Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

Primary energy consumption is one of the key drivers of global CO₂ emissions that, in turn, heavily depend on the efficiency of involved technologies. Either the improvement in technology efficiency or the expansion of non-fossil fuel consumption require large investments. The planning and financing of such investments, by policy makers or global energy firms, require, in turn, reliable measures of associated global spreads and their evolution in time. In this paper, our main contribution is the introduction of index measures for accessing global spreads (that is, measures of inequality or inhomogeneity in the statistical distribution of a related quantity of interest) of technology efficiency and CO₂ emission in primary energy consumption. These indexes are based on the Gini index, as used in economical sciences, and generalised entropy measures. Regarding primary energy sources, we consider petroleum, coal, natural gas and non-fossil fuels. Between our findings, we attest some stable relations in the evolution of global spreads of technology efficiency and CO₂ emission, and a positive relation between changes in global spreads of technology efficiency and use of non-fossil fuel.

Beer is a fermented beverage with a history as old as human civilization and its productive process has been spread all around the world becoming unique in every country and iconic of entire populations. Ales and lagers are by far the most common beers; however, the combination of raw materials, manufacture techniques and aroma profiles are almost infinite, so it is not surprising to notice that there is a large amount of different beer styles, each of them with unique characteristics. Nowadays, diversification is becoming increasingly important in the brewing market and the brewers are continuously interested in improving and extending the already wide range of products, especially in craft brewery. One of the major components that can have a deep impact on the final product is yeast, since it is able to convert carbohydrates in wort, especially maltose and maltotriose, into ethanol, carbon dioxide and other minor aroma-active compounds. Saccharomyces cerevisiae (top‐fermenting yeasts used to produce ales) and Saccharomyces pastorianus (cryotolerant bottom‐fermenting hybrids between S. cerevisiae and Saccharomyces eubayanus responsible for the fermentation of lagers) are most used in breweries. However, an increasing number of different yeast starter cultures are commercially available, to improve the production efficiency also at relative low temperatures and to obtain desirable and diversified aroma profiles avoiding undesired compounds. Four main genetic engineering-free trends are becoming popular in craft brewing yeast development: 1) the research for novel reservoirs as source of new performant S. cerevisiae yeasts; 2) the creation of synthetic hybrids between S. cerevisiae and Saccharomyces non-cerevisiae in order to mimic lager yeasts by expanding their genetic background; 3) the exploitation of evolutionary engineering approaches; 4) the usage of non-Saccharomyces yeasts either in co-coculture or in sequential fermentation with S. cerevisiae. In the present work we summarized pro and contra of these approaches and provided an overview on the most recent advances on how brewing yeast genome evolved and domestication took place. Finally, we delineated how the correlations maps between genotypes and relevant brewing phenotypes can assist and further improve the search for novel craft beer starter yeasts.

In recent years, numerous topologies of single phase and three phase Field Excited Flux-Switching Machine (FEFSM) have been developed for several applications. Comparative study of three types of single-phase low-priced Field Excited Flux-Switching Machine (FEFSM) is presented in this paper. Both the conventional 8S/4P sub-part rotor design and 6S/3P salient rotor design have an overlapped winding arrangements between armature coil and field excitation coil that depicts high copper losses as well as results in increased size of motor. Additionally, FEFSM with salient structure of the rotor have high flux strength in the stator-core that has much impact on high iron losses. Copper consumption and iron loss being a crucial proportion in total machine losses. Therefore a novel topology of single phase modular rotor field excited FSM with 8S/6P configuration is proposed, which enable non-overlap arrangement between armature coil and FEC winding that facilitates devaluation in the copper losses. The proposed modular rotor design acquires reduced iron losses as well as reduced active rotor mass comparatively to conventional rotor design. It is very persuasive to analyze the best range of speed for these rotors to avoid cracks and deformation, the maximum tensile strength (can be measured with principal stress in research) of the rotor analysis is conducted using JMAG. A deterministic optimization technique is used to enhance the performance of 8S/6P modular rotor design. The electromagnetic performance of conventional sub-part rotor design, F1-A3-3P design and proposed novel-modular rotor design are analyzed by 3D-Finite Element Analysis (3D-FEA), includes flux linkage, flux distribution, flux strength, back-EMF, cogging torque, torque characteristics, iron losses and efficiency.

Thunderstorm electrification has been studied for hundreds of years. Several mechanisms have been proposed to elucidate the electrification, including convective charging, inductive precipitation charging, and ice crystal-graupel collision charging. Field observations and model studies have demonstrated the vital roles that graupel and ice crystals play in the electrification, but the mechanism of the collision charging is still unclear. The fundamental essence of relative growth rate theory used for explaining the tripole charge structure in thunderclouds also needs a further exploration. We analyze the processes of ice crystal-graupel collision charging from charge migration inside hydrometeors to charge separation between two hydrometeors. The driving effects of temperature gradient and chemical potential gradient in charge migration are clarified, as well as the applicability of the relative growth rate theory, thermoelectric effect and surface tension gradient in different humidities. Based on the understanding from these electrification mechanisms, we propose that the essence of charge separation is driven by non-thermal equilibrium, and future studies on thunderstorm electrification should focus on the dynamical non-thermal equilibrium of cloud particles.

Magnetic nanoparticles are met across many biological species ranging from magnetosensitive bacteria, fishes, bees, bats, rats, birds, to humans. They can be both of biogenetic origin and due to environmental contamination, being either in paramagnetic or ferromagnetic state. The energy of such naturally occurring single-domain magnetic nanoparticles can reach up to 10-20 room k_BT in the magnetic field of the Earth, which naturally led to supposition that they can serve as sensory elements in various animals. This work explores within a stochastic modeling framework a fascinating hypothesis of magnetosensitive ion channels with magnetic nanoparticles serving as sensory elements, especially, how realistic it is given a highly dissipative viscoelastic interior of living cells and typical sizes of nanoparticles possibly involved.

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Panel data of our interest consist of a moderate number of panels, while the panels contain a small number of observations. An estimator of common breaks in panel means without a boundary issue for this kind of scenario is proposed. In particular, the novel estimator is able to detect a common break point even when the change happens immediately after the first time point or just before the last observation period. Another advantage of the elaborated change point estimator is that it results in the last observation in situations with no structural breaks. The consistency of the change point estimator in panel data is established. The results are illustrated through a simulation study. As a by-product of the developed estimation technique, a theoretical utilization for correlation structure estimation, hypothesis testing, and bootstrapping in panel data is demonstrated. A practical application to non-life insurance is presented as well.

This study presents a novel lake ecosystem model that captures the intricate dynamics of nutrient cycling through nonlinear interactions. The model incorporates external phosphorus loading and internal recycling rates to explore a range of ecological outcomes, from stable equilibria to chaotic oscillations. We investigate the bifurcation phenomena within this model, revealing how changes in parameters can lead to significant shifts in ecosystem behavior. Our analysis demonstrates that the model can replicate behaviors similar to the Hénon map under specific parameter settings. Through numerical simulations, we examine the system's sensitivity to variations in nutrient parameters, uncovering the potential for unpredictable dynamics and chaos as the recycling rate increases. The emergence of chaotic behavior is further supported by entropy analysis, highlighting the model's complexity and its implications for real-world ecosystems. Notably, our findings resonate with the work of Tay et al., demonstrating that increased nutrient recycling can lead to bistability and abrupt shifts in ecosystem stability, emphasizing the critical importance of effective nutrient management to avert detrimental ecological consequences. This research contributes valuable insights into the dynamics of freshwater ecosystems, underscoring the intricate interplay between nutrient inflow, recycling, and bifurcation in maintaining ecological balance.

Market dynamics is based on classical electrodynamics and uses quantum electrodynamics as a reference model framework. Its construction is always based on Bourbaki structuralism. Market dynamics studies the interaction between price, demand and supply. Quantum electrodynamics studies the interaction between photons, electrons and positrons. Both belong to the category of single charge dynamics and share a symmetry group. Market dynamics introduces market charge and defines demand and supply respectively. By examining the market hesitation phenomenon, spin is introduced as the intrinsic property of demand and supply. Therefore, demand and supply can be defined by Dirac spinors. By introducing the coin cone and valence shell, virtual prices are defined; demand and supply interact by exchanging virtual prices. These interactions can be described by Feynman diagrams. The cognitive field has the function of polarizing decision-making and is described by the magnetic field. Market dynamics believes that the social economy itself is an experiment and every market participant is an observer. We established the non-commutative relationship of market observation and the market version of the uncertainty principle of observation information, and defined the quantum version of the invisible hand. On the basis of classical electrodynamics, the relationship between price field and Maxwell field is discussed, and the concept of gauge potential is introduced. Market fluctuations (including mesoscopic and quantum fluctuations) caused by high-order cognition (including gaming, decision-making and reasoning). The fluctuation phenomena inherent in various markets are the basis for understanding both the cognition of market participants and the phase transition of the market. Six components of the market wave function are defined, namely the global phase factor, global gauge potential and global gauge field strength, as well as the local phase factor, local gauge potential and local gauge field strength. Gauge transformation is a integral part of quantum electrodynamics and market dynamics. The gauge principle is then given to show that global symmetry is a necessary condition for local symmetry. Four operators are introduced, namely the Newton mean operator, the Einstein cone operator, the Schrödinger evolution operator and the Dirac field theory operator. These four operators are applied to the market wave function respectively, presenting four operator phases of the market wave function. The change of operator state is called the phase transition of the market wave function.

Microgrid (MG) control is essential for efficient, reliable, and sustainable energy management in distributed energy systems. Genetic Algorithm-based energy management systems (GA-EMS) can optimally control a MG by finding global optima and handling complex, non-linear, and non-convex problems, but they can be computationally intensive, making real-time control challenging. Model Predictive Control (MPC)-based EMS predicts future behaviour over a defined horizon, ensuring optimal performance and constraint satisfaction but typically relies on linear models. This paper proposes a novel Genetic Predictive Control (GPC) method, combining GA and MPC to enhance resource allocation, balance multiple objectives, and adapt dynamically to changing conditions. Integrating GA with MPC significantly improves the handling of non-linearities and non-convexity in the system model, leading to more accurate and effective control. Comparative analysis shows that GPC significantly reduces excess power production—surplus power generated beyond load demand—improving resource allocation efficiency. For instance, in the Mutation–Random Selection scenario, GPC reduced excess power to 76.0W compared to 87.0W with GA. Additionally, GPC balances cost, emissions, and power efficiency. In the Crossover-Elitism scenario, GPC achieved a daily cost of $113.94 compared to GA's $127.80, and carbon emissions of 52.83 kg CO2e compared to GA's 69.71 kg CO2e, demonstrating GPC's cost efficiency and environmental benefits. While MPC optimizes a weighted sum of objectives, designing appropriate weights can be challenging and may result in non-convex problems. GA handles multiple, conflicting objectives through multi-objective optimization, providing Pareto-optimal solutions. GPC's dynamic adaptability maintains optimal performance by forecasting future load demands and adjusting control actions. GPC consistently achieves lower emissions than GA across various scenarios and, although it sometimes incurs higher costs, such as $113.94 compared to $131.90 in the Crossover–Random Selection scenario, its holistic approach balances these costs with other metrics, making it cost-effective in the long run. By reducing excess power production and emissions, GPC contributes to economic savings and promotes sustainable practices. These findings underscore GPC's potential as a versatile, efficient, and environmentally beneficial optimization tool for power generation systems.

In order to solve the problem of large eddy current loss and high temperature rise caused by large amount of permanent magnet, a new type of combined magnetic pole permanent magnet motor is proposed in this paper. The sinusoidal distribution subdomain model of non-uniform air gap rotor is established by using Laplace equation, and the analytical expression of eddy current loss of rotor in uniform air-gap and non-uniform air-gap is derived. The effect of rotor eccentricity on eddy current loss is obtained. According to the characteristics of distributed winding of non-uniform air gap combined pole permanent magnet motor, equivalent treatment is performed to obtain the equivalent thermal conductivity, so as to establish equivalent thermal network model of motor, calculate the temperature value of each component of the motor, and verify the correctness of the thermal network model through the method of magnetothermal bidirectional coupling. Finally, an experimental platform is set up to carry out temperature rise experiments on the two prototypes respectively. Experimental results show that the non-uniform air-gap rotor structure can effectively reduce the rotor eddy current loss and motor temperature rise, and also verify the accuracy of the analytical model calculation results.

Utilizing bioinformatics tools, this study expands our understanding of secondary metabolism in Botrytis cinerea, identifying novel genes within polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), sesquiterpene cyclase (STC), diterpene cyclase (DTC), and dimethylal-lyltryptophan synthase (DMATS) families. These findings enrich the genetic framework associ-ated with B. cinerea's pathogenicity and ecological adaptation, offering insights into uncharted metabolic pathways. Significantly, the discovery of previously unannotated genes provides new molecular targets for developing targeted antifungal strategies, promising to enhance crop pro-tection and advance our understanding of fungal biochemistry. This research not only broadens the scope of known secondary metabolites but also opens avenues for future exploration into B. cinerea's biosynthetic capabilities, potentially leading to novel antifungal compounds. Our work underscores the importance of integrating bioinformatics and genomics for fungal research, paving the way for sustainable agricultural practices by pinpointing precise molecular interven-tions against B. cinerea. This study sets a foundation for further investigations into the fungus's secondary metabolism, with implications for biotechnology and crop disease management.

The mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

‘Inner mitochondrial membrane peptidase 2 like’ (IMMP2L) is a nuclear encoded mitochondrial peptidase that has been conserved through evolutionary history as has its target enzyme ‘mitochondrial glycerol phosphate dehydrogenase 2’ (GPD2). IMMP2L is known to cleave the mitochondrial transit peptide from GPD2 and another nuclear encoded mitochondrial respiratory related protein cytochrome C1 (CYC1). However, it is not known whether IMMP2L peptidase activates or alters the activity or respiratory related functions of GPD2 or CYC1. Previous investigations found compelling evidence of behavioural change in the Immp2lKD-/- KO mouse and in this study EchoMRI analysis found that many organs of the Immp2lKD-/- KO mouse were smaller and that the KO mouse had significantly less lean mass and overall body weight compared with wildtype littermates (p<0.05). Moreover, all of the organs analysed from the Immp2lKD-/- KO had lower relative levels of mitochondrial reactive oxygen species (mitoROS). The kidneys of the Immp2lKD-/- KO mouse displayed the greatest decrease in mitoROS levels that were over 50% less compared with wildtype litter mates. Mitochondrial respiration was also lower in the kidney of the Immp2lKD-/- KO mouse compared with other tissues when using succinate as the respiratory substrate, whereas respiration was similar to wildtype when glutamate was used as substrate. When glycerol-3-phosphate (G3P) was used as the substrate for Gpd2 we observed ~20% and ~7% respective decreases in respiration in female and male Immp2lKD-/- KO mice over time. Together these findings suggest that the respiratory related functions of mGpd2 and Cyc1 have been compromised to different degrees in different tissues in the Immp2lKD-/- KO mouse. Structural analyses using AlphaFold2-Multimer further predicted that the interaction between Cyc1 and mitochondrial encoded cytochrome b (Cyb) in Complex III had been altered as had the homodimeric structure of the mGpd2 enzyme within the inner mitochondrial membrane of the Immp2lKD-/- KO mouse. mGpd2 functions as an integral component of the glycerol phosphate shuttle (GPS) which positively regulates both mitochondrial respiration and glycolysis. Interestingly, we found that nonmitochondrial respiration (NMR) was also dramatically lowered in the Immp2lKD-/- KO mouse. Primary mouse embryonic fibroblast (MEF) cell lines derived from the Immp2lKD-/- KO mouse displayed a ~27% decrease in total respiration comprised of a ~50% decrease in NMR and a ~12% decrease in total mitochondrial respiration where the latter was consistent with the decreases in substrate specific mitochondrial respiration reported here. This study is the first to report the role of Immp2l in enhancing Gpd2 structure and function, mitochondrial respiration, nonmitochondrial respiration, organ size and homeostasis.

There were designed and synthesized two new sulfone 2-aminobenzimidazole derivatives. Coordination compounds were obtained with nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) and these novel ligands. There were fully characterized by spectroscopic and analytical techniques. Single crystal X-ray structural analysis was performed on order to study the relevant intra and inter non-covalent interactions, mainly H...π, lone pair·...π, π...π, highlighting the difference between the ethyl and phenyl groups in such interactions. Dimeric and trimeric supramolecular syntons were found for some of these compounds. Their biological activity was investigated, being the copper(II) compounds with the sulfone phenyl derivative the most active.

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

Petrochemical plants use on-stream inspection more often to detect and monitor the corrosion on the equipment and piping system. Compared to ultrasonic thickness gauging and pulse-echo A-scan, phased array corrosion mapping has better coverability and can scan a large area to detect general and localized corrosion. This paper's objective is to obtain documentary evidence on the accuracy of corrosion detection from 30°C to 250°C on A36 low-carbon steel by carrying out simulation experiments every 10°C steps. A minimum of three sets of phased array corrosion mapping data in each temperature were collected to study and evaluate the detectability. The data evidence could enhance the confidence level of the plant's end users to use the phased array mapping in the future during an inspection. The experiments were found to be insufficiently thorough despite addressing the initial concerns, leaving more area for discussion in further studies, such as expanding the investigation to thicker carbon steel, stainless steel, and wedge materials.

Seed germination and seedling growth represent two vulnerable stages in a plant life cycle and it is important to determine how they will be affected by environmental changes associated with climate change. This study examines the impact of salinity levels (0, 50, 100, and 150 mM) at each of three temperatures (15, 25, and 35˚C) on seed germination and radicle growth for three dormant and three non-dormant varieties of conventional, glyphosate resistant, or reduced lignin alfalfa. The genetic basis and phenotypic plasticity for seed germination and seedling growth in response to salinity and temperature were determined. Both traits were phenotypically plastic with respect to temperature and salinity. Seed germination was 87.0% ± 1.7 at 25˚C, 0mM (no salinity), but decreased to 33.9% ± 3.9 germination at 35˚C and 150mM. Radicle length went from 36.7 ± 1.5 mm after four days at 25˚C, 0mM, to 10.5 ± 0.7 mm at 35˚C, 150mM. The phenotypic response brought seed germination and radicle length away from their optimum, but we detected standing genetic variation for both seed germination and radicle length. Selection to increase both traits at high temperature and salinity would facilitate alfalfa establishment under climate change.

Since its emergence, COVID-19 has caused a great impact in health and social terms. Governments and health authorities have attempted to minimize this impact by enforcing different mandates. Recent studies have addressed the relationship between various socioeconomic variables and compliance level to these interventions. However, little attention has been paid to what constitutes people's response and whether people behave differently when faced with different interventions. Data collected from different sources show very significant regional differences across the United States. In this paper, we attempted to shed light on the fact that a response may be different depending on the health system capacity and each individuals’ social status. For that, we analyzed the correlation between different societal variables (i.e. education, income levels, population density, etc.) along with healthcare capacity related variables (i.e. hospital occupancy rates, percentage of essential workers, etc.) with regards to people's level of compliance with three main governmental mandates in the United States: mobility restrictions, mask adoption, and vaccine participation. Our aim was to isolate the most influential variables impacting behavior in response to these policies. We found that there was a strong relationship between individuals' educational levels and political preferences with respect to compliance with each of these mandates.

Seniors safety is a compelling need, which necessitates 24/7 real-time monitoring and timely dangerous action recognition. Being able to mirror characteristics of physical objects (PO) to corresponding logical objects (LO) and seamlessly monitor their footprints thus detect anomaly parameters, Digital Twins (DT) has been considered a practical way to provide virtual health services for seniors safety. Meanwhile, widely adopted Internet of Medical Things (IoMT) consisting of wearable sensors and non-contact optical cameras for self and remote health data monitoring also raises concerns on information security and privacy violation. Therefore, security of POs, LOs and reliable data sharing among healthcare professionals are challenging as constructing trust and privacy-preserving virtual health services. Thanks to characteristics of decentralization, traceability and unalterability, Blockchain is promising to enhance security and privacy properties in many areas like data analysis, finance and healthcare. This paper envisions a lightweight authentication framework (LAF) to enable secure and privacy-preserving virtual healthcare services. Leveraging Non-Fungible Token (NFT) technology to tokenize LOs and data streams on blockchain, anyone can certify the authenticity of a digital LO along with its synchronized data between PO without relying on a third-party agency. In addition, the NFT-based tokenization not only allows owners fully control their IoMT devices and data, but it also enables verifiable ownership and traceable transferability during data sharing process. Moreover, NFT only contains references to encrypted raw data that are saved on off-chain storage like local files or distributed databases, such a hybrid storage strategy ensures privacy-preservation for sensitive information. A proof-of-concept prototype is implemented and tests are conducted on a case study of seniors safety. The experimental evaluation shows the feasibility and effectiveness of the proposed LAF solution.

In this paper, we study the deflection angle for wormhole-like static aether solution by using Gibbons and Werner technique in non-plasma, plasma and dark matter mediums. For this purpose, we use optical spacetime geometry to calculate the Gaussian optical curvature, then implement the Gauss-Bonnet theorem in weak field limits. Moreover, we compute the deflection angle by using a technique known as Keeton and Petters technique. Furthermore, we analyze the graphical behaviour of the bending angle ψ with respect to the impact parameter b, mass m as integration constant and parameter q in non-plasma and plasma mediums. We examine that deflection angle is exponentially increasing as direct with charge. Also, we observe that for small values of b, ψ increases and for large values of b the angle deceases. We also considered an analysis to the shadow cast of the wormhole relative to an observer at various locations. Comparing it the the Schwarzschild shadow, shadow cast is possible for wormhole as r<2m. At r>2m, the Schwarzschild is larger. As r → ∞, we have seen that the behavior of the shadow, as well as the weak deflection angle, approaches that of the Schwarzschild black hole. Overall, the effect of plasma tends to decrease the value of the observables due to the wormhole geometry.

When gravity is quantum, the point structure of space-time should be replaced by a non-commutative geometry. This is true even for quantum gravity in the infra-red. Using the octonions as space-time coordinates, we construct a pre-spacetime, pre-quantum Lagrangian dynamics. We show that the symmetries of this non-commutative space unify the standard model of particle physics with $SU(2)_R$ chiral gravity. The algebra of the octonionic space yields spinor states which can be identified with three generations of quarks and leptons. The geometry of the space implies quantisation of electric charge, and leads to a theoretical derivation of the mysterious mass ratios of quarks and the charged leptons. Quantum gravity is quantisation not only of the gravitational field, but also of the point structure of space-time.

Transverse momentum spectra of +, p, Λ, Ξ or ¯Ξ+, Ω or ¯Ω+ and deuteron (d) in different centrality intervals in Gold-Gold (Au-Au) and Lead-Lead (Pb-Pb) collisions at 62.4 GeV and 2.76 TeV respectively, are analyzed by the blast wave model with Boltzmann Gibbs statistics. We extracted Kinetic freeze out temperature,transverse flow velocity and kinetic freezeout volume from the transverse momentum spectra of the particles. It is observed that the non-strange and strange (multi-strange) particles freezeout separately due to different reaction cross-sections. While the freezeout volume and transverse flow velocity are mass dependent which decrease with the rest mass of the particles. The present work reveals the scenario of double kinetic freezeout in collisions at STAR and ALICE Collaborations. Furthermore, the kinetic freezeout temperature and freezeout volume are larger in central collisions than the peripheral collisions and they decrease from central to periphery. However the transverse flow velocity remains almost unchanged from central to peripheral collisions.

Five-day exposure of clary sage (Salvia sclarea) to 100 μM cadmium (Cd) in hydroponics was sufficient to increase Cd concentrations significantly in roots and aboveground parts and affect negatively whole plant levels of calcium (Ca) and magnesium (Mg), since Cd competes for Ca channels, while reduced Mg concentrations are associated with increased Cd tolerance. Total zinc (Zn), copper (Cu), and iron (Fe) uptake increased but their translocation to the aboveground parts decreased possible due to translocation barriers. Despite the substantial levels of Cd in leaves, without any observed defects on chloroplast ultrastructure, an enhanced photosystem II (PSII) efficiency was observed, with a higher fraction of absorbed light energy to be directed to photochemistry (ΦPSΙΙ). The concomitant increase in the photoprotective mechanism of non-photochemical quenching of photosynthesis (NPQ) resulted in an important decrease in the dissipated non-regulated energy (ΦNO), modifying the homeostasis of reactive oxygen species (ROS), through a decreased singlet oxygen (1O2) formation. Thus, when clary sage was exposed to Cd for a short period, tolerance mechanisms were triggered, with PSII photochemistry to be regulated by NPQ in such a way that PSII efficiency to be enhanced. However, exposure to a combination of Cd and high light or for longer duration (8 days) to Cd alone, resulted in an inhibition of PSII functionality pointing out towards Cd toxicity. Thus, the rapid activation of PSII functionality at short time exposures and the inhibition at longer duration suggests a hormetic response and describes these effects in terms of “adaptive response” and “toxicity”, respectively.

To expand the application scope and increase the demand for non-crimp fabrics (NCFs) as a lightweight vehicle material, the delamination and thermal strain in NCF composites must be restricted. Accordingly, to simultaneously improve the interfacial bonding and thermal stability of the NCF composites, in this study the epoxy resin, in which SiO2 nanoparticles was modified by a silane coupling agent, were infused to the stacked NCFs and between the layers of NCFs through the vacuum-assisted resin infusion molding (VARIM) process.

Background: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the unknown risk of severity and mortality in COVID-19 patients with underlying kidney and liver diseases. Method: We retrieved data on the clinical features and primary composite end point of COVID-19 patients released from inception till 16^th of April 2020 from Medline and Embase. The data on two comorbidities, liver diseases and chronic kidney disease, present in COVID-19 were pooled and statistically analysed to explain the associated severity and mortality rate. Results: 142 abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and CKD were 3% (95%CI; 2%-3%) and 1% (95%CI; 1%-2%) respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) cases were severe with 17.65% mortality. While in CKD patients with COVID-19, 83.93% (47/56) severity and 53.33% (8/15) mortality were reported. Conclusion: This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases and CKD. This will allow for better clinical management and inform more stringent preventative measures for this group of patients.

The remaining capacity can only be measured with offline method. This brings great challenge for the online prediction of Li-ion battery’s RUL. A novel online prediction method for Li-ion battery’s RUL was proposed, which is based on multiple health indicators (HIs) and can be derived from the batteries’ historical operation data. Firstly, four indirect HIs were built according to the battery’s operation current, voltage and temperature data respectively. On that basis, a generalized regression neural network (GRNN) was developed to estimate the battery’s remaining capacity, and the non-linear autoregressive approach (NAR) was utilized to predict the battery’s RUL based on the estimated capacity value. Furthermore, to reduce the interference, twice wavelet denoising were performed with different thresholds. A case study is conducted with a NASA battery dataset to demonstrate the effectiveness of the method. The result shows that the proposed method can obtain Li-ion batteries’ RUL effectively.

Cooperative non-orthogonal multi access communication is a promising paradigm for the future wireless networks because of its advantages in terms of energy efficiency, wider coverage and interference mitigating. In this paper, we study the secrecy performance of a downlink cooperative non-orthogonal multi access (NOMA) communication system under the presence of an eavesdropper node. Smart node selection based on feed forward neural networks (FFNN) is proposed in order to improve the physical layer security (PLS) of a cooperative NOMA network. The selected cooperative relay node is employed to enhance the channel capacity of the legal users, where the selected cooperative jammer is employed to degrade the capacity of the wiretapped channel. Simulations of the secrecy performance metric namely the secrecy capacity ($C_S$) are presented and compared with the conventional technique based on fuzzy logic node selection technique. Based on our simulations and discussions the proposed technique outperforms the existing technique in term the of secrecy performance.

The early embryonic heart is a multi-layered tube consisting of (1) an outer myocardial tube; (2) an inner endocardial tube; and (3) an extracellular matrix layer interposed between myocardium and endocardium, called “cardiac jelly” (CJ). During the past decades, research on CJ has mainly focused on its molecular and cell biological aspects. This review focuses on the morphological and biomechanical aspects of CJ. Special attention is given to (1) the spatial distribution and fiber architecture of CJ; (2) the morphological dynamics of CJ during the cardiac cycle; and (3) the removal/remodeling of CJ during advanced heart looping stages, which leads to the formation of ventricular trabeculations and endocardial cushions. CJ acts as a hydraulic skeleton displaying striking structural and functional similarities with the mesoglea of jellyfish. CJ not only represents a filler substance, facilitating end-systolic occlusion of the embryonic heart lumen. Its elastic components antagonize the systolic deformations of the heart wall and thereby power the refilling phase of the ventricular tube. Non-uniform spatial distribution of CJ generates non-circular cross sections of the opened endocardial tube (initially elliptic, later deltoid), which seem to be advantageous for valveless pumping. Endocardial cushions arise from non-removed remnants of the original CJ.

Search for periodic signals from blazars has become widely discussed topic in recent years. This is because periodic signals bear imprints of the processes occurring near the innermost regions of blazars which are mostly inaccessible to our direct view. Such signals provide insights into various aspect of blazar studies including disk-jet connection, magnetic field configuration and, more importantly, strong gravity near the supermassive black holes and release of gravitational waves from the binary supermassvie black hole systems. In this work, we report detection of a periodic signal in the radio light curves of the blazar J1043+2408 spanning ~10.5 years. We performed multiple methods of time series analysis, namely, epoch folding, Lomb-Scargle periodogram, and discrete auto-correlation function. All three methods consistently reveal a repeating signal with a periodicity of ~563 days. To robustly account for the red-noise processes usually dominant in the blazar variability and other possible artifacts, a large number of Monte Carlo simulations were performed. This allowed us to estimate a high significance (99.9% local and 99.4% global) against possible spurious detection. As possible explanations, we discuss a number of scenarios including binary supermassive black hole system, Lense-Thirring precession, and jet swing and precession.

In this paper, the connections between quantum non-locality and permutation symmetries are explored. This includes two types of symmetries: permutation across a superposition and permutation of qubits in a quantum system. An algorithm is proposed for nding the separability class of a quantum state using a method based on factorizing an arbitrary multipartite state into possible partitions, cyclically permuting qubits of the vectors in a superposition to check which separability class it falls into and thereafter using a reduced density-matrix analysis of the system is proposed. For the case of mixed quantum states, conditions for separability are found in terms of the partial transposition of the density matrices of the quantum system. One of these conditions turns out to be the Partial Positive Transpose (PPT) condition. A graphical method for analyzing separability is also proposed. The concept of permutation of qubits is shown to be useful in dening a new entanglement measure in the `engle'.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

Compared to conventional allothermal gasification of solid fuels (e.g. biomass, charcoal, lignite etc.), plasma-assisted gasification offers an efficient method to apply energy into the gasification process to increase the flexibility of operation conditions and to increase the reaction kinetics. In particular, non-thermal plasmas (NTP) are promising, in which thermal equilibrium is not reached and electrons have substantially higher mean energy than gas molecules. Thus it is generally assumed that in NTP the supplied energy is utilized more efficiently for generating free radicals initiating gasification reactions than thermal plasma processes. In order to investigate this hypothesis, we compared purely thermal to non-thermal plasma assisted gasification of biomass in steam in a drop tube reactor at atmospheric pressure. The NTP was provided by means of gliding arcs between two electrodes aligned in the inlet steam flow. Electric power of about 1 kW was supplied using a high voltage generator operating at frequencies between 70 and 150 kHz and voltage amplitudes up to 10 kV. A laser-assisted optical method (Raman spectroscopy) was applied for measuring the gas temperature both in the conventionally heated steam and flow-down of the visible plasma filaments of the gliding arcs. Reaction yields and rates were evaluated using these measured gas temperatures. The first experimental results have shown that the non-thermal plasma not only promotes the carbon conversion of the fuel particles, but also accelerates the reaction kinetics. The carbon conversion is increased by nearly 10% using wood powder as the fuel. With charcoal powder more than 3% are converted into syngas.

Below T_CO=157 K the quasi-one-dimensional charge-transfer salt (TMTTF)_2SbF_6 undergoes a pronounced phase transition to a charge-ordered ground state. We have explored the non-linear and photoconductive behavior as a function of applied voltage, laser pulse energy and temperature. Besides a decay of the photoconductive signal in a double exponential fashion in the millisecond range, we discover current oscillations in the kHz range induced by the application of short laser pulses. While the resonance frequencies do not depend on voltage or laser intensity and vary only slightly with temperature, the amplitude changes linearly with the laser intensity and voltage. The findings are discussed and compared to comparable phenomena in other low-dimensional electron systems.

In recent years, the demand for efficient and accurate measurement techniques has surged across various industries, driving the development of non-invasive methods that leverage computer vision technology. This paper explores the principles and applications of non-invasive measurement techniques utilizing computer vision, emphasizing their ability to deliver precise measurements without the need for physical contact or specialized sensors. We delve into the underlying algorithms, including image processing, machine learning, and deep learning methods, that enable the extraction of dimensional data from visual inputs. Case studies across diverse fields such as manufacturing, healthcare, and logistics illustrate the effectiveness of these techniques in enhancing operational efficiency and reducing measurement errors. Furthermore, we discuss the challenges and limitations of implementing computer vision-based measurement systems, including the need for robust algorithms capable of functioning in varied environmental conditions. By highlighting the transformative potential of non-invasive measurement techniques, this paper aims to provide insights into future developments in computer vision and its role in advancing measurement practices across multiple sectors.

The inability to delineate a unified physical ontology that accounts simultaneously for the laws of special relativity and the results of quantum experiments has been a defining problem in physics for more than 100 years. This analysis addresses the problem by positing a novel mixed ontology composed of a “discrete” 4D spacetime and a physical, ultra-high dimensional (3 x N) “Planck Space.” Together, Planck Space and the three spatial dimensions of 4D spacetime form a tightly integrated ((3 x N) + 3) hyperspace (the “Dual Ontology”).Critically, the Dual Ontology’s structure replaces 1) the continuous, differentiable manifold of 4D spacetime with a discrete, background-independent 4D spacetime that is intrinsically curved and 2) mathematical spaces with a physical (3 x N) Planck Space. Moreover, the Dual Ontology is structurally and dynamically predicated on the one-to-one mapping and identity between the discrete spatial units that simultaneously form 4D spacetime and Planck Space. The one-to-one mapping and identity of the discrete spatial units support an integrated quantum dynamics based upon the dynamic evolution of single and N-body quantum states in 4D spacetime in full compliance with the laws of special relativity and the instantaneous collapse of all quantum states in an ontic Planck Space, where special and general relativity and more generally, 4D spacetime’s laws of physics, do not apply.

This article deals with an analytical approach to determining the stress state in trochoidal profiles under shear bending. The transverse shear stresses cannot be neglected, especially in the case of (space-saving) shafts with a low aspect ratio (l/d). In addition to bending stresses, the transverse shear stresses are a significant component of the principal stresses. The approach is based on a formulation of the elastic behavior of a non-circular-profiled shaft using complex stress functions, according to Muskhelishvili. In order to determine the shear stresses, similar to the torsion load case, a conformal mapping must be found that can completely transform the unit circle in the model plane to the profile area in the real plane. For simple and higher epiotrochoidal profiles, an exact and complete mapping was determined from the contour equation. The method was applied to such profiles as an example. Equations were derived to determine the maximum shear and bending stresses and the bending deformations. For practical applications, additional equations for the main stresses that are decisive in dimensioning were determined. Accompanying numerical investigations were carried out and compared with the analytical results, where a very good agreement was observed.

The West Pomeranian Anti-Crisis Package was an effective tool of the Voivodeship Executive Board of West Pomeranian self-government, which was used to combat and counteract and counteract the social and economic effects of the COVID-19 pandemic. The Anti-Crisis Package was prepared with a view to undertaking systemic, but also point-based measures in order to save and protect regional health care, entrepreneurs, the labour market, but also to use the existing social capital of non-governmental organizations involved in measures reducing the effects of the COVID-19 pandemic. The West Pomeranian Anti-Crisis Package, as evidenced not only by the financial outlays incurred, but also by the outcome of implementing measures achieved in 2020 and their continuation in 2021.

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed transcriptomic changes observed in epidermal PPARγ deficient mice (Pparg-/-epi). Gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis and cell survival. Single cell sequencing of Pparg-/-epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-epi and publicly available human and or mouse actinic keratoses (AK) and cutaneous squamous cell carcinomas (SCCs) revealed strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AK and SCC. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably. these changes are not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes while Ppard was highly expressed in myofibroblasts, suggesting a role for PPARδ in myofibroblast differentiation. In conclusion, these data indicate PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs.

The paper is focused on researching the behavior of heating companies in connection with current developments in the electricity market and flexibility in the context of market behavior. The work assesses the increase in profitability through the creation of a technical-economic model using an objective function with profit maximization. The paper objective is presented the procedure and methodology for creating a model using the basic scheme of production processes integrated into the system platform. The result of the work is a comparative analysis of modelled cases of implemented operation deployment according to a defined period and modelling modes in selected time series. The description of individual outputs demonstrates the economic advantage of using combinations of modes of combined electricity and heat production, and non-combined electricity and heat production, including the use of the heat suppression mode because of overproduction of electricity.

The shortage of physicians in rural communities contributes to increased mortality rates among Medicare beneficiaries. This increase in mortality risk is commonly due to diseases such as heart disease and cancer, including melanoma and non-melanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is considered the gold-standard treatment for NMSC tumors, however, due to a shortage of dermatologists and Mohs surgeons in rural areas, access to MMS is limited. In these areas, image guided superficial radiation therapy (IGSRT) serves as a viable option for the treatment of NMSC lesions, with fewer recurrences and 99% cure rates, which are comparable to MMS cure rates. IGSRT is performed in dermatology clinics with support from a multidisciplinary team, including radiation therapists, medical physicists, radiation oncologists, and dermatologists. As IGSRT is able to be performed by general dermatologists, Medicare beneficiaries in rural communities will have an increase in access to treatment options and a decrease in delayed skin cancer treatment.

Multilingual classrooms are becoming more common worldwide due to increasing mobility. Teaching foreign languages using the mother tongue in multilingual classrooms has become problematic; some of the significant concerns in Japanese language acquisition – such as the high contextuality of the language, vocabulary and kanji learning – make the direct teaching method confusing for many students, especially at the beginner and elementary levels. This article provides the preliminary results of a study carried out as a component of a more extensive empirical research project on instructional languages in classrooms teaching Japanese as a foreign language. It aims to gather, analyse and synthesise data from a survey conducted at a supranational level. The results of the first two sections of a questionnaire containing closed and open-ended questions were used for a quantitative analysis of the profile of Japanese language instructors with a focus on finding possible connections. The wide geographic distribution of the respondents (274 teachers from fifty-seven countries and regions) made it possible to collect data from a more representative sample and draw meaningful conclusions about the spread of multilingual classrooms that would be impossible in smaller-scale research. The study’s primary results show the proportion of multilingual classrooms among countries in different regions and across different educational stages, the distribution of Japanese language instructors in various educational stages depending on the highest level of formal education attained, and the proportion of part-time instructors working in different academic institutions.

The method for quantitative analysis is based on the direct measurement of the analyte using differential pulse voltammetry (DPV), exploiting its oxidation peak. Calibration curves are set up to evaluate the figures of merit of the analytical method (LOD, LOQ, linear range). The application of the sensor for the dosing of GA in real matrices is carried out by analyzing non-alcoholic and alcoholic beverages and comparing the results with those reported in the literature and with the content of total polyphenols determined by the Folin-Ciocalteu method. In all cases, concentrations of GA align with those previously found in the literature for the beverages examined. Moreover, the values are always lower than the total polyphenols content; this demonstrates the good selectivity of the sensor that can discriminate the target molecule from other polyphenols present.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

Terahertz tomography is a promising method among non-destructive inspection techniques to detect faults and defects in dielectric samples. Image quality recently significantly improved through the incorporation of a priori information and off-axis data. However, this improvement has come at the cost of increased measurement time. To aim toward industrial applications, it is therefore necessary to speed up the measurement by parallelizing the data acquisition employing multi-channel setups. In this work, we present two tomographic frequency-modulated continuous wave (FMCW) systems working at a bandwidth of 230-320 GHz, equipped with an eight-channel detector array, and compare their imaging results with a single-pixel setup. While in the first system, the additional channels are used exclusively to detect radiation refracted by the sample, the second system features an f-θ lens, focusing the beam at different positions on its flat focal plane, and thus utilizing the whole detector array directly. The usage of the f-θ lens in combination with a scanning mirror eliminates the necessity of the formerly used slow translation of a single-pixel transmitter. This opens up the potential for a significant increase in acquisition speed, in our case by a factor of four to five, respectively.

Perovskite solar cells have shown significant progress, but their commercialization remains hindered by lead-based toxicity. Many nontoxic perovskite-based solar cells have demonstrated potential such as Cs2AgBi0.75Sb0.25Br6, but their power-conversion efficiency is inadequate. To address this issue, some researchers are focusing on emerging acceptor-donor-acceptor'-donor-acceptor (A-DA'D-A) type non-fullerene acceptors (NFAs) for Cs2AgBi0.75Sb0.25Br6 to find effective electron transport layers for high-performance photovoltaic responses with low voltage drops. In this comparative study, four novel A-DA'D-A types NFAs such as BT-LIC, BT-BIC, BT-L4F, and were used as an electron transport layer (ETL) for the proposed devices, FTO/PEDOT: PSS/ Cs2AgBi0.75Sb0.25Br6/ETL/Au. Comprehensive simulations were conducted to optimize the devices. The simulations showed that all optimized devices exhibit photovoltaic responses, with the BT-BIC device having the highest power conversion efficiency (13.2%) and the BT-LIC device having the lowest (6.8%). The BT-BIC as ETL provides fewer interfacial traps and better band alignment, enabling greater open-circuit voltage for efficient photovoltaic responses.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

This mini-review deals with some non-starter lactic acid bacteria (NSLAB) species with a controversial nature known to be both human and animal pathogens but also health-promoting and probiotic. The focus is put on Lactococcus garvieae, two Streptococcus species (Str. uberis and Str. parauberis), four Weissella species (W. hellenica, W. confusa, W. paramesenteroides and W. cibaria) and Mammalicoccus sciuri which worldwide are often found within the microbiotas of different kinds of cheese, mainly traditional artisanal ones made from raw milk and/or relying on environmental bacteria for their ripening. Based on literature data, their virulence and health-promoting effects are examined, and some of the mechanisms of these actions are investigated. Additionally, their possible roles in cheese ripening are also discussed. The analysis so far showed that, in general, the pathogenic and the beneficial strains, despite belonging to the same species, show pretty different genetic constitutions. Yet, when the safety of a given strain is assessed, genomic analysis on its own is not enough, and a polyphasic approach is needed including additional physiological and functional tests.

Coffee processing generates a huge amount of waste which contains many natural products. Here, we report the discovery of a panel novel cell-penetrating and metal-ion binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and database search, we showed that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif but without a chitin-binding domain. NMR determination of cC1a revealed a compact structure that confers it resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis revealed that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement like ginsentide precursors. Molecular modeling together with experimental validation revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, and which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have potential to target intracellular proteins.

Regular regimes of oil and oil products pipelines are studied. The problem is to develop an algorithm of effective pipeline system control that ensures the fulfillment of specified boundary conditions at the system boundaries. The product is pumped in batches, the flow is characterized by a change in temperature and pressure flow parameters over time. The developed solution method uses the principle of decomposition in the sense that each computational iteration is im-plemented in 3 stages, in three nested loops. The inner cycle is connected with the material bal-ance relations, at the next cycle the flow equations are introduced and the fulfillment of the 2nd Kirchhoff's law is monitored. If the flow process is significantly affected by temperature, then an external cycle is also implemented, correcting the solution so that the energy conservation equa-tion is satisfied. In the calculation procedure, some computational difficulties may arise, which consist in choosing an appropriate optimization method. On a specific example, the possibility of using various library programs to solve the problem was checked. The developed method is suita-ble for the analysis of systems of arbitrary topology. Since the method is not time-consuming, it can be recommended for online control of oil and oil products supply systems. The paper opens a new direction in the theory of hydraulic circuits. It uses both traditional methods of continuum mechanics and stochastic models.

The present study evaluates ratcheting response of notched and press-fitted Al 7075-T6 specimens under stress-controlled asymmetric cycles. The degree of interference fit (DIF) directly influenced progressive plastic strain magnitude and rate at notch root region. Local ratcheting at the hole-pin interference region was analyzed by means of two kinematic hardening rules of Ahmadzadeh-Varvani (A-V) and Chaboche coupled with the Neuber rule. Ratcheting strains at notch root of aluminum samples with DIF=0 (non-press-fitting samples) were measured to be highest in magnitude. For the press-fitted samples, however ratcheting strains dropped noticeably as DIF increased from 1% to 2%. Press-fitted samples plastically deformed the perimeter edge of notches and improved materials locally at the notch edge, resulting in a better resistance against ratcheting progress. Local ratcheting at different distances of 0.5, 1.3 and 3.0 mm from the notch root were evaluated for both pinned and unpinned samples through the hardening rules and compared with those of measured values. The predicted ratcheting curves by means of the A-V and Chaboche hardening rules closely agreed with experimental data and respectively positioned above and below the measured data.

This study aimed to explore the feasibility of using airborne acoustic emission in laser beam butt welding for the development of an automated classification system based on neural networks. The focus was on monitoring the formation of joint gaps during the welding process. To simulate various sizes of butt joint gaps, controlled welding experiments were conducted, and the emitted acoustic signals were captured using audible to ultrasonic microphones. To implement an automated monitoring system, a method based on short-time Fourier transformation was developed to extract audio features, and a convolutional neural network architecture with data augmentation was utilized. The results demonstrated that this non-destructive and non-invasive approach was highly effective in detecting joint gap formations, achieving an accuracy of 98%. Furthermore, the system exhibited promising potential for low latency monitoring of the welding process. The classification accuracy for various gap sizes reached up to 90%, providing valuable insights for characterizing and categorizing joint gaps accurately. Additionally, increasing the quantity of training data with quality annotations could potentially improve the classifier model's performance further. This suggests that there is room for future enhancements in the study.

I show how the quantum paradoxes occurring when we adopt a standard realist framework (or a framework in which the collapse implies a physical change of the state of the system) vanish if we abandon the idea that a measurement is related (directly or indirectly) to a physical change of state. In Convivial Solipsism, similarly to Everett’s interpretation, there is no collapse of the wave function. But contrary to Everett’s interpretation, there is only one world. This allows also to get rid of any non-locality and to provide a solution to the Wigner’s friend problem and its more recent versions.

Patients with pT1 high-grade (HG) bladder cancer (BC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resections (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. Our aim was to validate ROL system on a large mono-institutional prospective series of primary urothelial carcinomas. From 2016 to 2020, we adopted ROL for all patients with pT1 HG BC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1HGBC were analyzed. Median age was 74 years, with male predominance (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%) and 131 ROL2 (59%). At a median follow up of 26.9 months (IQR 13.8-40.6), we registered 80 recurrences and 40 progressions. ROL was a significant predictor of tumor progression at both univariable (HR 3.53; CI 95% 1.56 – 7.99; p&lt;0.01) and multivariable (HR 2.90; CI 95% 1.25 – 6.75; p=0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed correlation with both PFS (p=0.0012) and RFS (p=0.0167). Our results confirmed the strong predictive value of ROL for progression on a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG BC, and improving risk tables for urological decision making.

Theories on life’s origin generally acknowledge the advantage of a semi-permeable vesicle (protocell) for enhancing the chemical reaction-diffusion processes involved in abiogenesis. However, more and more evidence indicates that the origin of life concerned the photo-chemical dissipative structuring of the fundamental molecules under UV-C light. In this paper, we analyze the Mie UV scattering properties of such a vesicle made from long chain fatty acids. We find that the vesicle could have provided early life with a shield from the faint, but dangerous, hard UV-C ionizing light (180-210 nm) that probably bathed Earth’s surface from before the origin of life and until perhaps 1,500 million years after, until the formation of a protective ozone layer as a result of the evolution of oxygenic photosynthesis.

This paper focuses on the so-called proportional intensity-based software reliability models (PI-SRMs), which are extensions of the common non homogeneous Poisson process (NHPP)-based SRMs, and describe the probabilistic behavior of software fault-detection process by incorporating the time-dependent software metrics data observed in the development process. Especially we generalize the seminal PI-SRM in Rinsaka, Shibata and Dohi (2006) by introducing eleven well-known fault-detection time distributions, and investigate their goodness-of-fit and predictive performances. In numerical illustrations with four data sets collected in real software development projects, we utilize the maximum likelihood estimation to estimate model parameters with three time-dependent covariates; test execution time, failure identification work and computer time-failure identification, and examine the performances of our PI SRMs in comparison with the existing NHPP-based SRMs without covariates. It is shown that our PI-STMs could give better goodness-of-fit and predictive performances in many cases.

In this review, we trace the evolution of the quantum spin-wave theory treating non-collinear spin configurations. Non-collinear spin configurations are consequences of the frustration created by competing interactions. They include simple chiral magnets due to competing nearest-neighbor (NN) and next-NN interactions and systems with geometry frustration such as the triangular antiferromagnet and the Kagomé lattice. We review here spin-wave results of such systems and also systems with the Dzyaloshinskii-Moriya interaction. Accent is put on these non-collinear ground states which have to be calculated before applying any spin-wave theory to determine the spectrum of the elementary excitations from the ground states. We mostly show results from a self-consistent Green’function theory to calculate the spin-wave spectrum and the layer magnetizations at finite T in two and three dimensions as well as in thin films with surface effects. Some new unpublished results are also included. Analytical details and the validity of the method are shown and discussed.

: In the last years, materializations of neuromorphic circuits based on nanophotonic arrangements have been proposed, which contain complete optical circuits, laser, photodetectors, photonic crystals, optical fibers, flat waveguides, and other passive optical elements of nanostructured materials, which eliminate the time of simultaneous processing of big groups of data, taking advantage of the quantum perspective and thus highly increasing the potentials of contemporary intelligent computational systems. This article is an effort to record and study the research that has been conducted concerning the methods of development and materialization of neuromorphic circuits of Neural Networks of nanophotonic arrangements. In particular, an investigative study of the methods of developing nanophotonic neuromorphic processors, their originality in neuronic architectural structure, their training methods and their optimization has been realized along with the study of special issues such as optical activation functions and cost functions.

This paper presents an exact solution to the Timoshenko beam theory (TBT) for first-order analysis, second-order analysis, and stability. The TBT covers cases associated with small deflections based on shear deformation considerations, whereas the Euler–Bernoulli beam theory (EBBT) neglects shear deformations. Thus, the Euler–Bernoulli beam is a special case of the Timoshenko beam. The moment-curvature relationship is one of the governing equations of the EBBT, and closed-form expressions of efforts and deformations are available in the literature. However, neither an equivalent to the moment-curvature relationship of EBBT nor closed-form expressions of efforts and deformations can be found in the TBT. In this paper, a moment-shear force-curvature relationship, the equivalent in TBT of the moment-curvature relationship of EBBT, was presented. Based on this relationship, first-order and second-order analyses were conducted, and closed-form expressions of efforts and deformations were derived for various load cases. Furthermore, beam stability was analyzed and buckling loads were calculated. Finally, first-order and second-order element stiffness matrices were determined.

In this paper, a complete tool for real-time detection of atypical energy behaviors of airplanes is presented. The methodology extends in real time an existing offline process using Dubins trajectories as a predictor of the remaining distance to the runway threshold. Two major contributions are presented in this paper. First, a real-time measure of the aircraft energy behaviour is defined, indicating whether the aircraft is in good condition to intercept the extended runway centreline from its current position. Secondly, a 2D trajectory suggestion is given, allowing safe management of the approach path according to atypical criteria of historical data. Finally, this document proposes a comprehensive tool for air traffic controllers, which is a major step forward in understanding, becoming aware of and resolving critical situations that could lead to accidents.

Eating disorder (ED) symptoms often co-occur with nonsuicidal self-injury (NSSI). This comorbidity is consistent with evidence that trait negative urgency increases risk for both of these phenomena. We previously found that impaired late-stage negative emotional response inhibition (i.e., negative emotional action termination or NEAT) might represent a neurocognitive mechanism for heightened negative urgency among people with NSSI history. The current study evaluated whether relations between negative urgency and ED symptoms similarly reflect deficits in this neurocognitive process. One hundred and five community adults completed an assessment of ED symptoms, negative urgency, and an emotional response inhibition task. Results indicated that, contrary to predictions, negative urgency and NEAT contributed independent variance to the prediction of ED symptoms, while controlling for demographic covariates and NSSI history. Worse NEAT was also uniquely associated with restrictive eating, after accounting for negative urgency. Our findings suggest that difficulty inhibiting ongoing motor responses triggered by negative emotional reactions (i.e., NEAT) may be a shared neurocognitive characteristic of ED symptoms and NSSI. However, negative urgency and NEAT dysfunction capture separate variance in the prediction of ED-related cognitions and behaviors, distinct from the pattern of results we previously observed in NSSI.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

E-commerce businesses employ recommender models to assist in identifying a personalized set of products for each visitor. To accurately assess the recommendations’ influence on customer clicks and buys, three target areas—customer behavior, data collection, user-interface —will be explored for possible sources of erroneous data. Varied customer behavior misrepresents the recommendations’ true influence on a customer due to the presence of B2B interactions and outlier customers. Non-parametric statistical procedures for outlier removal are delineated and other strategies are investigated to account for the effect of a large percentage of new customers or high bounce rates. Subsequently, in data collection we identify probable misleading interactions in the raw data, propose a robust method of tracking unique visitors, and accurately attributing the buy influence for combo products. Lastly, user-interface issues discuss the possible problems caused due to the recommendation widget’s positioning on the e-commerce website and the stringent conditions that should be imposed when utilizing data from the product listing page. This collective methodology results in an exact and valid estimation of the customer’s interactions influenced by the recommendation model in the context of standard industry metrics such as Click-through rates, Buy-through rates, and Conversion revenue.

Biomimicry in additive manufacturing often refers to topology optimization and the use of lattice structures, due to the organic shape of the topology-optimized designs, and the lattices often looking similar to many light-weight structures found in nature such as trabecular bone, wood, sponges, coral, to name a few. Real biomimetic design however involves the use of design principles taken in some way from natural systems. In this work we use a methodology whereby high resolution 3D analysis of a natural material with desirable properties is “reverse-engineered” and the design tested for the purpose. This allows more accurate replication of the desired properties, and adaption of the design parameters to the material used for production (which usually differs from the biological material). One such example is the impact-protective natural design of the glyptodont body armour. In this paper we report on the production of body armour models in metal (Ti4Al4V) and analyze the resulting mechanical properties, assessing their potential for impact protective applications. This is the first biomimetic study using metal additive manufacturing to date.

The most common liver disorder nowadays is non-alcoholic fatty liver disease(NAFLD) and it is a progressive disease that rises in severity from steatosis to nonalcoholic steatohepatitis(NASH), fibrosis and cirrhosis to increase risk of developing hepatocellular carcinoma. It is a cause of great concern as there is an estimated seventy million Americans who are currently affected by NAFLD, and this is expected to only increase because of its association with obesity and diabetes and also a lack of therapies to keep its development and progression in check. In this particular study we performed a gene set enrichment analysis(GSEA) of differentially expressed genes in a green tea against methionine-choline deficient diet in high-fat patients in the development of non-alcoholic fatty liver disease(NAFLD). The downregulated genes were used to perform an enrichment analysis and in the ARCHS4 TFs Coexpression database the most significant gene was found to be KLF5_human_tf_ARCHS4_coexpression. In the ARCHS4 Kinases Coexpression pathway database STYK1_human_kinase_ARCHS4 Coexpression was found to be the most significant gene. And finally for the upregulated genes a similar enrichment analysis was performed and in the humancy database γ-linolenate biosynthesis_Homo sapiens_PWY-6000 gene was discovered to be the most significant one. This study has used bioinformatics tools and the Enrichr software to perform a comparative analysis of differentially expressed gene sets for high-fat patients having a diet consisting of green tea against a methionine-choline deficient diet. Green tea is known to contain several antioxidants and polyphenols which provide protection against many liver diseases such as non-alcoholic fatty liver disease(NAFLD). The present study simply tries to build awareness of this to the general public and allow them to learn more about certain diets which have protective effects against liver diseases. Hopefully by implementing these in their daily lifestyles the public can gain some form of protection against these types of liver disorders.

Meixner's historical remark in 1969 "... it can be shown that the concept of entropy in the absence of equilibrium is in fact not only questionable but that it cannot even be defined...." is investigated from today's insight. Several statements --such as the three laws of phenomenological thermodynamics, the embedding theorem and the adiabatical uniqueness-- are used to get rid of non-equilibrium entropy as a primitive concept. In this framework, Clausius inequality of open systems can be derived by use of the defining inequalities which establish the non-equilibrium quantities contact temperature and non-equilibrium molar entropy which allow to describe the interaction between the Schottky system and its controlling equilibrium environment.

In this article, the linear non-equilibrium thermodynamic approach is used to analyze the energy regularities of the interior permanent magnet synchronous motor (IPMSM) taking into account iron losses. The IPMSM is considered a linear power converter (PC) that is multiple linearized at operating points with given angular velocity and load torque. A universal description of such a PC by a system of dimensionless parameters and characteristics made it possible to analyze the perfection of energy conversion in the object. For IPMSM, taking into account iron losses, a mathematical model of the corresponding PC has been built, and an algorithm and research program have been developed, which is valid in a wide range of machine speed regulations. This allows you to obtain the efficiency maps for IPMSM and choose the optimal points of PC operation according to the maximum efficiency criteria. The results of the studies demonstrate the effectiveness of the proposed method for determining the optimal reference of the components d and q of the armature current for both the MTPA strategy at motor speed adjusting below the nominal value and for the FW strategy at its adjusting above the nominal value.

Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are highly prevalent and a significant cause of morbidity. Image-guided su-perficial radiation therapy (IGSRT) uses integrated high-resolution dermal ultrasound to improve lesion visualization, but it is unknown whether efficacy varies by histology. This large retro-spective cohort study was conducted to determine the effect of tumor histology on freedom from recurrence in 20,069 biopsy-proven NMSC lesions treated with IGSRT, including 9,928 BCC (49.5%), 5,294 SCC (26.4%), 4,648 SCCIS (23.2%), and 199 lesions with ≥2 NMSCs (1.0%). Freedom from recurrence at 2, 4, and 6 years was 99.60%, 99.45%, and 99.45% in BCC; 99.58%, 99.49%, and 99.49% in SCC; and 99.96%, 99.80%, and 99.80% in SCCIS. Freedom from recurrence at 2, 4, and 6 years following IGSRT did not differ significantly comparing BCC vs. non-BCC or SCC vs. non-SCC but were slightly lower among SCCIS vs. non-SCCIS (p = 0.002). There were no significant differences in freedom from recurrence when stratifying lesions by histologic subtype. This study demonstrates that there is no significant effect of histology on freedom from recurrence in IGSRT-treated NMSC except in SSCIS. These findings support IGSRT as a first-line therapeutic option for NMSC regardless of histology.

Previous research has indicated that ultra-high pressure (UHP) technology is useful in speeding up the extraction process of cold brew (CB) coffee. However, the impact of different degrees of roasting on UHP CB coffee is still unclear. Therefore, this study aimed to investigate the effects of three different degrees of roasting (light, medium, and dark) on the physicochemical and flavor characteristics of UHP CB coffee. The results of this study showed that most physicochemical characteristics of UHP coffee were similar to those of conventional CB coffee, regardless of the degree of roasting. However, the majority of physicochemical characteristics, non-volatile components, and sensory evaluation significantly increased with an increase in roasting degree. The HS-SPME-GC/MS analysis showed that most volatile components, such as pyrazines, furans (except furfural), esters, pyrrole, pyridine, and most aldehydes, increased from light to dark roasting, and this was significantly evident in CB coffee compared with UHP. The content of volatile components in UHP coffee was significantly (P<0.05) higher than that in CB coffee at the same degree of roasting, especially with dark roasting. The combination of orthogonal partial least squares-discriminant analysis (OPLS-DA) and principal component analysis (PCA) indicated that the distance between coffee samples at different degrees of roasting under CB coffee was greater than that under UHP coffee. However, the distance between these two extraction methods at medium roasting was evidently closer than that at light and dark roasting. Moreover, 15 representative differential compounds, such as were Hazelnut pyrazine, linalool, butane-2,3-dione, 3- methylbutanal found by the calculation of odor-active values (OAVs) indicating the main contributing compounds to odor. Overall, the effect of roasting degrees on UHP coffee was less than that on CB coffee, which was consistent with the results of physicochemical characteristics, volatile components, and sensory evaluation.

High-frequency circuit performance is significantly impacted by impedance variations, particularly within the low-resistance regime. Traditional Ohm’s Law based modeling approaches often fail to accurately predict circuit behavior in these conditions, leading to design inaccuracies and potential system failures. The Standard Ohm’s Law based model’s prediction of infinite current as resistance approaches zero is physically unrealistic and hinders its application in practical scenarios. Despite the recognition of these limitations, existing models have not comprehensively addressed the complex impedance behavior observed in high-frequency circuits. To overcome these challenges, this paper introduces a modified version of the Ohm’s Law incorporating an exponential correction term. The Modified Ohm’s Law’s accuracy was evaluated through simulated experiments across a wide frequency range (1kHz to 1GHz) using various electronic components. The findings demonstrate the superior performance of the modified model in predicting currents under low-resistance and high-current conditions compared to the Standard Ohm’s Law model. By providing finite and accurate current values, the proposed model effectively mitigates the unrealistic infinite current predictions of the standard approach. The enhanced predictive capabilities of the Modified Ohm’s Law hold significant implications for high-frequency circuit design and analysis. Its application can lead to improved performance and reliability in power electronics, telecommunications, and other high-frequency systems. By incorporating non-linear impedance behavior, the model offers a more accurate representation of real-world circuit conditions. Future research should focus on refining the exponential term’s parameters to optimize the model's accuracy across a broader range of applications. Additionally, real-time implementation and hardware validation are essential to assess the model's practical utility in complex circuit environments.

Several cities are experiencing an increase in flood hazard and exposure, and consequentially in flood risk, attributable to the coupled effect of climate change and urbanization. Non-structural protection strategies demonstrate significant potential in the short term for mitigating hydraulic risk in urban areas, particularly where the implementation of structural measures is impeded by a complex urban environment. This work proposes an Early Warning System (EWS) for fluvial floods developed for the city of Palermo (Italy). It is based on the preliminary definition of po-tential Flood Event Scenarios (FESs) as a function of typical potential precursors. Each FES pre-dicts first points of flooding, flood areas and water depths, also providing specific hazard maps for people, vehicles, and buildings. The EWS uses rainfall depth-duration thresholds to assess the expected hydrograph as a function of rainfall forecasts and the water stage observed in real time at an upstream section of the river crossing the city. This last also allows for estimating the ante-cedent wetness conditions. Based on this information, the EWS retrieves an expected FES from a pre-built library with a preannouncement time up to 36 h. The EWS is here successfully tested on a historical flood event.

In our study, we investigated the prognostic significance of hematological markers—NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width - Coefficient of Variation)—in 117 glioblastoma patients. Data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan-Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in NLR, PLR, and RDW-CV across different treatment stages. NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p=0.007, η2p=0.06; PLR: p=0.001, η2p=0.23), while RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p &lt; 0.001, η2p=0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR=1.03, p=0.029; RDW-CV at progression: HR=1.14, p=0.004). We proposed specific marker cutoffs that demonstrated significant associations with survival outcomes when applied to Kaplan-Meier survival curves (NLR at 2nd line &lt; 5: p&lt;0.017; RDW-CV at progression &lt; 15: p=0.007). Elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Background: The scaffold protein tyrosine kinase substrate 4 (TKS4) undergoes tyrosine phos-phorylation by the epidermal growth factor receptor (EGFR) pathway via Src kinase. The TKS4 deficiency in humans is responsible for the manifestation of a genetic disorder known as Frank-Ter Haar syndrome (FTHS). Based on our earlier investigation, the absence of TKS4 triggers migration, invasion, and epithelial-mesenchymal transition (EMT)-like phenomena while concurrently suppressing cell proliferation in HCT116 colorectal carcinoma cells. This indicates that TKS4 may play a unique role in the progression of cancer. In this study, we demonstrated that the enhancer of zeste homolog 2 (EZH2) and the histone methyltransferase of polycomb repressive complex 2 (PRC2) are involved in the migration, invasion, and EMT-like changes in TKS4-deficient cells (KO). EZH2 is responsible for the maintenance of the trimethylated lysine 27 on histone H3 (H3K27me3). Methods: We performed the transcriptome sequencing, chromatin immunoprecipitation, protein and RNA quantitative studies, cell mobility, invasion, and proliferation studies combined with/without EZH2 activity inhibitor 3-deazanoplanocine (DZNep) Results: We detected an elevation of global H3K27me3 levels in the TKS4 KO cells, which could be reduced with treatment with DZNep, an EZH2 inhibitor. Inhibition of EZH2 activity reversed the phenotypic effects of the knockout of TKS4, reducing the migration speed and wound healing capacity of the cells as well as decreasing the invasion capacity, while the decrease in cell prolif-eration became stronger. In addition, inhibition of EZH2 activity also reversed most epithelial and mesenchymal markers. We investigated the wider impact of TKS4 deletion on the gene expression profile of colorectal cancer cells using transcriptome sequencing of wild-type and TKS4 knockout cells, particularly before and after treatment with DZNep. Additionally, we observed changes in the expression of several protein-coding genes and long non-coding RNAs that showed a recovery in expression levels following EZH2 inhibition. Conclusions: Our results indicate that the removal of TKS4 causes a notable disruption in the gene expression pattern, leading to the disruption of several signal transduction pathways. Inhibiting the activity of EZH2 can restore most of these transcriptomics and phenotypic effects.

The exploration of three-dimensional (3D) DNA structures marks a pivotal shift in genomics, offering unprecedented insights into the intricacies of cellular regulation, disease genesis, and the potential for novel diagnostic and therapeutic strategies. This study delves into the dynamic nature of 3D genome organization, investigating how these structures influence cellular functions in response to environmental changes and over time. Through a combination of real-time imaging and advanced computational models, we aim to unravel the complex interplay between 3D DNA structures, non-coding RNAs, and chromatin organization, and their collective impact on gene expression and cellular differentiation. A significant focus is placed on understanding the role of 3D DNA structures in the development and progression of genetic disorders. By employing comprehensive genomic and epigenomic profiling, this research seeks to identify structural aberrations linked to diseases, paving the way for the development of targeted diagnostics and therapies. Additionally, the study explores the potential of genome editing technologies, such as CRISPR-Cas systems, in correcting these structural abnormalities, while also addressing the ethical, legal, and social implications (ELSI) of such interventions. Integrating data from various genomic analyses, we propose the development of advanced computational models to predict the effects of 3D DNA structures on gene expression and cellular function. This integrative approach not only promises to enhance our understanding of genomic regulation but also sets the stage for groundbreaking advances in genomics-based diagnostics and therapeutics. The findings of this study have the potential to revolutionize our approach to treating genetic disorders, offering a new frontier in personalized medicine.

This article discusses how, in today’s world of disruptive and dramatic social change (DSC), non-sports related coaching, which includes a wide range of services such as life coaching, career coaching, executive coaching, and team coaching, can inadvertently fuel undesirable social dynamics. There is little or no awareness of this risk among coaches and coachees. The global, fast-growing, multi-billion-dollar industry aimed at supporting people and organisations to perform better and increase wellbeing while managing and adapting to change has been developed with limited sociological input. The article is based on 15 years of social constructionist-informed reflective practice by a sociologist-turned-coach, and uses a multi-layered autoethnographic account to argue for a sociologically informed paradigm shift in coaching, as well as relevant sociological knowledge and social and human sciences research methodology in coaches’ education. It presents the rationale and key features of a new coaching approach that places DSC-relevant sociological concepts at the heart of the coaching process, helps people develop psycho-sociological awareness, and uses a learning-to-develop through research design. A new definition of coaching to address DSC is derived. Coaching practitioners will find DSC-relevant sociological concepts, critical reflections, coaching questions, and procedures to expand coaching effectiveness. Interdisciplinary research topics combining coaching sociology and coaching psychology are suggested.

This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) among non-carbapenemase producing (NCP) and carbapenemase producing (CP) Escherichia coli and Klebsiella pneumoniae. As mutations for ertapenem resistance establish the genetic background for non-carbapenemase meropenem resistance, there is a great need for antibiotic stewards and researchers to understand the determinants of a strain’s propensity to become resistant. Whole genome sequencing was conducted on clinical carbapenem-resistant E. coli (CREC) and K. pneumoniae (CRKP) across 5 hospitals in San Antonio, U.S. from 2012-2018. The majority of carbapenem resistant Enterobacterales (CRE) were NCP (54%; 41/76). The blaCTX-M was found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Antimicrobial susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p &lt; 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p &lt; 0.001). ErMs strains carrying blaCTX-M, had approximately 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem and meropenem susceptible (EsMs) isolates (3.7 v. 0.9, p &lt; 0.001). ErMs also carried more mobile genetic elements (MGEs), particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p &lt; 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. To thwart potential mismanagement of CRE infected patients, future efforts should focus on understanding the mechanism(s) underlying OmpC loss, developing rapid methods to detect blaCTX-M copy number variants, and targeted antimicrobials for NCPE and ErMs strains.

In the evolving landscape of Portfolio Management (PM), the fusion of advanced machine 1 learning techniques with traditional financial methodologies has opened new avenues for innovation. 2 Our study introduces a cutting-edge model combining Deep Reinforcement Learning (DRL) with 3 a Non-stationary Transformer architecture. This model is specifically designed to decode complex 4 patterns in financial time series data, enhancing portfolio management strategies with deeper insights 5 and robustness. It effectively tackles the challenges of data heterogeneity and market uncertainty, 6 key obstacles in PM. Our approach integrates key macroeconomic indicators and targeted news 7 sentiment analysis into its framework, capturing a comprehensive picture of market dynamics. This 8 amalgamation of varied data types addresses the multifaceted nature of financial markets, enhancing 9 the model’s ability to navigate through the complexities of asset management. Rigorous testing 10 demonstrates the model’s efficacy, highlighting the benefits of blending diverse data sources and 11 sophisticated algorithmic approaches in mastering the nuances of PM.12

The goal of this study was to evaluate the feasibility of methods based on the Worldwide Harmonized Light-Duty Vehicles Test Procedure Brake Cycle to measure brake wear particle emissions for currently used electrified vehicles. Our results indicated that reducing brake friction work reduced brake wear particle emissions. Commercially available, plug-in hybrid electric vehicles reduced emissions by 85% for PM₁₀, 78% for PM_2.5, and 87% for particle numbers (PNs) compared to vehicles with internal combustion engines. Brake friction work showed a linear relationship with PM₁₀ and PM_2.5. Nanoparticle PM emissions tended to increase slightly with regenerative braking, but did not contribute significantly to the overall PM percentage. the emission events of high number concentrations of nuclei mode particles (<20 nm in diameter) in electric vehicle brake assemblies designed for regenerative braking use under high-temperature, high-load braking conditions with full-friction brakes. The nuclei mode particles amplified the PN emissions and led to a high variability. In strict regulatory certification tests, where measurement reproducibility and stability are required, it is appropriate to measure PNs under brake conditions appropriate for the actual use of electric vehicles rather than under full-friction brake conditions or to remove particle measurements smaller than 20 nm.

This study investigated co-constructed research poetry as a way to understand the lived experiences of people affected by rarer dementia and as a means to use poetry to convey those experiences to healthcare professionals. Using mixed-methods, 71 people living with rarer dementia and care-partners (stakeholders) contributed to co-constructing 27 poems with professional poets; stakeholders’ verbatim words were analysed with descriptive qualitative analysis. Stakeholders were also surveyed and interviewed about their participation. Healthcare professionals (n = 93) were surveyed to elicit their responses to learning through poetry and its acceptability as a learning tool. Poems conveyed a shared narrative of different aspects of lived experience, often owing to atypical symptoms, misunderstandings by professionals, lack of support pathways, and a continuous struggle to adapt. Stakeholder surveys indicated it was a valuable experience to both co-create and respond to the poems, whilst group interviews revealed people’s experiences of the research poetry were characterised by reflection on lived experience, curiosity and exploration. Healthcare professionals’ responses reinforced the poetry’s capacity to stimulate cognitive and affective learning specific to rare dementia support and prompt both empathy and critical thinking in practice. As the largest poetry-based study that we are aware of, this novel accessible approach of creating group poems yielded substantial information about the experiences and needs of those affected by rarer dementia and how poetry can contribute to healthcare education and training.

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 the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. In this review, we discuss the role of IL-1β in NSCLC, its involvement in inflammatory pathways, and explore its potential role in the treatment of NSCLC.

People must have particular personality traits and social resources, also known as health literacy, in order to access, comprehend, and use information to make decisions about their health. Patients' ability to engage in complex disease management and self-care is strongly related to their level of health literacy. It can help us stay healthy by preventing illness and effectively managing existing illnesses. People with low health literacy (LHL) may find it difficult to manage their condition and prevent illness, which may lead to increased use of healthcare services. Furthermore, LHL is associated with increased hospitalizations, increased use of emergency care, decreased use of preventative services, and a worsened ability to understand labels and health messages, a worsened state of health, higher mortality, and more expensive medical care.

: Seasonal influenza (a.k.a flu) is responsible for considerable morbidity and mortality across the globe. The three recognized pathogens that cause epidemics during the winter season are influenza A, B and C. The influenza virus is particularly dangerous due to its mutability. Vaccines are an effective tool in preventing seasonal influenza, and their formulas are updated yearly according to WHO recommendations. However, in order to facilitate decision-making in the planning of the intervention, policymakers need information on the projected costs and quantities related to introducing the influenza vaccine, in order to help governments obtain an optimal allocation of the vaccine each year. In this paper, an approach based on a Controlled Elitism Non-Dominated Sorting Genetic Algorithm (CENSGA) model is introduced to optimize the allocation of influenza vaccination. A bi-objective model is formulated to control the infection volume, and reduce the unit cost of the vaccination campaign. An SIR (Susceptible–Infected–Recovered) model is employed for representing a potential epidemic. The model constraints are based on the epidemiological model, time management, and vaccine quantity. A two-phase optimization process is proposed: guardian control followed by contingent controls. The proposed approach is an evolutionary metaheuristic multi-objective optimization algorithm with a local search procedure based on a hash table. Moreover, in order to optimize the scheduling of a set of policies over a predetermined time to form a complete campaign, an extended CENSGA is introduced with a variable-length chromosome (VLC) along with mutation and crossover operations. To validate the applicability of the proposed CENSGA, it is compared with the classical Non-Dominated Sorting Genetic Algorithm (NSGA-II). The results are analyzed using graphical and statistical comparisons in terms of cardinality, convergence, distribution and spread quality metrics, illustrating that the proposed CENSGA is effective and useful for determining the optimal vaccination allocation campaigns.

Pericentromeric regions of chromosomes enriched in tandemly repeated satellite DNA although representing a significant part of eukaryotic genomes are still understudied mainly due to interdisciplinary knowledge gaps. Recent studies suggest their important role in genome regulation, karyotype stability and evolution. Thus, the idea of satellite DNA as a junk part of the genome was refuted. Integration of data about molecular composition, chromosome behaviour and details of in situ organization of pericentromeric regions is of great interest. The objective of this work was a cytogenetic analysis of the interactions of pericentromeric regions non-homologous chromosomes in mouse spermatocytes using immuno-FISH. We analysed two events: the associations between cerntomeric regions of X chromosome and autosomes, and associations between centromeric regions of autosomal bivalents forming chromocenters. We conclude that X chromosome form temporary synaptic associations with different autosomes in early meiotic prophase I which normally can be found at pachytene-diplotene without signs of pachytene arrest. These associations are formed between the satellite DNA-enriched centomeric regions of X chromosome and different autosomes but not involve the satellite-poor centromeric region of Y-chromosome. We suggest the mechanism of X chromosome competitive replacement from such associations during synaptic correction. We showed that centromeric region of the X chromosome remains free of γH2Ax-dependent chromatin inactivation, while Y chromosome is completely inactivated. This findings highlights the predominant role of associations between satellite DNA-enriched regions of different chromosomes including X. We assume that X-autosome temporary associations is a manifestation of an additional synaptic disorders checkpoint. These associations are normally corrected before the late diplotene. We revealed that the intense spreading conditions applied to the spermatocytes I nuclei did not lead to destruction of stretched chromatin fibers i.e. elongated chromocenters enriched in satellite DNA. Revealed by us tight associations between pericentromeric regions of different autosomal bivalents and X chromosome may represent the basis for repeat stability maintenance in autosomes an X chromosome. The consequences of our findings are discussed. We obtained the preparations of mouse spermatocytes nuclei in the meiotic prophase I using two approaches: standard and extremely intense surface spread techniques. Using immuno-FISH we visualized tandemly repeated mouse Major and Minor satellite DNA located in the pericentromeric regions of chromosomes and performed a morphological comparison of the standard- and intensely spreaded meiotic nuclei. Based on our results, we assume the remarkable strength of the chromocenter-mediated associations, “chromatin “bridges”, between different bivalents at the pachytene and diplotene stages. We have demonstrated that the chromocenter “bridges” between the centromeric ends of meiotic bivalents are enriched in both tandemly repeated Major and Minor satellite DNA. Association of centromeric regions of autosomal bivalents and X-chromosome but not with Y-chromosome correlates with the absence of Major and Minor satellites on Y-chromosome. We suggest that revealed tight associations between pericentromeric regions of bivalents may represent the network-like system providing dynamic stability of chromosomal territories, as well as add new data for the hypothesis of ectopic recombination in these regions which supports sequence homogeneity between non-homologous chromosomes and does not contradict the meiotic restrictions imposed by the crossing-over interference near centromeres. We conclude that nuclear architecture in meio-sis may play an essential role in contacts between the non-homologous chromosomes providing the specific characteristics of pericentromeric DNA.

In humans, age-associated degrading changes are observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psy-chological abilities, and memory. Cross talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, ge-nome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirali-ty, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging re-lated to irreversible PTMs SP has been associated with the nontrivial interplay between poor so-matic and mental health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet un-der-appreciated hallmark of aging.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

Vitamin C is an essential nutrient that must be obtained through the diet in adequate amounts to prevent hypovitaminosis C and the potentially fatal deficiency disease scurvy. Global vitamin C status and prevalence of deficiency has not previously been reported, despite vitamin C’s pleiotropic roles in both non-communicable and communicable disease. This review highlights the global literature on vitamin C status and the prevalence of hypovitaminosis C and deficiency. Related dietary intake is reported if assessed in the studies. We also explore if global vitamin C status has changed over time. Overall, the review illustrates the shortage of high quality epidemiological studies of vitamin C status in many countries, particularly low- and middle-income countries. The available evidence indicates that vitamin C deficiency is common in low- and middle-income countries and not uncommon in high income settings. Further high quality studies are required to confirm these findings, including in the countries not yet represented, and to fully understand associations with a range of disease processes. Our findings suggest a need for interventions to prevent deficiency in a range of at risk groups and regions of the world.

Liquid manipulation by photoisomerization attracts recent attentions as a new active droplet control method for micro-chemical analysis. Such a non-inverse manipulation can be realized by a use of solution liquid of surfactant that exhibits the \emph{cis}-\emph{trans} isomerization triggered by light irradiation with a specific wavelength such as ultraviolet light. Since the isomerization is accompanied by changes in fluid properties, a light irradiation on one of liquid-air interfaces of a liquid column in a tube would generate differences in the wettability accompanied between the both sides of the finite liquid column. Although this technique has been demonstrated experimentally by Muto et al. (\emph{Euro.~Phys.~J.~Special Topics}, {\bf 226}, 2016, 1199--1205), its dynamics and developments of each isomer distribution are not understood. In order to reveal the liquid-column migration phenomenon, we have performed numerical simulations of air-liquid two-phase flows and its scalar transport of the isomer, using the Volume-of-Fluid method in conjunction with the Continuum-Surface-Force model and Continuous-Species-Transfer method. We validated present results by comparison with experimental result in terms of the migration distance of the liquid column. We confirmed a termination of the liquid-column migration occurs when the \emph{cis} isomer distribution reaches the non-irradiated region. The migration speed was less dependent on the liquid-column length and was proportional to the tube diameter.

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.

Anthocyanins, the naturally occurring pigments responsible for most red to blue colours of flowers, fruits and vegetables, have also attracted interests because of their potential health effects. With the aim of contributing to major insights into their structure-activity relationship (SAR), we have evaluated the radical scavenging and biological activities of selected purified anthocyanin samples (PASs) from various anthocyanin-rich plant materials: two fruits (mahaleb cherry and blackcurrant) and two vegetables (black carrot and ‘Sun Black’ tomato). PASs from the above-mentioned plant material have been evaluated for their antioxidant capacity, using TEAC and ORAC assays. In human endothelial cells, we analysed the biological activity of different PASs by measuring their effects on the expression of endothelial inflammatory markers, including endothelial adhesion molecules VCAM-1 and ICAM-1. We demonstrated that all the different PASs showed biological activity. They exhibited antioxidant capacity of different magnitude, higher for samples containing non-acylated anthocyanins (typical for fruits) compared to samples containing more complex anthocyanins acylated with cinnamic acid derivatives (typical for vegetables), even though this order was slightly reversed when ORAC assay values were expressed on molar basis. Concordantly, PASs containing non-acylated anthocyanins reduced the expression of endothelial inflammatory antigens more than samples with aromatic acylated anthocyanins, suggesting the potential beneficial effect of structurally diverse anthocyanins in cardiovascular protection.

The paper discusses the 2022 Nobel Prize in physics for experiments of entanglement “establishing the violation of Bell inequalities and pioneering quantum information science” in a much wider, including philosophical context legitimizing by the authority of the Nobel Prize a new scientific area out of “classical” quantum mechanics relevant to Pauli’s “particle” paradigm of energy conservation and thus to the Standard model obeying it. One justifies the eventual future theory of quantum gravitation as belonging to the newly established quantum information science. Entanglement, involving non-Hermitian operators for its rigorous description, non-unitarity as well as nonlocal and superluminal physical signals “spookily” (by Einstein’s flowery epithet) synchronizing and transferring some nonzero action at a distance, can be considered to be quantum gravity so that its local counterpart to be Einstein’s gravitation according to general relativity therefore pioneering an alternative pathway to quantum gravitation different from the “secondary quantization” of the Standard model. So, the experiments of entanglement once they have been awarded by the Nobel Prize launch particularly the relevant theory of quantum gravitation grounded on “quantum information science” thus granted to be nonclassical quantum mechanics in the shared framework of the generalized quantum mechanics obeying rather quantum-information conservation than only energy conservation. The concept of “dark phase” of the universe naturally linked to the very well confirmed “dark matter” and “dark energy” and opposed to its “light phase” inherent to classical quantum mechanics and the Standard model obeys quantum-information conservation, after which reversible causality or the mutual transformation of energy and information are valid. The mythical Big Bang after which energy conservation holds universally is to be replaced by an omnipresent and omnitemporal medium of decoherence of the dark and nonlocal phase into the light and local phase. The former is only an integral image of the latter and borrowed in fact rather from religion than from science. Physical, methodological and proper philosophical conclusions follow from that paradigm shift heralded by the 2022 Nobel Prize in physics. For example, the scientific theory of thinking should originate from the dark phase of the universe, as well: probably only approximately modeled by neural networks physically belonging to the light phase thoroughly. A few crucial philosophical sequences follow from the break of Pauli’s paradigm: (1) the establishment of the “dark” phase of the universe as opposed to its “light” phase, only to which the Cartesian dichotomy of “body” and “mind” is valid; (2) quantum information conservation as relevant to the dark phase, furthermore generalizing energy conservation as to its light phase, productively allowing for physical entities to appear “ex nihilo”, i.e., from the dark phase, in which energy and time are yet inseparable from each other; (3) reversible causality as inherent to the dark phase; (4) the interpretation of gravitation only mathematically: as an interpretation of the incompleteness of finiteness to infinity, for example, following the Gödel dichotomy (“either contradiction or incompleteness”) about the relation of arithmetic to set theory; (5) the restriction of the concept of hierarchy only to the light phase; (6) the commensurability of both physical extremes of a quantum and the universe as a whole in the dark phase obeying quantum information conservation and akin to Nicholas of Cusa’s philosophical and theological worldview.

Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the DNA sequence, is revolutionizing our understanding of psychiatric disorders. This article provides a comprehensive overview of the role of epigenetics in psychiatry, discussing its implications for genomics, evolution, inheritance patterns, and the development of biomarkers. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, are explored in the context of psychiatric conditions such as depression, schizophrenia, and post-traumatic stress disorder (PTSD). The discussion highlights how epigenetic modifications can influence brain dynamics, as measured by electroencephalography (EEG), and how artificial intelligence (AI) can accelerate the development of treatment options. The potential for epigenetic biomarkers to improve diagnosis, prognosis, and treatment is emphasized, along with the role of behavioral interventions in inducing beneficial epigenetic modifications. Future directions in epigenetic research, including the development of epigenetic therapies and the elucidation of molecular mechanisms underlying epigenetic inheritance, are also discussed. This article underscores the transformative potential of epigenetics in advancing our understanding of mental health and disease, paving the way for novel therapeutic interventions.

The emergence of acquired resistance to EGFR-TKIs is almost inevitable even after a remarkable clinical response. Secondary mutations such as T790M and C797S are responsible for the resistance to 1st/2nd generation (1/2G) TKIs and 3G TKIs, respectively. To overcome both the T790M and C797S mutations, novel 4G EGFR-TKIs are now under early clinical development. In this study, we evaluated the efficacy of a 4G EGFR-TKI in the treatment of lung cancer with EGFR mutation as well as explored resistance mechanisms to a 4G TKI. First, we compared the efficacies of seven TKIs including a 4G TKI, BI4020, against Ba/F3 cell models that simulate resistant tumors after frontline osimertinib treatment failure because of a secondary mutation. We also established acquired re-sistant cells to BI4020 by chronic drug exposure. Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib). BI4020 inhibited the growth of C797S-positive cells; however it was not effective against L718Q-positive cells. Erlotinib was active against all Ba/F3 cells tested. In the analysis of resistance mechanisms of BI4020 resistant (BIR) cells, none harbored secondary EGFR mutations. HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020. HCC4006BIR and H1975BIR cells exhibited epithelial to mesenchymal transition. This study suggests that erlotinib may be more suitable than 4G TKIs to overcome sec-ondary mutations after front-line osimertinib. We found that off-target mechanisms that cause re-sistance to earlier generation TKIs will also cause resistance to 4G TKIs.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), may increase LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed de-identified electronic health records of 1,040,341 T2DM patients treated between 2005-2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Acute lower respiratory tract infection is a major health problem that affects more than 15% of the total population of Saudi Arabia each year. Epidemiological studies conducted over the last three decades have indicated that viruses are responsible for the majority of these infections. The epidemiology of respiratory viruses in Saudi Arabia is believed to be affected mainly by the presence and mobility of large numbers of foreign workers and the gathering of millions of Muslims in Mecca during the Hajj and Umrah seasons. Knowledge concerning the epidemiology, circulation pattern, and evolutionary kinetics of respiratory viruses in Saudi Arabia are scant, with the available literature being inconsistent. After reviewing the available data on epidemiology and evolution of respiratory viruses, this study examines the effect of varying vaccination rates across different age groups during the 2019/2020 influenza season in Saudi Arabia. Utilizing an age-structured SEIR (Susceptible–Exposed–Infectious–Recovered) model, it develops customized vaccination policies by considering age-specific incidence rates. This pioneering research segments the population into five age groups—infants and school-aged children, junior and older youth, young adults and adults, middle-aged, and seniors—across five regional areas in Saudi Arabis: Eastern, Central, Northern, Western, and Southern. A contact matrix, compiled from multiple sources, is used to delineate the dynamics of influenza transmission. The study undertakes a thorough comparison of three distinct vaccination scenarios: no vaccination, national vaccination, and optimized vaccine allocation policy, under various potential pandemic situations. It examines their impact on vaccination campaigns in terms of the total number of infections, mortality, and morbidity rates. The results emphasize the crucial impact of population demographics on disease transmission and vaccine distribution. According to the findings, the optimized vaccination scenario proved to be the most effective strategy in all scenarios.