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.

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.

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.

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.

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.

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.

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.

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.

SHANK3 encodes scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+inhibitory neurons – the key players in generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response(ASSR). Here we describe a clinical and neurophysiological phenotype of a 15-years old girl (SH01) with microduplication of 16389 bp in 22q13.33, affecting the SHANK3 gene in comparison to typically developing children (n=32). EEG were recorded during the binaurally presentation of 40-Hz clicks’ trains lasting for 500 ms with inter-trial intervals 500-800 ms. SH01 was diagnosed with mild mental retardation and learning disabilities(F70.88) and had problems with reading and writing, as well as smaller vocabulary than TD peers. Her clinical phenotype generally resembled the phenotype of previously described patients with 22q13.33 microduplication. SH01 had mild autistic symptoms but below the threshold for ASD diagnosis. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential(ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD’s ASSR. Absence of 40-Hz ASSR in patient with microduplication, affected SHANK3 gene, indicates deficient temporal resolution of the auditory system, that might underlie language problems, and represent neurophysiological biomarker of SHANK3 abnormalities.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Research shows that in earthquakes the ground response changes in areas where there are underground cavities. Due to the fact that subways and underground tunnels pass from beneath buildings in urban areas, these changes in ground response have a direct impact on the seismic behavior of structures. In this study, first by model validity and reliability of the results, steel structures modeling was conducted and steel structure behavior was evaluated due to Tunnel-Soil-Structure seismic interaction. Parameters studied are number of stories, soil type, tunnel depth, horizontal tunnel-structural distance and dynamic loading. Considering that one of the most important parameters of structural control is drift and story displacement, so this important factor will be considered. The results show that tunneling has a direct effect on the rate of structural displacement and increases the structural response. Also, the behavior of the structure is affected by the position of the structure at the ground level and the position of the tunnel and this should be considered during the design phase of the structures.

This paper presents performed Ansys numerical simulation on WindFloat structures. It contributes to the methodology of calculation based on CFD instruments to study the movements of the waves on semi-submersible stationary structures and highlights the importance of using RAO functions. RAO numerical approach developed can be applied to design semisubmersible WindFloat structures in order to fulfill essential requirements regarding operational safety and design. Numerical methodology was designed in accordance marine loads and the I.T.T.C. recommendations. The numerical RAO results for regular wave movements include many elements for the semi-submergible structure. Close results to open sea operation can be achieved by constant improvement in numerical simulation methodologies. The work opens the way for further hydrodynamic development on irregular waves for realistic hydrodynamic and structural response of the actual semi-submersibles at sea. The results demonstrate the accuracy of RAO function approach for specific WindFloat in Jonswap spectrum.

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.

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.

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.

Traditional potential transformers have problems of large volume, difficulty in insulation, iron core saturation, ferroresonance overvoltage and poor transient response characteristics. The voltage sensor based on the principle of electric field coupling and differential input structure does not need to contact the measured object or ground, and can avoid the above problems. However, it requires a sufficiently high capacitance between the differential electrodes to obtain sufficient accuracy and a high voltage division ratio. The existing method of using mutual capacitance between the differential electrodes will cause many problems and fail to meet the practical needs. To solve the above problems, this paper innovatively uses multi-layer ceramic capacitor to replace the mutual capacitance and designs a new type of voltage sensor. In addition, by using single bypass small resistance grounding method to increase the input impedance of the differential signal processing circuit, error of the sensor is further reduced. The experimental results show that the sensor has excellent accuracy and great transient response characteristics. The ratio error under power frequency is within ±0.5% and the phase error is within 1. The ratio error in the range of 500 Hz∼30 kHz is within ±5% and the phase error is within 5. Moreover, it has the advantages of low cost, miniaturization, flexible shape and easy to adjust the voltage division ratio. These characteristics indicate that the sensor has good voltage measurement and sensor network potential.

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.

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.

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.

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 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).

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.

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.

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.

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.

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.

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.

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.

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.

Metabolic disorders have become among the most serious threats to human health, leading to severe chronic diseases such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, as well as cardiovascular diseases. Interestingly, despite the fact that each of these maladies has different physiological and clinical symptoms, they appear to share certain pathological traits such as intracellular stress and inflammation induced by metabolic derangements stemmed from over nutrition frequently aggravated by modern sedentary life style. These modern ways of living inundate cells and organs with saturating levels of sugar and fat, leading to glycotoxicity and lipotoxicity that induce intracellular stress signaling ranging from oxidative to ER stress response to cope with the metabolic insults [1]. In this review, we discuss the roles played by cellular stress and its responses in shaping metabolic disorders. We have summarized here current mechanistic insights explaining the pathogenesis of these disorders. These are followed by a discussion of the latest therapies targeting the stress response pathways.

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.

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.

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.

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.

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.

The role of the immune response to SARS-CoV-2 infection is not yet well known, in particular about the persistence of circulating antibodies. The aim of the study is to compare the results of two automated systems for the determination of IgG antibodies against SARS CoV-2 and to assess the time course of the IgG response after the onset of symptoms for a period longer than that evaluated to date. IgG were measured in 98 specimens of 55 subjects with COVID-19 (time from the onset of symptoms from 3 to 109 days) using the automated tests "Abbott SARS-COV-2 IgG" and the "MAGLUMI 2019-nCoV IgG". The two methods had a concordance of 91.8%, but the quantitative correlation showed very dispersed results. All the specimens resulted positive after 17 days from the onset of the synptoms. However, the median concentrations of IgG, after a rapid increase up to about 20 days, quickly decrease to about 15% of the maximum for Maglumi. The same samples measured by Architect showed a quite constant trend up to 80 day, and then an only moderate decline. The titer of IgG against SARS-CoV-2 in patients exposed to COVID-19 may significantly and rapidly decrease, with a different time-course depending on the method used for the determination.

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.

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.

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.

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.

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

This paper proposes the use of non-uniform extended surfaces installed externally to the tubes of the radiation section of fired heaters, in order to obtain a better heat flux distribution to the coils. To this end, the heat transfer mechanisms present in such equipment were studied through computational fluid dynamics (CFD), using simplified geometries that represent typical sizes of fired heaters. Also, a simplified model for the combustion was considered. Although this model oversimplifies the physics of the problem, it was able to give satisfactory results for the parameters being optimized, considering the main objective of this paper, that is to minimize the non-uniformity of heat flux in the tubes of the radiant section of fired heaters. It was possible to obtain optimized geometric parameters for different types of extended surfaces evaluated, coupling the results of these models with the Particle Swarm optimization method through the use of a response surface technique,. The results indicate a significant improvement in the uniformity of the heat flux distribution to the tubes through the use of the proposed extended surfaces. Thus, this solution reveals to be an interesting alternative to reduce the risks of fluid degradation and coking formation. Future studies must investigate the non-uniformity of the heat flux due to the presence of the flame and consider the interaction between the reactive flow and the participating medium. Nevertheless, this paper presents some results that justify the optimization of such extended surfaces taking into consideration thermal radiation.

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.

We present a new perspective of the link between QED and Maxwell's equations. We demonstrate that the interpretation of $\mathbf{D}=\varepsilon_{0} \mathbf{E}$ as vacuum polarization is consistent with QED. A free electromagnetic field polarizes the vacuum, but the polarization and magnetization currents cancel giving zero source current. The speed of light is a universal constant, while the fine structure constant, which couples the electromagnetic field to matter, runs as it should.

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.

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.

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.

Bacterial pathogens have been attributed to poultry housing structure, financial strength, and incessant use of antibiotics, variable seasons and management systems practiced. Variant forms of bacterial pathogens can be detected by recognizing the molecular pattern of the pathogens through an innate immune mechanism such as mannose-binding lectin. Mannose-binding lectin (MBL) possesses an innate pattern recognition molecule that easily sequestered to region of infections and inflammations. This works by attaching itself to antigen surface thus hinders proliferation and disease activity in the host organism. Baker’s method, nephelometric assays technique, Enzyme-Linked Immunosurbent Assay technique, Polymerase Chain Reaction, Deoxyribonucleic Acid typing and other biotechnology related methods are techniques used in detecting and quantifying MBL. Mannose-binding lectin levels in serum can be influenced by age, management systems, feed formulation strategies and seasons. Therefore, knowledge of MBL should be encouraged in all aspect of poultry production, in order to discourage incessant use of drugs at a slight exposure to prevailing bacterial which can help in maximizing cost.

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.

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.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e. the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (&gt;30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (&lt;30.6%) N30-CTav group (P&lt;0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of &gt;30.6% might be a　predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

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.

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

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.

Depending on human body conditions and environmental conditions, it is sometimes difficult to conduct subject experiments. In such cases, it is effective to use a thermal manikin. There are few studies that investigate the effect of the non-uniform and asymmetric outdoor thermal environment on the mean skin temperature. The purpose of this study is to clarify the influence of the non-uniform and asymmetric thermal radiation of short-wavelength solar radiation in an outdoor environment on the calculation of the mean skin temperature. The skin temperature of the front of the coronal surface, which was facing the sun and where the body received direct short-wavelength solar radiation, and the skin temperature of the rear of the coronal surface, which was in the shadow and did not receive direct short-wavelength solar radiation were respectively measured. The feet, upper arm, forearm, hand and lower leg, which are susceptible to short-wavelength solar radiation in a standing posture, had a noticeable difference in skin temperature between sites in the sun and in shade. The mean skin temperature of sites facing the sun was significantly higher than the mean skin temperature of those in the shade.

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.

Abstract Introduction:The Robert Koch Institute (RKI) managed the exchange of cross-border contact tracing data between public health authorities (PHA) in Germany and abroad during the COVID-19 pandemic. Aim: We aimed to describe the extent of RKI cross-border contact tracing and the challenges experienced. Methods:We analysed cross-border COVID-19 contact tracing events from 03 February to 05 April 2020 using information exchanged through the European “Early Warning Response System” (EWRS) as well as communication with International Health Regulation (IHR) national focal points. We described events by PHA involved, number of contact persons and exposure context. Results:The RKI processed 467 events, initiating contact to PHA 1,099 times (median 1, IQR [1;2]) and sharing data on 5,099 contact persons. Of 327 (70%) events with known exposure context, most common reported were exposures on aircraft 64 (14%), on cruise ships 24 (5%) and exposures related to non-transport contexts 210 (45%). Cruise ship and aircraft exposures yielded higher median numbers of authorities contacted (10[2;16], 4[2;11]) and contact persons (60 [9;269], 2[1;3]) than non-transport related exposures (1[1;6] and 1[1;2]), respectively. The median time spend on contact tracing activities was the highest for cruise ships: 5 days [IQR 3;9]. Conclusion:In the current COVID-19 pandemic cross-border contact tracing is considered a critical component of the outbreak response. While the majority of international contact tracing activities did not relate to exposure events in transport, they contributed substantially to the workload. The numerous communications highlight the need for fast and efficient global outbreak communication channels between PHA.

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.

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.

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.

Background: The COVID-19 has put global health institutions on alert. Organizations such as the CDC and WHO have developed preparedness and prevention checklist of 2019-nCoV infection to be used by public and healthcare professionals. Since COVID 19 pandemic is unexpected and no country aware of it prior to outbreak, there is limited information on the overall preparations of healthcare providers in Ethiopia. Therefore, the aim of this study was to assess early healthcare professionals’ preparedness and response to COVID 19 Pandemic in Oromia regional state, Ethiopia. Methods: The study was conducted on healthcare professionals working in public hospitals of Oromia regional state. The study was carried out by online questionnaire prepared using SurveyMonkey©. The collected data was analyzed and One-way ANOVA was used to determine the significant differences between health professionals working in different hospitals. The statistical significance associations of variables of interest was determined at 95% confidence intervals. Results: Healthcare professionals in the public hospitals of Oromia regional state, Ethiopia perceived that they are not yet well prepared and may not respond to the pandemic quickly and efficiently. Even though, they have positive response towards identifying signs and symptoms, provide education and utilization of PPE, they are still lacking in practical responses like managing cases, implementing emergency plans and isolation procedures from many others. Conclusion: As the Federal Ministry of Health, Ethiopia Public health institute and Oromia health bureau are vigilant and continually conducting preventive measures programs, extensive and maximum effort should be done to improve healthcare providers’ preparedness and response towards any emergency related to COVID-19 pandemic.

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.

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.

innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan can be used to create biocompatible and biodegradable scaffolds with 3D architectures similar to human structures, allowing their efficient and safe use as tissue engineering and drug delivery systems in chronic wounds. Locally heated tumors above polymer lower critical solution temperature can induce its conversion into a hydrophobic form, enhancing drug release until the thermal stimulus is gone, where a lower release is due to the swelling of the material. This paper integrates the relevant reported contributions of bioengineered scaffolds for thermo-responsive drug delivery in wound healing. Therefore, we present a comprehensive review that aims to demonstrate the capacity of these systems to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D-printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to the patient’s convenience, as well as reduce drug toxicity and side effects.

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.

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.

A real-time two-way direct load control (TWDLC) of central air-conditioning chillers in wide area is proposed to provide demand response. The proposed TWDLC scheme is designed to optimize the load shedding ratio of every customer under control to ensure the target load to be shed is met at every scheduling period. In order to overcome the load reduction uncertainties of TWDLC, an innovative solution is proposed by applying a certain degree of loosening on the constraint of the actual shed load. Fuzzy linear programming is utilized to solve the optimization problem with fuzzy constraints. The proposed fuzzy linear programming problem is solved by delicately transforming it into a regular liner programming problem. A selection scheme used to obtain the feasible candidates set for load shedding at every sampling interval of TWDLC is also designed along with the fuzzy linear programming.

Although the existing paradigm states that CMV reactivation is under control of cellular immune response, the role of humoral counterpart is underestimated. Anti-CMV positive woman after conditioning with Bu-Flu-ATG underwent stem cell transplantation from fully matched, seronegative sibling donor. In immunodeficient recipient fast and significant decrease of specific immune response was observed but reconstitution of marrow-derived B and NK cells was prior thymic origin T cells. The lowest CMV-IgG(89 U/ml) was observed just before CMV viremia. Noteworthy, the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was observed later, but in the first phase immune reconstitution of the PHA-induced IFNγ release was significantly lower than that CMV-induced. It corresponds with NK cells increase at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells by pentamer technique. Most of NK cells are CD16+, thus are stimulated by residual IgG. In immunocompetent donor the cellular and humoral immune response increases in parallel manner but symptoms of CMV mononucleosis were observed till the increase of specific IgG. Our observations shed light on a unique host-CMV interaction: indicate that significant decrease of CMV-IgG is a good predictor for CMV reactivation during secondary immunodeficiency.

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.

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.

The world is progressing towards a more advanced society where end-consumers have access to local renewable-based generation and advanced forms of information and technology. Hence, it is in a current state of transition between the traditional approach to power generation and distribution, where end-consumers of electricity have typically been inactive in their involvement with energy markets and a new approach that integrates their active participation. This new approach includes the use of distributed energy resources (DER) such as renewable-based generations and demand response (DR), which are being rapidly adopted by end-consumers, where incentives are strong. This paper presents the role of DR aggregator to effectively integrate DER technologies as a new source of energy capacity, into the electricity networks using information communication technology and industry knowledge. This framework based on DR aggregators will facilitate renewable energy integration and customer engagement in electricity market efficiently. To this aim, advantages and disadvantages of DR aggregators are discussed in this paper from political, economic, social and technological (PEST) point of views. Based on this analysis, a strengths, weaknesses, opportunities, and threats (SWOT) analysis for a typical DR aggregator is presented.

The crack in the blade is the most common type of fatigue damage for Francis turbines. However, the crack sometimes is difficult to be detected in time using the current monitoring system even when the crack is very large. To better monitor the crack, it is imperative to research the effect of a crack on the dynamic behavior of a Francis turbine. In this paper, the dynamic behavior of a Francis turbine runner model with a crack was researched numerically. The intact numerical model was first validated by the experimental data available. Then, a crack was created at the intersection line between one blade and the crown. The change in dynamic behavior with increasing crack length was investigated. Crack-induced vibration localization theory was used to explain the dynamic behavior changes due to the crack. Modal analysis showed that the adopted theory could basically explain the modal behavior change due to the crack. The FFT results of the modal shapes and the localization factors (LF) were used to explain the forced response changes due to the crack. Based on the above analysis, the challenge of crack monitoring was analyzed. This research can also provide some references for more advanced monitoring technologies.

Background: Cytokines and chemokines are critical regulators of innate and adaptive immunities during viral infection. We examined innate and adaptive immune responses to hepatitis C virus (HCV) and hepatitis B virus (HBV) at baseline and against controls. Methods: Twenty-seven cytokines were evaluated before treatment in 27 patients with chronic hepatitis C(CHC) [genotype1 (n=20), genotype2 (n=7), HCVRNA 5.72IU/ml] and 12 chronic hepatitis B(CHB) [e-antigen (Ag) (+) (n=5), e-Ag (-) (n=7), HBVDNA 6.191.31Logcopies/ml] and against controls(n=5). Results: Th1 and Th2 cytokines were significantly higher (p<0.05) in CHB than in CHC. The levels of IL-IL10 in CHC and CHB, and IL15 in CHC(genotype2) and CHB were significantly lower (p<0.05) than in controls. The levels of CXCL8 in CHC and CHB, IL12 in CHC and CHB [e-Ag (-)] and CXCL10 in CHC and CHB were significantly higher (p<0.05) than in controls. IFN-γwas higher in CHB than in controls. Conclusion: Cytokines levels differed between CHB and CHC before treatment. Innate immune responses were impaired in CHB with HBeAg(-) and CHC, but not in CHB with HBeAg(+) with high viral loads. Adaptive immune responses were impaired in CHB and CHC and appear to reflect the distinct state of virus-host immune interactions between CHB and CHC.

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.

Previous studies investigated the effects of seed rates and seed recycling practices on the yield and yield related variables. However, higher yield does not always guarantee cost-efficiency. This study aimed at investigating the yield effects of plot-level seed rate along with the cost-benefit analysis of seed recycling practices. This study has introduced the dose-response model to the existing analytical methods used in analyzing the effect of different agrochemicals on crop yield. A multi-stage stratified sampling technique was used to select a total of 450 sample respondents. Data was gathered using a mix of data collection tools. Descriptive statistics along with the dose-response model have been applied for data analysis. Farmers of the study were found to be dissimilar in terms of their seed rate application. The dose-response analysis indicated that the highest average wheat yield has been associated with a seed rate of 50 kg ha-1 above what is recommended. The yield effect of seed recycling has also been assessed and a one-time seed recycling has caused a yield decline of 665 kg ha-1 as compared to the non-recycled seeds. The cost reduced by using recycled seed is by far lower than the economic gains associated with using unrecycled and fresh seeds. The cost-benefit analysis made clear that farmers can reduce their seed costs through seed recycling but their yields and net income can be best improved by using unrecycled CBWS. Thus, farmers must be encouraged to make use of unrecycled seed by establishing agricultural credit schemes geared towards seed procurement and seed price subsidy as key strategies to reduce economically wasteful seed recycling practices.

Background. Adhesives and sealants can be used to repair and preserve solid damaged organs. This study explores the activity of different matrix metalloproteinases (MMP) during the healing of liver injuries treated with two biological adhesives (Tachosil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex®). Methods. Liver traumatic injuries were experimentally induced in 90 male Wistar rats using a Stiefel biopsy punch in the liver. Wound healing was evaluated 2, 6, and 18 days after injury by determining MMP1, 2, 8, 9, and 13 expression. The histopathological repair was assessed by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining. The three sealants used supported complete healing of the liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong initial inflammatory reaction. Results. All the MMPs measured disclosed higher values at early stage of the healing process in animals treated with Adhflex® and Tachosil, being the expression of for MMP2 and MMP9 significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not influence negatively the histological healing process of the hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered as a suitable treatment option.

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.”

An emerging picture in cancer biology is that, paradoxically, chemotherapy can actively induce changes that favor cancer progression. These pro-cancer changes can be either inside (intrinsic) or outside (extrinsic) the cancer cells. In this review, we will discuss the extrinsic pro-cancer effect of chemotherapy; that is, the effect of chemotherapy on the non-cancer host cells to promote cancer progression. We will focus on metastasis, and will first discuss recent data from mouse models of breast cancer. Intriguingly, despite reducing the size of primary tumors, chemotherapy changes the tumor microenvironment, resulting in an increased escape of cancer cells into the blood stream. Furthermore, chemotherapry changes the tissue microenvironment at the distant sites, making it more hospitable to cancer cells upon their arrival. We will then discuss the idea and evidence that these devastating pro-metastatic effects of chemotherapy can be explained in the context of stress response. At the end, we will discuss the potential relevance of these mouse data to human breast cancer and their implication on chemotherapy in the clinic.

Approaches to identification of metabolites have progressed from early biochemical pathway evaluation to modern high dimensional metabolomics which is a powerful tool to identify and characterize biomarkers of health and disease. While traditionally considered relevant in the context of classic metabolic diseases, immunometabolism has emerged as an important area of study as leukocytes generate key metabolites important to innate and adaptive immunity. Herein we discuss the metabolomic signatures and pathways perturbed during infection as well as vaccination. For example, changes in lipid and amino acid pathways (e.g., tryptophan, serine, and threonine) have been noted during infection while carbohydrate and bile acid pathways have shift upon vaccination. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying host response to infection and vaccination, and its integration with other systems biology platforms will add further impact to our studies of health and disease.

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.

In this study, a preload monitoring method using impedance signatures obtained from a piezoelectric-based smart interface is presented for bolted girder connections. Firstly, the background theory of the piezoelectric-based smart interface and its implementation into health monitoring of bolted connections are outlined. A simplified electro-mechanical (EM) impedance model of a smart interface-embedded bolted connection system is formulated to interpret mechanistic understanding of EM impedance signatures under the effect of bolt preload. Secondly, finite element modeling of a bolted connection is carried out to show the numerical feasibility of the presented method and to predetermine the sensitive frequency band of impedance signatures. Finally, impedance measurements are conducted on a lab-scaled bolted girder connection to verify the predetermined sensitive frequency range and to assess the bolt preload changes in the test structure.

Multiphase systems are important in minerals processing, and usually include solid-solid and solid-fluid systems. Examples of operations in multiphase systems include flotation, dewatering, and magnetic separation, among several other unit operations. In this paper, the current trends in the process system engineering tasks of modeling, design, and optimization, in multiphase systems, are analyzed. Different scales of size and time are included, and therefore the analysis includes modeling at the molecular level and unit operation level, and the application of optimization for the design of a plant. New strategies for the modeling and optimization of multiphase systems are also included, with a strong focus on the application of artificial intelligence (AI) and the combination of experimentation and modeling with response surface methodology (RSM). The paper finishes with tools to study the uncertainty, both epistemic and stochastic, which is present in all mineral processing operations. It is shown that all these areas are very active and can help to understand, operate, design, and optimize mineral processing that involves multiphase systems.

Principal component analysis (PCA) is used to reduce the dimensionalities of high dimensional datasets in a variety of research areas. For example, biological macromolecules, such as proteins, exhibit many degrees of freedom, allowing them to adopt intricate structures and exhibit complex functions by undergoing large conformational changes. Therefore, molecular simulations of and experiments on proteins generate a large number of structure variations in high dimensional space. PCA and many PCA-related methods have been developed to extract key features from such structural data, and these approaches have been widely applied for over 30 years to elucidate macromolecular dynamics. This review mainly focuses on the methodological aspects of PCA and related methods, and their applications for investigating protein dynamics.

The integrated stress response (ISR) is an adaptational signaling pathway that is induced in response to different stimuli, such as accumulation of unfolded and misfolded protein, hypoxia, amino acid deprivation, viral infection and ultraviolet light. It has been known that viral infection can activate ISR, but the role of ISR during viral infection is still unclear. In some cases, ISR is a protective mechanism of host cell against infection with virus whilst ISR may be hijacked by viruses for facilitating its replication. In this review, we highlighted recent advances on induction of ISR upon viral infection and the downstream responses involved such as autophagy, apoptosis, formation of stress granules and innate immunity response. We then discussed the molecular mechanism of ISR regulating viral replication and how viruses antagonize this cellular stress response resulting from ISR.

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.

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 NETTER-1 study has proven peptide receptor radionuclide therapy (PRRT) to be one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival. However, PRRT response assessment is challenging and no consensus on methods and timing has yet been reached among experts in the field. This issue is owing to the suboptimal sensitivity and specificity of clinical biomarkers, limitations of morphological response criteria in slowly growing tumors and necrotic changes after therapy, a lack of standardized parameters and timing of functional imaging, and the heterogeneity of PRRT protocols in the literature. The aim of this article is to review the most relevant current approaches for PRRT efficacy prediction and response assessment criteria in order to provide an overview of suitable tools for safe and efficacious PRRT.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological 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.

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.

Motorcycles can be considered a new form of smart vehicle when taking into account their small and modern structure and due to the fact that nowadays they are used in the new role of ambu-lance to rapidly reach emergency patients in large cities with traffic congestion. However, there is no study regarding the measuring of access time for motorcycle ambulances in large cities of Thailand. Therefore, this study aims to compare access times to patients between motorcycle ambulances and conventional ambulances, including analysis of the use of AED installed on motorcycle ambulances to contribute to the sustainable development of public health policies. In two hundred and seventy-one operations, it was found that the times from dispatch to vehicle (ambulance and motorlance) being en route and times from the 1669 center (center for com-mand-and-control EMS in Thailand) call receipt to arrival on scene (response time) of motorcycle ambulances was shorter than that of a conventional ambulance and the use of AED on a motor-cycle ambulance can increase the chances of survival for patients with cardiac arrest outside the hospital in public places where AEDs are not available and in all cases where access to an AED was less than eight minutes.