In the article we present the results concerning the impact of structural and chemical properties of zinc oxide in various morphological forms, on its gas-sensitive properties tested in an atmosphere containing a very aggressive gas such as chlorine. Two types of ZnO sensor layers obtained by two different technological methods were used. Their morphology, crystal structure, specific surface area, porosity, surface chemistry and structural defects were characterized, and then compared with gas-sensitive properties in a chlorine-containing atmosphere. To achieve this goal scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and photoluminescence spectroscopy (PL) methods were used. The sensing properties of obtained active layers were tested by temperature stimulated conductance method (TSC). We have noticed that their response in chlorine atmosphere is not determined by the size of the specific surface or porosity. The obtained results showed that the structural defects of ZnO crystals play the most important role in chlorine detection. We demonstrated that the Cl2 adsorption is a concurrent process to oxygen adsorption. Both of them occur on the same active species (oxygen vacancies). They concentration is higher on the side planes of the zinc oxide crystal than the others. Thanks to the conducted studies authors demonstrated that to develop a new gas sensor devices not only changing of active layer chemical composition but also controlling its crystal structure and morphology could be used.

Aim: This research is aimed at examining the cost-effectiveness of olanzapine versus risperidone in dementia patients with behavioural and psychological symptoms in Thailand. Methods: An existing Markov model based on a critical review through the comprehensive literature search and a justification for the most appropriate model for a Thai setting was adapted to simulate the disease progression of patients with dementia with behavioural disturbances until their need for full-time care (FTC). The time to the FTC state was estimated by a predictive equation developed by Rive et al. (2010). The model was conducted to assess the expected costs and outcomes associated with olanzapine compared with risperidone for Thai patients with BPSD aged 60 years and above. This model performed over a five-year time horizon with a one-month cycle length based on a societal perspective. The incremental cost-effectiveness ratio was used as the estimated outcome. Sensitivity analyses were also conducted to demonstrate the robustness of the results. Results: Over 5 years, olanzapine was found to be a cost-effective therapeutic option for the treatment of behaviourally disturbed patients with dementia compared with risperidone, in Thailand from a societal perspective (ICER < THB 160,000). The model underwent extensive sensitivity analyses, which also confirmed that olanzapine was the dominant strategy following the base-case findings. Conclusions: By comparison with risperidone, the model suggests that olanzapine can be regarded as a cost-effective therapeutic strategy for the management of patients with behavioural and psychological symptoms in Thailand.

We applied a framework to assess climate change vulnerability of 52 major vegetation types in the western United States to provide spatially-explicit input to adaptive management decisions. The framework addressed climate exposure and ecosystem resilience; the latter derived from analyses of ecosystem sensitivity and adaptive capacity. Measures of climate change exposure used observed climate change (1981-2014) and then climate projections for the mid-21st century (2040-2069 RCP 4.5). Measures of resilience included (under ecosystem sensitivity) landscape intactness, invasive species, fire regime alteration, and forest insect & disease risk, and (under adaptive capacity), measures for topo-climate variability, diversity with functional species groups, and vulnerability of any keystone species. Outputs are generated per 100km² hexagonal area for each type. As of 2014, moderate climate change vulnerability was indicated for >50% of the area of 50 of 52 types. By the mid-21^st century, all but 19 types face high or very high vulnerability with >50% of the area scoring in these categories. Measures for resilience explain most components of vulnerability as of 2014, with most targeted vegetation scoring low in adaptive capacity measures and variably for specific sensitivity measures. Elevated climate exposure explains increases in vulnerability between the current and mid-century time periods.

The function of sleep in mammal and other vertebrates is one of the great mysteries of biology. Many hypotheses have been proposed, but few of these have made even the slightest attempt to explain the essence of sleep - the uncompromising need for reversible unconsciousness. During sleep, epiphenomena - often of a somatic character - occur, but these cannot explain the core function of sleep. One answer could be hidden in the observations made for long periods of time of the function of the central nervous system (CNS). The CNS is faced with conflicting requirements on stability and excitability. A high level of excitability is desirable, and is also a prerequisite for sensitivity and quick reaction times; however, it can also lead to instability and the risk of feedback, with life-threatening epileptic seizures. Activity-dependent negative feedback in neuronal excitability improves stability in the short term, but not to the degree that is required. A hypothesis is presented here demonstrating how calibration of individual neurons - an activity which occurs only during sleep - can establish the balanced and highest possible excitability while also preserving stability in the CNS. One example of a possible mechanism is the observation of slow oscillations in EEGs made on birds and mammals during slow wave sleep. Calibration to a genetically determined level of excitability could take place in individual neurons during the slow oscillation, so that action potentials are generated during the oscillations “up-phase”. This can only take place offline, which explains the need for sleep. The hypothesis can explain phenomena such as the need for unconsciousness during sleep, with the disconnection of sensory stimuli, slow EEG oscillations, the relationship of sleep and epilepsy, age, the effects of sleep on neuronal firing rate and the effects of sleep deprivation and sleep homeostasis. This is with regard primarily to mammals, including humans, but also all other vertebrates.

The design of curved surface sliders (CSS) based on the elastic response spectrum is done by iteration to find the combination of friction coefficient and displacement capacity which satisfies the condition that the maximum horizontal CSS force is equal to the horizontal force of the structure. Although this CSS design is valid it does not necessarily minimize structural acceleration. This paper therefore describes the optimum CSS design for minimum structural acceleration. All valid CSS designs and the optimum CSS design are represented by their associated trajectory in the elastic response spectrum plane which visualizes the optimization problem. The results demonstrate that the optimum CSS design is not obtained at maximum tolerated effective damping ratio. The subsequent sensitivity analysis describes how much the structural acceleration increases if the actual friction coefficient of the real CSS deviates from its optimum design value. The analysis points out that the increase in structural acceleration is approximately one order of magnitude smaller than the deviation in friction. The sensitivity data may be used by structural engineer to determine tolerable deviations in friction coefficient which still results in acceptable structural accelerations.

The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC₅₀) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Sensory Processing Sensitivity (SPS) is a trait describing inter-individual differences in sensitivity to environments, both positive and negative ones. SPS has attracted growing societal interest. However, (neuro)scientific evidence is lagging behind. We critically discuss how to measure SPS, how it relates to other theories of Environmental Sensitivity and other temperament and personality traits, how SPS interacts with environments to influence (a)typical development, what the underlying aetiologies and mechanisms are, and its relation to mental disorders involving sensory sensitivities. Drawing on the diverse expertise of the authors, we set an agenda for future research to stimulate the field. We conclude that SPS is a heritable, evolutionarily conserved trait, linked to increased risk for psychopathology and stress-related problems in response to negative environments, as well as to greater benefits (e.g., intervention responsivity, positive mood) in positive environments. We need advances in objective assessment of SPS, understanding mechanisms, differentiating it from (seemingly) related mental disorders, to exploit the potential of SPS to improve mental health, preserve human capital, and prevent adverse effects.

Empirical findings support the important role played by prosocial behavior and scholastic per-formance in significantly affecting adolescents’ long term psychosocial adjustment. Furthermore, several studies showed the positive impact of academic self-efficacy in affecting adolescents’ social and academic functioning; however, no studies have investigated the effect of other important personality structures, such as students’ feedback sensitivity. The present study aims at investi-gating the effects of adolescents’ feedback sensitivity (reward sensitivity/punishment sensitivity) on their prosocial behavior and scholastic performance also examining the potential indirect effect of academic self-efficacy on the association between reward/punishment sensitivity and prosocial behavior/scholastic performance. Participants were 132 adolescents (53.1% males; Mage = 16.42, SD) from Rome (Italy). Students’ reward/punishment sensitivity, academic self-efficacy, prosocial behavior and scholastic performance were self-reported. A path analyses model showed a positive and significant effect of academic self-efficacy on scholastic performance, a positive significant ef-fect of punishment sensitivity on prosocial behavior, a positive significant effect of reward sensi-tivity on academic self-efficacy and a significant indirect effect of academic self-efficacy on the association between reward sensitivity and scholastic performance. Results of this study are useful in term of practical implications to promote students’ adjustment.

Modern automotive systems should must satisfy strict reliability requirements. Most of the real vehicle systems and safety-critical networks have complex interconnections. Sensitivities and probabilistic uncertainties of reliability of System with Complex Interconnections (SwCI) can be investigated by the Monte-Carlo Simulation (MCS). The paper focuses on sensitivities and parametrical uncertainties of SwCIs reliability. The proposed method can be used forimplemented in the investigation of uncertainties of SwCIs reliability – in other wordsi.e., for in the determination of critical system elements and to estimateion of the Required Number of Spare Parts (RNSP) of the system, which depends on the probability of allowable spare equipment shortage.

In response to the fairness issue arising from the unequal delay of vehicles in different phases at intersections, considering the actual situation of small and variable delays for vehicles in low-saturation intersection phases, this paper proposes the concept of "sacrificing efficiency for fairness." Firstly, the universality of unfair delay phenomena at intersection phases is explained, especially at low-saturation intersections where the fluctuation in phase delays is 1.87 times higher than at other intersections. Then, a fairness evaluation index is constructed using information entropy, and the feasibility of the proposed approach is demonstrated. Subsequently, a signal optimization model that balances efficiency and fairness is proposed. Finally, the proposed model is validated through case studies, showing that it not only simultaneously considers efficiency and fairness but also has minimal impact on efficiency. Moreover, the changes to timing schemes in the efficiency model are much smaller compared to the model that only considers fairness. Sensitivity analysis reveals that the model performs better under low-saturation intersection conditions.

Throughout history, the pursuit of diagnosing and predicting crop yields has evidenced genetics, environment, and management practices' intertwined roles in achieving food security. However, the sensitivity of crop phenotypes and genetic responses to weather and climate remains unclear, hampering the identification of the underlying abilities of plants to adapt to climate change. We hypothesize that the PAWN global sensitivity analysis (GSA) coupled with a genetic by environment (GxE) model -built of environmental covariance and genetic markers structures- can evidence the contributions of climate on the predictability of maize yields in the U.S. and Ontario, Canada (US-CA). The GSA-GxE modeling framework estimates the relative contribution of climate variables such as solar radiation, temperature, rainfall, and relative humidity on improving maize yield predictions in US-CA. We use an improved version of the Genomes to Fields (G2F) initiative multi-dimensional database to build the environmental covariance matrices for the proposed GSA-GxE framework. The PAWN indices show that the aggregated GxE model’s highest sensitivity levels over US-CA were attributed to solar radiation, temperature, rainfall, and relative humidity. In one-third of the locations, rainfall was the primary climate variable responsible for maize yield predictability. Also, a consistent pattern of top sensitivity indices by location indicates that Relative Humidity, Solar Radiation, and Temperature were distributed as the main or the second most relevant drivers of maize yield predictability.

Currently, the most promising work seems to be aimed not so much at the development of new drugs, but rather at creating ways of targeted delivery of existing drugs. In this paper, we show that polymeric micelles based on chitosan, heparin grafted with lipoic and oleic acids residues demonstrate the potential for doxorubicin delivery to tumors due to pH-, glutathione-sensitivity. Smart delivery systems use the Aikido principle, i.e. they target tumor cells according to their features. Natural polysaccharides (heparin and chitosan) provide the pH sensitivity of micelles: the release of doxorubicin (Dox) is enhanced in a slightly acidic environment (model tumor microenvironment). Fatty acid residues are necessary for the formation of micelles and solubilization of cytostatics in a hydrophobic core. Lipoic acid residues formed a labile S-S cross-linking between polymer chains (the first method), and also covalently attached doxorubicin molecules through glutathione-sensitive S-S bridges (the second option) – determine Redox sensitivity of micelles to tumors. The characterization of polymeric micelles and prodrugs (Dox-polymer) was carried out using FTIR spectroscopy. The release of doxorubicin from micelles occurs slowly (20% / 6h) in an environment with a pH of 7.4 and the absence of glutathione, while in a slightly acidic environment and in the presence of 10 mM glutathione, the rate increases up 6 times, with an increase in the effective concentration up to 5 times after 7 h. The permeability of free doxorubicin, micellar formulations (covalent S-S crosslinked and not) into Raji, K562, A875 cancer cells was studied using confocal laser scanning microscopy (CLSM), demonstrated an increase in the permeability of micellar formulations based on Dox. Thus, we have presented micellar formulations of doxorubicin for targeted delivery to tumor, what is important in the aspects of reducing non-target toxicity, increasing the selectivity of cytostatics against tumors and overcome multidrug resistance.

In order to study the influence of falling rock shape on its rolling characteristics and realize the optimization of falling rock protection design, the following research was carried out. Design model experiments to explore the rolling characteristics of different shapes of rockfalls. Based on the experimental results, it was found that the slenderness ratio, center of gravity, and rotational inertia of the rockfalls can affect their rolling characteristics, leading to swaying and changing the rolling axis during the rolling process, thereby affecting their rolling speed. On this basis, the formation mechanism of rolling resistance is analyzed, and the main cause of energy loss is the rolling resistance arm formed with the rolling surface during rockfall rolling, and a shape parameter to quantify the rolling resistance is proposed. The parameters are substituted into the kinematic formula, in which the influence of the rockfall shape, slope and slope roughness on the rolling speed is considered. Combined with the offset and initial position of the rockfall, the formula can be used to calculate the rolling speed and impact energy in the rolling region and any position in the region. The calculation formula was validated using model experimental data, and the results showed that the error between the experimental and calculated values was small. The error was corrected based on the experimental data. After on-site testing and verification, it can provide reference for the management of rockfall disasters.

While considering the sensitivity over the parameter optimization, it is essential to determine which parameters have the most significant implications on model performance. This study focuses on the baseflow recession constant as one of the independent basin parameters to forecast low flows, perform hydrograph analysis, and calibrate rainfall-runoff models for significant improvement. Prior studies examined that the optimization of data adjustment parameters can improve the hydrological model performance and determine the minimum acceptable data length for data scarce regions using the Xinanjaing model. However, it is essential to pay special attention to the sensitivity of the recession constant, which can also impact the model performance during the data scarcity. Therefore, this study extends the research to comprehend the recession constant sensitivity over data adjustment parameters in the shorter datasets leading to more reliable parameter estimation. In terms of that, this study explores how recession constant affects hydrological parameter estimation on annual scale while keeping data adjustment parameters constant in continuous hydrological modeling, employing the Xinanjiang (XAJ) model as a case study. This study considered two approaches of recession constant (cg); (i) assessing the relationship between cg and the data adjustment parameter (Cep), for the 28-year datasets, (ii) investigating the significant impacts of the sensitivity of cg over Cep in shorter datasets which can affect the estimation of the acceptable minimum data length in the data scarce basins. The study underscores the importance of the recession constant sensitivity for reliable continuous hydrological model predictions, especially in data-scared areas. The study’s outcomes enhance the understanding of the importance of parameter sensitivity and its relationship in conceptual hydrological modeling during the data limitations.

The Chiltan Formation is a potential hydrocarbon-producing reservoir in the Indus Basin, Pakistan. However, its diagenetic alterations and heterogeneous behavior lead to significant challenges in accurately characterizing the reservoir and production performance. This manuscript aims to utilize Chiltan Limestone core samples to conduct a detailed analysis of the diagenetic impacts on reservoir quality. The formation evaluation was carried out through thin section analysis, SEM-EDS and FTIR investigation, as well as plug porosity and permeability measurements under different stress conditions. In results, Petrography revealed three microfacies with distinct diagenetic features and micro-nano fossil assemblages, including intraclasts, pelloids, bioclasts, and stylolites. Diagenesis has a significant impact on petrophysical properties, leading to increased reservoir heterogeneity. The specified depositional environment exposed the alteration of the Chiltan formation during distinct diagenetic phases in marine, meteoric, and burial settings. Pore morphology and mineralogy reveals complex micro-pore structure with various carbonate mineral phases and cement types in the formation samples. The average porosity and permeability of the core samples were found to be 3.4% and 0.449 mD respectively, indicating poor reservoir quality. Stress sensitivity was determined using Klinkenberg corrected permeability, which indicated a reduction in measured and absolute permeability due to increasing confining stress, further reducing the pore throat structure of the formation. In conclusion, the Chiltan formation possesses intricate reservoir heterogeneity and varied micro-pore structure caused by diagenesis and depositional settings. The formation is classified as a low-quality reservoir due to its non-uniform pore geometry, which exhibits low petrophysical properties resulting from overburden stress. The results of this study provide solid foundation in reservoir characterization and quality assessment which has implications for exploring and exploitation of indigenous resources.

Covid-19 pandemic has greatly affected the whole world since the beginning and it continues to affect it. The main aim of this study is to show how Covid-19 affect other mortal diseases; cancer, heart diseases, and diabetes in near future. With this purpose two mathematical models are proposed via Ordinary Differential Equations (ODEs); one for the relationship between Covid-19 and cancer and one for the relationship between Covid-19, diabetes and heart diseases. Afterwards, stability analyses of these models are demonstrated. In order to see the effect of parameters on the disease compartments, sensitivity analysis is applied. Results of sensitivity analysis revealed that huge percentage of people are still scared of visiting doctors and this may lead a massive increase in the diagnosis of other diseases for upcoming years. Moreover, figures displayed that there exists a relationship between diabetes and heart diseases. Especially, diabetes patients should be careful about their health situations and take care of their heart. In order to provide these, awareness of people should be developed.

This paper describes the optimal design of a miniature fiber-optic linear displacement sensor. It is characterized by its ability to measure displacements along a millimetric range with sub-micrometric resolution. The sensor consists of a triangular reflective grating and two fiber-optic probes. The measurement principle of the sensor is presented. The design of the sensor's triangular grating has been geometrically optimized by considering the step angle of the grating to enhance the sensor's resolution. The optimization method revealed a global optimum at which the highest resolution is obtained

To assess the impact of tourism on the incidence of HIV and AIDS using Malaysian epidemiological data over the period of 1986-2011 with additional consideration for newborns infected with HIV. A population-level mathematical model was used to investigate: i) the role of tourism in the spread of HIV and measures used to reduce HIV spread in Malaysia; ii) whether the stability of infectious disease transmission is dependent on the flow of visiting tourists. We first derived an equation for the reproduction number (R0) threshold to quantify the contagiousness of HIV in Malaysia. Sensitivity analyses were used to determine the effect of various parameters on HIV transmission with respect to the increase in tourism. Our findings suggest that a stable disease-free state is sustainable based on the low value of R0 was 0.0017. This result is encouraging from a public health perspective. Approximately 14% of outbound tourists who leave the country return infected with HIV and the difference between the rate at which tourists move to the susceptible category and the rate at which tourists leave the susceptible is category is 12%. Estimated parameters for the influx of tourist rates, δ=1.1540x10-3[1.1477x10-3 - 1.15954x10-3], δ1=7.7901x10-4[7.7867x10-4 - 7.79418x10-4], and δ2=1.4030x10-8[-7.2287x10-7-7.5096x10-7], significantly impacted the spread of HIV in Malaysia. Some significant adjustments were made to the expected parameters. The methods used are helpful to public health analyses and provide a framework for epidemiological modeling of HIV spread among tourists. The trend and magnitude of tourist inflows may be determinants in the incidence of HIV and AIDS in Malaysia.

Most of the literature on the optimization problem of transportation in supply chain networks (SCN) considered fixed costs (FC). However, in the practical applications of this problem it is important to study the effect of FC. This paper examines the impact of fixed cost increase as well as the variable cost on the optimization of a Two-Stage SCN. To do so, two mathematical models for mixed-integer nonlinear programming are developed. The first model optimizes fixed and variable costs in addition to the opening cost, whereas the second model only optimizes variable and opening costs. To evaluate the effect of considering FC on the optimization supply chain problem, four groups of instances are randomly generated, and solved using Lingo. The results of the two models are compared utilizing the average percentage deviation. In addition, sensitivity analysis is performed to determine the impact of changes in opening and variable costs on the considered optimization problem. The computational results and the sensitivity analysis show that the first model with minimized FC outperforms the second model, which does not consider the FC in minimization and FC affect the optimization.

Paper is a material whose mechanical properties are highly dependent on humidity and temperature. Which naturally also builds the relationship between the stiffness and strength of corrugated board and changing weather conditions. In this paper, attention is focused on the dependence of the physical properties of the cardboard on changes in humidity and temperature, which undergo dynamic fluctuations both during the production of corrugated board and during its storage. Two techniques were used to test this effect, namely numerical homogenization and global sensitivity analysis. Both methods were implemented to determine the theoretical relationships between the change in humidity and/or temperature in each layer of corrugated board and its global bending, compression and shear stiffness. The procedure was used to analyze different types of 5-ply and 3-ply cardboard. The obtained results allowed to build a complete map of the relationship between the change in humidity of selected layers and the strength characteristics of the full assembly.

The growing interest in heat-conducting nanofluids requires highly sensitive methods for analyzing thermal properties. Thermal-lens spectrometry, despite its advantages over classical methods, does not have a general approach to measuring and interpreting results for dispersed systems. In this paper, by the example of nanofluids of silicon oxide in water in a wide range of concentrations and sizes, the selection of measurement parameters for transient and steady-state thermal lensing is justified, and the interpretation of the results of thermal diffusivity measurements is substantiated. The features of measurements of thermal diffusivity by thermal lens spectrometry under stationary state for dispersed systems are considered. Using this approach, it is possible to detect and distinguish thermal effects with high accuracy. For dispersions of silicon oxide, with increasing concentration, the thermal diffusivity passes through a minimum. Silicon oxide dispersions can be used both as a coolant or as a heat-removing liquid by selecting the particle size and concentration.

Water resource management and flood forecasting are crucial societal and financial stakes requiring reliable predictions of flow parameters (depth, velocity), the accuracy of which is often limited by uncertainties in hydrodynamic numerical models. In this study, we assess the effect of two uncertainty sources, namely breach characteristics induced by overtopping and the roughness coefficient, on water elevations and inundation extent. A two-dimensional (2D) hydraulic solver was applied in a Monte Carlo integration framework to a reach of the Loire river (France) including about 300 physical parameters. Inundation hazard maps for different flood scenarios allowed highlighting the impact of the breach development chronology. A special attention was paid to proposing a relevant sensitivity analysis to exam the factors influencing the depth and extent of flooding. The spatial analysis of vulnerability area induced by a levee breach width exhibits that, with increasing the flood discharge, the rise of the parameter influence is accompanied by a more localized spatial effect. This argues for a local analysis to allow a clear understanding of the flood hazard. The physical interpretation, highlighted by a global sensitivity analysis, showed precisely the dependence of the flood simulation on the main factors studied, i.e. the roughness coefficients and the characteristics of the breaches.

The modeling and prediction of crop seed yield can be a vital improvement in the precision agriculture industry as it provides reliable assessments of the effectiveness of agro-traits. Here, multiple machine learning (ML) techniques are established for predicting sesame (Sesamum indicum L.) seed yield (SSY) and incorporating agro-morphological features. Models utilized for coupled PCA-ML (Principal component analysis-Machine Learning) methods were compared with original ML models to evaluate predicted efficiency. The Gaussian process regression (GPR) and Radial basis function neural network (RBF-NN) models exhibited the most accurate SSY predictions with determination coefficients or R2 values of 0.99 and 0.91, respectively. The root-mean-square error (RMSE) for the ML models fluctuated between 0 to 0.30 t/ha (metric tons/hectare) for the varied modeling process phases. Estimation of sesame seed yield with coupled PCA-ML models improved performance accuracy. The K-fold process suggested the utilization of datasets with the lowest error rates to ensure the continued accuracy of GPR and RBF models. Sensitivity analysis revealed the capsule number per plant (CPP), seed number per capsule (SPC), and 1000-seed weight (TSW) were the most significant seed yield determinants.

Wind energy in Europe is aimed to grow at a steady, high pace, but opposition from residents to local wind farm plans is one of the obstacles to further growth. A large body of evidence shows that local populations want to be involved and respected for their concerns, but in practice this is a complex process that cannot be solved with simple measures such as financial compensation. The visual presence and the acoustic impact of a wind farm is an important concern for residents. Generally environmental noise management aims to reduce the exposure of the population, usually based on acoustics and restricted to a limited number of sources (such as transportation or industry) and sound descriptors (such as Lden). Individual perceptions are taken into account only at an aggregate, statistical level (such as percentage of exposed, annoyed or sleep-disturbed persons in the population). Individual perceptions and reactions to sound vary in intensity and over different dimensions (such as pleasure/fear or distraction). Sound level is in fact a weak predictor of the perceived health effects of sound. The positive or negative perception of and attitude to the source of the sound is a better predictor of its effects. This article aims to show how the two perspectives (based on acoustics and on perception) can lead to a combined approach in the management of a wind farm aimed to reduce annoyance, not primarily of sound level. An important aspect in this approach is what the sound means to people: is it associated with the experience of having no say in plans, does it lead to anxiety or worry, is it appropriate? The available knowledge will be applied to wind farm management: planning as well as operation.

This paper proposes a curved link-slab (CLS) structure, simplified into a hingeless-arch model, to address the current cracking phenomenon of CLS concrete. The stress formula of the hingeless arch under various loads is derived based on the classical mechanic's method. Based on an actual bridge example, the mechanical properties of CLS are analyzed under different loads and load combinations. The results show that: (1) the CLS stress is significantly lower than that of the flat link-slab structure (FLS), (2) its stress values are less than the concrete tensile limit, and (3) the CLS can effectively solve the concrete cracking phenomenon on the link-slab. The rationality of the stress formula derived from the simplified model of the hingeless arch is verified using the finite element method (FEM). The parametric sensitivity analysis shows that variation of the reinforcement ratio of the CLS has a limited impact on it. Considering both the concrete tensile and compressive limit, the thickness of the CLS should be 15 cm to 20 cm, and its design span should be about 5% to7.5% of the main beam length.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

The current systematic review examines whether there is an association between the genetic 5-HTTPLR pol-ymorphism and parenting and the mechanisms by which this association operates. The literature was searched in various databases such as PubMed, Scopus and ScienceDirect. In line with our inclusion criteria, nine articles were eligible out of 22. Most of the studies, analysed in this review, found an association between 5HTTLPR and parenting. Four studies found a direct association between 5-HTTLPR and parenting with conflicting findings: two studies found that mothers carrying the short variant were more sensitive to their infants, while two studies found that parents carrying the S allele were less sensitive. In addition, several studies found strong interaction between genetic and environmental factors, such as childhood stress and disruptive child behaviour, quality of early care experiences, poor parenting environment, and quality of environment. Only one study found an association between children’s 5HTTLPR and parenting. Parenting can be described as a highly complex construct influenced by multiple factors, including environmental, parenting and child charac-teristics. According to the studies, maternal 5-HTTLPR polymorphism is most likely associated with sensitive parenting.

Helicobacter pylori is the most common human gastric infection. H. pylori stool antigen lateral flow immunochromatography assay (HpSA-LFIA) is considered one of the most cost-effective and rapid non-invasive assays (active tests). The evaluation of this test is crucial for accuracy and utility assurance. This study aimed to evaluate the polyclonal antibody-based HpSA-LFIA in comparison to a monoclonal antibody-based ELISA kit. Methodology: Stool samples were collected from 200 gastric patients for HpSA-LFIA and semi-quantitative HpSA-ELISA. Statistical analysis of the diagnostic values was performed using MedCalc software. Chi-square tests were used to determine the effects of gender and age. Results: The obtained results found that HpSA-LFIA achieved promising sensitivity (93.75%) and NPV (98.00%). However, it had poor specificity, PPV, and accuracy, respectively, 59.76%, 31.25%, and 65.31%. LR+ & LR- were 2.33% & 0.1%, respectively. Gender had no significance on the di-agnostic parameters of HpSA-LFIA. Age groups had irrelevant sensitivity; however, specificity was significantly higher in patients over 45 years. Conclusion: It was concluded that HpSA-LFIA was not accurate enough to be the sole test for di-agnosis and needs other confirmatory tests in case of positive conditions

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

As fossil-fueled heating in the building sector is responsible for 16 % of Germanys total CO2 emissions, it is of great importance to use climate-neutral alternatives for the decarbonization of this sector. Options for the climate-neutral heating of buildings include electricity or hydrogen as energy carriers, both explicitly considered by German policy. In this paper, bottom-up studies are conducted to investigate the role of hydrogen for the climate-neutral energy supply of ten selected residential buildings in comparison to electricity-based systems. Based on a selection of as different typical buildings as possible for single- (SFH) and multi-family houses (MFH) of different construction years, demand profiles are simulated for each building and the respective cost-optimal supply system is determined. For the construction of this system, the electricity-based technologies available are electric heater and heat pump as well as the hydrogen-based technologies hydrogen boiler and fuel cell combined heat and power (CHP) system. Based on the results of the optimization, sensitivity analyses are performed. These analyses aim to identify threshold values of the hydrogen price for the use of hydrogen in building energy systems as well as to make the quantities of hydrogen consumed visible.The identified threshold values show the significant role of hydrogen-operated CHP in MFH if the hydrogen price reaches 0.17 €/kWh_H2 in 2050 at an electricity price of 0.31 €/kWh_el. So, hydrogen-based energy systems represent an economically viable alternative to electricity-based systems with heat pumps. We identify electricity to hydrogen price ratios for the economically viable use of hydrogen in the examined buildings that range from 1.67 to 2.82. According to these ratios, the economically reasonable use of hydrogen in buildings can be derived. For the individual building groups for the year 2050, a ratio of 2.5 can be determined for SFH and 1.8 for MFH, that is favored by the use of CHP which also supplies electricity to the buildings. However, the role hydrogen will finally play in German residential buildings in the future depends to a large extent on political decisions on distribution issues and price signals.

Immunostaining is an essential histochemical technique for analyzing pathogenesis and making a histopathological diagnosis. The needs are prompted by technical development and refinement, commercial availability of a variety of antibodies, deepened knowledge of immunohistochemical markers, accelerated analysis of morphofunctional correlations, progress in molecular target therapy, and the expectation of advanced histopathological diagnosis. However, immunostaining does have various pitfalls and caveats. We should learn from mistakes and failures, as well as from false positivity and false negativity. The present review article describes various devices, technical hints and trouble-shooting guides to keep in mind in performing immunostaining.

Background: Flow-through dot-blot assay (FT-DBA) for SARS-CoV-2 specific IgG detection will provide a reliable and affordable immunoassay for the rapid serosurveillance against COVID-19. Method: SARS-CoV-2 antigens were immobilized on nitrocellulose membrane to capture IgG immunoglobulins, which were then detected with AuNP anti-human IgG. A total of 181 samples were characterized with in-house and commercial immunoassay. The positive panel consisted of RT-PCR positive samples from patients with both <14 days and >14 days from the onset of symptoms, while the negative panel contained samples collected either from the pre-pandemic era dengue patients from healthy donors during the pandemic period. Results: In-house ELISA selected a total of 79 true seropositive and 100 seronegative samples. The sensitivity of samples with <14 days using FT-DBA was 94.7% which increased to 100% for samples >14 days. The overall detection sensitivity and specificity were 98.8% and 98%, respectively, whereas the overall PPV and NPV were 97.6% and 99%. Moreover, comparative analysis between ELISA and FT-DBA revealed clinical agreement of Cohen’s Kappa value of 0.944. Conclusion: The assay can confirm past SARS-CoV-2 infection with high accuracy within 2 minutes compared to ELISA. It can help track SARS-CoV-2 disease progression, population screening, and vaccination response.

Global population is predicted to approach 10 billion by 2050, an increase of over 2 billion from today. To meet the demands of growing, geographically and socio-economically diversified nations, we need to diversity and expand agricultural production. This expansion of agricultural productivity will need to occur under increasing biotic, and environmental constraints driven by climate change. Clustered regularly interspaced short palindromic repeats-site directed nucleases (CRISPR-SDN) and similar genome editing technologies will likely be key enablers to meet future agricultural needs. While the application of CRISPR-Cas9 mediated genome editing has led the way, the use of CRISPR-Cas12a is also increasing significantly for genome engineering of plants. The popularity of the CRISPR-Cas12a, the type V (class-II) system, is gaining momentum because of its versatility and simplified features. These include the use of a small guide RNA devoid of trans-activating crispr RNA (tracrRNA), targeting of T-rich regions of the genome where Cas9 is not suitable for use, RNA processing capability facilitating simpler multiplexing, and its ability to generate double strand breaks (DSB) with staggered ends. Many monocot and dicot species have been successfully edited using this Cas12a system and further research is ongoing to improve its efficiency in plants, including improving the temperature stability of the Cas12a enzyme, identifying new variants of Cas12a or synthetically producing Cas12a with flexible PAM sequences. In this review we provide a comparative survey of CRISPR-Cas12a and Cas9, and provide a perspective on applications of CRISPR-Cas12 in agriculture.

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based studies using these datasets require thoughtful modification to sample selection and analytic strategies, relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings. This paper offers some practical guidance to the full analytical process, demonstrates methods for estimating causal treatment effects on several types of outcomes common to such studies, such as binary, count, time to event and longitudinally varying repeated measures outcomes, and aims to increase transparency and reproducibility. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insurees from 2001-2016.

This brief note aims to explain the scope in conducting large-scale serological surveys of SARS-CoV-2 to define the landscape of population immunity without overlooking the inherent uncertainty steaming from sampling design and diagnostic validity. The note completes with a succinct statistical appendix of simple methods for estimating prevalence from random population samples using imperfect diagnostic tests.

Digital Elevation Models (DEMs) are essential in watershed delineation, but the sensitivity of simulated runoff to DEM resolution is poorly understood. This study investigates the impact of DEM resolution on topological attributes and simulated runoff in the Mahabad Dam watershed, Iran. To delineate the watershed, DEMs with 12.5 m, 30 m, and 90 m resolutions were acquired from the ALOS PALSAR, Space Shuttle Radar Topography Mission (SRTM), and ASTER global DEM data source, respectively. Watershed and streamlines were delineated in ArcGIS, with hydrologic analyses performed using the Soil and Water Assessment Tool (SWAT). Sensitivity analysis on parameters contributing to runoff was done using Sequential Uncertainties Fitting Ver-2 (SUFI-2) Algorithm, in SWAT Calibration and Uncertainty Procedures (SWAT-CUP) software. Results showed the watershed area, reach lengths, and elevations in the watershed varied due to DEM resolutions. Higher amounts of runoff were generated when DEMs with finer resolutions were implemented. The 12.5 m DEM generated 3.48% and 0.42% more runoff compared with 90 m and 30 m DEMs, respectively. SWAT-CUP results showed the sensitivity of parameters contributing to runoff changes under different DEM resolutions. Regardless of DEM resolution, surface properties, available water capacity, and moisture levels in the soil are the most sensitive parameters. As the distribution of slope changes in different DEM resolutions, surface parameters are most affected. The findings indicate to reduce computation time and speed up computation procedures, researchers may use DEMs with coarser resolutions at the expense of minor decreases in accuracy.

Using nanoindentation under various strain rates, the mechanical properties of a selective laser melted (SLM) SKD61 at the 800 mm/s scan speed was investigated and compared to SLM H13. No obvious pile-up due to the ratio of the residual depth (h_f) and the maximum depth (h_max) being lower than 0.7 and no cracking were observed on any of the indenter surfaces. The nanoindentation strain-rate sensitivity (m) of SLM SKD61 was found to be 0.034, with hardness increasing from 8.65 GPa to 9.93 GPa as the strain rate increased between 0.002 s⁻¹ and 0.1 s⁻¹. At the same scan speed, the m value of SLM H13 (m = 0.028) was lower than that of SLM SKD61, indicating that the mechanical behavior of SLM SKD61 was more critically affected by the strain rate compared to SLM H13. SLM processing for SKD61therefore shows higher potential for advanced tool design than for H13.

The value of QuantiFERON in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 128 cases with active PTB and 128 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. Their IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; P < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.

This study presents the complexity and sensitivity of chaotic system dynamics in the case of the double pendulum. It applied detailed numerical analyses of the double pendulum in multiple computing platforms in order to demonstrate the complexity in behavior of the system of double pendulums. The equations of motion were derived from the Euler-Lagrange formalism, in order to capture the system's dynamics, which is coupled nonlinearly. These were solved numerically using the efficient Runge-Kutta-Fehlberg method, implemented in Python, R, GNU Octave, and Julia, while runtimes and memory usage were extensively benchmarked across these environments. Time series analyses, including the calculation of Shannon entropy and the Kolmogorov-Smirnov test, quantified the system's unpredictability and sensitivity to infinitesimal perturbations of the initial conditions. Phase space diagrams illustrated the intricate trajectories and strange attractors, as further confirmation of the chaotic nature of the double pendulum. All the findings have a clear indication of the importance of accurate measurements of the initial condition in a chaotic system, contributing to an increased understanding of nonlinear dynamics. Future research directions are faster simulations using Numba and GPU computing, stochastic effects, chaotic synchronization, and applications in climate modeling. This work will be useful for understanding chaos theory and efficient computational approaches in complex systems of dynamical nature.

Abstract: The VSI represents a significant advancement in the assessment of gastrointestinal-specific anxiety among patients with Irritable Bowel Syndrome (IBS) and other Chronic Inflammatory Bowel Diseases (IBD). However, an Italian version of the instrument is not yet available for the reference population. This study utilized a national sample of 500 individuals, including healthy controls and patients with Ulcerative Colitis and Crohn's Disease, to test the validity and reliability of the Italian VSI. Using back-translation methodology to ensure translation fidelity, the research applied a questionnaire and the VSI through an online format to 500 participants. Data analysis revealed that the Italian VSI had excellent psychometric properties, demonstrating high internal consistency (Cronbach’s α = 0.95) and construct validity. The scale proved sensitive in detecting significant differences in visceral sensitivity among groups, highlighting its utility as a clinical and research assessment tool. Specifically, the Italian VSI exhibited a unidimensional factorial structure and maintained a strong correlation with other measures of anxiety and the severity of gastrointestinal symptoms, confirming its role in enhancing the understanding and management of IBS and IBD in Italy.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

The type III receptor tyrosine kinase FLT3 is a pivotal kinase for hematopoietic progenitor cell regulation, with significant implications in acute myeloid leukemia (AML) through mutations like internal tandem duplication (ITD). This study delves into the structural intricacies of FLT3, the roles of activation loop mutants, and their interaction with tyrosine kinase inhibitors. Coupled with this, the research leverages molecular contrastive learning and protein language modeling to examine interactions between small molecule inhibitors and FLT3 activation loop mutants. Utilizing the ConPLex platform, over 5.7 million unique FLT3 activation loop mutants-small molecule pairs were analyzed. The binding free energies of three inhibitors were assessed, and cellular apoptotic responses were evaluated under drug treatments. Notably, the introduction of the Xepto50 scoring system provides a nuanced metric for drug efficacy. The findings underscore the modulation of molecular interactions and cellular responses by Y842 mutations in FLT3-KD, highlighting the need for tailored therapeutic approaches in FLT3-ITD-related malignancies.

This study aims to theoretically address the design and analysis of an efficient pressure sensor designed by using a polymer-based defective 1D annular photonic crystal (APC). The 1D APC comprises an alternate arrangement of Si and SiO2 in a cylindrical fashion, incorporating a central defect layer. The investigation of the reflectance characteristics of the proposed structure is conducted by separately considering the polystyrene (PS) and the polymethyl methacrylate (PMMA) polymer materials as the defect layer. The pressure-sensitive refractive index of the polymers and the constituent materials of the APC plays a vital role in envisaging the pressure-sensing application. The cornerstone of this study is represented by the shift analysis in the wavelength of the defect mode inside the band gap using different applied pressures by employing the modified transfer matrix method (MTMM). Various geometrical parameters like the defect polymer layer’s thickness and the APC period were carefully optimized to achieve higher sensing performance. The proposed design demonstrated a remarkable pressure sensitivity and FoM of 51.29 nm/GPa and 301.7 GPa-1, respectively, which is considerably high in the current research scenario. It is believed that the proposed structure can be an apt candidate as an innovative high-performance pressure sensor, and it can play a key role in photonic integrated circuits.

In order to study the surface settlement law of subway tunnel engineering site overlying soft soil layer under the action of earthquake, ABAQUS finite element analysis software was used to study the surface settlement law of subway tunnel construction site overlying soft soil layer under the action of three different seismic waves, including El-Centro wave, Kobe wave, and artificial seismic wave with exceedance probability of 10%, based on the Dalian Metro Line 5 with overlying soft soil layer as the engineering background, and the law was analyzed theoretically. Then, the surface settlement law of tunnel top was studied based on El-Centro wave and soft soil parameters, and the sensitivity analysis of soft soil parameters on surface settlement of tunnel top was carried out by orthogonal test method. The results show that under earthquake action, the settlement of the strata within a certain range of the tunnel roof is significantly greater than that of the surrounding strata, forming a settlement trough with a width of about 8 to 20 meters. The width of the settlement trough under the El-Centro wave is the largest, about 19.6 meters, surpassing the artificially synthesized seismic waves with a probability of 10%, which is about 15.6 meters, while the width of the settlement trough under the Kobe wave is the smallest, about 8.5 meters. The ground surface within a range of about 20 meters above the tunnel roof is most strongly affected by the seismic waves and the special lithology of the overlying soft soil layer, and the settlement is the largest. The settlement law of the settlement trough in the overlying strata of the tunnel conforms to the Peck formula. Increasing the elastic modulus of the silty soil can reduce the settlement of the ground surface above the tunnel roof, increasing the Poisson's ratio of the silty soil will increase the settlement of the ground surface above the tunnel roof, increasing the cohesive force of the silty soil to 20 kPa will basically stabilize the settlement of the ground surface above the tunnel roof, and increasing the internal friction angle of the silty soil will basically not change the settlement of the ground surface above the tunnel roof. The sensitivity of the soft soil parameters to the settlement of the ground surface above the tunnel roof is in the order of Poisson's ratio, elastic modulus, cohesive force, and internal friction angle.

Musculoskeletal models (MSKMs) are used to estimate the muscle and joint forces involved in human locomotion, often associated with the onset of degenerative musculoskeletal pathologies (e.g. osteoarthritis). Subject-specific MSKMs offer more accurate predictions than their scaled-generic counterparts. This accuracy is achieved through time-consuming personalisation of models and manual tuning procedures that suffers from potential repeatability errors, hence limiting the wider application of this modelling approach. In this work we have developed a methodology for identifying and ranking the muscles that are more important to the determination of the joint forces, thus producing reduced but still accurate representation of the musculoskeletal system in shorter timeframes. The methodology hinges on Sobol's sensitivity analysis (SSA) for ranking the muscle importance. The thousands of data points required for SSA are generated using Gaussian Process emulators, a Bayesian technique to infer the input-output relationship between nonlinear models from a limited number of observations. Results show that there is a pool of muscles whose personalisation has little effects on the model predictions. Furthermore, joint forces in subject generic and subject generic models are influenced by different set of muscles, suggesting the existence of a model specific component of the sensitivity analysis.

Predicting the tidal wave is essential not only to better understand hydrological cycle at the boundary between land and ocean but also to improve energy production in the coastal area. As affected by various factors such as astronomical, meteorological, and hydrological effects, predicting the tidal wave at the estuary remains uncertain. In this study, we present a novel method to improve short-term tidal wave predictions using a fixed-lag smoother based on sequential data assimilation (DA). The proposed method is implemented for the tidal wave predictions at the estuary of Nakdong River. As a result, the prediction accuracy was improved by 63.9% with DA and the calibration using the regression. Although the accuracy of DA diminished for increasing forecast lead times, the 1-hr lead forecast by DA had still 44.4% improvement over the open loop without DA. Plus, the optimal conditions for the fixed-lag smoother were analyzed in terms of the order of a smoothing function and the length of assimilation window and forecast lead time. It was suggested that the optimal DA configuration could be obtained with the 8th order polynomial as a smoothing function assimilated under 6-hr or longer past and future DA windows.

The combination of statistical learning technologies with large databases of psychophysiological data has appropriately generated enthusiastic interest in future clinical applicability. It is argued here that this enthusiasm should be tempered with the understanding that significant obstacles must be overcome before the systematic introduction of psychophysiological measures into neuropsychiatric practice becomes possible. The nonspecificity of psychophysiological measures complicates their use in diagnosis. Low test-retest reliability complicates use in longitudinal assessment, and quantitative psychophysiological measures can normalize in response to placebo intervention. Ten cautionary observations are introduced and, in some instances, possible directions for remediation are suggested.

Trachsummaroma is an eye infectious disease caused by Chlamydia Trachomatis bacterium, which may lead to irreversible blindness. The disease is spread directly or indirectly by contacting a contaminated material. It can also be transmitted through the disease vector known as “Musca sorbens” or “Bazaar fly”. To curtail the spread of the disease in a population, a meaningful information on the spread and possible control of the disease is required. Mathematical modeling provides efficient tools that can be used to understand and analyze the dynamics of the disease and its control. Several compartmental epidemic models have been proposed in the literature to study the dynamics of trachoma; including SI, SIR and SEIR. However, majority of the existing trachoma models consider only person to person transmission. Thus, the information provided by such models is insufficient since they did not capture the disease vector transmission. The current study proposed a novel SEIR-SEI model that consider both person-person and vector transmission dynamics. The threshold quantity, basic reproduction number R0 is obtained using the next generation matrix, and it was proved that the disease-free equilibrium is asymptotically stable when R0 < 1, and the endemic equilibrium is globally asymptotically stable when R0 > 1. Some simulation results with the aid of mesh plots for the reproductive number as a function of two different biological parameters were obtained. Furthermore, a comprehensive sensitivity analysis is conducted to identify the influence of the individual parameters on the R0. Numerical results show that the vector contact rate has the highest sensitivity with respect to R0, and the value of R0 increases with increase in, hence, the disease can be controlled by decreasing the vector contact rate. Similarly, improving the rate of environmental hygiene and facial cleanliness will decrease the size of R0 and result in the declination of the disease transmission. Moreover, a detailed parameter estimation of the model parameters and model fitting was presented with the use of field data cases from Northern Nigeria using least-square fitting method. The study provides alternative tools that can be used for planning trachoma control program to achieve global eradication of trachoma as a public heath challenge as targeted by WHO in 2030.

The narrow process window during intercritical annealing and discontinuous yielding have limited the commercialisation of medium Mn steels. In this study, a double annealing process based on the commercial continuous annealing line is proposed. The cold-rolled medium Mn steels were first fully austenitized and quenched during the first annealing, followed by the intercritical annealing for reverted austenite transformation. The microstructure of duplex lath-shaped austenite and ferrite is produced and the steel exhibit a desirable continuous yielding during tensile deformation. Al is added into the medium Mn steel to enlarge the process window and to improve partitioning efficiency of Mn. The produced steel is more robust with temperature fluctuation during the industrial process due to the enlarged intercritical region. Mn partitioning is more efficient owing to elevated annealing temperature, which results in the improvement of ductility in the Al-added steel with increased austenite stability.

Background and Aim: Cancer is a disease characterized by uncontrolled cell growth and invasion of tissues. It seems that personality differences and psychological factors are important factors that lead to different reactions to cancer. Therefore, the main purpose of the present study was to investigate the relationship between type D, stress level of life events, personality traits, and anxiety sensitivity in people with breast cancer attending to Tehran Bu-ali Hospital. Methods: The study was a correlational study in which 100 cancer patients referred to Bu-ali Hospital in Tehran, selected by the available sampling method from April to June 2018. The tools used included the Denollet DS-14 Type D Questionnaire, the Paykel Life events Questionnaire, the Eysenck Personality Questionnaire, the ASI Anxiety Scale, Floyd et al., Data analysis in this study is taken place by using SPSS software, two descriptive levels (percentage, frequency, etc.) and regression. Results: The study results showed that there is a relationship between type D personality with stress of life events, neurosis, extraversion, and psychopath dimensions of personality and anxiety sensitivity in breast cancer patients. Conclusion: Psychological factors play a role in the incidence and exacerbation of breast cancer, and ultimately patients with personality type D and personality traits such as psychosis and high anxiety sensitivity and more stress of life events show more symptoms.

This paper proposes a model based on gene expression programming for predicting discharge coefficient of triangular labyrinth weirs. The parameters influencing discharge coefficient prediction were first examined and presented as crest height ratio to the head over the crest of the weir (p/y), crest length of water to channel width (L/W), crest length of water to the head over the crest of the weir (L/y), Froude number (F=V/√(gy)) and vertex angle () dimensionless parameters. Different models were then presented using sensitivity analysis in order to examine each of the dimensionless parameters presented in this study. In addition, an equation was presented through the use of nonlinear regression (NLR) for the purpose of comparison with GEP. The results of the studies conducted by using different statistical indexes indicated that GEP is more capable than NLR. This is to the extent that GEP predicts the discharge coefficient with an average relative error of approximately 2.5% in such a manner that the predicted values have less than 5% relative error in the worst model.

Recently, light traps using light-emitting diode (LED) lights have been applied to monitor or control insect pests. The oriental armyworm, Mythimna separata Walker, is an important insect pest that has caused damage to several cereal crops, including corn, wheat and rice. The present study aims to seek out a sensitive wavelength causing high phototactic response in M. separata. The study evaluated the phototactic responses of M. separata moths to several LED lights of different wavelengths and luminance intensities under laboratory condition. Results showed that green (520 nm) LED light resulted in significant phototactic response of M. separata moths compared to LED lights of other wavelengths. Additionally, the highest attraction rate of the moths to green LED light appeared in luminance intensity group of 200 lux compared to the other intensities groups. Experiments under optimum conditions based on the above experiments revealed that the green LED light exhibited the strongest attraction rate (64.44%) among all experimental groups. An experiment performed in a net cage also showed that green LED light resulted in the highest phototactic response of M. separata moths, 1.7 times more than a commercial black light used as control. These findings clearly demonstrate that M. separata moths have a high sensitivity to the green LED light. Therefore, a light trap equipped with green LED light could be useful for monitoring and controlling M. separata moths.

Earth's global surface temperature shows variability on an extended range of temporal scales and satisfies an emergent scaling symmetry. Recent studies indicate that scale invariance is not only a feature of the observed temperature fluctuations, but an inherent property of the temperature response to radiative forcing, and a principle that links the fast and slow climate responses. It provides a bridge between the decadal- and centennial-scale fluctuations in the instrumental temperature record, and the millennial-scale equilibration following perturbations in the radiative balance. In particular, the emergent scale invariance makes it possible to infer equilibrium climate sensitivity (ECS) from the observed relation between radiative forcing and global temperature in the instrumental era. This is verified in ensembles of Earth system models (ESMs), where the inferred values of ECS correlate strongly to estimates from idealized model runs. For the range of forcing data explored in this paper, the method gives best estimates of ECS between 2.3 and 3.4 K.

Recent evidence suggests the existence of shared neural resources for rhythm processing in language and music. Such overlaps could be the basis of the facilitating effect of regular musical rhythm on spoken word processing previously reported for typical children and adults, as well as adults with Parkinson’s disease and children with developmental language disorders. The present study builds upon these previous findings by examining whether musical rhythmic priming also influences visual word processing, and the extent to which such cross-modal priming effect of rhythm is related to individual differences in musical aptitude and reading skills. EEG was recorded while participants listened to a rhythmic tone prime, followed by a visual target word with a stress pattern that either matched or mismatched the rhythmic structure of the auditory prime. Participants were also administered standardized assessments of musical aptitude and reading achievement. ERPs elicited by target words with a mismatching stress pattern showed an increased fronto-central negativity. Additionally, the size of the negative effect correlated with individual differences in musical rhythm aptitude and reading comprehension skills. Results support the existence of shared neurocognitive resources for linguistic and musical rhythm processing, and have important implications for the use of rhythm-based activities for reading interventions.

Magneto-optic surface plasmon resonance (MOSPR) based sensors are highly attractive as next generation biosensors. However, these sensors suffer from oxidation leading to degradation of performance, reproducibility of the sensor surface because of the difficulty of removing adsorbed materials, and degradation of sensor surface during surface cleaning, and these limit their applications. In this paper, I propose MOSPR-based biosensors with 0 to 15 nm thick inert polycarbonate laminate plastic as a protective layer and theoretically demonstrate the practicability of our approach in water-medium for three different probing samples: ethanol, propanol, and pentanol. I also investigate microstructure and magnetic properties. The chemical composition and layered information of the sensor are investigated using X-ray reflectivity and X-ray diffraction analyses and these show distinct fcc-Au (111) phases, as dominated by the higher density of conduction electrons in Au as compared to Co. The magnetic characterization measured with the in-plane magnetic field to the sensor surface for both the as-deposited and annealed multilayers showed isotropic easy axis magnetization parallel to the multilayer interface at a saturating magnetic field of <100 Oe. The sensor showed a maximum sensitivity of 5.5 × 10⁴%/RIU for water-ethanol media and the highest detection level of 2.5 × 10⁻⁸ for water-pentanol media as the protective layer is increased from 0 to 15 nm.c

This work presents the mathematical framework of the Second-Order Comprehensive Adjoint Sensitivity Analysis Methodology for Response-Coupled Forward/Adjoint Linear Systems (abbreviated as “2nd-CASAM-L”), which enables the most efficient computation of exactly obtained mathematical expressions of first- and second-order sensitivities of a generic system response with respect to functions (“features”) of model parameters. Subsequently, the first- and second-order sensitivities with respect to the model’s uncertain parameters, boundaries, and internal interfaces are obtained analytically and exactly, without needing large-scale computations. Within the 2nd-FASAM-L methodology, the number of large-scale computations is proportional to the number of model features (defined as functions of model parameters), as opposed to being proportional to the number of model parameters, which are considerably more than the number of features, being incomparably more efficient and more accurate than any other methods (statistical, finite differences, etc.) for computing exact expressions of response sensitivities (of any order) with respect to the model’s features and/or primary uncertain parameters, boundaries, and internal interfaces. The application of the 2nd-CASAM-L methodology is illustrated using a simplified energy-dependent neutron transport model of fundamental significance in nuclear reactor physics.

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, Brancati et al.1 observe that mutations in poliovirus receptor related protein 4 (PVRL4), encoding cell adhesion molecule nectin-4, causes Ectodermal dysplasia-syndactyly syndrome. Interaction with cad- herins also implies an influence of nectin-4 on Wnt signaling, which plays a relevant role in limb development (Brancati et al.1). However, not much work has been done to explore the relation of Wnts and PVR family. In CRC cells treated with ETC-1922159, both were found up regulated. In a recent unpublished work in Open Science Framework, Sinha2, we had the opportunity to rank these unknown biological hypotheses for both up and down regulated genes at 2nd order level after drug administration. The search engine alloted high nu- merical valued rankings to some combinations of PVR-WNT, thus indicating a possibility of high combinatorial synergy also. The in-silico derived influences can be represented graphically as - PVR w.r.t WNT with PVR <- WNT9A; and WNT w.r.t PVR with WNT-7B/9A <- PVR and WNT4 <- PVRL2; In the light of the recent findings of PVR with IFN (interferon) and the known interactions between IFN and Wnts, there might be a possibilty to explore the bridge of PVR, IFN and WNTs. The 3 fold (PVR - IFN; IFN - WNT; WNT - PVR), 2 way cross family analysis might shed light on the possible combinations that might be of import. Here, we present a 2-way cross family analysis of multiple, such in-silico ranked 2nd order synergistic combinations, after ETC-1922159 treatment of CRC cells. Via this 2-way cross family analysis, we are able to discover through majority voting, the combinations that might of interest to biologists and also derive plausible influences of components of combinations among themselves. Note that these form biological hypotheses which indicate whether a particular combination and the direction of influence within the combination, exist synergistically in CRC cells. Wet lab tests will indicate the veracity of these combinations and if proven true, will lead to further study of mechanism between the components.

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combinations of factors/genes/proteins that might be affecting the pathway under certain conditions. In colorectal cancer (CRC) cells treated with ETC-1922159, many genes were found up and down regu- lated, individually. A recently developed search engine ranked combinations of Inter- leukin (IL)-X (X, a particular gene/protein) at 2nd order level after drug administration. These rankings reveal which IL-X combinations might be working synergistically in CRC. If found true, oncologists can further test the combination of interest in wet lab and determine the mechanism of functioning between the IL and X. In this research work, we cover combinations of IL with nuclear factor κ B (NFκB), Potassium ion channel sub- family members (KCN), mucin (MUC), TP53, STAT, TNF receptor as- sociated factor (TRAF), STEAP4 metalloreductase, STEAP3 metalloreductase, ATP- binding cassette (ABC) transporters and tumor necrosis factor (TNF).

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combinations of factors/genes/proteins that might be affecting the pathway under certain conditions. In colorectal cancer (CRC) cells treated with ETC-1922159, many genes were found up and down regu- lated, individually. A recently developed search engine ranked combinations of DNA repair gene-X (X, a particular gene/protein) at 2nd order level after drug administration. These rankings reveal which Wnt-X combinations might be working synergistically in CRC. If found true, oncologists can further test the combination of interest in wet lab and determine the mechanism of functioning between the Wnt and X. In this re- search work, we cover combinations of RAD with X-ray repair cross complementing (XRCC) family, 5’-3’ exoribonuclease 2 (XRN2), NFKB repressing factor (NKRF), B cell CLL/lymphoma (BCL) family, exosome component (EXOSC) family, FA comple- mentation group (FANC) family and XRCC with EXOSC.

The development of straddle-type monorail tour-transit systems (MTTSs) has received keen attention, raising the need for revisions on related design codes. This work presents a comprehensive assessment of the lateral stiffness limit of steel substructures in MTTSs. Firstly, a wind‒vehicle‒bridge coupling model was established, integrating multibody dynamics and finite element methods. This model was then validated against field test results, considering measured track irregularities as the excitation. Afterwards, a trend analysis and a variance-based sensitivity analysis was performed to investigate the effect of various factors on the dynamic response of MTTS. Referring to existing specifications, an evaluation index for the lateral stiffness of pier columns and track beams was proposed. Results indicate that the pier height significantly impacts the lateral displacement of the pier top, accounting for 87% of the first-order sensitivity index and 75% of the total sensitivity index. In comparison, the lateral stiffness of track beams contributes over 70% to the maximum lateral acceleration and displacement at the mid-span. Finally, the lateral limited values for the displacement at the pier top and the deflection–span ratio of the track beam were determined as 8.04 mm and L/4200, respectively. These findings can serve as valuable references for future research and designs in this field.

The rapid advancements in satellite technology have led to a significant increase in high-resolution remote sensing (RS) images, necessitating advanced processing methods. Additionally, a patent analysis revealed a significant increase in deep learning and machine learning applications in remote sensing, highlighting the growing importance of these technologies. Therefore, this paper introduces the Kolmogorov-Arnold Network (KAN) model to remote sensing, aiming to enhance efficiency and performance in RS applications. We conducted several experiments to validate KAN's applicability, starting with the EuroSAT dataset, where we combined the KAN layer with multiple pretrained CNN models. The optimal performance was achieved with ConvNeXt, leading to the development of the KonvNeXt model. KonvNeXt was evaluated on the Optimal-31, AID, and Merced datasets for validation, and it achieved accuracies of 90.59%, 94.1%, and 98.1%, respectively. The model also showed fast processing speed, with the Optimal-31 and Merced datasets completed in 107.63 seconds each, while the bigger and more complicated AID dataset took 545.91 seconds. This result is meaningful since it achieved faster speeds and comparable accuracy compared to the existing study which utilized VIT and proved KonvNeXt's applicability for remote sensing classification tasks. Furthermore, we investigated the model's interpretability by utilizing Occlusion Sensitivity and by displaying the influential regions, it validated its potential use in a variety of domains including medical imaging and weather forecasting. This paper is meaningful in that it is the first use of KAN in remote sensing classification, proving its adaptability and efficiency.

The aim of this study was to synthetize a hydroxyapatite-capsaicin composite (HAp-CAP) and to evaluate its physicochemical data for further use in hydrogen peroxide in-office dental bleaching gel. The HAp-CAP was prepared by the precipitation method, performed in a 4:1 ratio using 3.2 g of nano-hydroxyapatite (nano-HAp) and 0.8 g of capsaicin (CAP) in 99.5% ethyl alcohol (q.s.p) and zirconia beads at SpeedMixer®. The HAp-CAP was characterized by morphological, spectroscopic, and thermal analyses. In the following, the HAp-CAP was added to an in-office dental bleaching to test its effect on reducing hydrogen peroxide diffusion into the pulp chamber, as well as the effect in the color alteration during dental bleaching. The HAp-CAP were suitably obtained by the precipitation method, and the results demonstrates that the thermal stability of the CAP is greatly improved after reaction of HAp and CAP. The HAp-CAP into a bleaching gel slightly decreased the amount of hydrogen peroxide inside the pulp chamber and didn’t interfering in the bleaching effectiveness of dental bleaching. The HAp-CAP synthesis and characterization were successfully carried out, and its use in dental materials is a challenging task that needs further study since its addition.

Zambia recently experienced extended hours of load shedding due to reduced hydroelectricity generation attributed to poor rainfall patterns. The inability to meet energy demand has influenced the government to consider alternative energy sources. This study aims to assess the economic feasibility of the eight sites using a 25-turbine layout for a 4 MW generic wind turbine at 130m hub height. An economic evaluation mathematical model was developed to analyze the economic feasibility using net present value, simple payback period, internal rate of return, and levelized cost of electricity (LCOE). The study shows that the Lusaka wind farm was the most economical with 386 GWh energy yield analysis (EYA), wind speed of 8 m/s, NPV of 316 million dollars, SPP of 2.9 years, IRR of 82%, and LCOE of $0.182/ kWh. The results also show that the other seven sites are economically feasible, with Petauke being the lowest. The study's economic sensitivity analysis conducted by varying the average electricity tariff shows that Lusaka was the most financially viable site. Therefore, policymakers should develop cost-reflective feed-in tariff (FiT) schemes and power purchase agreements for the country to have cost-reflective electricity tariffs that will motivate independent power producers to invest in Zambia.

Flood inundation causes socioeconomic losses for coastal tourism under climate extremes, progressively attracting global attention. Mapping, evaluating, and predicting the flood inundation risk (FIR) is significant for coastal tourism. The study develops a spatial tourism–aimed framework integrating a weighted k-Nearest Neighbors (WkNN), Geographic Information Systems, and flood-related spatially environmental criteria such as precipitation, elevation, soil, and drainage systems. These model inputs were standardized and weighted using distance, and integrated into WkNN to infer regional probability and distribution of FIR. Zhejiang province, China, was selected as a case study. The resulting map was pictured to denote the likelihood of the criteria at various risk categories, which was validated by historical Maximum Inundation Extent (MIE) extracted from World Environment Situation Room. The result indicates 80.59% of WkNN results reasonably confirm the MIE. Precipitation and elevation make a negative contribution to high-medium risk, and drainage systems positively alleviate the regional stress of FIR. The results can help stakeholders make suitable strategies to protect coastal tourism, and also weigh WkNN is superior to kNN in FIR assessment. The framework provides a productive way to yield a reliable assessment of FIR and can also be extended to other risk-related environmental studies under climate change.

Research background – In the conditions of a modern developed market economy, a rather important characteristic of the activities of a public company is its activity in the stock market (market activity), which involves the development of a dividend policy, which, on the one hand, should contribute to the achievement of the main goal of financial management - maximizing the material well-being of shareholders, and, on the other hand, take into account the interests of all other stakeholders interested in the activities of a public company (including potential investors) to ensure its sustainable development in the long term. Fulfillment of this requirement is possible only within the framework of a neutral approach to the implementation of the dividend policy of a public company.Purpose – The article is devoted to the consideration of the conceptual foundations for analyzing the sensitivity of key indicators of the activity of a public company in the stock market (market activity) to the main determining factors in the context of a neutral approach to the implementation of its dividend policy.Design/methodology/approach – The methodological basis of the study was the concept of a neutral approach to the dividend policy of a public company and the concept of sensitivity analysis, developed earlier by the author of this article.Findings – It is shown that the key indicators of the market activity of a public company include the dividend yield ratio, dividend coverage ratio, the expected price of an ordinary share, the dividend yield of an ordinary share and the quote ratio of an ordinary share (price and earnings ratio per ordinary share). An analysis of the sensitivity of these indicators to the main determining factors in the context of a neutral approach to the implementation of the dividend policy of a public company involves the construction of appropriate elasticity models that allow determining the change in key indicators of market activity depending on changes in the factors that determine them. The constructed elasticity models of the key indicators of market activity listed above can be used in predictive and analytical assessments of their changes, and also make it possible to identify the causes of these changes by calculating the impact on the specified elasticity of the determinants contained in their models, performed by the appropriate methods of factor analysis, under the conditions of a neutral approach to the implementation of the dividend policy of a public company.Originality/value – The author comes to the conclusion that the elasticity models developed by him for key indicators of the activity of a public company in the stock market in terms of the main factors determining them are a fairly effective tool for managing the market activity of a public company in the context of a neutral approach to the implementation of its dividend policy.

Pseudomonas aeruginosa is an antibiotic-resistant priority pathogen as listed by the World Health Organization. P. aeruginosa, a gram-negative, rod-shaped bacterium, is frequently encountered in hospital settings as an opportunistic pathogen in nosocomial infections. P. aeruginosa has shown high antibiotic resistance, which has been attributed to several mechanisms, such as intrinsic, acquired, and adaptive resistance. This study investigates several genes which may be attributed to the acquisition of antibiotic resistance in the bacteria P. aeruginosa, as it transitions from its planktonic form to the more threatening and resistant biofilm form. Subsequently, the study assesses the comparative efficacy of three antibiotics, Ofloxacin (OFX), Tobramycin (TOB), and Ceftazidime (CAZ), in altering the expression levels of the identified multidrug efflux pump genes associated with the ability to extrude antibiotics from the cell when in the biofilm form. Efflux transporter gene expression in P. aeruginosa was conducted via extraction of total RNA in planktonic and biofilm- both untreated and treated - with Tobramycin (TOB), Ofloxacin (OFX), and Ceftazidime (CAZ). Real-time quantitative reverse transcriptase PCR was employed to analyze alterations in expression levels of the Mex A, Mex B, Mex X, Mex Y, OprM, and RPSL genes in the collected samples. In samples where no antibiotics were administered, an increase in expression of the Mex B efflux pump gene was observed compared to all other efflux pump genes in the biofilm form, providing multidrug resistance when active. The gene of interest, Mex B, was assessed for antibiotic resistance by P. aeruginosa culturing in the planktonic and biofilm forms with simultaneous treatment with TOB, OFX, and CAZ. Of the three antibiotics used, OFX showed more effectiveness in preventing biofilm growth by reducing the expression level of the Mex B efflux pump gene in the biofilm form, making P. Aeruginosa more antibiotic sensitive to OFX. TOB has similar results compared to OFX but was slightly less effective in reducing the expression of Mex B. Conversely, CAZ was not effective in reducing expression of the Mex B gene in the biofilm form or the planktonic form and was determined to be ineffective at eradicating the organism.

Metformin, the treatment of first choice in type 2 diabetes (T2D), is known to mainly act by decreasing endogenous glucose production (EGP) in the liver. Paradoxically, in the last decade several reports documented increased EGP after metformin treatment. This increase, was often attributed to pronounced rises in glucagon, consistent with counter-regulatory response to the glucose lowering effect of metformin. However, considering that hyperglucagonemia, but not hypoinsulinemia, is a main driver of EGP in T2D, increased EGP should have been a common finding. This observation, together with the finding that metformin antagonizes glucagon effects on energy expenditure and protein synthesis, concurrently to its effects on EGP and the emerging evidences demonstrating increased branched chain and gluconeogenic amino acids in response to metformin treatment may points to a liver alpha-cell skeletal muscle cross talk similar to that observed in the liver-alpha cell axis. Here, we provide a mechanistic perspective to this latter possibility, based on mechanistic studies of metformin’s transcriptional targets; retaining thus its glucagon antagonistic and presumably anti-gluconeogenic effects on liver and attributing the increase in EGP to renal gluconeogenesis. We finally discuss how increased EGP might reflect an adverse response to metformin treatment, providing support from clinical and epidemiological data.

The effects of transcranial magnetic stimulations (TMS) show that the human brain is impacted by some magnetic fields (EMFs). Moreover, after a delay, it produces potentials that reveal a subsequent processing of this impact. The human brain might also be sensitive to very weak magnetic fields of extremely low frequencies (vwEMFelf). Namely, to the vwEMelf produced by the brain of other persons when they process visual stimuli. In effect, two studies report that the event-related brain potentials (ERPs) that are evoked by presenting a picture to a participant can be modulated by simultaneously presenting a picture to a partner. To confirm it here, we followed most of the methods of these studies. We recorded the ERPs evoked by presenting, at each trial, the photograph of a face. Simultaneously and, most importantly, privately, we presented a partner with the same or with a different face photograph. ERPs of participants were found to depend on that sameness (p0.001), unbeknownst to them. These joint processing effects (JPEs), confirm a sensitivity of the human brain to the vwEMFelf produced by other brains.

Objectives: This paper presents a statistical review of modelling simulations for frequency and sensitivity of COVID-19 testing paradigms. Methods: We performed a review of preprints and published articles on PubMed from January 1, 2020 – March 1, 2021 using the search terms “COVID screening testing”, “COVID testing frequency”, “COVID testing frequency screening” and “SARS-CoV-2 testing frequency”.Results: Several authors’ conclusions support the claim that test frequency and test sensitivity both play a role in reducing SARS-CoV-2 transmission. We highlight the interplay between frequency of testing, test sensitivity and the speed at which test results are available in our review. Conclusions: Evidence suggests that sensitivity and frequency of testing both play a part in decreasing transmission of disease. We conclude that, overall, test sensitivity plays less of a role in reducing disease transmission in a population compared to the frequency of testing and how quickly test results are available.

While the link between Sensory-processing sensitivity (SPS) and internalizing symptoms has been well-established, a link to externalizing problems is still to be explored. This study aimed to further examine the relation between SPS and behavioral problems by testing the potential mediating roles of trait emotional intelligence (TEI) and decision-making styles. Pathway analyses were conducted on data from 268 community sample participants (Mage= 25.81, SD=2.41, 61.2% females). Results indicated gender differences in the pathway level outcomes of SPS, as well as potential partial mediators in men and women. SPS both directly and via the mediating effects of well-being factor (TEI) and avoidant decision-making influenced depression, regardless of gender. Direct effects on aggression were, however, obtained only in the male sample. Indirect effects of SPS on aggression were found in spontaneous decision-making for men, and in self-control and sociability factors of TEI for women. Directions for future research were discussed. sensory-processing sensitivity, depression, aggression, emotional intelligence, decision-making style, gender differences

Chemotherapy treatment based on Cisplatin (CDDP) is established as the drug of choice for head and neck squamous cell carcinoma (HNSCC). Malignant tumors respond to microenvironment alteration through a dynamic balance of mitochondrial fission and fusion. HNSCC is known to have hypoxic conditions, yet the effects and underlying mechanisms of hypoxia on chemosensitivity and mitochondrial dynamics remain unclear. We found that hypoxia promoted mitochondrial fission and CDDP sensitivity in HNSCC cells. Importantly, Mff was shown to be correlated with chemosensitivity in clinical samples of HNSCC that underwent a hypoxic condition. Hypoxia-inducible factor 1 α-subunit (HIF-1α) dramatically increased Mff transcriptional expression and directly bound to Mff. Hypoxia enhanced the release of reactive oxygen species (ROS) and upregulated the expression of Mff via HIF-1α in HNSCC cells. ROS depletion in HNSCC cells attenuated HIF-1α, Mff expression, and mitochondrial fission. Moreover, a knockdown of Mff suppressed hypoxia-induced mitochondrial fission and decreased CDDP chemosensitivity in vivo and in vitro. Our findings revealed that the hypoxia-induced release of ROS promoted mitochondrial fission and CDDP chemosensitivity via the regulation of HIF-1α/Mff in HNSCC cells, indicating that Mff may serve as a new biomarker to predict neoadjuvant chemosensitivity in HNSCC patients

Since the beginning of the year 2020, the global healthcare system has been challenged by the threat of the SARS-COV 2 virus. Molecular, antigen, and antibody testing are the mainstay to identify infected patients and fight the virus. Molecular and antigen tests that detect the presence of the virus are relevant in the acute phase only. Serological assays detect antibodies to the Sars-CoV-2 virus in the recovering and recovered phase. Each testing methodology has its advantages and disadvantages. To evaluate the test methods, sensitivity (percent positive agreement - PPA) and specificity (percent negative agreement – PNA) are the most common metrics utilized, followed by the positive and negative predictive value (PPV and NPV), the probability that a positive or negative test result represents a true positive or negative patient. In this paper, we illustrate how patient risk and clinical costs are driven by false-positive and false-negative results. We demonstrate the value of reporting PFP (probability of false positive results), PFN (probability of false negative results), and costs to patients and healthcare. These risk metrics can be calculated from the risk drivers of PPA and PNA combined with estimates of prevalence, cost, and Reff number (people infected by one positive SARS COV-2).

In this paper, a solenoid based linearly movable armature system is designed using robust control theory in order to improve the performance of the system. Reference track method is the best performance analysis for position control systems. Among the robust controllers, H infinity mixed-sensitivity and Mixed H 2 /H∞ with Regional Pole Placement Controllers are used to improve the performance of the system. Comparison of the proposed controllers for tracking a reference displacement signals (step and sine wave) and a promising simulation result have been obtained.

The present novel corona virus (2019-nCoV) infection has created a global emergency situation by spreading all over the world in a large scale within very short time period. The infection induced death rate is also very high. There is no vaccine or anti-viral medicine for such infection. So at this moment a major worldwide problem is that how we can control this pandemic. On the other hand, India is a high population density country, where the corona virus disease (COVID-19) has started to spread from $1^{st}$ week of March, 2020 in a significant number of COVID-19 positive cases. Due to this high population density human to human social contact rate is very high in India. So control of the pandemic COVID-19 in early stage is very urgent and challenging problem. Mathematical models are employed in this paper to study the COVID-19 dynamics, to identify the influential parameters and to find the proper prevention strategies to reduce the outbreak size. In this work, we have formulated a deterministic compartmental model to study the spreading of COVID-19 and estimated the model parameters by fitting the model with reported data of ongoing pandemic in India. Sensitivity analysis has been done to identify the key model parameters. The basic reproduction number has been estimated from actual data and the effective basic reproduction number has been studied on the basis of reported cases. Some effective preventive measures and their impacts on the disease dynamics have also been studied. Future trends of the disease transmission has been Predicted from our model with some control measures. Finally, the positive measures to control the disease have been summarized.

The effect of sensitivity points (sequence order and position of every element) of sequences following comparative optinalysis under two proposed mechanisms, the paranodic and synodic skewization, was studied to develop a modeling approach to comparative optinalysis of sequences. The results show that the outcomes of comparative optinalysis (similarity measurement) in a set of paranodically skewed sequences can be modeled deterministically by suitable line regression functions. The sensitivity points (nodes) of a sequence display two important and distinct zones, the K-zones and the B-zones. Continues paranodic skewization within these zones (KB zones) operates within probability space, but at hyperskewization level and at the K-zones only, the outcomes of comparative optinalysis operate outside the probability space. Moreover, the outcomes of comparative optinalysis by synodic skewization can be modeled deterministically by some regression line functions, but a general regression function cannot be identified. At certain limit of skewization value space, following paranodic and synodic skewization, the outcomes of comparative optinalysis at the left-sided sequence form a similar pattern with the right-sided sequence.

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into into a volatile group. To balance the use of remifentanil between groups, a balanced group (n=1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450-0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554-1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194-0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion.

Analysis of 49 strains of F. langsethiae originating from northern Europe (Russia, Finland, Sweden, UK, Norway, and Latvia) revealed the presence of spontaneous auxotrophic mutants that reflect natural intraspecific diversity. Our investigations detected that 49.0% of F. langsethiae strains were auxotrophic mutants for biotin, and 8.2% of the strains required thiamine as a growth factor. They failed to grow on vitamin-free media. For both prototrophic and auxotrophic strains, no growth defect was observed in rich organic media. Without essential vitamins, a significant reduction in the growth of the auxotrophic strains results in a decrease of the formation of T-2 toxin and diacetoxyscirpenol. In addition, all analysed F. langsethiae strains were distinguished into two subgroups based on PCR product sizes. According to our results, 26 and 23 strains of F. langsethiae belong to subgroups I and II respectively. We determined that the deletion in the IGS region of the rDNA of F. langsethiae belonging to subgroup II is linked with temperature sensitivity and causes a decrease in strain growth at 30 °C. Four thiamine auxotrophic strains were found in subgroup I, while 21 biotin auxotrophic strains were detected in subgroups II. To the best of our knowledge, the spontaneous mutations in F. langsethiae observed in the present work have not been previously reported.

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combinations of factors/genes/proteins that might be affecting the pathway under certain conditions. In colorectal cancer (CRC) cells treated with ETC-1922159, many genes were found up and down regu- lated, individually. A recently developed search engine ranked combinations of ATP- binding cassette (ABC) transporters-X (X, a particular gene/protein) at 2nd order level after drug administration. These rankings reveal which ABC-X combinations might be working synergistically in CRC. If found true, oncologists can further test the com- bination of interest in wet lab and determine the mechanism of functioning between the ABC and X. In this research work, we cover combinations of ABC with ubiquitin- conjugating enzymes (UBE2), Interleukin (IL), BCL and Caspase (CASP).

Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combinations of factors/genes/proteins that might be affecting the pathway under certain conditions. In colorectal cancer (CRC) cells treated with ETC-1922159, many genes were found up and down regulated, individually. A recently developed search engine ranked combinations of Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-X (X, a particular gene/protein) at 2^nd order level after drug administration. These rankings reveal which NFκB-X combinations might be working synergistically in CRC. If found true, oncologists can further test the combination of interest in wet lab and determine the mechanism of functioning between the NFκB and X. In this research work, we cover combinations of caspase (CASP) with receptor interacting serine/threonine kinase (RIPK) family, mucin (MUC) family with RIPK, tumor necrosis factor (TNF) with NF-κB family and NF-κB-Inhibitor (NF-κB-I), NFκB-2/I with STAT family, IκB kinase ε (IKBKE) with STAT family, IKBKE with conjugal transfer protein (TRAF), ATP-binding cassette (ABC) domain transporters with NFκB, IKBKE with ubiquitination modifier enzyme and ubiquitination conjugating enzymes (UBA/UBE) and REL-A/B with NFκB .

Traumatic brain injury (TBI) affects millions of people each year. Previous studies using the central fluid percussion injury (CFPI) model in adult male rats indicated that elevated intracranial pressure (ICP) was associated with long-term effects, including neuronal cell loss and increased sensory sensitivity post-injury and secondary ICP elevation, that were not seen following injury alone. Investigations also indicated that Cathepsin B (Cath B), a lysosomal cysteine protease, may play a role in the pathological progression of neuronal membrane disruption; however, the specific impact of Cath B inhibition following CFPI remains unknown. Thus, the focus of this study was to evaluate the effects of Cath B inhibition via intracerebroventricular infusion of CA-074Me 2w following injury with or without secondary elevation of ICP. This was accomplished using adult male rats continuously infused with CA-074Me or 10% DMSO as a vehicle control for 2w following either sham injury, a CFPI only, or a CFPI with subsequent ICP elevation to 20mmHg. We assessed Cath B activity in the lateral neocortices and liver, evaluated protein levels of Cath B and Cath B binding partners AIF, Bcl-XL, and Bak. We also conducted histological analyses of total cell counts to assess for cell loss, membrane disruption, and Cath B localization. Finally, we investigated somatosensory changes with the whisker nuisance task. Overall, this study demonstrated that Cath B is not a direct driver of membrane disruption, however, administration of CA-074Me alters Cath B localization and reduced hypersensitivity, emphasizing Cath B being an important component in late secondary pathologies.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

The relationship between the structure characteristics and performances of coal based hydrogenation isomeric base oil (CTL) and metallocene catalyzed coal based polyalphaolefin (mPAO) base oil was clarified here. CTL and mPAO were compared with typical petroleum based and natural gas based commercial API Class III and IV base oils. Pressurized differential scanning calorimetry (PDSC), Rotary Bomb Oxidation Test (RBOT) and four-balls friction tester were used to evaluate the oxidation stability and lubrication performance of base oils under different working conditions. The sensitivity of different base oils to typical antioxidants and extreme pressure antiwear agents was compared. Specially, the composition and structure of CTL base oil are obviously different from GTL and mineral base oil. The coal-based CTL and mPAO base oils exhibit commendable viscosity-temperature properties, characteristics, coupled with low-temperature fluidity, fire safety, and minimal evaporation loss. The lubricating properties, oxidation stability and the sensitivity to extreme pressure antiwear agents of CTL are close to those of similar base oils. But the sensitivity of CTL to typical antioxidants is relatively poor. Besides, compared with commercial PAO base oil, mPAO has lower isomerization degree and fewer isomerization types. The oxidation stability and sensitivity to typical antioxidants of mPAO base oil are comparable with those of commercial PAO base oil, while its lubrication performance and sensitivity to typical extreme pressure antiwear agents are significantly better than those of commercial PAO base oil.

Two-dimensional (2D) materials show advantages as surface enhanced Raman scattering (SERS) substrate over traditional noble metals, such as chemically inert flat surface and uniform SERS signals. However, due to the low density of free electrons of 2D materials, the enhancement mechanism is mainly restricted to chemical enhancement instead of electromagnetic enhancement, resulting a relatively low enhancement factor. In this work, we reported a sensitive 2D SERS substrate based on chemical vapor deposited MoN nanosheets with electromagnetic enhanced mechanism. The maximum enhancement factor can be 3×105 with a limit of detected concentration of 4×10-8 M, which is comparable to those noble metal SERS substrates without hot spots. The MoN nanosheets show strong surface plasmon resonance in the visible range as evidenced by the UV-vis absorption spectroscopy and first principle calculation. The MoN nanosheets SERS substrates exhibit excellent Raman signal uniformity within the nanosheets. Meanwhile, Distinct thickness dependent sensitivity was observed in the MoN nanosheets, higher sensitivity can be achieved by decreasing the thickness of the nanosheets. Furthermore, the MoN nanosheets SERS substrate also show high thermal stability, which can be annealed in air for more than 300℃ and maintain its SERS activity. The high stability of MoN nanosheets allows it to be reused for 20 cycles without obvious signal decay. The high sensitivity, stability, reusability and Raman signal uniformity, makes MoN nanosheets an ideal 2D SERS substrate for practical applications.

Numerous studies were published suggesting that troponin level is related to adverse outcomes in chronic cardiac and non-cardiac conditions. Our study investigated whether troponin levels gathered from an unselected blood sample taken during outpatient care are associated with adverse outcomes in a population with stable coronary artery disease. In a cohort of 949 patients with stable coronary artery disease, average age of 67.5 ± 9.5 years, 69.5% male, 52.1% diabetics, 51.6% with previous myocardial infarction, 57.9% with triple-vessel disease, 21.7% of patients encountered new events during an average period of monitoring of 2.07 ± 0.81 years. Troponin I/99th percentile categorized into tertiles emerged as an independent predictor of death and combined events risk (hazard ratio: 2.02 (1.13-3.60), p=0.017; 2.30 (1.37-3.88, p=0.002, respectively). A troponin ratio > 0.24 was able to identify 53.3% of patients at risk of death and heart failure hospitalization. In patients with stable coronary artery disease and adherent to treatment, troponin level is independently associated with death and heart failure hospitalization in a medium-term follow up.

The mechanical behavior, microstructures as well as the crystallographic textures of the Ti57-Nb43 alloy were investigated on cylindrical specimens compressed at high temperatures, in the range of 700-1000 °C, and strain rates between 0.001 and 1.0 s-1. Hardening, followed by softening behaviours were observed as a function of strain, due to the occurrence of dynamic recrystallization/recovery in hot deformation. The modified five-parameter Voce type equation described well the stress-strain curves, but for the present alloy, it was also possible with only four parameters. A new two-variables polynomial function was employed on the four parameters that described well the flow curves as a direct function of temperature and strain rate. It permitted to reduce the number of parameters and had the predictive capacity for the flow stress at any temperature, strain, and strain rate in the investigated range. The crystallographic textures were similar at all temperatures with an increase of intensity from 900 °C. The textures could be characterized by a double &lt;100&gt; and &lt;111&gt; fiber and a unique component of (001)&lt;110&gt;, the latter inherited from the initial hot rolling texture. Viscoplastic polycrystal self-consistent deformation modeling reproduced the measured textures showing that dynamic recrystallization did not alter the development of the deformation texture, only increased it intensity.

The nature of the fracture and fragmentation process of concrete medium under blast loading is the transformation process of the medium from continuum to discontinuity, coupled with the significant rate correlation of concrete medium, its mechanical behavior presents a high degree of complexity. Problems such as grid distortion and even negative volume are often encountered in the finite element method and others when solving this problem, while the material point method can effectively avoid these problems. In addition, the widely used HJC concrete constitutive model does not take into account the segmented characteristics of the calculation function for dynamic increasing factor. Therefore, in this paper, firstly, the calculation function for dynamic increasing factor in the HJC concrete model is modified by SHPB experiment, and the improved HJC concrete model is proposed; secondly, the material point method simulation program is developed, and the improved HJC concrete model is embedded into the simulation program; finally, the simulation program is verified by numerical examples, and the results show that the developed simulation program can better simulate the fracture and fragmentation process of concrete medium under blast loading, especially the pulverization characteristics of the medium in the near zone of the load.

University course scheduling (UCS) is one of the most important and time-consuming issues that all educational institutions face yearly. Most of the existing techniques to model and solve UCS problems have applied approximate methods, which are different in terms of efficiency, performance, and optimization speed. Accordingly, this research aims to apply an exact optimization method to provide an optimal solution to the course scheduling problem. In other words, in this research, an integer programming model is presented to solve the USC problem. In this model, hard and soft constraints include the facilities of classrooms, courses of different levels and compression of students' curriculum, courses outside the faculty and planning for them, and the limited time allocated to the professors. The objective is to maximize the weighted sum of allocating available times to professors based on their preferences in all periods. To evaluate the presented model's feasibility, it is implemented using the GAMS software. Finally, the presented model is solved in a larger dimension using a real data set from a college in China and compared with the current program in the same college. The obtained results show that considering the mathematical model's constraints and objective function, the faculty courses' timetable is reduced from 4 days a week to 3 working days. Moreover, master courses are planned in two days, and the courses in the educational groups do not interfere with each other. Furthermore, by implementing the proposed model for the real case study, the maximum teaching hours of the professors are significantly reduced. The results demonstrate the efficiency of the proposed model and solution method in terms of optimization speed and solution accuracy.

African swine fever (ASF) is one of the major threats to pig production, and real-time PCR (qPCR) protocols are integral part of ASF laboratory diagnosis. With the pandemic spread of ASF, commercial kits have risen on the market. In Germany, the kits have to go through an approval process and thus, general validation can be assumed. However, they were never compared to each other. In this study, 12 commercial PCR kits were compared to an OIE recommended method. Samples representing different matrices, genome loads, and genotypes were included in a panel that was tested under diagnostic conditions. The comparison included user-friendliness, internal controls, and the time required. All qPCRs were able to detect ASFV genome in different matrices across all genotypes and disease courses. With one exception, there were no significant differences when comparing the overall mean. The overall specificity was 100 % [95 % CI 87.66 - 100], and the sensitivity was between 95 % and 100 % [95 % CI 91.11 - 100]. As can be expected, variability concerned samples with low genome load. Concluding, all tests were fit for purpose. The test system can therefore be chosen based on compatibility and prioritization of the internal control system.

Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute cor-onary syndrome (NSTE-ACS) requiring revascularization remain undefined. Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included and 300 matched patients with normal renal function were selected as a control cohort. Results: Diagnostic performance for patients with severe CKD was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p=0.68) and the ROC-derived cutoff value at presentation was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3-hour changes, sensitivity increased to 98%, PPV and NPV improved up to 93% and 86%, re-spectively. (4) Conclusions: In patients with severe CKD and suspected ACS the diagnostic accu-racy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay specific cutoff levels combined with early absolute changes.

Although wheat is used worldwide as a staple food, it can give rise to adverse reactions, for which the triggering factors have not been identified yet. These reactions can be caused mainly by kernel proteins, both gluten and non-gluten proteins. Among these latter, -amylase/trypsin inhibitors (ATI) are involved in baker’s asthma and realistically in Non Celiac Wheat Sensitivity (NCWS). In this paper, we report characterization of three transgenic lines obtained from the bread wheat cultivar Bobwhite silenced by RNAi in three ATI genes CM3, CM16 and 0.28. We have obtained transgenic lines showing an effective decrease of the activity of target genes that, although showing a higher trypsin inhibition as a pleiotropic effect, generate a lower reaction when tested with sera of patients allergic to wheat, accounting for the important role of the three target proteins in wheat allergies. Finally, these lines show unintended changes differences in high molecular weight glutenin subunits (HMW-GS) accumulation, involved in technological performances, but do not show differences in terms of yield. The development of new genotypes accumulating a lower amount of proteins potentially or effectively involved in such pathologies, not only offers the possibility to use them as a basis for the production of varieties with a lower impact on adverse reaction, but also to test if these proteins are actually implicated in those pathologies for which the triggering factor has not been established yet.

G protein-coupled receptors (GPCRs) play a key role in many cellular signaling mechanisms, and must select among multiple coupling possibilities in a ligand-specific manner in order to carry out a myriad of functions in diverse cellular contexts. Much has been learned about the molecular mechanisms of ligand-GPCR complexes from Molecular Dynamics (MD) simulations. However, to explore ligand-specific differences in the response of a GPCR to diverse ligands, as is required to understand ligand bias and functional selectivity, necessitates creating very large amounts of data from the needed large-scale simulations. This becomes a Big Data problem for the high dimensionality analysis of the accumulated trajectories. Here we describe a new machine learning (ML) approach to the problem that is based on transforming the analysis of GPCR function-related, ligand-specific differences encoded in the MD simulation trajectories into a representation recognizable by state-of-the-art deep learning object recognition technology. We illustrate this method by applying it to recognize the pharmacological classification of ligands bound to the 5-HT2A and D2 subtypes of class A GPCRs from the serotonin and dopamine families. The ML-based approach is shown to perform the classification task with high accuracy, and we identify the molecular determinants of the classifications in the context of GPCR structure and function. This study builds a framework for the efficient computational analysis of MD Big Data collected for the purpose of understanding ligand-specific GPCR activity.

Typhoon Durian forming over the Western North Pacific Ocean and entering into the South China Sea (SCS), caused extreme and widespread damages in 2006. In this research, sensitivity analyses on different physical parameterization schemes of the Weather Research and Forecasting Atmospheric Model (WRF-ATM) have been utilized to study typhoon Durian. Model accuracy and performance testing were investigated with different initial conditions during the tropical cyclone simulation in the SCS. The initial and boundary conditions (IBCs) for all experiments were derived from the European Centre for Medium Range Weather Forecasts (ECMWF), Re-Analysis Interim (ERAI), and the National Centers for Environmental Prediction (NCEP) with Final (FNL) analysis data compiled through the WRF-ATM model. The sensitivity analysis results indicated a major improvement for the cumulus scheme by using the Grell-Devenyi scheme along with the PBL scheme of Yonsei University, mixed-phase microphysics scheme of the WRF Single Moment 5-class and IBCs for ECMWF-ERAI of TC simulation under the context of Wind-Pressure Relationships. This predicted better track and intensity comparing with these of the Joint Typhoon Warning Center. The results revealed that the TC track and intensity were well simulated by the WSM5-GD combination for the WRF-ATM model with an intensity error of 1.69 hPa for minimum surface level pressure, maximum wind speed of 1.83 knots and average track error of 25 km in 72 hours. The simulations showed that the potential track and intensity error decreased with the delayed IBCs, suggesting that the model simulation is more dependable when the coast is approached by the TC.

Background: Systemic lupus erythematosus (SLE) is characterized by inflammation and cardiovascular complications. Our study aimed to investigate subclinical and early indicators of systolic myocardial dysfunction in SLE patients using advanced echocardiographic methods and biomarkers. Methods: In this cross-sectional study, we enrolled 102 SLE patients without known cardiac impairment and 51 healthy controls. Demographics, disease characteristics, laboratory results, disease activity (SLEDAI) and organ damage (SDI) indices were recorded. Left ventricular global longitudinal strain (GLS) and myocardial work indices were assessed by utilizing speckle tracking echocardiography. In addition, high sensitivity C-reactive protein (hsCRP), high sensitivity troponin (hsTn) and N-terminal-pro B-type natriuretic peptide (NT-proBNP) levels were measured in blood samples. Results: In comparison to controls, SLE patients had significantly higher GLS (-19.94±2.71%vs-21.15±1.55%, p&lt;0.001) and global wasted work (GWW) (94±71mmHg%vs71±49 mmHg%, p=0.025). Notably, NT-proBNP and hsTn were threefold and twofold higher in SLE group compared to control group, respectively (p&lt;0.001). Within SLE cohort, patients with at least moderate disease activity (SLEDAI≥4) both biomarkers were significantly elevated than those with low disease activity (SLEDAI&lt;4). Conclusion: Advanced echocardiographic parameters combined with specific biomarkers have a promising role in detecting systolic dysfunction at an early phase in SLE patients, potentially enabling timely interventions to mitigate cardiovascular risk.

Tularemia is a zoonotic disease caused by {\it Francisella tularensis} bacteria, a gram-negative coccobacillus-shaped bacterium. There are multiple transmission routes of the infection to humans such as consumption of contaminated food or water, handling of infected animals or bites from {\it haematophagous} arthropods (such as ticks, deer flies, or mosquitoes). In this study we focus on transmission via the bites of ticks and developed a deterministic model of ordinary and impulsive differential equations to gain insight in the differential effect of prescribed fire on {\it Demacenta variablis} and {\it Amblyomma americanum} ticks and the prevalence of tularemina. We found that prescribed fire differentially reduce the number of the two ticks with {\it A. americanum} reduced the least compare to {\it D. variablis} subsequently leading to differential increase of tularemia new infected cases in humans and rodents. Our result further indicates that the spatial arrangement of burn against unburn areas may not matter as either arrangement led to fewer ticks and reduction in tularemia transmission when prescribed fire was implemented. The results of this study provide important new understandings of the intricate effect of prescribed fire on tick species, and the dynamics of the tick-borne disease, tularemia disease in this study.

: Intracellular tripeptide glutathione is an important agent of cell survival in hypoxia. Glutathione covalently binds to SH-groups of hemoglobin cysteine residues, protecting them from irreversible oxidation and changes its affinity to oxygen. Reduced glutathione (GSH) can also form a non-covalent complex with hemoglobin. Previously, we showed that hemoglobin tetramer has four noncovalent binding sites of glutathione GSH molecules inside, two of which are released during hemoglobin transition to deoxy form. In this study, we characterized the conserved cysteine residues and residues of non-covalent glutathione binding sites in the sequences of a number of hypoxia tolerant and hypoxia-sensitive mammals. The alpha subunit of all species considered was found to have no conserved cysteines, whereas the beta subunit contains Cys94 residue, which is conserved across species and whose glutathionylation changes the affinity of hemoglobin for oxygen 5-6-fold. In addition, the key residues of noncovalent glutathione binding sites in both alpha and beta subunits are absolutely conserved in all species considered, suggesting a common mechanism of hemoglobin redox regulation for both hypoxia-sensitive and hypoxia-tolerant mammals. The solvent accessibility of all HbA and HbB residues in oxy- and deoxy- forms was analyzed. The key residue betaCys94 is solvent accessible only in the deoxy form.

In this work, we demonstrate the preparation of easy-to-fabricate nanogranular, strontium ferromolybdate/strontium molybdate core-shell ceramics and examine their properties including tunnel magnetoresistance, magnetic field sensitivity and temperature coefficient of the tunnel magnetoresistance. The tunnel magnetoresistance of nanogranular, strontium ferromolybdate/strontium molybdate core-shell ceramics was modeled yielding values suitable for magnetoresistive sensor application. Such structures possess a narrow peak of magnetic flux sensibility located at about 125 mT. For magnetic flux measurement, single domain granules with superparamagnetic behavior should be applied. The predicted TMR magnetic flux sensitivities for granules with superparamagnetic behavior amount to about 7.7 % per T and 1.5 % per T for granules sizes of 6.8 nm and 4 nm, respectively. A drawback of the tunnel magnetoresistance of such nanogranular core-shell ceramics is the unacceptable large value of the temperature coefficient. Acceptable values, lower than 2 % per K, are obtained only at low temperatures (less than 100 K) or large magnetic flux densities (exceeding 6 T). Therefore, a Wheatstone bridge configuration should be adopted for magnetoresistive sensors design to compensate the effect of temperature.

The subtropical forest soil plays a pivotal role in terrestrial carbon (C) cycling. Although global warming is expected to influence subtropical soil C cycling, a consensus on its impact on soil C dynamics remains elusive. Given the significant response of soil microbial respiration to temperature in subtropical soils, understanding its behavior under varying temperature regimes is critical for predicting soil organic C (SOC) responses to climate warming. We conducted a short-term laboratory soil warming incubation experiment, sampling both warmed and un-warmed soils from a subtropical plantation in southeastern China, incubating them at 20 °C, 30 °C, and 40 °C. Our aim was to study the SOC mineralization response to increasing temperatures. Our findings revealed that the temperature sensitivity (Q10) of SOC mineralization to short-term experimental warming varied between the warmed soil and the un-warmed soil. The Q10 of the un-warmed soil escalated with the temperature treatment (20-30 ℃: 1.31, 30-40℃: 1.63). Conversely, the Q10 of the warmed soil decreased (20-30 ℃:1.57, 30-40 ℃:1.41). Increasing temperature treatments enhanced hydrolytic enzyme activity but decreased soil substrate availability in both un-warmed and warmed soil. The Q10 of un-warmed soil was positively correlated with the response ratio of DOC. Additionally, soil microbial biomass exhibited a significant decline, leading to a reduced total amount of PLFAs and a decreased abundance of bacteria, fungi, and Gram-negative bacteria (GN). The changes in temperature also considerably altered the composition of the warmed soil microbial community. A drop in the microbial quotient coupled with a rise in the metabolic quotient indicated that warming amplified microbial respiration over microbial growth. The differential Q10 of SOC mineralization, in response to temperature across varying soil, can largely be attributed to shifts in soil nutrients, C-degrading enzyme activities, and microbial communities (the ratio of fungal to bacterial PLFAs).

This review article explores the convergence of virtual reality (VR) and architectural design from an inclusive lens. It underscores the crucial role of virtual reality (VR) in serving as a catalyst for the incorporation of social and cultural sustainability principles in architectural projects. The exploration is guided by inclusive design principles, which encompass several aspects such as accessibility, cultural sensitivity, diversity and inclusivity, user-centered design, and empathy. These concepts serve as the basis for further investigation into the potential of virtual reality (VR) technology to enhance and heighten these features within architectural design, therefore promoting the progress of social and cultural sustainability. The review article highlights the profound impact that virtual reality (VR) may have, going beyond mere visualisation to generate architectural experiences that are immersive, interactive, and empathetic. These experiences are designed to take into account diverse perspectives and needs.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

Blind image quality assessment (BIQA) aims to evaluate image quality in a way that closely matches human perception. To achieve this goal, the strengths of deep learning and the characteristics of human visual system (HVS) can be combined. In this paper, inspired by the ventral pathway and dorsal pathway of HVS, a dual-pathway convolutional neural network is proposed for BIQA task. The proposed method consists of two pathways: “what” pathway, which mimics the ventral pathway of HVS to extract the content features of distorted images, and the “where” pathway, which mimics the dorsal pathway of HVS to extract the global shape features of distorted images. Then, the features from the two pathways are fused and mapped to an image quality score. Additionally, the gradient images weighted by the contrast sensitivity are used as the input to the “where” pathway, allowing it to extract global shape features that are more sensitive to human perception. Moreover, a dual-pathway multi-scale feature fusion module is designed to fuse the multi-scale features of the two pathways, enabling the model to capture both global features and local details, thus improving the overall performance of the model. The experiments conducted on six databases show that the proposed method achieves the state-of-the-art performance.