA) (2004), encourage adding layers of protection, barriers, strengthened control loops and better safety critical systems, in the hope that they are making the systems safer. But without a valid model to test the effectiveness of these add-ons, we cannot be sure that they will not have an opposite effect, of making the systems even more complex, unreliable and unpredictable. For complex systems, the careful gathering and documentation of system components and their relationships is still a necessary first step, but we need an additional capacity to model these complex systems to test out and prove they work safely and successfully in the real world. (not just draw fixed component relationships as system “models” (wiring diagrams)) In the last 10 years, an original approach developed by Hollnagel, (2012), to model systems as sets of interactive, interdependent “functions”, (abstracted from and independent of component details), has now been developed to the point where it can take the basic data and structures from the current component focussed system engineering “models”, such as MBSE( Goldberg (1994)), and can pull it all together in a dynamic system model from which analysts can discern how it really works in practice, and predict the emergent behaviours characteristic of complex systems. The paper describes how this methodology developed and how it is currently used to model real situations, to analyse incidents and anticipate events.

This paper addresses the input coupling problem for the shape memory alloy (SMA) actuated parallel platform with completely unknown nonlinear dynamics. The problem means that in a parallel platform with multiple SMA actuators acting together, the displacement of one of the actuators will simultaneously affect the remaining actuators to change. Due to the coupling problem and nonlinear characteristics of the SMA actuators, it is not easy to control the platform to achieve bi-directional swing with completely unknown nonlinear dynamics. Therefore, a model-free adaptive sliding mode control method is proposed to improve the control accuracy of the complex motion of the platform, avoiding the complex modeling process of the SMA actuated parallel platform. Based on the model-free adaptive control (MFAC) theory, a multiple input and multiple output (MIMO) dynamic linearized mathematical model of the parallel platform is established using the online input and output data of the system. Then, a sliding mode controller is designed based on the dynamic model. A rigorous theoretical analysis proves that the proposed model-free adaptive sliding mode controller is able to stably control the SMA actuated parallel platform, and its tracking error is uniformly ultimately bounded (UUB). Finally, experiments are conducted on the established SMA actuated parallel platform. The results show that the proposed model-free controller is feasible and effective, and can control the system well to achieve the complex motion of bi-directional swing.

A groundbreaking integrated predictive model, termed Cyber Forensics Behavioral Analysis (CFBA), has been developed in an environment characterized by rapidly evolving and increasingly sophisticated cyber threats. This model merges Cyber Behavioral Sciences with Digital Forensics to enhance the prediction accuracy and effectiveness of cyber threats originating from specific Autonomous System Numbers (ASNs). It has been observed that traditional cybersecurity strategies, predominantly focused on technical aspects, must be improved in addressing the complex landscape of cyber threats. Consequently, a novel approach has been proposed in this research, combining technical expertise with insights into the behavior of cybercriminals, thereby addressing a significant gap in existing methodologies. A mixed-methods approach has been employed in the study, integrating quantitative and qualitative research methods. This approach has created a comprehensive framework incorporating digital forensics, cybersecurity, computer science, forensic psychology, and the cyber behavioral sciences which incorporates disciplines scuch as cyberpsychology and forensic cyberpsychology. The study is anchored around four key concepts: (1) Forensic Cyberpsychology, which focuses on understanding psychological aspects of cybercriminal behavior; (2) Digital Forensics, involving the collection and analysis of digital evidence from cyber incidents; (3) Predictive Modeling, which utilizes historical data and patterns to anticipate potential cyber threats; and (4) the Cyber Behavioral Analysis Metric (CBAM) and Cyber Behavioral Score (CBS), tools designed for evaluating and scoring ASNs based on their behavior in terms of cybersecurity threat risks. Challenges encountered in the development of this integration have been significant. Initial setbacks included the misalignment of traditional cyber defense methods with the evolving nature of cyber threats and the absence of a holistic approach in pre-existing models. Through the narrative of these challenges and the subsequent development of the CFBA model, the research highlights the necessity for an interdisciplinary approach to cybersecurity. The outcomes of this study are not merely theoretical but provide practical, actionable tools and frameworks that markedly improve the precision of predicting cyber threats, especially from ASNs. The CFBA model represents a significant shift in cybersecurity strategies, highlighting the importance of integrating behavioral insights with technical knowledge. The study emphasizes the need for ongoing research and collaboration in cybersecurity, advocating for an approach that is as comprehensive and multifaceted as the cyber threats it seeks to mitigate. This research has been conducted to contribute significantly to cybersecurity, offering new perspectives and methodologies in a rapidly changing domain.

Nucleosomes are non-uniformly distributed across eukarytic genomes, with stretches of ‘open’ chromatin strongly associated with transcriptionally active promoters and enhancers. Understanding chromatin accessibility patterns in normal tissue and how they are altered in pathologies can provide critical insights to development and disease. With the advent of high-throughput sequencing, a variety of strategies have been devised to identify open regions across the genome, including DNase-seq, MNase-seq, FAIRE-seq, ATAC-seq, and NicE-seq. However, the broad application of such methods to FFPE (formalin-fixed paraffin embedded) tissues has been curtailed by the major technical challenges imposed by highly fixed and damaged genomic material. Here we review the most common approaches for mapping open chromatin regions, recent optimizations to overcome the challenges of working with FFPE tissue, and a brief overview of a typical data pipeline with analysis considerations.

Inflammatory bowel disease (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from origin cell and able to circulate into bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also plays a role in IBD. In this review we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.

This research uses a gravity model method to investigate the factors determining the number of tourists visiting Australia. Understanding the variables that draw visitors to specific locations is essential for policymakers and other stakeholders in the tourism sector since tourism continues to play a significant role in the economy of many countries worldwide. Despite the widespread use of gravity models in the analysis of international tourism flows, only a tiny amount of attention has been paid to particularly researching the flow of tourists to Australia. This research addresses this knowledge gap by analyzing the variables influencing travel patterns to Australia. The gravity model framework is used, and it considers factors like gross domestic product, gross domestic product per capita, migratory stocks, distance, population size, cost of living, and cultural similarities. The purpose of this research is to aid in developing focused marketing strategies by providing insights into the factors that influence the flow of tourists to Australia via the analysis of these variables. The results are anticipated to add to the current literature on gravity modeling in tourist research and give practical implications for industry stakeholders and policymakers. The discussion of the findings, their ramifications, and possible directions for further study serves as the conclusion of the work.

The socioeconomic sectors increasingly rely on prompt and affordable tools to predict climatic conditions. This study uses a decision tree classifier model to identify similar monthly ENSO 3.4 indices from March 2001 to February 2011 through monthly historical ENSO3.4 indices (December 1950 – February 2001). Historical monthly ENSO3.4 indices were used to extract available high-resolution monthly historical precipitation grids (1950-2001) for Mexico and constructed monthly ensembles (March 2001 – February 2011 hindcasts). Formerly, a precipitation categorization of monthly observed and simulated precipitation (2001-2011 hindcasts) was employed. Thereafter, global vector data and spatial map assessments were performed seasonally (winter, spring, summer, and fall). Global KSS and HSS metrics indicated the model approach has skill, especially in the spring and fall. Spatial metrics exposed large areas with hit rates > 0.60 in winter and spring, though in winter and spring (dry seasons), it was due to the precipitation categorization hindcast and observed were within the first classification. Lower hit rates, but still acceptable (> 0.40), were detected in summer and fall (during the rainy season and at the end, respectively) because more precipitation classifications were tested and prone to miss. Spatial Spearman correlations provided specific areas of significant model performances and found that high hit rates during the winter and spring are spurious. Meanwhile, it was also found that during the fall the model approach is reliable in most of Mexico, followed by the spring, and in constraint areas in summer and winter across the country. It also appears that dominant ENSO neutral events followed by balanced ENSO cooling and warming events do not prefer the model skill. Overall, the empirical method shows promise (low-cost human and computational resources if ENSO indices expose certainty in its Lead months to forecast) and has the potential to be used in other developing countries influenced by El Niño phenomena.

Purpose: To construct a hidden Markov model (HMM) for vigilance assessment to improve the real-time performance and accuracy of current vigilance measurement. Methods: ECG signal was collected by sensors, while the noise and baseline drift was eliminated from the original ECG signal. 10 volunteers were randomly selected. Their heart rate variability (HRV) were measured and trained parameters of the modified Hidden Markov model for vigilance assessment. Then, these data were collected to optimize using the Baum-Welch algorithm and obtained the state transition probability matrix A ̂ and the observation probability matrix B ̂. Finally, the data of three volunteers with different transition patterns of mental state were selected randomly and used the Viterbi algorithm to find the optimal state, which compared with the actual state. Results: The constructed vigilance assessment model had a high accuracy rate the accuracy rate of data prediction for these three volunteers exceeded 80%. Conclusion: The Hidden Markov model for vigilance assessment can accurately predict the vigilance level and indicate broad application prospects.

With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute to a consolidated global response. Here, we summarise community-driven approaches based on Free and Open Source scientific and medical Hardware (FOSH) currently being developed and deployed to bolster access to personal protective equipment (PPE), patient treatment and diagnostics.

In this paper we will present a simplified approach for extracting the ground level – a digital terrain model (DTM) – from the surface provided in a digital surface model (DSM). Most existing algorithms try to find the ground values in a digital surface model. Our approach works the opposite direction by detecting probable above ground areas. The main advantage of our approach is the possibility to use it with incomplete DSMs containing much no data values which can be e.g. occlusions in the calculated DSM. A smoothing or filling of such original derived DSMs will destroy much information which is very useful for deriving a ground surface from the DSM. Since the presented approach needs steep edges to detect potential high objects it will fail on smoothed and filled DSMs. After presenting the algorithm it will be applied to a test area in Salzburg and compared to a terrain model freely available from the Austrian government.

This paper introduces new improvements to the modified version of the BIRECT (BI secting RECTangles) algorithm referred to as BIRECTv. We explore various approaches, by first including a grouping strategy for hyper-rectangles having almost the same sizes by categorizing them into different classes. Therefore constraining them not to exceed a certain pre-defined threshold (a small positive value to define the tolerance level). This approach allows for more efficient computation and can be particularly useful when dealing with a large number of hyper-rectangles with varying sizes. To avoid over-sampling, and preventing redundant or excessive sampling, at some shared vertices in descendant subregions, a particular vertex database is used to limit the number of samples taken within each subregion to two. The experimental investigation shows that these improvements have a positive impact on the performance of the BIRECTv(imp.) algorithm and the proposal is a promising global optimization algorithm compared to the original BIRECTv algorithm and its variants. Additionally, the BIRECTv(imp.) algorithm showed particular efficacy in solving high-dimensional problems.

Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialised multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains, developed in 2018 and validated in 2023, to identify the level of complexity in patients with advanced cancer. Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. Method: An observational, prospective, multicentre study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were: a) instability ratio (IR), defined as the probability of level change or death; b) emergency department visits; c) days of hospitalisation; d) hospital death; e) survival. All variables were analysed monthly according to the level of complexity assigned at the baseline visit. Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p

Autonomous unmanned aerial vehicles (UAVs) require highly reliable navigation information. Generally, navigation systems with the inertial navigation system (INS) and global navigation satellite system (GNSS) have been widely used. However, the GNSS is vulnerable to jamming and spoofing. The terrain referenced navigation (TRN) technique can be used to solve this problem. In this study, to obtain reliable navigation information even if a GNSS is not available or the degree of terrain roughness is not determined, we propose a federated filter based INS/GNSS/TRN integrated navigation system. we also introduce a TRN system that combines batch processing and an auxiliary particle filter to ensure stable flight of UAVs even in a long-term GNSS-denied environment. As an altimeter sensor for the TRN system, we use an interferometric radar altimeter (IRA) to obtain reliable navigation accuracy in high altitude flight. In addition, a parallel computing technique with general-purpose computing on graphics processing units (GPGPU) is applied to process a high resolution terrain database and a nonlinear filter in real time on board. Finally, we verify the performance of the proposed system through software-in-the-loop (SIL) tests and captive flight tests in a GNSS unavailable environment.

Despite their obvious differences, biological systems at different scales tend to exhibit common organizational patterns. Unfortunately, these commonalities are usually obscured by the parcelled terminology employed by various scientific sub-disciplines. To explore these commonalities, this papers a comparative study of diverse applications of the maximum entropy principle, ranging from amino acids up to societies. By presenting these studies under a common language, this paper establishes a unified view over seemingly highly heterogeneous biological scenarios.

Indoor Positioning Systems (IPSs) are designed to provide solutions for location-based services. Wireless local area network (WLAN)-based positioning systems are the most widespread around the globe and are commonly found to have a ready-to-use infrastructure composed mostly of access points (APs). They provide useful information on signal strength to be processed by adequate location algorithms, which are not always capable of achieving the desired localization error only by themselves. In this sense, this paper proposes a new method to improve the accuracy of IPSs by optimizing some of their most relevant infrastructure components. Included are the arrangement of APs over the environment, the number of reference points (RPs), and the number of samples per location estimation test. A simulation environment is also proposed, in which the impact of key influencing factors on system accuracy is analyzed. Finally, a case study is simulated to validate an optimal combination of design parameters and its compliance with the requirements of localization error and the limited number of access points. Our simulation results clearly show that the desired localization accuracy, which is set as a goal, can be achieved while maintaining the factors already mentioned at minimal levels, which decreases both system deployment costs and computational effort.

Despite the uptake of tobacco smoking declining in the UK, smoking is still the leading cause of preventable poor health and premature death. While improved approaches to smoking cessation are necessary, encouraging and assisting smokers to switch by using substantially less toxic non-tobacco nicotine products may be a possible option. To date few studies have investigated the rates of smoking cessation and smoking reduction associated with the free provision of electronic-cigarettes (e-cigarette) to smokers. In this study the Blu Pro e-cigarette was given to smokers for use in place of tobacco for 90 days. The rates of smoking abstinence and daily smoking patterns were assessed at baseline 30 days, 60 days and 90 days. The response rate was 87%. After 90 days, the complete abstinence rate was 36.5% from 0% at baseline. Frequency of daily smoking reduced from 88.7% to 17.5% (P<0.001) and median consumption of cigarettes/day from 15 to 5 (P<0.001). Median days per month participants smoked also dropped from 30 to 13 after 90-days (P<0.001). On the basis of these results there may be value in smoking cessation services and other services ensuring that smokers are provided with e-cigarettes at zero or minimal costs for at least a short period of time.

Serologic measures of tissue transglutaminase (tTG) immunoglobulin A (IgA) and deamidated gliadin peptide (DGP) IgA and immunoglobulin G (IgG) are hallmark tests utilized when diagnosing individuals for celiac disease (CeD) and for monitoring adherence to a gluten-free diet (GFD), currently the only available treatment for CeD. We address two issues in this study: (i) the relapse to seropositivity for CeD patients who resume a gluten containing diet and (ii) the correlation between two different tTG-IgA assays near the upper limit of normal (ULN) designated thresholds. Regarding the first issue, often a suspected CeD individual is put back on a gluten diet to return to their serologic levels. However, we show it requires a substantial amount of gluten for serology to return to a positive level. For example, in one study of 22 patients treated with placebo and taking 84 g of gluten over 6 weeks, only 2 converted from seronegative to seroposi-tive for tTG-IgA. Regarding the second topic, we compare the relationship for different serologic assays, namely tTG-IgA AB (recombinant, ULN=4 Units/mL) vs. tTG-IgA (non-recombinant, ULN=20 Units). There is a strong correlation by both measurements as evidenced by a Pearson coefficient of R = 0.8584. However, we observed that the cross-correlation in terms of sensitivity and specificity improved substantially by using an ULN value of 3 instead of 4 for the tTG-IgA AB (recombinant) assay. This result suggests that assay thresholds used for initial diagnosis in patients who have not yet started a GFD may need to be adjusted for monitoring and in the setting of a diagnostic gluten challenge.

Configuration techniques have been used in several fields, such as the design of business process models. Sometimes these models depend on the data dependencies, being easier to describe "what" has to be done instead of "how". Configuration models enable to use a declarative representation of business processes, deciding the most appropriate work-flow in each case. Unfortunately, data dependencies among the activities and how they can affect the correct execution of the process, has been overlooked in the declarative specifications and configurable systems found in the literature. In order to find the best process configuration for optimizing the execution time of processes according to data dependencies, we propose the use of Constraint Programming paradigm with the aim of obtaining an adaptable imperative model in function of the data dependencies of the activities described declarative.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

The relation between CO2 emissions and atmospheric CO2 concentration has traditionally been treated with more or less complex models with several boxes. Our approach is motivated by the question of how much CO2 must necessarily be absorbed by sinks. Observations lead to the model assumption, that carbon sinks like oceans or biosphere are linearly dependent on CO2 concentration on a decadal scale. In particular this implies the falsifiable hypothesis that oceanic and biological CO2 buffers have not significantly changed in the past 50 years and are not saturated in the forseeable future. The simple model with 2 parameters explains very well the CO2 emission and historical CO2 concentration data. The model gives estimates of the natural emissions, the pre-industrial CO2 equilibrium concentration levels, the half-life time of an emission pulse, and the future CO2 concentration level from a given emission scenario. This is validated by an ex-post forecast of the last 20 years. The important result is that with the stated polices scenario of the IEA future CO2 concentrations will not rise above 475 ppm. The model is compared with the Carbon modul of the Bern model, mapping their complex IRFs to a single time variant parameter.

Delineating chilling and forcing periods is one of the challenging topics in understanding how temperatures drive the timing of budburst and bloom in fruit tree species. Here, we investigated this question on olive trees, using flowering data collected over six years on 331 cultivars in the worldwide collection of Marrakech, Morocco. Using a Partial Least Squares approach on a long-term phenology (29 years) of ‘Picholine Marocaine’ cultivar, we showed that the relevance of delineating the chilling and forcing periods depends more on the variability of inter-annual temperatures than on the long-term datasets. In fact, chilling and forcing periods are similar between those delineated by using datasets of 29 years and those of only 6 years (2014–2019). We demonstrated that the variability of inter-annual temperatures is the main factor explaining this pattern. We then used the datasets of six years to assess the chill and heat requirements of 285 cultivars. We classified Mediterranean olive cultivars into four groups according to their chill requirements. Our results, using the Kriging interpolation method, indicated that flowering dates of most of these cultivars (92%) were governed by both chilling and forcing temperatures. Our investigations provided first insights to select adapted cultivars to global warming.

In this study, based on our previous study, we examined the mathematical properties, especially the stability of the equilibrium for our proposed mathematical model. By means of the results of the stability in this study, we also used actual data representing transient booms and resurgent booms, and conducted parameter estimation for our proposed model using Bayesian inference. In addition, we conducted a model fitting to five actual data. By this study, we reconfirmed that we can express the resurgences or minute vibrations of actual data by means of our proposed model.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in-silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physiological conditions. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in-silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared to the pertuzumab-HER2 complex.

The complex interplay among pathogens, host factors, and the integrity and composition of the endogenous microbiome determine the course and outcome of gastrointestinal infections. The model organism Yersinia entercolitica (Ye) is one of the five top frequent causes of bacterial gastroenteritis based on the Epidemiological Bulletin of the Robert Koch Institute (RKI) published on September 10, 2020. A fundamental challenge in predicting the course of an infection is to understand whether co-infection with two Yersinia strains differing only in their capacity to resist killing by the host immune system may decrease the overall virulence by competitive exclusion or increase it by acting cooperatively. Herein, we study the primary interactions among Ye, the host immune system and the microbiota, and their influence on Yersinia population dynamics. The employed model considers two host compartments, the intestinal mucosa and lumen, commensal bacteria, the co-existence of wild-type and mutant Yersinia strains, as well the host immune responses. We determine four possible equilibria: the disease-free, wild-type-free, mutant-free, and co-existence of wild-type and mutant equilibrium. We also calculate the reproduction number for each strain as a threshold parameter to determine if the population may either be eradicated or persist within the host. We conclude that the infection should disappear if the reproduction numbers for each strain fall below one, and the commensal bacteria’s growth rate exceeds the pathogens’ growth rates. These findings will help inform public health control strategies. The supplement includes MATLAB source script, Maple workbook, and figures.

The subject of this article is the dynamics of water in a soil pedostructure sample whose internal environment is subjected to a potential gradient created by the departure of water through surface evaporation. This work refers entirely to the results and conclusions of a fundamental theoretical study focused on the molecular thermodynamic equilibrium of the two aqueous phases of the soil pedostructure. The new concepts and descriptive variables of the hydro-thermodynamic equilibrium state of the soil medium, which have been established at the molecular level of the fluid phases of the pedostructure (water and air) in a previous article, are recalled here in the systemic paradigm of hydrostructural pedology. They allow access to the molecular description of water migration in the soil and go beyond the classical mono-scale description of soil water dynamics. We obtain a hydro-thermodynamic description of the soil's pedostructure at different hydro-functional scale levels including those relating to the water molecule and its atoms. The experimental results show a perfect agreement with the theory, validating at the same time the systemic approach which was the framework.

The paper presents a modeling framework to analyze the effect of episodic rainfall supply on groundwater dynamics in the Ionian coastal plain multilayered aquifer. The focus is essentially on the short-term behavior of the shallowest layer, with a specific analysis on episodic rainfall events. In the studied aquifer, groundwater level responds sensitively to rainfall events, highlighting the presence of preferential recharge zones. The hydraulic head peak is a function of groundwater level antecedent to the rainfall event. A kinematic dispersion wave model was used to model infiltration processes via preferential pathways. A one-dimensional and non-linear particle based numerical model was developed. Particles with constant water volume travel according to celerity and hydraulic dispersion to simulate the infiltration rate wave through the vadose zone. The flow rate that reaches the water table represents the input function to determine groundwater level fluctuations along groundwater flow direction and according to the lithological features of the surficial levels of the multilayered aquifer, its storage capacity changes passing from unconfined to confined conditions. The model was validated with high time resolution time series of precipitation and groundwater level coming from Terra Montonata meteo-climatic and groundwater level monitoring station. The developed model represents a basis for evaluating and predicting groundwater discharge of the shallowest layers of the Ionian coastal multilayered aquifer under natural conditions including episodic rainfall.

In this paper, we consider the one-dimensional Ising model (shortly, 1D-MSIM) having mixed spin-(s,(2t−1)/2) with nearest neighbors and the external magnetic field. We establish the partition function of the model by means of the transfer matrix. Under a null boundary condition, we compute certain thermodynamic quantities for the 1D-MSIM. We find some precise formulas to determine the model’s free energy, entropy, magnetization, and susceptibility. By examining the model’s associated iterative equations, we use the cavity approach to investigate the phase transition problem. We numerically determine the model’s periodicity.

Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related with a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide and it is estimated that is present in up to 25% of the world's population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthetized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allow the direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight about the mechanism and drugs action in NAFLD. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical disc. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using highly specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈ 0.39 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the lipid accumulation within the cells. Moreover, we discovered that at third day from lipids challenge, the hepatocytes increased the amount of albumin secreted. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation needed to unveil the biological significance of that cell behaviour.

The QBIT theory is an attempt toward solving the problem of consciousness based on empirical evidence provided by various scientific disciplines including quantum mechanics, biology, information theory, and thermodynamics. This theory formulates the problem of consciousness in the following four questions: (1) What is the nature of qualia? (2) How are qualia generated? (3) Why are qualia subjective? (4) Why does a quale have a particular quality or meaning?In sum, the QBIT theory proposes that (1) when a pack of quantum information is compressed beyond a certain threshold, a quale is generated; (2) a quale is a superdense pack of maximally entangled qubits in a pure state; (3) when information-theoretic certainty of a system about an external stimulus exceeds a particular level, the system becomes conscious of that stimulus; (4) subjectivity of consciousness is due to the fact that maximally entangled pure states are private and unshareable.

A rigorous model for the electron is presented by generalizing the Coulomb's Law or Gauss's Law of electrostatics, using a unified theory of electricity and gravity. The permittivity of the free-space is allowed to be variable, dependent on the energy density associated with the electric field at a given location, employing generalized concepts of gravity and mass/energy density. The electric field becomes a non-linear function of the source charge, where concept of the energy density needs to be properly defined. Stable solutions are derived for a spherically symmetric, surface-charge distribution of an elementary charge. This is implemented by assuming that the gravitational field and its equivalent permittivity function is proportional to the energy density, as a simple first-order approximation, with the constant of proportionality referred to as the Unifield Electro-Gravity (UEG) constant. The stable solution with the lowest mass/energy is assumed to represent a ``static'' electron without any spin. Further, assuming that the mass/energy of a static electron is half of the total mass/energy of an electron including its spin contribution, the required UEG constant is estimated. More fundamentally, the lowest stable mass of a static elementary charged particle, its associated classical radius, and the UEG constant are related to each other by a dimensionless constant, independent of any specific value of the charge or mass of the particle. This dimensionless constant is numerologically found to be closely related to the the fine structure constant. This possible origin of the fine structure constant is further strengthened by applying the proposed theory to successfully model the Casimir effect, from which approximately the same above relationship between the UEG constant, electron's mass and classical radius, and the fine structure constant, emerges.

In econometrics and finance, volatility modelling has long been a specialised field for addressing a variety of issues pertaining to the risk and uncertainties of an asset. This study presents a robust framework, through a step-by-step design, that is relevant for effective Monte Carlo simulation (MCS) with empirical verifications to estimate volatility using the Generalized Autoregressive Score (GAS) model. The framework describes an organised approach to the MCS experiment that includes "background (optional), defining the aim, research questions, method of implementation, and summarised conclusion". The method of implementation is a workflow that consists of writing the code, setting the seed, setting the true parameter a priori, data generation process, and performance assessment through meta-statistics. Among the findings, it is experimentally demonstrated in the study that the GAS model with a lower unconditional shape parameter value can generate a dataset that adequately reflects the behaviour of financial time series data, relevant for volatility estimation. This dynamic framework is intended to help interested users on MCS experiments utilising the GAS model for reliable volatility calculations in finance and other areas.

Tissue engineered heart valves can grow, repair, and remodel after implantation, presenting a more favorable long-term solution compared to mechanical and porcine valves. Achieving functional engineered valve tissue requires the maturation of human cells seeded onto valve scaffolds under favorable growth conditions in bioreactors. The mechanical stress and strain on developing valve tissue caused by different pressure and flow conditions in bioreactors are currently unknown. The aim of this study is to quantify the wall shear stress (WSS) magnitude in heart valve prostheses under different valve geometries and bioreactor flow rates. To achieve this, the study used fluid-structure interaction simulations to obtain the valve's opening geometries during the systolic phase. These geometries were then used in computational fluid dynamics simulations with refined near-wall mesh elements and ranges of prescribed inlet flow rates. The data obtained included histograms and regression curves that characterized the distribution, peak, and median WSS for various flow rates and opening configurations. The study also found that the upper region of the valve near the commissures experienced higher WSS magnitudes than the rest of the valve.

Analysis of Fatigue Strain, Fatigue Modulus and Fatigue Damage for the modeling of concrete plays a vital role in the evolution material behaviour which is heterogeneous and anisotropic in nature. In this paper, the Level-S nonlinear fatigue strain curve, fatigue modulus curve, residual strain curve of concrete in compression, tension, flexure and torsional fatigue loading were proposed using strain life approach. The parameters such as physical meaning, the ranges, and the impact on the shape of the curve were discussed. Then, the evolution model of fatigue modulus was established based on the fatigue strain evolution model, fatigue modulus evaluation model, residual strain evaluation model, secondary strain evaluation model. The hypothesis of fatigue modulus is inversely related with the fatigue strain amplitude. The fatigue evolution of concrete damages the bond between material grains, changed the orientation of structure of molecules and affects the elastic properties resulting in the reduction of material stiffness and modulus by utilizing strain life analysis, regarding stiffness degradation and inelastic deformation by formation of microcracking, macro cracking, cracking which is heterogeneous and anisotropic in nature . This paper presents the Fatigue Strain Life Model and analyses of fatigue strain, fatigue modulus and damage parameters of concrete which is capable of predicting stiffness degradation, inelastic deformation, strength reduction under fatigue loading. Hence, the obtainable results were compared with experimental results for the validation of the proposed model.

The evaluation of tourism sustainability has become of paramount importance for researchers and decision-makers to better protect tourist destinations, especially with the continuous increase in the number of tourists and visitors that alter the natural components of the environment and degrade ecosystems. Therefore, the use of geographical data is of great significance, particularly in environmental monitoring and land management, due to its ease of use and availability. However, calculating composite indices for sustainability involves several steps and requires a basic understanding of existing models. This article describes the development and design of a package of plugins in QGIS that serves as an easy-to-use tool for processing and automatically calculating economic, environmental, social indices, and the overall index of tourist sustainability. These plugins have been built in Python and designed as QGIS software plugins.

Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focus on the potential synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HT) strategy. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HT and AFM is essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of nanomaterials with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HT enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HT is ideally suited for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology, emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools.

Objective: To use mathematical models to predict the epidemiological impact of lifting the lockdown in London, UK, and alternative strategies to help inform policy in the UK. Methods: A mathematical model for the transmission of SARS-CoV2 in London. The model was parametrised using data on notified cases, deaths, contacts, and mobility to analyse the epidemic in the UK capital. We investigated the impact of multiple non pharmaceutical interventions (NPIs) and combinations of these measures on future incidence of COVID-19. Results: Immediate action at the early stages of an epidemic in the affected districts would have tackled spread. While an extended lockdown is highly effective, other measures such as shielding older populations, universal testing and facemasks can all potentially contribute to a reduction of infections and deaths. However, based on current evidence it seems unlikely they will be as effective as continued lockdown. In order to achieve elimination and lift lockdown within 5 months, the best strategy seems to be a combination of weekly universal testing, contact tracing and use of facemasks, with concurrent lockdown. This approach could potentially reduce deaths by 48% compared with continued lockdown alone. Conclusions: A combination of NPIs such as universal testing, contact tracing and mask use while under lockdown would be associated with least deaths and infections. This approach would require high uptake and sustained local effort but it is potentially feasible as may lead to elimination in a relatively short time scale.

Today, there is a time series analysis that has gained significant popularity across various industries to provide effective solutions for any specific challenges. Artificial intelligence logic is generally used to solve time-series problems with the help of various frameworks that are available for the development of AI-based applications. Currently, there is a significant framework in Python that is driven by its comprehensive libraries and their practical implementations. Time series analysis can be built with the help of some specific models that give results to differentiate the efficiency and domains of great work. This paper focuses on three diverse libraries of Python to predict the Gulf stock exchange market. These libraries are prediction models that are helpful in predicting future values. These models utilized include SARIMA (Seasonal Auto-Regressive Integrated Moving Average), Neural Prophet Model, and Fb Prophet model. Each model is trained using the provided datasets, which are followed by evaluation parameters such as MSE, RMSE, recall, MDAPE, accuracy, precision, etc. The main purpose of using these three models for stock market prediction is to find the better-suited models. In the past few decades, the stock market industry has seemed to have promising growth after 2022 onwards. This paper will help us make a significant decision about model usage for addressing such complex challenges. Especially, the research findings indicate that all three models demonstrate in different domains. SARIMA can perform well in overall prediction tasks, while the Prophet model works great with smaller datasets that contain seasonality trends.

The complexity of modern power grids, exacerbated by integrating diverse energy sources, espe-cially inverter-based resources (IBRs), presents a significant challenge to grid operation and plan-ning since linear models fail to capture the intricate IBR dynamics. This study employs the Sparse Identification of Nonlinear Dynamics (SINDy) method to bridge the gap between theoretical un-derstanding and practical implementation in power system analysis. It introduces the novel Volterra-based Nonlinearity Index (VNI) to examine system-level nonlinearity comprehensively. The distinction of dynamics into first-order linearizable terms, second-order nonlinear dynamics, and third-order noise elucidates the intricacy of power systems. The findings demonstrate a fundamental shift in system dynamics as power sources transit to IBRs, revealing system-level nonlinearity compared to module-level nonlinearity in conventional syn-chronous generators. The VNI quantifies nonlinear-to-linear relationships, enriching our comprehension of power system behavior and offering a versatile tool for distinguishing between different nonlinearities and visualizing their distinct patterns through the proposed VIN profile.

In this paper we investigate some properties of square-free numbers. In particular, we study a function that counts the number of square-free numbers no larger than the given number n. We show that this function has asymptotics consistent with the predictions of the Riemann hypothesis and use this to obtain new and better estimates of the density of square-free numbers. Finally, we present a well-known generalization of the concept of a square-free number to monoids and research on square-free factorizations.

This paper explores the suppression of ideas within academic scholarship by academics, either by self-suppression or because of the efforts of other academics. Legal, moral, and social issues distinguishing freedom of speech, freedom of inquiry, and academic freedom are reviewed. How these freedoms and protections can come into tension is then explored by an analysis of denunciation mobs who exercise their legal free speech rights to call for punishing scholars who express ideas they disapprove of and condemn. When successful, these efforts, which constitute legally protected speech, will suppress certain ideas. Real-world examples over the past five years of academics who have been sanctioned or terminated for scholarship targeted by a denunciation mob are then explored.