Complex systems exhibit critical thresholds at which they transition among alternative phases. Complex systems theory has been applied to analyze disease progression, distinguishing three stages along progression: (i) a normal non-infected state, (ii) a pre-disease state in which the host is infected and responds; therapeutic interventions could still be effective, (iii) an irreversible state, where the system is seriously threatened. The Dynamical Network Biomarker (DNB) theory sought for early-warnings of the transition from health to disease. Such DNBs might range from individual genes to complex structures in transcriptional regulatory or protein-protein interaction networks. Here we revisit transcriptomic data obtained during infection of tobacco plants with tobacco etch potyvirus to identify DNBs signaling the transition from mild/reversible to severe/irreversible disease. We identified genes showing a sudden transition in expression along disease. Some of these genes cluster in modules that show the properties of DNBs. These modules contain both genes known to be involved in response to pathogens (e.g., ADH2, CYP19, ERF1, KAB1, LAP1, MBF1C, PR1, or TPS5) and other genes not previously related to biotic stress responses (e.g., ABCI6, BBX21, NAP1, OSM34, or ZPN1).

Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients’ immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

Nearly three months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 550,000 confirmed cases and more than 25,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In the kingdom of Saudi Arabia, unprecedented precautionary strict measures were applied to slow virus entry and to mitigate the risk of the outbreak. Here, we review the experience learned during the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) epidemic in Saudi Arabia, which has been in the country since 2012, and is expected to have helped the country to be well prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far.

Pathogenic Salmonella strains have a set of virulence factors allowing them to generate systemic infections and damage in a variety of hosts. Among these factors, bacterial proteins secreted by specialized systems are used to penetrate the host’s intestinal mucosa, through the invasion and destruction of specialized epithelial M cells in the intestine. On the other hand, numerous studies have demonstrated that humans, as well as experimental animal hosts, respond to Salmonella infection by activating both innate and adaptive immune responses. Here, through live cell imaging of S. Typhimurium infection of zebrafish larvae, we showed that besides the intestinal colonization, a deformed cloacae region and a concomitant accumulation of S. Typhimurium cells was observed upon bacterial infection. The swelling led to a persistent inflammation of infected larvae, although the infection was non-lethal. The in vivo inflammation process was confirmed by the co-localization of GFP-tagged S. Typhimurium with mCherry-tagged neutrophils at 72 hours post exposition. Our live-cell analyses suggest that Salmonella Typhimurium induce cloacitis-like symptoms in zebrafish larvae. Typhimurium induce cloacitis-like symptoms in zebrafish larvae.

Since the recent legalization of medical and recreational use of cannabis (Cannabis sativa L.) in many regions worldwide, there has been high demand for research to improve yield and quality. With the paucity of scientific literature on the topic, this study investigated the relationships between light intensity (LI) and photosynthesis, inflorescence yield, and inflorescence quality of cannabis grown in an indoor environment. After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈ 425 μmol·m-2·s-1 and an 18-h light/6-h dark photoperiod, plants were grown for 12 weeks in a 12-h light/12-h dark ‘flowering’ photoperiod under canopy-level PPFDs ranging from 120 to 1800 μmol·m-2·s-1 provided by light emitting diodes. Leaf light response curves varied both with localized (i.e., leaf-level) PPFD and temporally, throughout the flowering cycle. Therefore, it was concluded that the leaf light response is not a reliable predictor of whole- plant responses to LI, particularly crop yield. This may be especially evident given that dry inflorescence yield increased linearly with increasing canopy-level PPFD up to 1800 μmol·m-2·s-1, while leaf-level photosynthesis saturated well below 1800 μmol·m-2·s-1. The density of the apical inflorescence and harvest index also increased linearly with increasing LI, resulting in higher-quality marketable tissues and less superfluous tissue to dispose of. There were no LI treatment effects on cannabinoid potency, while there were minor LI treatment effects on terpene potency. Commercial cannabis growers can use these light response models to determine the optimum LI for their production environment to achieve the best economic return; balancing input costs with the commercial value of their cannabis products.

SARS-CoV-2 is a novel coronavirus that is the causative agent of Coronavirus infectious disease 2019 (COVD-19). As of the 17^th April 2020, it has infected 2 114 269 people resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

Global pandemic COVID-19 is in stage 4 of widespread local transmission in Bangladesh- the country which did not have a noteworthy health policy and legislative structures to combat COVID-19 like a pandemic. Early strategic planning and groundwork for evolving and established challenges are crucial to assemble resources and react in an appropriate timely manner. This article, therefore, focuses on the public perception of comparative lockdown scenario analysis and how they may affect the sustainable development and the strategic management regime of COVID-19 pandemic in Bangladesh socioeconomically. Response from 159 respondents was collected via a purposive sampling survey method through a questionnaire, and 54 statements were collected for scenario analysis. Datasets were analyzed through a set of statistical techniques including Principal Component Analysis (PCA), hierarchical Cluster Analysis (CA), Pearson’s correlation matrix (PCM), Linear regression analysis (LRA), and psychometric characteristics were included in the Classical Test Theory (CTT) analysis. There were good associations among the lockdown scenarios and response strategies to be formulated. A strong significant positive relationship was observed between people who will start moving towards regular life and the formal and informal economic activities will be started in lockdown scenario 1(r=0.671, p<0.01). The scenario one describes how the death and infection rate will increase if Govt withdraw the partial lockdown before 40 to 50 days. Scenario 2 outlines people’s movement will enable low-level community transmission of COVID-19 with the infection and death rate will increase slowly (r=0.540, p<0.01). Moreover, there will be less supply of necessities of daily use with a price hike (r= 0.680, p<0.01). Scenario 3, full lock down will reduce the community transmission and death from COVID-19 (r=0.545, p<0.01). Moreover, along with the other problems gender discrimination and gender-based violence will increase rapidly (r=0.661, p<0.01). Form regression analysis, due to full lockdown, the formal and informal business, economy and education sector will be hampered severely (R=0.695), there was a strong association between the loss of livelihood and unemployment rate will increase due to business shutdown (p<0.01) and poor communities both in urban and rural areas will be affected severely (p<0.01).All these will further aggravate the humanitarian needs of the most vulnerable groups in the country in the coming months to be followed which needs to be dealt with proper response plans. It will undoubtedly affect the targets of global sustainable development goals (SDGs) of 2030 and all other development targets.

Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L^-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L^-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.

This study was designed for the first time to improve phenolic yield and antioxidant activity of ultrasonic-assisted extraction from Acer truncatum leaves (ATL) using response surface methodology, and phenolic composition in ATL extracted under the optimized condition were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X₁), material-to-liquid ratio (X₂), ultrasonic temperature (X₃) and power (X₄) for an optimal total phenol yield (Y₁) and DPPH• antioxidant activity (Y₂). The results showed that the optimal combination was ethanol: water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent /100 g d.w. and a maximal DPPH• antioxidant activity of 74241.61 μmol Trolox equivalent/100 g d.w.. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic composition in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloyl-glucoside was interpreted. All these results provided practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.

XGBoost is recognized as an algorithm with exceptional predictive capacity. Models for a binary response indicating the existence of accident claims vs. no claims can be used to identify the determinants of traffic accidents. We compare the relative performances of logistic regression and XGBoost approaches for predicting the existence of accident claims using telematics data. The dataset contains information from an insurance company about individuals’ driving patterns – including total annual distance driven and percentage of total distance driven in urban areas. Our findings show that logistic regression is a suitable model given its interpretability and good predictive capacity. XGBoost requires numerous model-tuning procedures to match the predictive performance of the logistic regression model and greater effort as regards interpretation.

Structural health monitoring has been studied by a number of researchers as well as various industries to keep up with the increasing demand for preventive maintenance routines. This work presents a novel method for reconstruct prompt, informed strain/stress responses at the hot spots of the structures based on strain measurements at remote locations. The structural responses measured from usage monitoring system at available locations are decomposed into modal responses using empirical mode decomposition. Transformation equations based on finite element modeling are derived to extrapolate the modal responses from the measured locations to critical locations where direct sensor measurements are not available. Then, two numerical examples (a two-span beam and a 19956-degree of freedom simplified airfoil) are used to demonstrate the overall reconstruction method. Finally, the present work investigates the effectiveness and accuracy of the method through a set of experiments conducted on an aluminium alloy cantilever beam commonly used in air vehicle and spacecraft. The experiments collect the vibration strain signals of the beam via optical fiber sensors. Reconstruction results are compared with theoretical solutions and a detailed error analysis is also provided.

Background: Superspreading events are important drivers of the SARS-CoV-2 pandemic. By analyzing two outbreaks associated with choir rehearsals in March 2020, we demonstrate the risk of indoor, long-range (LR) transmission and singing, to help prevent similar outbreaks. Methods: We conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses.Results: We included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively. WGS confirmed strain identity in both choirs and the primary case of choir 1 (transmitting presymptomatically). Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases’ emitted particles was 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (median: 89% vs. 18%, 95%CI: 80-95% vs. 6-36%). Observed AR in choir 1 (89%) was significantly higher than in choir 2 (24%). According to a risk model, first transmission in choir 1 occurred likely after 7 minutes of singing. The number of inhaled particles emitted by an infectious case, sufficient to infect 50% of exposed, was calculated to 1039-2883 particles (95%CI).Conclusions: Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. Given the potential for presymptomatic infectiousness, greatest caution is required wherever aerosols can accumulate.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

The spread of the infection caused by the new coronavirus SARS-CoV-2 (COVID-19) became pandemic on March 11, 2020. From the time of the first cases (in November 2019, Wuhan, China), to date, a large number of COVID-19 observations have been accumulated in different age groups of patients both in China and abroad. Published scientific data allows us to conclude that children suffer from COVID-19 much less often than adults and tolerate the disease in a milder form, often appear to be asymptomatic. There is currently no final answer why children are less susceptible to this virus; however, scientists are increasingly inclined to consider a complex effect of the immune response and components of the renin-angiotensin system (RAS), which according to recent studies affects not only the cardiovascular system, but is also responsible for the activation of inflammatory reactions. A hypothesis of genetic predisposition to the development of severe forms of COVID-19 has recently been made. We conducted a search for publications in the databases and showed current scientific ideas about COVID-19 pathogenesis and factors influencing the disease development in childhood. Childhood immunity may have several protective features against SARS-CoV-2: immaturity of particular elements of the innate immune response, constitutional lymphocytosis with a shift towards anti-inflammatory Th2-response, as well as "trained" immunity. The influence of renin-angiotensin system reactions in this review is shown from two perspectives: expression of ACE2 receptors and polymorphisms of certain genes of this system. It was established that ACE2 transmembrane protein is not only the entry point for the virus but also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1-7), which has vasodilating properties. Higher ACE2 content in children compared with adults helps maintain balance in the renin-angiotensin system and prevents the development of complications. It was also shown that the presence of certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) could determine the imbalance inside the RAS, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift towards vasoconstrictor, proliferative and profibrotic mechanisms.

Soil-structure interaction (SSI) could affect the seismic response of structures. Since liquid storage tanks are vital structures and must continue their operation under severe earthquakes, their seismic behavior should be studied. Accordingly, the seismic response of liquid storage tanks founded on half space soil is scrutinized under different earthquake ground motions. To better comparison, the six considered ground motions are classified based on their pulse like characteristics, into two groups, named far and near fault ground motions. To model the liquid storage tanks, the simplified mass-spring model is used and the liquid is modeled as two lumped masses known as sloshing and impulsive, and the interaction of fluid and structure is considered using two coupled springs and dashpots. The SSI effect, also, is considered using a coupled spring and dashpot. Besides, four types of soils are used to consider wide variety of soil properties. To this end, after deriving the equations of motion, the MATLAB programming is employed to obtain the time history responses. Results show that although the SSI effect leads to decrease the impulsive displacement, overturning moment and normalized base shear, the sloshing (or convective) displacement is not affected by such effects due to its long period.

Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.

Some studies have demonstrated that in vivo degradation processes are influenced by the material’s physico-chemical properties. The present study compares two hydroxyapatites manufactured on an industrial scale, deproteinized at low and high temperatures, and how physico-chemical properties can influence the mineral degradation process of material performance in bone biopsies retrieved 6 months after maxillary sinus augmentation. Residual biomaterial particles were examined by field scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) to determine the composition and degree of degradation of the bone graft substitute material. According to the EDX analysis, the Ca/P ratio significantly lowered in the residual biomaterial (1.08±0.32) compared to the initial composition (2.22±0.08) for the low-temperature sintered group, which also presented high porosity, low crystallinity, low density, a large surface area, and poor stability and a high resorption rate compared to the high-temperature sintered material. This demonstrates that variations in the physico-chemical properties of bone substitute material clearly influence the degradation process. Further studies are needed to determine whether the resorption of deproteinized bone particles proceeds slowly enough to allow sufficient time for bone maturation to occur.

With the rapid development of wind power generations, the inertial response of wind turbines (WTs) are widely concerned recently, which is important for grid frequency dynamic and stability. This paper recognizes and understands the inertial response of type-3 and type-4 WTs from the view of equivalent internal voltage, in analogy with typical synchronous generators (SGs). Due to the dynamic of the equivalent inertial voltage different from SGs, the electromechanical inertia of WTs is completely hidden. The rapid power control loop and synchronization control loop is the main reasons that the WT's inertial response is disenabled. On the basis of the equivalent internal voltage's dynamic, the existing inertia control method for WTs are reviewed and summarized as three approaches from the view of WT's control, i.e. optimizing the power control or synchronization control or both. At last, the main challenges and issues of these inertia controls are attempted to explain and address.

Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multi-function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography. Optimization was started with central composite design based experiments to characterize the importance of different decision variables. The three variables used in the optimization were flow rate, length of gradient and final salt concentration in the linear elution gradient step. The obtained empiric functional model represented the effect of the significant factors on the yield as the objective function. Afterwards, the calibrated mechanistic model was employed to predict accurate optimal set of variables. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results while keeping purity, a product quality characteristic, equal or above to a predefined value.

A 24 week-controlled trial was conducted in menopausal women (mean age:61.5) to assess serum 25-hydroyvitaminD (s25OHD) evolution in relation to three interdependent determinants: doses of supplemented (Suppl.) vitamin D₃ (VitD₃); baseline status; seasonality. Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time-controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125 g servings of VitD₃-fortified yogurts with 5 and 10 µg daily doses, respectively. The 16 intervention-weeks lasted from early-January to mid-August, the 8 follow-up-weeks from late-August to mid-October. Before enrollment, subjects were randomized into two s25OHD strata: “Low stratum (LoStr)“: 25-50 nmol/L; “High stratum (HiStr)“: >50-75 nmol/L. All enrolled participants remained compliant until study end: Gr.Suppl.0 (n=45), Gr.Suppl.5 (n=44) Gr.Suppl.10 (n=44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than Gr.Suppl.5. The constant rate of s25OHD per supplemental VitD₃ microgram was greater in LoStr than HiStr. s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. In conclusion, this randomized trial demonstrates: -a dose-dependent s25OHD improvement related to fortified yogurt consumption; -an inversely baseline-dependent increase in s25OHD; -a seasonal effect that highlights the importance of vitamin D₃ supplementation during winter, even at 5µg/d, in healthy menopausal women.

In this study, the efficiency of an anaerobic treatment system for wastewater from a South African poultry slaughterhouse was evaluated using a lab-scale static granular bed reactor (SGBR). The down-flow SGBR (2 L) was operated continuously for 138 days under mesophilic conditions (35-37 ˚C), at hydraulic retention times (HRTs) ranging from 24 to 96 h and average organic loading rates (OLRs) of 0.78 to 5.74 g COD/L.day. The SGBR achieved an average chemical oxygen demand (COD) removal efficiency of 80% and the maximum COD removal achieved was 95%, at an HRT of 24 h and average OLR of 5.74 g COD/L.day. The optimization of the SGBR, with regard to a suitable HRT and OLR, was determined using response surface methodology (RSM). The optimal SGBR performance with regard to the maximum COD removal efficiency was predicted for an OLR of 12.49 g COD/L.day and a HRT of 24 h, resulting in a 95.5% COD removal efficiency. The model R2 of 0.9638 indicated that the model is a good fit and is suitable to predict the COD removal efficiency for the SGBR.

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. In addition, it is the largest ionic calcium reservoir in cells, tightly regulating the levels of this second messenger according to cellular necessities. Disturbed ER homeostasis triggers the activation of an intricate and conserved molecular machinery, termed the unfolded protein response (UPR). Given the impact of this signaling network upon an extensive list of cellular processes, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the tools available design a study of this nature.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here we describe how IAV infection triggers cellular apoptosis, and how this process can be exploited towards development of new therapeutics, which might be more effective than the currently available anti-influenza drugs.

In this paper, we study the performance of various deep reinforcement learning algorithms to enhance the energy management system of a microgrid. We propose a novel microgrid model that consists of a wind turbine generator, an energy storage system, a set of thermostatically controlled loads, a set of price-responsive loads, and a connection to the main grid. The proposed energy management system is designed to coordinate among the different flexible sources by defining the priority resources, direct demand control signals, and electricity prices. Seven deep reinforcement learning algorithms were implemented and are empirically compared in this paper. The numerical results show that the deep reinforcement learning algorithms differ widely in their ability to converge to optimal policies. By adding an experience replay and a semi-deterministic training phase to the well-known asynchronous advantage actor-critic algorithm, we achieved the highest model performance as well as convergence to near-optimal policies.

Nutrition support is increasingly recognized as a clinically relevant aspect of the intensive care treatment of cardiac surgery patients. However, evidence from adequate large-scale studies evaluating its clinical significance for patients’ mid- to long-term outcome remains sparse. Considering nutrition support as a key component in the perioperative treatment of these critically ill patients, led us to review and discuss our understanding of the metabolic response to the inflammatory burst induced by cardiac surgery. In addition, we discuss how to identify patients who may benefit from nutrition therapy, when to start nutritional interventions, present evidence about the use of enteral and parenteral nutrition and the potential role of pharmaconutrition in cardiac surgery patients. Although the clinical setting of cardiac surgery provides advantages due to its scheduled insult and predictable inflammatory response, researchers and clinicians face lack of evidence and several limitations in the clinical routine, which are critically considered and discussed in this paper.

There is a large body of research on determining the impact of field variability of soil on crop yields. In contrast, site-specific information about crop responses to agronomic treatments is less frequent. On-Farm Precision Experimentation (OFPE) brings important information to understand the spatial variation of crop response to agronomic practices and thus to improve agronomic decisions. The objective of this work was to investigate the spatial variability of corn yield responses to nitrogen and seed rates using OFPE in four fields in the US Midwest. Geographically weighted regression was applied to generate local regression coefficients, which were used to delineate response zones in each field. The results showed the existence of great potential to adjust the rates of these inputs according to the response of each zone identified by the proposed method. The results of this study can be applied to reevaluate expectations on variable rate prescriptions guided largely by soil and variability.

Demand response flexible loads can provide fast regulation and ancillary services as reserve capacity in power systems. This paper proposes a joint optimization dispatch control strategy for source-load system with stochastic renewable power injection and flexible thermostatically controlled loads (TCLs) and plug-in electric vehicles (PEVs). Specifically, the optimization model is characterized by a chance constraint look-ahead programming to maximal the social welfare of both units and load agents. By solving the chance constraint optimization with sample average approximation (SAA) method, the optimal power scheduling for units and TCL/PEV agents can be obtained. Secondly, two demand response control algorithms for TCLs and PEVs are proposed respectively based on the aggregate control models of the load agents. The TCLs are controlled by its temperature setpoints and PEVs are controlled by its charging power such that the DR control objective can be fulfilled. The effectiveness of the proposed dispatch and control algorithm has been demonstrated by the simulation studies on a modified IEEE 39 bus system with a wind farm, a photovoltaic power station, two TCL agents and two PEV agents.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To contain the virus, numerous preventive measures have been taken including isolation of patients, careful infection control, social distancing, and taking vaccine. So far, new confirmed and death cases are still increasing. SARS-CoV-2 invades cells by using the angiotensin converting enzyme 2 (ACE2). ACE2 is an essential enzyme of the renin-angiotensin system (RAS) which converts angiotensin II (Ang II) to angiotensin (1-7). ACE2 is expressed in different organs, including lung, heart, and kidney. A high number of COVID-19 patients developed kidney injury has been reported. Renal impairment and acute injury are associated with mortality of COVID-19, which is 14-16 times higher than other general patients. Acute Kidney Injury has been occured in 2.9 up to 43% of intensive care unit patients. The increasing evidence show that the components of RAS can activate the complement cascade, and cytokines production. Kidney injury caused by SARS-CoV-2 is related mainly to systemic and local inflammation. Moreover, the uncontrolled immune responses mediated by SARS-CoV-2 including hypercytokinaemia, secondary hemophagocytic lymphohistiocytosis, antibody dependent enhancement, complement system, and phagocytic cells activation can contribute in the virus pathogenesis leading to associated renal dysfunction. However, the role and crosstalk between of RAS components and immune response in mediating kidney injury remain undefined. In this review, we focus on the recent studies to provide the pathogenesis of SARS-CoV-2 interacting with RAS and immune responses to mediate kidney injury.

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.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). The replication rate generates a high polyprotein integration that can contribute to ER stress. Therefore, the host cell can develop an Unfolded Protein Response (UPR) to this protein accumulation which will stimulate appropriate cellular responses in the infectious context (Adaptation, autophagy or cell death). These different stress responses can help to overcome the virus and usually support antiviral strategies initiated by infected cells. In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in epithelial A549 cells with a special focus on the causal factors behind it. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway but surprisingly without activation of the ATF6 branch. When we examined the effects of modulating the ER stress response we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV can altered the UPR in order to escape to the host cell defense system.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Part of philosophy is to subject assertions to critical scrutiny, clarifying exactly what the assertion is saying, its implications, and thus its direct plausibility. The goal is to ensure clarity, logical consistency, and rational argumentation in order to arrive at reasoned conclusions. A common problem is that arguments have missing implied premises that, unless explicitly stated, are mistakenly assumed to be true. Here we subject conclusions made regarding the SARS-CoV-2 pandemic to critical scrutiny, revealing their implied premises so that these premises can be explicitly examined and refuted. Specifically, we refute the conclusions that “no one is protected until everyone is protected” and “population lockdowns are required to protect those at high risk of adverse outcomes.” In the end, we argue for the conclusion that “an Emergency Management principles based response to the pandemic, compared to population-wide lockdowns, offers a way to prevent more adverse outcomes from COVID-19, better prevent overwhelmed healthcare, and prevent most of the collateral damage to the wellbeing of the population that has resulted from the lockdowns.”

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

Nuclear export of viral mRNAs, is an essential step in the HIV replication cycle. This role is played by a small regulatory protein of HIV-1 called Rev.The N-terminal region of Rev contains an arginine-rich sequence. The arginine-rich motif (ARM) is located between amino acids 38-50 and forms an alpha-helical secondary structure. Expression of the structural proteins of human immunodeficiency virus type 1 requires the direct interaction of multiple copies of the viral Rev protein with its highly structured RNA target sequence, the Rev Response element (RRE). The major viral proteins are not produced if this transport of RNA is stopped. Therefore, knowledge of Rev structure is essential for understanding of its cooperative binding to the RRE, for understanding the mechanism of HIV infection and for the development of antiviral drugs that interfere with Rev’s essential functions and for acknowledgment of good candidate drugs for treatment of AIDS. To understand how REV interact with RRE element of HIV-RNA and its formation of oligomeric complex it is better to characterize the domain wise structure of REV with regard in function of each domain. Due to lack of structural data on Rev no single compound is reported as inhibitor of REV expect antiviral drugs. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev Protein is much more important. The ARM is a highly specific sequence which allows for the multimerization of Rev and also binding of REV with RNA. Here we are first time exploring the structural characteristics of REV protein both in free form and in complex with RNA at domain function level especially explore the role of ARM motif in REV HIV-1 protein as RNA binding sites by molecular dynamics (MD) simulation and homology modeling studies. Results indicate that the arginine-rich motif (ARM) is crucial in stability of this complex. The residues ARG38, 39, 41, 43, 44, 48, 50, and ASN40 are most interacting with nucleobases of RRE in Crystal structure of Rev and Rev-response-element RNA complex. Our study plays a major role in elaboration of binding of RNA with REV and pave the way for further investigation for therapeutically agent for HIV.

Theory of the Thermal Response Testing (TRT) is a well-known part of sizing process of the geothermal exchange system. Multiple parameters influence accuracy of effective ground thermal conductivity measurement; like testing time, variable power, climate interferences, groundwater effect etc. To improve accuracy of the TRT we introduced procedure to additionally analyze falloff temperature decline after power test. Method is based on a premise of analogy between TRT and petroleum well testing, since origin of both procedures lies in diffusivity equation with solutions for heat conduction or pressure analysis during radial flow. Applying pressure build-up test interpretation technique to the borehole heat exchanger testing, greater accuracy could be achieved since ground conductivity could be obtained from this period. Analysis was conducted on coaxial exchanger with five different power steps, and with both direct and reverse flow regime. Each test was set with 96hr of a classical TRT, followed by 96hr of temperature decline, making it almost 2000 hours of cumulative borehole testing. Results showed that ground conductivity value could vary as much as 25% depending on test time, seasonal period and power fluctuations while thermal conductivity obtained from a falloff period gives more stable values with only 10% value variation.

The performance of ground heat exchangers systems depends on the knowledge of the thermal parameters of the ground like thermal conductivity, thermal capacity and diffusivity. The knowledge of these parameters often requires quite accurate experimental analysis, known under the name of Thermal Response Test (TRT). In this paper, after a general analysis of the various available types of TRT and the study of the theoretical basics of the method, the perspective of the definition of a simplified routine method of analysis based on the combination of a particular version of TRT and the routine geotechnical tests for the characterization of soil stratigraphy and of the ground characteristics, mandatory before the construction of a new buildings, even if limited to quite short drilling depth (lower than 30 m). The idea of developing TRT in connection with geotechnical test activity has the objective of promoting a widespread use of in-situ experimental analysis and of reducing TRT costs and time duration of the experimental analysis. The considerations exposed in the present paper lead to reconsider a particular variety of the TRT in particular the version known as Thermal Response Test while Drilling (TRTWD).

Ransomware is continually evolving. The most recent tactic is to combine crypto-ransomware with data exfiltration, mandate fraud, and other such schemes to steal from victims and attempt to blackmail them. This paper examines the new trend, its underlying motives, and proposes practical recommendations to help organizations defend against this menace

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

This paper studies the optimization method of pump hydraulic performance based on the response surface method. A parametric model of impeller and diffuser is established. Three-dimensional optimization is carried out on the basis of the initial model obtained by one-dimensional design method. We select the pump hydraulic efficiency and the head as objective function and constraint function. Response surface models are constructed to analyze the relationship between the objectives and the design variables, and the global optimization of hydraulic performance is realized. According to the internal flow characteristics of pump, this paper proposes the strategy of two steps optimization, which aims at meridional plane and blade shape, respectively, to solve the problem of large numbers of design parameters and computational cost. The optimization results show that the hydraulic efficiency of pump increased by 3.7%, and the head is nearly the same.

Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.

Increased nutrient withdrawal by rapidly expanding intensive cropping systems, in combination with imbalanced fertilization, is leading to potassium (K) depletion from agricultural soils in Asia. There is an urgent need to better understand the soil K-supplying capacity and K-use efficiency of crops to address this issue. Maize is increasingly being grown in rice-based systems in South Asia, particularly in Bangladesh and North East India. The high nutrient extraction, especially K, however, causes concerns for the sustainability of maize production systems in the region. The present study was designed to estimate, through a plant-based method, the magnitude, and variation in K-supplying capacity of a range of soils from the maize-growing areas and the K-use efficiency of maize in Bangladesh. Eighteen diverse soils were collected from several upazillas (or sub-districts) under 11 agro-ecological zones to examine their K-supplying capacity from the soil reserves and from K fertilization (@ 100 mg K kg-1 soil) for successive seven maize crops grown up to V10-V12 in pots inside a net house. A validation field experiment was conducted with five levels of K (0, 40, 80, 120 and 160 kg ha-1) and two fertilizer recommendations based on “Nutrient Expert for Maize-NEM” and “Maize Crop Manager-MCM” decision support tools (DSSs) in 12 farmers’ fields in Rangpur, Rajshahi and Comilla districts in Bangladesh. Grain yield and yield attributes of maize responded significantly (P < 0.001) to K fertilizer, with grain yield increase from 18 to 79% over control in all locations. Total K uptake by plants not receiving K fertilizer, considered as potential K-supplying capacity of the soil in the pot experiment, followed the order: Modhukhali >Mithapukur >Rangpur Sadar >Dinajpur Sadar >Jhinaidah Sadar >Gangachara >Binerpota >Tarash >Gopalpur >Daudkandi >Paba >Modhupur >Nawabganj Sadar >Shibganj >Birganj >Godagari >Barura >Durgapur. Likewise in the validation field experiment, the K-supplying capacity of soils was 83.5, 60.5 and 57.2 kg ha-1 in Rangpur, Rajshahi, and Comilla, respectively. Further, the order of K-supplying capacity for three sites was similar to the results from pot study confirming the applicability of results to other soils and maize-growing areas in Bangladesh and similar soils and areas across South Asia. Based on the results from pot and field experiments, we conclude that the site-specific K management using the fertilizer DSSs can be the better and more efficient K management strategy for maize.

Automated controlling the harvesting systems can significantly increase the efficiency of the agricultural practices and prevent food wastes. Modeling and improvement of the combine harvester can increase the overall performance. Machine learning methods provide the opportunity of advanced modeling for accurate prediction of the highest performance of the machine. In this study, the modeling of combine harvesting id performed using radial basis function (RBF) and the hybrid machine learning method of adaptive neuro-fuzzy inference system (ANFIS) to predict various variables of the combine harvester for the optimal performance. Response surface methodology (RSM) is also used to optimize the models. The comparative study shows that the ANFIS method outperforms the RBF method.

This paper reports the efforts made and experiences gained in developing the Flood Prevention and Emergency Response System (FPERS) powered by Google Earth Engine, with focus on its applications at the three stages of floods. At the post-flood stage, FPERS integrates various remote sensing imageries, including Formosat-2 optical imagery, to detect and monitor barrier lakes, synthetic aperture radar imagery to derive an inundation map, and high-spatial-resolution photographs taken by unmanned aerial vehicles to evaluate damage to river channels and structures. At the pre-flood stage, a huge amount of geospatial data are integrated in FPERS and are categorized as typhoon forecast and archive, disaster prevention and warning, disaster events and analysis, or basic data and layers. At the during-flood stage, three strategies are implemented to facilitate the access of the real-time data: presenting the key information, making a sound recommendation, and supporting the decision-making. The example of Typhoon Soudelor in August of 2015 is used to demonstrate how FPERS was employed to support the work of flood prevention and emergency response from 2013 to 2016. The capability of switching among different topographic models and the flexibility of managing and searching data through a geospatial database are also explained, and suggestions are made for future works.

Dietary polyphenols exist in two forms; extractable polyphenols (EPP) or compounds solubilised by aqueous/organic solvents, and non-extractable polyphenols (NEPP) or compounds remain in the corresponding residues after the extraction. At present, most researchers focus on EEP fractions, while NEPP is neglected. Thus, this study aimed to release NEPP from the remaining powder residue of Barhi date palm kernels (BDPK) with acid hydrolysis. The related extraction conditions were determined and optimised using response surface methodology (RSM) for maximisation of NEPP with highest cytotoxic and antioxidant activities. The face-centred central composite design (FCCCD) was used to establish treatments based on three independent variables, namely; extraction temperature, time, and solvent/sample ratio. Under the optimal conditions, the experimental values for DPPH radical-scavenging capacity of NEPP (IC50=57.52µg/mL), and cytotoxicity of NEPP against A549 and HT29 cells were IC50=17.4 µg/mL and 31.4µg/mL, respectively. The experimental values were in agreement with those predicted by RSM models, confirming the suitability of the model employed and the success of RSM for optimisation of the extraction conditions for NEPP from BDPK. These results indicate that NEPP from industrial date fruit waste could be a promising candidate as natural antioxidants with significant antiproliferation effect against A549 and HT29 cancer cells in-vitro.

To understand lung damage caused by COVID-19, we deduced two-phase lung damage mechanisms. After the lungs are infected with SARS-CoV-2 virus, the affected lung tissue swells and surface properties of pulmonary capillaries change, resulting in an increased flow resistance of affected capillaries. If a sufficient number of capillaries are affected by the infection, the swelling and increased cell wall adhesion collectively raise pulmonary vascular resistance. The increased vascular resistance further increases the dwell times of WBCs in affected capillaries and nearly capillaries. When pulmonary pressure is sufficiently higher, WBCs are forced to squeeze into interstitial spaces or alveolar spaces when local pressures are higher than what the capillaries can withstand. When more and more WBCs are dynamically retained, the flow resistance of more capillaries rises, pulmonary vascular resistance rises, and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When capillary pressures around the alveoli are sufficiently high, they cause interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alveolar space and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and alveolar spaces further reduce compressible volume, and thus cause further rise in the pulmonary vascular resistance and pulmonary pressure. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. The available free volume in the thorax cage, organ usable capacities, temperature and humid are expected to have great impacts on degree of lung damages. The free volume in the thorax cage, lung usable surplus capacity, and other organ usable capacities determine the arrival time of last-phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain leukecytes are recruited and migrated into inflamed tissues by increasing their dwell times caused by increased local flow resistance.

In this study, the optimal condition for the extraction of antioxidants from the fruit Buah Mahkota Dewa (Phaleria macrocarpa) was determined by using Response Surface Methodology (RSM). The optimization was applied using central composite design (CCD) to investigate the three independent variables, namely extraction temperature (^oC), extraction time (minutes) and extraction solvent to-feed ratio (%v/v) on the responses of free radical scavenging activity (DPPH), ferric ion reducing power assay (FRAP), total phenolic content (TPC) and total flavonoid content (TFC).The optimal conditions for the antioxidants extraction were found to be extraction temperature (64^oC), extraction time (66 minutes) and solvent to-feed ratio (75 %v/v) with the highest percentage yield of DPPH, FRAP, TPC and TFC were 86.85%, 7.47%, 292.86 mg/g and 3.22 mg/g respectively. Moreover, the data were subjected to response surface methodology (RSM) and the results showed that the polynomial equations for all models were significant, did not show lack of fit, and presented adjusted determination coefficients (R²) above 99%, proving the yield of phenolic, flavonoid and antioxidants activities obtained experimentally were close to the predicted values and the suitability of the model employed in RSM to optimize the extraction conditions. Hence, in this study, the fruit from P.macrocarpa could be considered to have the strong antioxidant ability and can be used in various cosmeceutical or medicinal applications.

The initiation of micro-cracks in concrete is primarily due to its brittleness, which causes severe impacts on the overall behavior of the concrete. However, incorporating fibers in concrete could significantly improve its mechanical properties. The current study demonstrates the influence of two types of fibers on the mechanical properties of concrete. Nylon Fiber Threads (NFT) and Nylon Fiber Strands (NFS) at a fiber content of 2.5 kg/m³ were incorporated in the concrete mix. Concrete with a compressive strength of 30 MPa and a water-cement ratio of 0.4 was produced to investigate the fresh and mechanical properties of conventional and nylon-fiber reinforced concrete (NFRC). The concrete prims and cylinders were tested for compressive, splitting, and flexural strength using ASTM standards (ASTM C-39, C-496, and D-790, respectively). It was found that NFT-reinforced samples achieved higher mechanical properties of concrete (13.05%) compared to NFS-reinforced samples. Test results showed that incorporation of nylon fibers (NF) in concrete decreased the compressive strength of cylindrical and cubical specimens by 0–10% and 5–15%, respectively. However, it increased the splitting tensile and flexural strengths by 0-15%, and 5-15% respectively. Furthermore, the incorporation of NF in concrete significantly improved the ductility and delayed the crack initiation in concrete.

Understanding the evolutionary role of environmentally-induced phenotypic variation (i.e., environmental plasticity) is an important issue in developmental evolution. One of the major physiological responses to environmental changes is cellular stress, which is counteracted by a generic stress reaction that detoxifies the cell, refolds proteins, and repairs DNA damage. In this paper, we elaborate on a previous finding suggesting that the cell differentiation cascade of human decidual stromal cells, a cell type critical for embryo implantation and the maintenance of pregnancy, evolved from a cellular stress reaction. We hypothesize that the stress reaction in these cells was elicited ancestrally through the inflammation caused by embryo attachment and invasion. We describe a model, Stress-Induced Evolutionary Innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types. After reviewing similarities and differences between SIEI and the “plasticity first hypothesis” (PFH) of evolution, we argue that SIEI is a distinct form of plasticity-based evolutionary change because it leads to the origin of novel structures rather than the adaptive transformation of a pre-existing character.

The new WHO Environmental Noise Guidelines for the European Region have recommendations for limiting noise exposure associated with adverse health effects. The limits are said to be based on a systematic review of existing evidence. This paper gives a systematic assessment of the presented evidence with respect to aircraft noise annoyance and demonstrates that the new guidelines are based on an arbitrary selection of existing studies comprising an imperfect and faulty set of data not representative for the general airport population.

To understand great disparities in disease outcomes between CIVID-19 patients, we explore infection and host responses in kinetics. From existing data, we deduced a model that the lungs are damaged by rapidly rising flow resistance as a result of retaining white blood cells in lung tissues. The retention of white blood cells is initially triggered by viral infection but aggravated by injuries caused by low temperature. Lungs are initially damaged by fluid leakage, rapidly followed by extruding blood into alveolar spaces. The step of blood extruding is predicted to take place in a very short time. Our simulations show that as little as 0.1% retention of white blood cells in the lungs can lead to their failure in 5 to 10 days. The small degrees of imbalance implies that this imbalance could be corrected by a large number of factors that are known to reduce flow resistance. The model implies that the top priority is maintaining blood micro-circulation and preserving organ functions in the entire disease course, especially after the virus has spread the whole lungs. From exploring a large number of hypothetical infection modes, we propose preventive, mitigating and treatment strategies for ultimately ending the pandemic. The first strategy is avoiding exposures that could result in widespread damages to lungs and taking post exposure mitigating measures that would reduce disease severity. The second strategy is reducing death rate and disability rate from the current levels to one tenth for infected patients by using multiple factors health optimization method. The double reduction strategies are expected to generate a series of chain reactions that favor mitigating or ending the pandemic. Some reactions include a big reduction of the amount of viral discharges from infected patients into the air, the avoidance of panic, chronic stress and emotional distress, and cross-infections which are expected in quarantines. The double reductions would have a final effect of ending the pandemic.

Improved understanding of climate-growth relationships of multi-species is fundamental to understand and predict response of forest growth to future climate change. Forests are mainly composed of conifers in Northwestern Yunnan Plateau, but variations of growth response to climates among the species are not well understood. To detect growth response of multiple species to climate change, we developed residual chronologies of four major conifers, i.e. Abies georgei, Picea likiangensis, Pinus densata and Larix potaninii at upper distributional limits in Shika Snow Mountain. By using dendroclimatology method, we analyzed correlations between the residual chronologies and climate variables. The results showed that conifer radial growth was influenced by both temperature and precipitation in Shika Snow Mountain. Previous November temperature, previous July mean maximum temperature (T_max) and current June precipitation were the common climatic factors, which had consistent influences on radial growth of four species. Temperature in previous post growing season (September–October) and current growing season (June-August), and precipitation in previous August were the common climatic factors, which had divergent impacts on four species radial growth. Current May T_max and early growing season (April-May) precipitation showed positive and negative influences on growth of P. likiangensis, respectively. Temperature in current post growing season positively affected growth of A. georgei. According to the prediction of climate models and our understanding in growth response of four species to climate variables, we may understand growth response to climate change at species level. It is difficult to predict future forest growth in the study area, since future climate change might cause both increases or decreases for four species and indirect effects of climate change on forest should be considered.

Photosynthetic activities of the sago palm (Metroxylon sagu Rottb.) were studied to find out its sensitivity to changes in ambient air temperature. The minimum ambient air temperature designed for the experiment was 25–29⁰C, while the higher end was 29–33⁰C. Several photosynthetic parameters were studied to support our analysis in sago photosynthetic activity, including diurnal leaf gas exchange, assimilation rate vs. CO₂ concentration, leaf greenness, leaf chlorophyll content, and photosynthetic rate vs. irradiance. We found that sago palm photosynthetic activity tends to be more sensitive to minimum than to maximum ambient air temperature. The plants exposed to higher air temperatures had dark green leaf color associated with higher rates of diurnal photosynthesis, chlorophyll content, and rubisco limited photosynthetic activity. They also exhibited higher trend in optimum irradiance absorption level. Consequently, maximum light energy dissipation occurred at higher temperatures.

Music has the ability to evoke a wide variety of emotions in human listeners. Research has shown that treatment for depression and mental health disorders is significantly more effective when it is complemented by music therapy. However, because each human experiences music-induced emotions differently, there is no systematic way to accurately predict how people will respond to different types of music at an individual level. In this experiment, a model is created to predict humans’ emotional responses to music from both their electroencephalographic data (EEG) and the acoustic features of the music. By using recursive feature elimination (RFE) to extract the most relevant and performing features from the EEG and music, a regression model is fit and accurately correlates the patient’s actual music-induced emotional responses and model’s predicted responses. By reaching a mean correlation of r = 0.788, this model is significantly more accurate than previous works attempting to predict music-induced emotions (e.g. a 370% increase in accuracy as compared to Daly et al. (2015)). The results of this regression fit suggest that accurately predicting how people respond to music from brain activity is possible. Furthermore, by testing this model on specific features extracted from any musical clip, music that is most likely to evoke a happier and pleasant emotional state in an individual can be determined. This may allow music therapy practitioners, as well as music-listeners more broadly, to select music that will improve mood and mental health.

Biological control provides a safer alternative to reduce the population of agricultural pest. Mirabilis jalapa is one of biopesticides containing chemical substances that have a feeding deterrent property against Spodoptera litura as folifagus insect pest. This study aimed to analyze the humoral and cellular immunes responses of S. litura after exposure to biopesticide extracted from M. jalapa. The measured indicator immune responses were activity of hemocyte, lectin, phenoloxidase (PO), and phagocytic activity. The results showed that the average total hemocyte was different significantly depending on the treatment. Exposure to 0.1% and 0.2% (w/v) of M. jalapa extract increased the total number of hemocytes as much as 38.08% and 64.15%, respectively. Lectin was quickly formed at 0.1% and 0.2% (w/v) concentrations. The amount of PO enzymes was significantly different at sublethal concentrations compared with control samples (P < 0.05). The highest increase in PO activity occurred at 2 h post-treatment and at M. jalapa extract concentrations of 0.2% (592.33 IU/mg) and 0.1% (521.33 IU/mg), whereas the highest concentration of the extract (0.8% w/v) caused a decrease in lectin and PO activities. In terms of phagocytic activity, the proportion of phagocytosis cells were 47.62% in control group, and decreased significanlty in both concentrations exposure.

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

Small non-coding RNAs (sRNAs) are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing, and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting), are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3’ UTR, 5’ UTR, CDS-binding). These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting). While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved, and how sRNAs integrate with complex regulatory networks.

In this study, we applied a central composite design to estimate independent variables and establish optimal conditions of filtration rate and feces production that enhance filtration of suspended organic matter by the freshwater mussels Sinanodonta woodiana. The results indicated that statistical design methodology offers an efficient and feasible approach for high filtration and low feces production condition optimization. The proposed model equation takes into account the quantitative effect of variables and also the influence of interactions among variables on mussel filtration rate. Under the optimal experimental conditions (mussel size, 13.0 ± 0.2 cm; water current, 17.5 L/h), the experimental filtration rate of 4.47 ± 1.82 L/mussel/h showed a degree of correspondence with the predicted value of 8.4 L/mussel/h, which verified the practicability of this optimum strategy.

Study background and aims: Laparoscopic cholecystectomy is one of the most frequently performed interventions in departments of general surgery. One of the most important aims in achieving perioperative stability of these patients is diminishing the impact of general anesthesia on the hemodynamic stability and the optimization of anesthetic drug doses based on the individual clinical profile of each patient. The objective of this study is the evaluation of the impact monitoring the depth of anesthesia through Entropy (state entropy – SE and response entropy -RE) has on the hemodynamic stability and on the doses of volatile anesthetic. Material and Methods: This is a prospective, observational, randomized, monocentric study carried out between January 2019 and December 2019 in the Clinic of Anesthesia and Intensive Care from the “Pius Brînzeu” Emergency County Hospital in Timișoara, Romania. The patients included in the study were divided in two study groups; patients in Group A (target group) received multimodal monitoring that included monitoring of standard parameters and of Entropy (SE and RE), while patients in Group B (control group) only received standard monitoring. Anesthetic dose in group A were optimized to achieve a target entropy of 40-60. Results: 68 patients met the inclusion criteria and were allocated to one of the two study groups, Group A (N=43) and Group B (N=25). There were no statistically significant differences identified between the two groups for both demographical and clinical data (p>0.05). Statistically significant differences have been identified for the number of hypotensive episodes (p = 0.011, 95% CI 0.1851 to 0.7042) and for the number of episodes of bradycardia (p < 0.0001, 95% CI 0.3296 to 0.7923). Moreover, there was a significant difference in the Sevoflurane consumption between the two study groups (p = 0.0498, 95% CI -0.3942 to 0.9047). Conclusions: The implementation of the multimodal monitoring protocol that includes the standard parameters and the measurement of Entropy for determining the depth of anesthesia (SE and RE) lead to a considerable improvement in perioperative hemodynamic stability. Optimizing the doses of anesthetic drugs based on the individual clinical profile of each patient leads to a considerable decrease in drug consumption as well as to a lower incidence of hemodynamic side-effects.

Coronavirus disease 2019 (COVID-19) since its declaration as a pandemic by world health organization (WHO) has spread across the various continent with little known about the most effective public health response for containing and mitigating the transmission of the epidemic. It is important to state that some authors have published on the lessons learned from transmission and management of COVID-19 infection but only a few considered it from the Africa perspective. Despite the late arrival of the pandemic in Africa and the notion that the virus may not thrive because of the high temperature in the continent; today the narrative has changed with the number of infected patients increasing daily. Herein, the authors have shared their perspectives and opinions on the dynamics and response to COVID-19 from Africa context to create more awareness and approach in mitigating the spread of the virus should the continent becomes the epicenter of COVID-19.

The Galvanic Skin Response (GSR, also widely known as electrodermal activity EDA) is one of the signals related to this emotional reaction. Given the sparsity of studies related to and the variety of devices, we experimented at the Human Health Activity Laboratory with 17 healthy subjects. The goal is to know the variability of detection changes in the electrodermal activity among a test group with heterogeneous respondents in response to valence and arousal stimuli, correlating GSR biosignals measured from different body sites. We experiment with the right and left wrist, left fingers, the right foot's inner side using Shimmer3GSR, and Empatica E4 sensors. Results indicate as the most promising homogeneous GSR measure place the left fingers and right foot. Results suggest that due to a significantly strong correlation among the inner side of the right foot and left fingers and moderate correlations with the right and left wrist, the foot is a good place to measure EDA. This paper also contributes knowledge about some wearable sensor technologies available in the market. Shimmer3GSR sensor may be better reliable to homogenous detecting electrodermal activity changes, as these have fewer anomalies among the respondents. However, we found some anomalies in signals from the Empatica E4 sensor, which we discuss in this work.

Some wind farms have implemented automated camera\textendash based monitoring systems e.g. IdentiFlight to mitigate the impact of wind turbines on protected raptors. These systems have effectuated the collection of large amounts of data that can be used to describe flight behavior in a novel way. This data uniquely provides both flight trajectories and images of individual birds throughout their flight trajectories. The aim of this study was to evaluate how this unique data could be used to create a robust quantitative behavioral analysis, that could be used to identify risk prone flight behavior and avoidance behavior thereby in the future assess collision risk. This was attained through a case study at a wind farm on the Swedish island Gotland, where golden eagles (Aquila chrysaetos), white-tailed eagles (Haliaeetus albicilla), and red kites (Milvus milvus), were chosen as the selected bird species. The results demonstrate that flight trajectories and bird images can be used to identify high risk flight behavior and thereby also used to evaluate collision risk and avoidance behavior. This study presents a promising framework for future research, demonstrating how data from camera\textendash based monitoring systems can be utilized to quantitatively describe risk prone behavior and thereby assess collision risk and avoidance behavior.

Complete pathologic response (pCR) predicts the long-term outcome of neoadjuvant treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers able to guide adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether shifts in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1-4 and in a total of 131 patients before and 48h after cycle 1. The prognostic significance of the results was evaluated by log-rank tests of Kaplan–Meier estimates. Treatment resulted in a 2-fold increase of sTK1 before and 3-fold increase 48h after the cycles, except for the first cycle, where half of patients reacted with a decrease (post/pre sTK1- ratio <1.12) and the other half reacted with an increase (ratio >1.12). OS rates in ER+ patients with ratios of >1.12 and <1.12 were 97.7% and 78% (p=0.005), respectively, and DFS rates were 90.7% and 68% (p=0.006), respectively. Thus, response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.

Emergency Management has not developed in a cohesive or comprehensive manner. Differing terms are used to name identical concepts. A standard comprehensive doctrine for the important development of emergency management is needed. In this paper I explain a doctrinal framework for emergency management. The paper states a clear identification of the five dimensions, and each of their components, necessary to the informed practice of Emergency Management. Although emergencies vary in cause and severity, the process of Emergency Management necessary for optimal handling of these emergencies varies little. The “All Hazards Approach” to emergency management establishes and reinforces commonality in processes, procedures, planning templates and organizational structure. The three types of agencies associated with emergency management activities are discussed, including the subject matter agency, coordinating agency, and supporting agency. The four critical functions of emergency management are detailed, and include mitigation, preparedness, response, and recovery, often all carried out concurrently. The ten activities, and seven resources of emergency management are highlighted. There are many ways to represent the integration of these five dimensions, to ensure completeness, while ensuring clarity; the two most common are described. When experts in Emergency Management follow the doctrine, they can coordinate all those involved to be sure that all aspects of any hazard are considered, and that all organizations/agencies, functions, activities, and resources of Emergency Management are coordinated and optimally active. Following this process is the only way to ensure the best outcomes from any emergency.

Different water treatment regiments are revealed to have potential in enriching antibiotic resistant bacteria (ARB). Advanced oxidation processes (AOPs) based disinfection techniques have been studied widely in the recent times due to their advantages over conventional treatment methods. However, bacterial response and adaptations against the hostile environments of AOPs is not clearly understood yet. Based on the existing knowledge on the ways in which bacteria surpass the antibiotic treatment, here we propose few important aspects of bacterial adaptation which could be true for AOPs as well since both antibiotics and AOPs generate reactive oxygen species (ROS) during their modes of action. We discuss the plausible role of ROS in the selection of ARB and bacterial heterogeneity as a strategy to bypass the lethal action of AOPs. Understanding bacterial adaptation during disinfection plays a vital role in devising strategies to outclass the bacterial survival. Hence, more importance should be given to such studies in the near future for the successful implementation of AOPs.

Nonhost disease resistance is the most common type of plant defense mechanism against potential pathogens. In this study, the metabolic enzyme formate dehydrogenase (FDH1) was identified to be involved in nonhost disease resistance in Nicotiana benthamiana and Arabidopsis thaliana. In Arabidopsis, AtFDH1 was highly upregulated in response to both host and nonhost bacterial pathogens. Arabidopsis Atfdh1 mutants were compromised in nonhost resistance, basal resistance, and gene-for-gene resistance. The expression patterns of salicylic acid (SA) and jasmonic acid (JA) marker genes after pathogen infections in Atfdh1 mutant indicated that SA is most likely involved in the FDH1-mediated plant defense response to both host and nonhost bacterial pathogens. Previous studies reported that FDH1 localizes to only mitochondria, or both mitochondria and chloroplasts. Our results showed that the AtFDH1 localized to mitochondria and the amount of FDH1 localized to mitochondria increased upon infection with host or nonhost pathogens. Interestingly, the subcellular localization of FDH1 was observed in both mitochondria and chloroplasts after infection with a nonhost pathogen in Arabidopsis. We speculate that FDH1 plays a role in cellular signaling networks between mitochondria and chloroplasts to produce coordinated defense responses such as SA-induced reactive oxygen species (ROS) generation and hypersensitive response (HR)-induced cell death against nonhost bacterial pathogens.

In this work, an algorithm for the scheduling of household appliances to reduce the energy cost and the peak-power consumption is proposed. The system architecture of a home energy management system (HEMS) is presented to operate the appliances. The dynamics of thermal and non-thermal appliances is represented into state-space model to formulate the scheduling task into a mixed-integer-linear-programming (MILP) optimization problem. Model predictive control (MPC) strategy is used to operate the appliances in real-time. The HEMS schedules the appliances in a dynamic manner without any a priori knowledge of the load-consumption pattern. At the same time, HEMS responds to the real-time electricity market and the external environmental conditions (solar radiation, ambient temperature etc). Simulation results exhibit the benefits of proposed HEMS by showing the reduction of up to 47% in electricity cost and up to 48% in peak power consumption.

We are in amidst of COVID-19 pandemic. Since Dec 2019, severe acute respiratory corona virus (SAR-CoV-2) has infected more than half a billion people killing nearly 7 million people worldwide. Now the BA.5 variant of SARS-CoV-2 is causing mayhem and driving the global surge. Epidemiologist are aware of the fact that this virus is capable of escaping immunity and likely to infect the same person multiple times despite adequate vaccination status. Elderly people of age more than 60 years and those with underlying health conditions are considered as high-risk who are likely to suffer complications and death. While it is tempting to frame complications and mortality from COVID-19 as a simple matter of too much of a virulent virus in too weak of a host, much more is at play here. Framing the pathophysiology of COVID-19 in the context of the Chrousos and Gold model of the central stress response system can shed insight into its complex pathogenesis. Understanding the mechanisms by which pharmacologic modulation of the central stress response system via administration of clonidine and/or dexamethasone may offer an explanation as to why a viral pathogen can be well tolerated and cleared by one host while inflaming and killing another.

The efficiency of performance in various sports has the development of certain specific skills at its core. In ice hockey, both the technical aspects (techniques, stance) and the cognitive ones (keeping attention on the puck, game strategy, etc.) are highly important. This study is aimed at the identification of specific features that determine the performance efficiency of professional hockey players. We used virtual reality (VR) to study the differences between professional ice hockey players and novices in terms of motor responses to the puck’s presentation on different levels of difficulty. The study involved 22 participants, 13 of them being professional ice hockey players (M_age=20±2.9; mean age of training experience М=14.18±3.8) and 9 being not experienced participants (M_age=20±1.4). The study showed that the stick response time of professional hockey players is significantly higher (0.98 ms vs 1.5 ms, p≤0.05) in more difficult situations close to a real game. Moreover, professionals proved to have more stable movement patterns of the knee and hip joints. They also make fewer head movements as a response to stimuli during all runs (0.66 vs 1.25, p≤0.05). Therefore, the results indicate specific spatial-temporal, technical and tactical, and energetic determinants, that ensure higher performance efficiency in hockey players

Endometriosis is an oestrogen-dependant reproductive disease, with genetic, vascular, neural, inflammatory and auto-immune characteristics. There are many theories about the etiology of endometriosis, however, all of these theories have limitations and do not explain all the locations that endometriosis is found or types of patients with endometriosis. The objective of this paper is to postulate the hypothesis that endometriosis is caused by Maternal Microchimerism, the presence of maternal cells in the fetus. A literature review was conducted, analysing the characteristics, current etiological theories of endometriosis, theory limitations and relationship of maternal microchimerism and endometriosis. At time of writing, there was no literature on maternal microchimerism and endometriosis. These results suggest that Maternal Microchimerism could be a cause of endometriosis. This could account for the genetic and auto-immune characteristics seen in people with endometriosis, inducing a micro-environment for vascular, neural and epigenetic changes. This could also account for account for endometriosis seen in non-menstruating patients, such as men, fetuses and post-menopausal women and endometriosis found in non-peritoneal locations. If the hypothesis of Maternal Microchimerism is correct, endometriosis could be considered a pregnancy-related disease that could affect all humans, changing the accepted demographics of patients and potentially new diagnostic techniques and treatment options for patients with endometriosis. Further studies are needed to test this hypothesis.

We conducted many model simulations to understand the causes of the damages of coronavirus (COVID-19) to lung tissue and constructed a diagram showing apparent viral reproduction, immune response and damage accumulation curves. We found that lung damages include virus-caused damage, tissue damage caused by immune responses and tissue damage caused by accumulated wastes. The virus-caused damage is proportional to the phase lag between the viral reproduction curve and the delayed adaptive immune response curve, while waste-induced damage is attributed to imbalance in removing viral, cellular and metabolic by-products. We found that treatment strategies should slow down viral reproduction and speed up immune response, and improve blood micro-circulation in the lungs. Consistent with the strategies, measures are taken to void direct lung infection, strengthen innate responses, promote immune responses, dilute viral concentration in lung tissue, maintain waste removal balance, protect heart and kidneys, control other infections, avoid allergic reactions and other inflammation, etc. We show that medical, dietary, emotional, lifestyle, environmental, mechanical factors, etc. may be simultaneously used to mitigate lung damages and prove that multiple factor health optimization method is magnitudes more powerful than a single factor treatment. Such a method does not depend on molecular specificity and can be used in parallel to antiviral drugs.

In metastatic pancreatic cancer patients non eligible to surgery, signal-targeted therapies so far failed to show a significant amelioration of survival. These therapeutic options were tested in Phase II/III clinical trials mostly in combination with the reference treatment Gemcitabine. These innovative therapies aim at annihilating the oncogene dependency; they also aim at renormalizing the tumoral stroma to allow immune cell function or re-vascularisation. Transcriptomics and genomics large scale analysis show the great heterogeneity of pancreatic cancers and failed to clearly delineate specific oncogene dependency besides oncogenic Kras. In this review, we will describe the most recent proteomic data in pancreatic tumors and its metastasis, which could help at identifying their major signalling dependencies, as well as explain why they are intrinsically resistant to signal-targeted therapies. We will also discuss why PI3K signalling, as a paradigm of pro-tumorigenic cell signalling and of tumoral adaptative resistance to drugs, is a relevant target in this context.

Proteases are integral enzymes of the plant immune system. Multiple aspects of defence are regulated by proteases, including the hypersensitive response, pathogen recognition, priming and peptide hormone release. These processes are regulated by unrelated proteases residing at different subcellular locations. In this review we discuss ten prominent plant proteases contributing to the plant immune system, highlighting the diversity of roles they perform in plant defence.

Immune dysfunction has long been reported by medical professionals regarding astronauts suffering from opportunistic infections both during their time in space and a short time period afterwards once back on Earth. Various species of prokaryotes on board these space missions or cultured in a microgravity analogue exhibit increased virulence, enhanced formation of biofilms, and in some cases develop specific resistance for specific antibiotics. This poses a substantial health hazard to the astronauts confined in constant proximity to any present bacterial pathogens on long space missions with a finite number of resources including antibiotics. Furthermore, some bacteria cultured in microgravity develop phenotypes not seen in Earth gravity conditions, providing novel insights into bacterial evolution and research.

The Rasch model is one of the most prominent item response models. In this article, different item parameter estimation methods for the Rasch model are compared through a simulation study. The type of ability distribution, the number of items, and sample sizes were varied. It is shown that variants of joint maximum likelihood estimation and conditional likelihood estimation are competitive to marginal maximum likelihood estimation. However, efficiency losses of limited-information estimation methods are only modest. It can be concluded that in empirical studies using the Rasch model, the impact of the choice of an estimation method with respect to item parameters is almost negligible for most estimation methods. Interestingly, this sheds a somewhat more positive light on old-fashioned joint maximum likelihood and limited information estimation methods.

Background: Twitter is a major tool for communication in emergencies such as natural disasters. This online social network allows the user to produce content, and it is not designed exclusively for news releases, as opposed to other service providers. Aim: The aim of this study is to investigate Twitter uses in natural disasters and pandemics. Methods: The included studies reported the role of Twitter in natural disasters. The studies that report in settings other than the natural disasters (such as man-made disasters) and other social media were excluded. Electronic databases for a comprehensive literature search including MEDLINE, Web of Science, CINAHL, PsycINFO, Cochrane Register of Controlled Trials (CENTRAL) and EMBASE were used to identify the records that match the mentioned inclusion criteria published till May 2020. The study characteristics were extracted from the qualified studies including year of publication, findings, and geographical location of the study conduct. A narrative synthesis for this literature review was used. Results: The search identified 822 articles of which 780 articles were removed, 256 were not available, 311 papers were not relevant, 16 were duplicated articles, and 197 were non-related to the emergencies. 45 articles met the selection criteria and were included in the review. eleven themes were found in the narrative synthesis including early warning, disseminating information and misinformation, advocacy, personal gains, assessment, various roles of organizations, public mood, geographical analysis, charity, using influencers, and trust. Conclusions: It is recommended that influential individuals be identified in each country and community before disasters occur so that the necessary information can be disseminated in response to disasters. Preventing the spread of misinformation is one of the most important issues in times of disaster, especially pandemics. Disseminating accurate, transparent, and prompt information from relief organizations and governments can help. Also, analyzing Twitter data can be a good source for understanding the mental state of the community, estimating the number of injured people, estimating the points affected by natural disasters, and modeling the prevalence of epidemics. Therefore, various groups such as politicians, the government, non-governmental organizations, aid workers, and the health system can use this information to plan and implement interventions.

In 2014, the outbreak of adenoviral pneumonia occurred in Korean military training center. However, there is limited data on characteristics of fever and its response to antipyretics therapy in immunocompetent adults with adenoviral positive community-acquired pneumonia (CAP). Medical records of patients who were admitted to Armed Forces Chuncheon Hospital for treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. We evaluated demographics, clinico-laboratory findings and radiologic findings at admission were compared between adenovirus positive (Adv) group and adenovirus negative (non-Adv) group. Out of 251 military personnel with CAP during the study periods, 67 were classified into Adv group while 184 were Non-Adv group. Patients with Adv group had a longer duration of fever after admission and symptom onset. Adv group patients had a higher mean temperature at admission and more observed over 40 and 39 to 40℃. Adv group patients had more commonly observed no response to antipyretic treatment and adverse events after antipyretics use. Length of hospital stay had no significant difference between two groups and no patient died in both groups. In our study, Adv positive CAP in patients with immunocompetent military personnel had distinct characteristics of fever and response to antipyretic treatment.

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.

In this paper a dynamic relationship between the CO2 emissions in Finland, Norway and Sweden is presented. With the help of a VAR(2) model, and using the Granger terminology, it is shown that the emissions in Finland are affecting those in Norway and Sweden. Other aspects of this dynamic relationship are presented as well.

LncRNA are involved in multiple regulatory pathways, its versatile mode of action has disclosed a new layer in gene regulation. They are reportedly modulated during plant development, with specific tissue functions and in response to stresses. In this study, we analyzed LncRNA from leave samples collected from the legume Copaifera langsdorffii (copaiba) from two divergent ecosystems: Cerrado (CER) and Atlantic Rain Forest (ARF). We identified 8020 novel lncRNAs, from which 2893 transcripts were regulated above 2-fold and 566 above 5-folds in either condition. This putative lncRNA set was compared with seven Fabaceae genomes, of which 1747 and 1879 transcripts (from ARF and CER, respectively) aligned to at least two genomes. Further, 2194 copaiba lncRNAs were successfully mapped to at least one of six Fabaceae transcriptomes. The secondary structures of the lncRNAs that were conserved and differentially expressed between the populations were predicted using in silico methods. Our results indicate the potential involvement of lncRNAs in the adaptation of C. langsdorffii to two different biomes.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

Time recordings of impulse-type oscillation responses are short and highly transient. These characteristics may complicate the usage of classical spectral signal processing techniques for a) describing the dynamics and b) deriving discriminative features from the data. However, common model identification and validation techniques mostly rely on steady-state recordings, characteristic spectral properties and non-transient behavior. In this work, a recent method, which allows reconstructing differential equations from time series data, is extended for higher degrees of automation. With special focus on short and strongly damped oscillations, an optimization procedure is proposed that fine-tunes the reconstructed dynamical models with respect to model simplicity and error reduction. This framework is analyzed with particular focus on the amount of information available to the reconstruction, noise contamination and non-linearities contained in the time series input. Using the example of a mechanical oscillator, we illustrate how the optimized reconstruction method can be used to identify a suitable model and to extract features from uni-variate and multivariate time series recordings in an engineering-compliant environment. Moreover, the determined minimal models allow for identifying the qualitative nature of the underlying dynamical systems as well as testing for the degree and strength of non-linearity. The reconstructed differential equations would then be potentially available for classical numerical studies, such as bifurcation analysis. These results represent a physically interpretable enhancement of data-driven modeling approaches in structural dynamics.

Abstract: Polylactic acid (PLA) is brittle in nature with extensive deformation property. For improvement of the end-use quality, it is of significant importance to enhance the producibility of fused deposition modeling (FDM)-printed objects in PLA. The purpose of this investigation is to boost toughness and to reduce the production cost of the FDM-printed tensile test samples with the desired part thickness. To attain the research purpose number of experiments are designed and analyzed by the Response Surface Method (RSM). The statistical analysis is performed to deal with this concern considering layer thickness, infill percentage, and extruder temperature as controlled factors. The tensile test specimens are printed based on the designed experiments, and the tensile strength tests are conducted by SANTAM 150 universal testing machine based on ASTM D638. The honeycomb internal fill pattern is applied for the production of light-weight and high-strength specimens. The area under Force- Extension curve up to fracture is acquired as the toughness of the printed specimens. This study also developed a modeling process using ANN and ANN-GA techniques for developing an accurate estimation for toughness, part thickness, and production cost as dependant variables. Results were evaluated by correlation coefficient and RMSE values. According to the modeling results, ANN-GA as a hybrid ML technique could successfully improve the accuracy of modeling about 7.5, 11.5 and 4.5 % for toughness, part thickness, and production cost, respectively, in comparison with those for the single ANN method. In the other side, the optimization results confirm that the optimized specimen is cost-effective and able to comparatively undergo deformation, which develops the usability of printed PLA objects. The research is accomplished under the constraints of PLA compatibility with existing fused deposition modeling setup without changing the functional hardware/software of the machine. Although the mechanical properties and dimensional accuracy of PLA have already been studied, there is little literature on the toughness of the printed PLA with honeycomb internal fill pattern.

The regulation of hepatic very-low-density lipoprotein (VLDL) secretion plays an important role in the pathogenesis of dyslipidemia and fatty liver diseases. VLDL is controlled by hepatic microsomal triglyceride transfer protein (MTTP). Mttp is regulated by carbohydrate response element binding protein (ChREBP) and small heterodimer partner (SHP). However, it is unclear whether both coordinately regulate Mttp expression and VLDL secretion. Here, adenoviral overexpression of ChREBP and SHP in rat primary hepatocytes induced and suppressed Mttp mRNA, respectively. However, Mttp induction by ChREBP was much more potent than suppression by SHP. Promoter assays of Mttp and the liver type pyruvate kinase gene revealed that SHP and ChREBP did not affect the transactivity of each other. Mttp mRNA and protein levels of Shp^/– mice were similar to those of wild-type; however, those of Chrebp^–/–Shp^–/– and Chrebp^–/– mice were much lower. Consistent with this, the VLDL particle number and VLDL secretion rates in Shp^–/–- mice were similar to wild-type, but were much lower in Chrebp^–/– and Chrebp^–/–Shp^–/–- mice. These findings suggested that ChREBP rather than SHP regulates VLDL secretion and that ChREBP and SHP do not affect the transactivities of each other.

Missing item responses are prevalent in educational large-scale assessment studies like the programme for international student assessment (PISA). The current operational practice scores missing item responses as wrong, but several psychometricians advocated a model-based treatment based on latent ignorability assumption. In this approach, item responses and response indicators are jointly modeled conditional on a latent ability and a latent response propensity variable. Alternatively, imputation-based approaches can be used. The latent ignorability assumption is weakened in the Mislevy-Wu model that characterizes a nonignorable missingness mechanism and allows the missingness of an item to depend on the item itself. The scoring of missing item responses as wrong and the latent ignorable model are submodels of the Mislevy-Wu model. This article uses the PISA 2018 mathematics dataset to investigate the consequences of different missing data treatments on country means. Obtained country means can substantially differ for the different scaling models. In contrast to previous statements in the literature, the scoring of missing item responses as incorrect provided a better model fit than a latent ignorable model for most countries. Furthermore, the dependence of the missingness of an item from the item itself after conditioning on the latent response propensity was much more pronounced for constructed-response items than for multiple-choice items. As a consequence, scaling models that presuppose latent ignorability should be refused from two perspectives. First, the Mislevy-Wu model is preferred over the latent ignorable model for reasons of model fit. Second, we argue that model fit should only play a minor role in choosing psychometric models in large-scale assessment studies because validity aspects are most relevant. Missing data treatments that countries can simply manipulate (and, hence, their students) result in unfair country comparisons.

The study presents a comparative approach between response surface methodology (RSM) and hybridized, genetic algorithm artificial neural network (GA-ANN) in predicting the water absorption, compressive strength, flexural strength split tensile strength and slump for steel fiber reinforced concrete. The effect of process variables such as aspect ratio, water cement ratio and cement content were investigated using the central composite design of response surface methodology. This same experimental design was used in training the hybrid-training approach of artificial neural network. The predicting ability of both methodologies were compared using the root mean sqaured error (RMSE), mean absolute error (MAE), model predictive error (MPE) and absolute average deviation (AAD). The RSM model was found more accurate in prediction compared to hybrid GA-ANN.

An immune-inflammatory response is accompanied by increased nitro-oxidative stress. The aims of this mechanistic review are to review: a) the role of redox sensitive transcription factors and enzymes, ROS/RNS production and the activity of cellular antioxidants on the activation and performance of macrophages, dendritic cells, neutrophils, T cells, B cells and natural killer cells; b) the involvement of high-density lipoprotein (HDL), apolipoprotein (Apo)A1, paraoxonase (PON)-1, and oxidized phospholipids in the regulation of the immune response; and c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor (NF)-κB, HIF1alpha, the mechanistic target of rapamycin (mTor), the phosphatidylinositol 3‑kinase (PI3K) / protein kinase B (AKT) signalling pathway, mitogen-activated protein (MAP) kinases, 5' AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR). The performance and survival of individual immune cells is under redox control and sensitive to intracellular and extracellular levels of ROS/RNS and is heavily influenced by cellular anti-oxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2 (Nrf-2), and the HDL complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, those redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.

The Oryzaephilus surinamensis L. (Coleoptera: Silvanidae), is widely distributed all over the world, this beetle causes serious damage to stored products. Much attention has been paid to use food attraction or food volatile as a non-pollution method to achieve pest management. However, in this study, six most attractive food to O. surinamensis were selected among thirty eight food. Furthermore, the food mixture M17 with the best attractiveness were selected among the eighteen food mixtures combined by these six foods at different ratio. Subsequently food mixture M17 were tested in actual barn and compared with commercial attractant. We collected the volatile from food mixture, the volatile compounds attractive to this beetle also. We identified six electrophysio-logically active compounds responsible for the attraction of O. surinamensis, among the six chemically identified compounds, nonanal, dodecane, tridecaneand β-caryophyllene significantly attracted O. surinamensis when tested individually in behavioral assays. Blend of six chemicals according to food volatile concentration was most attractive to the beetles. The findings of this study reveal that food mixture M17 and food volatile can be potentially used for development of effective attractants for management of O. surinamensis.

Acrylamide (AA) present in food is considered a harmful compound for humans, but it exerts impact on microorganisms too. The aim of the study was to evaluate the impact of AA (at conc. 0-10 µg/mL) on the growth of bacteria (Leuconostoc mesenteroides, Lactobacillus acidophilus LA-5) and yeasts (Saccharomyces cerevisiae, Kluyveromyces lactis var. lactis), which naturally occur in food products. Moreover, we decided to verify whether these microorganisms could decompose acrylamide. Our results proved that AA can stimulated the growth of L. acidophilus and K. lactis. We have also reported, to the best of our knowledge for the first time, that probiotic strain of bacteria L. acidophilus LA-5 is able to degrade AA by amidase production and hence can utilize AA as a source of carbon and nitrogen if they lack in the environment. The conducted Response Surface Methodology indicated that pH as well as incubation time and temperature significantly influenced the amount of ammonia released from acrylamide by the bacteria. Concluding, our studies suggest that some strains of bacteria present in milk fermented products can exert additional beneficial impact by acrylamide degradation and preventing against its harmful impact on human body and other members of intestinal microbiota.

In plants and animals, endogenous biological molecules, termed damage-associated molecular patterns (DAMPs) or alarmins, are released by damaged, stressed or dying cells following abiotic stress such as radiation and drought stress. In turn, a cascade of downstream signaling events is initiated leading to the up-regulation of defense-related genes. In the present study, in an effort to investigate the conservation status of the molecular mechanisms implicated in the danger signaling, thorough in silico phylogenetic and structural analyses of the effector biomolecules were performed in taxonomically diverse plant species. On the basis of our results, the defense mechanisms appear to be largely conserved within the plant kingdom. Of note is our finding that the sequence and/or function of several components of these mechanisms were found to be conserved in animals, as well.

Spondyloarthritis comprises of a group of inflammatory diseases of the joints and spine with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

Biosensors are indispensable tools to follow plant’s immunity as its spatiotemporal dimension is key in withstanding the complex plant immune signaling. The diversity of genetically encoded biosensors in plants is expanding, covering new analytes with ever higher sensitivity and robustness, but their assortment is limited in some aspects, such as their use to follow biotic stress response, employing more than one biosensor in the same chassis and their implementation into crops. In this review, we focused on the available biosensors that encompass these aspects. We show that in vivo imaging of calcium and reactive oxygen species is satisfactorily covered with the available genetically encoded biosensors, while on the other hand they are still underrepresented when it comes to imaging of the main three hormonal players of the immune response, salicylic acid, ethylene and jasmonic acid. Following more than one analyte in the same chassis, upon one or more conditions has so far been possible by using the most advanced genetically encoded biosensors in plants which allow to monitor calcium and two main hormonal pathways involved in plant development, auxin and cytokinin. These kinds of biosensors are also the most evolved in crops. In the last section, we gathered the challenges in the use of the biosensors and showed some strategies to overcome them.

Although transplantation procedures have been developed for patients with end-stagec hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents, such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity is commonly occurred in clinical situations, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms whereby CNIs cause neurotoxicity include: increasing the permeability or injury of the blood-brain barrier, alterations of mitochondrial function, and alterations in electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures; mycophenolate mofetil induces depression and headache; methotrexate affects the central nervous system; mouse monoclonal immunoglobulin G2 antibody against cluster of differentiation 3 also induces headache; and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms have greatly reduced neurotoxic events. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, using drugs to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize the recent topics on the mechanisms of neurotoxicity of immunosuppressive drugs. In addition, some information about neuroprotective effects of several immunosuppressants are also discussed.

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

Aims: Adolescence is a critical period because the brain is involved in the process of maturation that entails cognitive functions. On the way of maturation, an individual’s inhibitory control undergoes many changes and becomes vulnerable to different thrill-seeking like smoking, drinking, and so on. Smoking is highly prevalent among teenagers that are trying to take control of their behaviors in order to join society. They experience antisocial behavior too which is a trait that can lead adolescents to addiction. This trait is an inevitable part of psychopathy. Inhibitory deficits and psychopathy have been widely reported in addiction studies. The current study tried to investigate the relationship between psychopathic traits and behavioral inhibition between male smokers and non-smoker teenage students.Materials & Methods: Statistical sample of this research is 62 teenage students aged 17 years that are divided into smoker and non-smoker groups. The participants have been chosen through random sampling from the population of 10 high schools. The data have been gathered in Kordkoy and Gorgan in Golestan province. Behavioral bias has been measured by Go/NoGo task and psychopathic traits through youth psychopathic traits inventory. Also, the short form of Wechsler Adult Intelligence Scale test has been executed and used as a control variable.Findings: A meaningful difference has been found between the performance of smoker and non-smoker groups in Go/No Go task and psychopathic traits that are smokers performed weaker in comparison with non-smokers and psychopathic traits of smokers were meaningfully higher than non-smokers. On the other hand, there was no significant difference between these two groups in their Wechsler Adult Intelligence Scale scores.Conclusion: The results have shown that smokers have higher psychopathic traits and lower behavioral inhibition when compared with their non-smoker peers. According to the results of current research, smoking can decline the cognitive functions.

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.