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

Predicting electricity prices is a very important issue in modern society, because the associated decision process under uncertainty requires accurate forecasts for the economic agents involved. In this paper, we apply the decision tree extension of Random Forests to the prediction of electricity prices in Spain, but with the novelty of modeling prices jointly with demand, with the purpose of achieving greater accuracy than with univariate response Random Forests, particularly in price prediction, as well as understanding the effect of the input variables (lagged values of price and demand, current production levels of available energy sources) on the joint of the two outputs. The results are very encouraging, providing significant increase in price prediction accuracy. Also, interesting methodological challenges appear as far as the appropriate choice of the relative weights of price and demand in the joint modeling is concerned and a new procedure to provide the importance variable ranking is proposed. The partykit (package of R software) library allowing for multivariate Random Forests has been used.

The paper examines the effects of crude oil price shocks on the Indian economy development and GDP Growth for the period of 2010 till 2018. The present Indian economy growth has been facing the identical issues of escalating the trade disparity and continuing inflation. In this connection, the study focused on the determine relationship between the speculation and crude oil price impact on the Indian economic development activity and GDP growth and the paper investigated the how oil price variations effect on the Indian economy development through different networks, viz. WPI, CP, IIP, GDP, Monetary policy, trade and investment. The paper used methods an GARCH model and description to tool the volatility on both the oil and stock markets and then developed an extension of the vector auto-regression (VAR) models are also applied to determine the oil price shocks effect on macroeconomic indicators and the outcomes of co-integration model propose that crude oil is pro‐cyclical to output, and the paper used VAR investigation to the discrepancy decomposition to capture the linear inter‐dependencies among the variables.

Accurate electricity price forecasting has become a substantial requirement since the liberalization of the electricity markets. Due to the challenging nature of the electricity prices, which includes high volatility, sharp price spikes and seasonality, various types of electricity price forecasting models still compete and can not outperform each other consistently. Neural Networks have been successfully used in machine learning problems and Recurrent Neural Networks (RNNs) have been proposed to address time-dependent learning problems. In particular, Long Short Term Memory and Gated Recurrent Units (GRU) are tailor-made for time series price estimation. In this paper, we propose to use Gated Recurrent Units as a new technique for electricity price forecasting. We have trained a variety of algorithms with rolling 3-year window and compared the results with the RNNs. In our experiments, 3-layered GRUs outperformed all other neural network structures and state of the art statistical techniques in a statistically significant manner in the Turkish day-ahead market.

SARS-CoV-2 is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. Like other members of this family, the virus possesses a positive-sense single-stranded RNA genome. The genome encodes for the nsp12 protein, which houses the RNA-dependent-RNA polymerase (RdRP) activity responsible for the replication of the viral genome. A homology model of nsp12 was prepared using the structure of the SARS nsp12 (6NUR) as a model. The model was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp12. This exercise showed that vitamin B12 (methylcobalamin) may bind to the active site of the nsp12 protein. A model of the nsp12 in complex with substrate RNA and incoming NTP showed that Vitamin B12 binding site overlaps with that of the incoming nucleotide. A comparison of the calculated energies of binding for RNA plus NTP and methylcobalamin suggested that the vitamin may bind to the active site of nsp12 with significant affinity. It is, therefore, possible that methylcobalamin binding may prevent association with RNA and NTP and thus inhibit the RdRP activity of nsp12. Overall, our computational studies suggest that methylcobalamin form of vitamin B12 may serve as an effective inhibitor of the nsp12 protein.

This paper investigates the impact of price and real exchange rate volatility on Foreign Direct Investment (FDI) inflows in a panel of 10 Latin American and Caribbean countries, observed between 1990 and 2012. Both price and exchange rate volatility series are estimated through the Generalized Autoregressive Conditional Heteroscedasticity model (GARCH). Our results, obtained employing the Fixed Effects estimator, confirm the theory of hysteresis and option value, in so far it is found a statistically significant negative effect of exchange rate volatility on FDI. Price volatility, instead, turns out to be positive but insignificant. Moreover, we show that human capital and trade openness are key for attracting foreign capital. From the policy perspective, our analysis suggests the importance of stabilization policies as well as the one of government credibility in promoting trade openness and human capital formation.

In 2019, Chinese government implemented the first round of National Centralized Drug Procurement (NCDP) pilot (so-called "4+7" policy) in mainland China, achieved a prominent price reduction of 52% on average for 25 bidding winning products. Under cross-price elasticity theory, the price behavior of pharmaceutical enterprises for policy-related drugs might change. This study used drug purchasing data from the Centralized Drug Procurement Survey in Shenzhen 2019, and applied single-group Interruption Time Series (ITS) design to examine the impact of "4+7" policy on the drug price index (DPI) of policy-related drugs. The ITS analysis showed that the DPI of winning (-0.183 per month, p<0.0001) and non-winning (-0.034 per month, p=0.046) products significantly decreased after the implementation of "4+7" policy. No significant difference was found for the immediate change of DPI for alternative drugs (p=0.537), while a significant decrease in change trend was detected in the post-"4+7" policy period (-0.003 per month, p=0.014). The DPI of the overall policy-related drugs significantly decreased (-0.261 per month, p<0.0001) after "4+7" policy. These findings indicate that the price behavior of pharmaceutical enterprises changed under NCDP policy, while the price linkage effect is still limited. It is necessary to further expand the scope of centralized purchased drugs and strengthen the monitoring of related drugs regarding price change and consumption structure.

This study investigates the asymmetric impacts of oil price changes on inflation in Algeria, Angola, Libya and Nigeria. Three different oil price data were applied in this study; the specific spot oil price of individual countries, the OPEC reference basket oil price and an average of the Brent, WTI and Dubai oil price. The dynamic panels ARDL were used to estimate the short and the long-run impacts. Also, this study partitioned the oil price into positive and negative changes to capture asymmetric impacts and found both positive and negative oil price changes positively influenced inflation. However, the impact was found to be more significant when oil prices dropped. The results from the study also found that money supply, the exchange rate and GDP are positively related to inflation while food production is negatively related to inflation. Accordingly, policymakers should be cautious in formulating policies between the positive and negative changes in oil prices as it was shown that inflation increased when the oil price dropped. Additionally, the use of contractionary monetary policy would help to reduce the inflation rate, and lastly, it is proposed that the government should encourage domestic food production both in quantity and quality to reduce inflation.

In this paper, we examine the mathematical and physical consistencies of the three primary couple stress theories: original Mindlin-Tiersten-Koiter couple stress theory (MTK-CST), modified couple stress theory (M-CST) and consistent couple stress theory (C-CST). As has been known for many years, MTK-CST suffers from some fundamental inconsistencies, such as the indeterminacy of the couple-stress tensor. Therefore, despite the fact that MTK-CST has a fundamental position in the evolution of size-dependent continuum mechanics, it is not a reliable theory within continuum mechanics, for example, in developing new size-dependent multi-physics formulations. We also observe that M-CST not only inherits all inconsistences from the original MTK-CST, but also suffers from new additional inconsistencies, such as the introduction of a new non-physical governing equation. These inconsistencies refute the claim of those who state that the couple-stress tensor may be chosen symmetric. Therefore, the apparent success of MTK-CST and M-CST in describing a size-effect for some problems, such as two-dimensional plate and beam bending, is not enough to justify these theories as suitable for general cases. In fact, the symmetric couple-stresses in M-CST create torsional or anticlastic deformation, not bending. On the other hand, C-CST, with a skew-symmetric couple-stress tensor, is the consistent continuum mechanics suitable for solving different size-dependent solid, fluid and multi-physics problems.

Day-ahead forecasting of electricity prices is important in deregulated electricity markets for all the stakeholders: energy wholesalers, traders, retailers, and consumers. Electricity price forecasting is an inherently difficult problem due to its special characteristic of dynamicity and non-stationarity. In this paper, we present a robust price forecasting mechanism that shows resilience towards aggregate demand response effect and provides highly accurate forecasted electricity prices to the stakeholders in a dynamic environment. We employ an ensemble prediction model in which a group of different algorithms participate in predicting the price for each hour of a day. We propose two different strategies, namely, Fixed Weight Method (FWM) and Varying Weight Method (VWM), for selecting each hour's expert algorithm from the set of participating algorithms. In addition, we utilize a carefully engineered set of features selected from a pool of features derived from information such as past electricity price data, weather data, and calendar data. The proposed ensemble model offers better results than both the Pattern Sequence-based Forecasting (PSF) method and our own previous work using Artificial Neural Networks (ANN) alone do on the datasets for New York, Australian, and Spanish electricity markets.

The purpose of this paper is to provide empirical evidence to water policy-makers and the evaluation of the application of economic instruments such as price and other factors affecting demand, they contribute to improved decision-making around water management in the Biosphere Reserve El Vizcaino, Mexico. It was estimated a dynamic function with average price specification and other price perception specification. The findings show that consumers react to average price perceived and not the marginal price; long-run price elasticity is higher than short-run and both elasticities are inelastic. Elasticities inelastic with rising prices generate high incomes to improve water planning, supply quality and expand service coverage. The results suggest that the level of knowledge of users on the price is key to take into account restructuring rates in a scenario where the consumer has asymmetric information and themselves achieve goals of economic efficiency, social equity and environmental sustainability.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

As the natural resources are getting exhausted, the concept of sustainable development of region has received increasing attentions, especially for resource-dependent cities. In this paper an innovative method that emergy analysis and IPAT (Human Impact Population Affluence Technology) model were combined in order to analyze the quantitative relationship of economic growth and energy consumption and further to evaluate its overall sustainability level. Taiyuan, a traditional, resource-dependent city in China, is selected as the case study region. The main results show that total emergy of Taiyuan increased from 9.023× 1023 sej in 2007 to 9.116× 1023sej in 2014, with 38% reduction on non-renewable emergy and 125% growth on imported emergy. Regional emergy money ratio (RMB) was reduced by 48% from 5.31× 1013sej/$ in 2007 to 2.74× 1013sej/$ in 2014, indicating that the increasing speed of consuming resources and energy was faster than the increase of GDP, and that Taiyuan’s money purchasing power declined. The lower emergy sustainability index (ESI) indicates that Taiyuan was explored and produced large quantities of mineral resources, which puts more stress on the environment as a consequence, and that this is not sustainable in the long run. The IPAT analysis demonstrates that Taiyuan sticks to the efforts of energy conservation and environmental protection, in order to promote regional sustainable development, it is necessary to take an integrated effort. Policy insights suggest that resourceful regions should improve include energy and resource efficiency, optimizing energy and resourceful structure.

ABSTRACT After locavore was chosen as “the best word of the year” in 2007, its popularity increased gradually. Today great number of locavores consciously prefer locally produced food for the benefit of themselves and their community. Undoubtedly this conscious movement has its consequences in marketing discipline. Accordingly, this paper is purposed to examine the how locavore perceptions affect loyalty towards retailers that sell locally produced food. In this context, a survey was applied to people residing in Istanbul and Kocaeli districts to measure the robustness of these effects. Furthermore, attitude towards locavore is used as a control variable to reveal to what extend locavorism affects these proposed connections. According to results, for participants with low attitude, Social Responsibility and Health Consciousness variables have significant effect on local retailer shopping loyalty. However, for participants with high attitude, all independent variables proved to have substantial effect on local retailer shopping loyalty. As the first empirical study in Turkey on the subject, this paper will provide important insight to academia and practicioners due to today’s ever-increasing consciousness in green marketing.

In this paper, we study the problem of controllability of impulsive neutral evolution integrodifferential equations with state dependent delay in Banach spaces. The main results are completely new and are obtained by using Sadovskii's fixed point theorem, theory of resolvent operators, and an abstract phase space. An example is given to illustrate the theory.

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Brine-dependent recovery process has seen much global research efforts in the past two decades because of their benefits over other oil recovery methods. The process involves the tweaking of the ionic composition and strength of the injected water to improve oil production. In recent years, several studies ranging from laboratory coreflood experiments by many researchers to field trials by several companies admit to the potential of recovering additional oil in sandstone and carbonate reservoirs. Sandstone and carbonate rocks are composed of completely different minerals, with varying degree of complexity and heterogeneity, but wettability alteration has been widely considered as the consequence rather than the cause of brine-dependent recovery. However, there is no consensus on the cause as several mechanisms have been proposed to relate the wettability changes to the improved recovery. This review paper aims to provide a state-of-the-art development in published research and various efforts of the industry. This review outlines an overview of laboratory and field observations, descriptions of underlying mechanisms and their validity, the complexity of the oil-brine-rock interactions, modelling works, and comparison between sandstone and carbonate rocks. The provided information is intended to provide the reader with up-to-date information, point to relevant studies for those who are new and those implementing either laboratory- or field-scale projects to speed up the process of further investigations in this research area. Overall, the outcome of this review would potentially be of immense benefit to the oil industry.

Using DCC-GARCH and EGARCH model, this paper finds that since 1990, the relationship between crude oil prices and the US dollar index is time-varying, demonstrating a process of “very weak correlation—negative correlation—enhanced negative correlation—weakening negative correlation”, but the existing research does not provide enough reasonable explanation. Therefore, this paper proposed a “key mediating factors” hypothesis which points out that whether there is a common “key mediating factor” is important source of the time-varying relationship between two assets. We argue that market trend and financial market sentiment undertook the role of “key mediating factor” during the period of “2002 to the financial crisis” and “financial crisis to 2013”, while other periods lack the “key mediating factors”.

DC residential distribution system (RDS) consisted by DC living home will be a significant integral part in the future green transmission. Meanwhile, the increasing number of distributed resources and intelligent devices will change the power flow between main grid and demand sides. The utilization of distributed generations (DGs) requires an economic operation, stability, environmentally friendly in the whole DC system. This paper not only presents an optimization schedule and transactive energy (TE) approach through centralized energy management system (CEMS), but a control approach to implement and ensure DG output voltages to various DC buses in DC RDS. Based on data collection, prediction and a certain objection, the expert system in CEMS can work out the optimization schedule, after this, the voltage droop control for steady voltage is aligned with the command of unit power schedule. In this work, a DC RDS is as a case study to demonstrate the process, the RDS is associated with unit economic models, cost minimization objective is proposed to achieve based on real-time electrical price. The results show that the proposed framework and methods will help the targeted DC residential system to reduce the total cost and reach stability and efficiency.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

The Estimation of systemic risk in India is still in its infancy stage. There are several methods which are available but none of the methods are fully compatible to forecast the systemic risk since under different circumstances the factors responsible for the risk differs. In this paper the systemic risk estimation in India being carried out based on spread in daily stock market price(Difference between the bid and ask price of a share) of the top 100 firms in India according to market capitalization for the period of July2007 to March 2016. The results were compared with the Financial Stability Report published by Reserve Bank Of India for the period of March 2010 to June 2016.The results clearly indicates that there exits relationship between market illiquidity represented by spread and risks associated with the Financial System. In most of the cases the Z score (deviation from the mean/Standard Deviation) of the spread has become negative which provides the spread which is farther from the mean, also a good indicator of volatility in market and risk to financial system. It is also seen that the Systemic Risk Survey conducted by Reserve Bank of India which started during October 2011 has supported the results.

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

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.

External quantum efficiency of industrial-grade green InGaN light-emitting diodes (LEDs) has been measured in a wide range of operating currents at various temperatures from 13 K to 300 K. Unlike blue LEDs, the efficiency as a function of current is found to have a multi-peak character, which could not be fitted by a simple ABC-model. This observation correlated with splitting of LED emission spectra into two peaks at certain currents. The characterization data are interpreted in terms of non-uniformity of the LED active region, which is tentatively attributed to extended defects like V-pits. We suggest a new approach to evaluation of temperature-dependent light extraction and internal quantum efficiencies taking into account the active region non-uniformity. As a result, the temperature dependence of light extraction and internal quantum efficiencies have been evaluated in the temperature range mentioned above and compared with those of blue LEDs.

With the rise of Blockchain technology, the cryptocurrency market has been gaining significant interest. In particular, the number of cryptocurrency traders and the market capitalization have grown tremendously. However, predicting cryptocurrency price is very challenging and difficult due to the high price volatility. In this paper, we propose a classification machine learning approach in order to predict the direction of the market (i.e., if the market is going up or down). We identify key features such as Relative Strength Index (RSI) and Moving Average Convergence Divergence (MACD) to feed the machine learning model. We illustrate our approach through the analysis of Bitcoin close price. We evaluate the proposed approach via different simulations. Particularly, we provide a backtesting strategy. The evaluation results show that the proposed machine learning approach provides buy and sell signals with more than 86% accuracy.

The transmission characteristic of COVID-19 is of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. The virus is now in more than 100 countries and on nearly all continents. The World Health Organization (WHO) declared the COVID-19 outbreak a pandemic. There is no current evidence from random clinical trials (RCTs) to recommend any specific anti-COVID-19 treatment for patients with suspected or confirmed COVID-19 infection. In order to mitigate the impact of the COVID-19 outbreak, here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated viruses might interact in co-infected patients. During SIT, the patient benefit from superinfection with an apathogenic dsRNA virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). Importantly, the epidemiological efficacy of a similar strategy to SIT had already been successfully tested in large controlled trials. Standard live orally administered enterovirus vaccines that stimulate the production of endogenous interferon of the host mitigated the seasonal outbreaks of influenza and other associated acute respiratory infections in 152,042 individuals without adverse reactions.

Magneto-electrochemistry (MEC) is a unique paradigm in science, where electrochemical experiments are carried out as a function of an applied magnetic field, creating a new horizon of potential scientific and technological applications. Over the time, detailed understanding of this research domain was developed to identify and rationalize the possible effects exerted by a magnetic field on the various microscopic processes occurring in an electrochemical system, such as: electrolyte properties governed by charge-transfer process (electric conductivity, viscosity, and diffusivity), mass transfer, electrochemical kinetics and on the structure/quality of products formed either at the working electrode or in the electrochemical cell. Particularly, magnetic field controlled chiral architecture obtained from deposited metal, alloys and catalyst and their excellent enantio-recognition in experimental frame is highly appealing. Interestingly, Hall effect was also demonstrated in electrolytic medium via an impressive experimental technique which is being employed for further theoretical understanding in the field of magneto-electrochemical science. Later, a highly reproducible local temperature variation was observed in electrochemical electrolytes exposed to perpendicular magnetic and electric fields. However, until recent studies, none of the above mentioned reports considered the possibility of a spin-dependent related charge-transfer process. Recent experimental and theoretical studies reveal that electron’s transmission through chiral molecules is spin-selective and this effect has been referred to as chiral-induced spin-selectivity (CISS) effect. The CISS effect pave the way for the building up of a system characterized by a net magnetic moment exploiting the spin-filtering ability of chiral molecules. This interplay between chirality and magnetism may shed light on fundamental scientific aspects underlying the enantio-recognition and highly efficient electron-transfer that occurs in biological process.

Economic development and advancements in information technology contributed to the shift on accounting objective from commission responsibility view to decision-making useful view. The decision-making useful view claims that the accounting measurement methods should be changed to improve the usefulness of accounting information, to enable information users to make correct decisions. In addition, the development of financial instruments leads to the birth of fair value accounting. In recent years, fair value has been one of the most important measurement methods in the International Accounting Standard and US Generally Accepted Accounting Principles. However, China has been quite cautious when it comes to applying fair value full time, especially after the global financial crisis happened in 2008, wherein fair value accounting was exposed to strong suspicion. Hence, studying the value relevance of fair value is of great significance to exploring the accounting profession and reforming accounting standards. This paper attempts to investigate the value-relevance of fair value based on the data of listed financial companies and manufacturing companies in China. The results indicate that the fair value information in the financial industry has a strong explanatory influence to corporate share price. In contrast, the fair value information shows limited relevance in the manufacturing industry. Finally, consulting with the results of normative analysis and empirical study, this paper suggests several rational advices for the application of fair value in China.

Ataxin-2 (human gene symbol ATXN2, protein ATXN2) is the disease protein of Spinocerebellar Ataxia type 2 (SCA2). The large expansions of a polyglutamine (polyQ) stretch above a threshold of ~33 glutamines cause the multi-system nervous atrophy SCA2, while intermediate expansions of 29-32 glutamines contribute to the risk of the motor neuron diseases Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Lobar Dementia (FTLD). To elucidate the cellular function of ATXN2, we further characterized its direct interaction with alpha-Actinin-1 (symbol ACTN1), which had been observed in high-throughput yeast-two-hybrid surveys. An endogenous complex of ATXN2 and ACTN1 proteins was detected by co-immunoprecipitation. In vitro GST-tag pull-down experiments showed that the Calponin-Homology-domain at the N-terminus of ACTN1 binds to the N-terminus of ATXN2. Although an impact of the polyQ expansion on the interaction was not evident in pull-down experiments, a recent characterization of aged Atxn2-CAG100-KnockIn mice provides evidence. Both proteins associated in the cytosol and at the plasma membrane, as determined by sedimentation experiments in mouse brain, and by immunofluorescence microscopy of a transfected monkey cell line and of rat primary hippocampal neurons. In view of the roles of ACTN1 for spine plasticity and postsynaptic receptor control via reassembly of cortical actin, our data help to explain the impaired dendrite maintenance in SCA2.

This study employs traditional OLS (ordinary least squares) regression analysis to investigate the influence of various external factors on Bitcoin price fluctuations from January 2014 to March 2023 using a multidimensional approach. We use factors from the traditional financial market, such as economic policy uncertainty (EPU), oil prices, the NASDAQ index, and gold prices, to identify factors contributing to Bitcoin volatility. Considering the unique situation in the Bitcoin market, that is, 24-hour trading and the short duration of its existence, we incorporate the broadest possible data range to achieve alignment between Bitcoin data and other datasets. The findings of the statistical analysis indicate that EPU and the NASDAQ index promote positive fluctuations in Bitcoin volatility, whereas gold prices act as a dampener. However, we find no empirical support for the influence of energy prices on Bitcoin volatility. These results suggest that Bitcoin should not be underestimated; all stakeholders should treat the issue of Bitcoin volatility seriously, including governments, who should actively regulate the Bitcoin market, and investors, who should recognize the dangers of this volatility, making rational decisions based on individual circumstances and employing flexible trading strategies.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19 in several countries. By acting as a substrate for RdRp, favipiravir gets incorporated into the nascent viral RNA and prevents strand extension. A high mutation rate of SARS-CoV-2 RdRp may facilitate antigenic drift as an answer to the host immune response, thereby generating resistance of virus to favipiravir. Therefore, it is extremely crucial to predict potential mutational sites in the RdRp and the emergence of structural modifications contributing to drug resistance. Here, we used high-throughput interface-based protein design to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp. Several mutants had lower binding affinities to favipiravir, out of which hotspot residues with a high propensity to undergo positive selection were identified. The results showed that the designs retained an average of 97 to 98% sequence identity, suggesting that SARS-CoV-2 can develop favipiravir resistance with just a few mutations. Notably, we observed that out of 134 mutations predicted designs, 63 specific mutations were already present in the CoV-GLUE database, thus attaining ~47% correlation match with the clinical sequencing data. The findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir and management of COVID-19. Furthermore, they can help develop exhaustive strategies for robust antiviral design and discovery.

Baggage overweight is a significant phenomenon in the air travel in- dustry which is both regulated by the governments and highly profitable for the airlines. The recent years increase in airlines' profits is attributed to so-called ancillary payments – all consumer costs excluding the actual transportation fare. Baggage overweight fees, being a part of such pay- ments, have high profit-generation potential. Is the pricing for baggage overweight positioned correctly? The rationality of policies currently used by airlines is questionable, as they lack a customer-oriented marketing ap- proach. The general purpose of this research is to explore the possibilities of rational baggage overweight pricing for airlines by developing a multi- level price optimization model aimed to maximize company revenue. The modeling is based on determining consumer Willingness-To- Pay values for baggage overweight, and providing an optimal ticket price for them to maximize company expected revenue. The total profit value is forecasted too, based on the company market share and revenue level.

Many systems in nature and laboratories are far from equilibrium and exhibit significant fluc- tuations, invalidating the key assumptions of small fluctuations and short memory time in or near equilibrium. A full knowledge of Probability Distribution Functions (PDFs), especially time- dependent PDFs, becomes essential in understanding far-from-equilibrium processes. We consider a stochastic logistic model with multiplicative noise, which has gamma distributions as stationary PDFs. We numerically solve the transient relaxation problem, and show that as the strength of the stochastic noise increases the time-dependent PDFs increasingly deviate from gamma distributions. For sufficiently strong noise a transition occurs whereby the PDF never reaches a stationary state, but instead forms a peak that becomes ever more narrowly concentrated at the origin. The addition of an arbitrarily small amount of additive noise regularizes these solutions, and re-establishes the existence of stationary solutions. In addition to diagnostic quantities such as mean value, standard deviation, skewness and kurtosis, the transitions between different solutions are analyzed in terms of entropy and information length, the total number of statistically distinguishable states that a system passes through in time.

This paper intends to examine whether a company’s policy of dividend would impact or influence the price fluctuation of respective common stock in the designated stock market particularly in Hong Kong. Hence, there are 354 companies in Hong Kong which are all listed company on the Stock Exchange of Hong Kong (HKEX), were chosen as sample data for analysis with their audited financial information ranged from 2001 to 2020. Two proxies, the yield and the ratio of pay-out of dividend were widely adopted for the measurement of the effect of dividend policy and the possible influence on the volatility of respective common stock price by employing two statistical models, which are the model of fixed and random effects to provide accurate regression coefficients. With the results from the model of fixed effects, the yield and the pay-out ratio of dividend have been found statistically associated to the price volatilization of respective common stock in Hong Kong. The statical results in this study also find the yield and the ratio of pay-out of dividend are apparently and negatively associated to the price volatilization of respective common stock in Hong Kong. The research outcomes will be a reference for further study on different variables may have effects or volatilize the price of common stock price particularly in Hong Kong capital market.

Measurements of copper and zinc in transfusion-dependent thalassemia (TDT) show contradictory results.Aim of the study: To examine serum levels of these minerals in TDT in relation to iron overload indices and erythron variables. Methods: This study recruited 60 children with TDT and 30 healthy children aged 3-12 years old.Results: Zinc was significantly higher in TDT children than in control children, whilst copper and the copper to zinc ratio were significantly lowered in TDT. Serum zinc was significantly associated with the number of blood transfusions and iron overload variables (including serum iron and TS%) and negatively with erythron variables (including hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin). Serum copper was significantly and negatively associated with the same iron overload and erythron variables. The copper to zinc ratio was significantly correlated with iron, TS%, ferritin, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. Albumin levels were significantly higher in TDT children than in control children. Conclusion: Our results suggest that the increase in zinc in children with TDT may be explained by iron loading anemia and hemolysis and the consequent shedding of high amounts of intracellular zinc into the plasma. Increased albumin levels and treatment with Desferral may further contribute towards higher zinc levels in TDT. We suggest that the elevations in zinc in TDT are a compensatory mechanism protecting against infection, inflammation, and oxidative stress. Previous proposals for prophylactic use of zinc supplements in TDT may not be warranted.

Purpose: The purpose of this paper is to explore and analyse the dynamic relationship between remittances inflows of Egyptians working abroad and asymmetric oil price shocks. Design: This study uses a vector autoregressive (VAR) model to explain the impulse response functions (IRFs) and the forecast error variance decomposition (FEVD). The rationale behind using these tools is its ability to examine the dynamic effects of our variables of interest. Findings: The impulse response functions confirmed that remittance inflows have various responses to asymmetric oil price shocks. For instance, inflowing remittances increase in response to positive oil price shocks, while it decreases in response to negative oil price shocks. Also, the results indicate that the responses are significant in the short and medium-run and insignificant in the long run. The magnitude of these responses reaches its peak or trough in the third year. Further, the variance decomposition reveals that oil price decreases are more influential than oil price increases. Originality: This means that remittances inflows in Egypt are pro-cyclical with oil price shocks. That explained by the fact that more than one-half of those remittances sent from GCC countries where real economic growth is very pro-cyclical with the oil prices. This empirical assessment will help policymakers to determine the behaviour of remittances and highlights the impact of different kinds of oil prices shocks on remittances. Unlike the little existing literature, this study is the first study applied the VAR model using a novel dataset spanning 1960-2016.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

Background and Research Highlights: Despite all the concerns and initiatives, natural resources like forests, as well as biodiversity are decreasing at an alarming rate worldwide. Conservation is considered as one of the major tools to prevent such loss and rapid degradation. Evidence around the world shows the adverse effects of conservation laws and policies on indigenous peoples and other local communities. Objectives: This study was conducted in one of the forest-dependent communities situated in Sundarban (world’s largest mangrove forest) to understand the impact of conservation laws and policies on their livelihood. Materials and Methods: A qualitative methodology was designed to collect data, using focus group discussions and case study with community people, and individual interviews with the personnel from NGOs and relevant government departments. Findings: Strict conservation policies and restrictions in accessing forest resources made lives and livelihoods of the local community insecure and unstable, thus putting the community in a vulnerable situation. The had to leave their traditional mode of income and look for alternative livelihood options. Almost no evidence was found in relation to upkeeping their rights in conservation activities. Prohibited movement, provision of punishment for entering into the forest without proper permission and struggles in everyday life were some of the highlighted issues. They had no participation in conservation activities, management of alternative livelihood options, and even they were not sensitized before putting restrictions. Although they had a history of emotional and physical attachment with the forest, existing activities did not consider these issues. In addition, corruption and abuse of power by law enforcement agencies towards the local community intensified the sufferings. Conclusion: This study argues that the realization of human rights in conservation activities and the sensitization of the implementing stakeholders are prerequisites for ensuring the sustainability of both biodiversity and the affected people.

The Rybczynski theorem describes the trade effect within production analyses between factor endowments and outputs. The Stolper-Samuelson theorem focuses on cost analyses between factor reward and commodity price. This paper examines the trade effect of changes of factor endowments on prices, based on general equilibrium. The study shows that changes of factor endowments cause domestic output changes (the Rybczynski effect), which affect output prices and factor prices (the Stolper-Samuelson effect). It is like a chain of effects that the Rybczynski’s trade effect triggers the Stolper-Samuelson’s trade effect. The analysis of this paper shows that a small increase of a factor endowment of any country rewards another factor and the commodity using the latter factor intensively. It displays a tuneful circle. Trade brings a well-balanced development to the world.

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal auto-inhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in site-specifically phosphorylated forms, the contribution of each activating phosphorylation site to auto-inhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

The impact of monetary policies and their implementation by exchange rate covered the economic condition of Ghana. The social inclusion and conversion factors change the implemented policies of nations, where the real price, trade, technology, a price rate and price level of ratio take an important part of growth. The reform of the financial sector favors the free floating of the exchange rate and global trade by under the premise of flexible exchange rates. The tragedy of country growth and exchange rate toward a trajectory of growth with the growth-enhancing effect through social inclusion, conversion factors, price level ratio, exchange rate, merchant rate, export and trade services. The research study is based on secondary study and social inclusion equity indicators with public resources, building human resources and social protection for economic development has determined. The monetary policies are classified by the different evidence and trade indicators. The significant influence of growth and internal policies has affected trade and exchange rates with growth and reserve policies. The results have computed by linear regression and it proved that social inclusion and alternative conversion factors impact on the global trade and create short term binary relationship.

Chinese investors are easily affected by hot topics on the media and Internet and likely take irrational behavior. They tend to consume rationally and invest emotionally. This research aims to analyze the Baidu index’s effect on share price of solar power industry in China. Three main models are established to identify the correlation between Baidu index and stock price of solar industry. The media index and searching index of Baidu are chosen as an independent variable to measure the influence from media and Internet, and stock price as the dependent variable. To improve and complete the analysis, Hexun index is taken into consideration as mediator variable. This study applied Multiple Linear Regression Model and VAR (Vector auto-regression) Model. The research mainly uses the tools of SPSS, Eviews and Excel to conduct data analysis. The test is based on the theories of Granger Causality, unit root test, F-test, and t-test. The research proves the relationship between the close price of stock and Baidu index, and it also created a model for further forecasting.

Empirical evidence is lacking on the nexus between coffee commodity output, climate change and commodity price volatility of Africa’s most populous country, Nigeria and other developing countries. To fill this gap, this study analyzed the reaction of coffee output to climate change and commodity price volatility. We used secondary data from 1961 to 2015 from reliable sources for Nigeria. The study adopted GARCH, ARCH and FMOLS in analysis of coffee output reaction to climate change and commodity price volatility. The findings show that coffee output in Nigeria is influenced by climate change and the international commodity price of coffee. The study demonstrates the potential benefits of improving coffee output and export through climate mitigation and adaptation measures and revival of Agricultural Commodity Marketing in Nigeria and other developing countries.

China combines green energy and industrial policy in its power market reform with various policy initiatives, including price support scheme for electricity from renewable sources and subsidies in the push for broader use of greener energy. This study focuses on the impacts of power market reform on the stock price volatility of listed power companies: 1) we use the Iterative Cumulative Sums of Squares (ICSS) algorithm to identify structural break points in stock prices; 2) we analyze the characteristics of stock price volatility based on the GARCH model; 3) we report the impact of power regulation on stock price fluctuations based on the Autoregressive Distributed Lag (ARDL) model. The result suggests three structural breaks in China’s power stock price volatility were related to the promulgation of power market reform policies. We find that industrial policies promote the reduction of power stock price fluctuations and its impact on power stock price volatility is consistent in the long run. However, our study also indicates the recent policies related to renewable energy do not have a very significant impact on the power stock market.

The main aim of this article is to examine the inter-relationships among the top cryptocurrencies on the crypto stock market in the presence and absence of the COVID-19 pandemic. The nine chosen cryptocurrencies are Bitcoin, Ethereum, Ripple, Litecoin, Eos, BitcoinCash, Binance, Stellar, and Tron and their daily closing price data are captured from coinmarketcap over the period from 9/13/2017 to 9/21/2020. To determine the order of integration, the Augmented Dickey-Fuller (ADF), Phillips-Perron (PP), and Kwiatkowski, Phillips, Schmidt, and Shin (KPSS) unit root tests were carried out, and all of the cryptocurrencies were found to be integrated of order 1 i.e. I(1). It has been found that there is strong evidence of a long-run relationship between Bitcoin and altcoins irrespective of whether it is pre-pandemic or pandemic period. Hence these cryptocurrencies' prices and their inter-relationship are resilient to the pandemic.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

Initial attempts to develop monoclonal antibodies as therapeutics to resolve influenza infections focused mainly on searching for antibodies with the potential to neutralise the virus in vitro with classical haemagglutination inhibition and micro-neutralisation assays. This led to the identification of many antibodies that bind to the head domain of haemagglutinin (HA) which generally have potent neutralisation capabilities that block viral entry or viral membrane fusion. However, this class of antibodies has a narrow breadth of protection in that they are usually strain specific. This led to the emphasis on stalk targeting antibodies which are able to bind a broad range of viral targets that span across different influenza subtypes. Recently, a third class of antibodies targeting the vestigial esterase (VE) domain have been characterised. In this review, we describe the key features of neutralising VE targeting antibodies and compare them with head and stalk class antibodies.

The transfer of protein-encoding genetic information from DNA to RNA to protein, a process formalized as the “Central Dogma of Molecular Biology”, has undergone a significant evolution since its inception. It was amended to account for the information flow from RNA to DNA, the reverse transcription, and for the information transfer from RNA to RNA, the RNA-dependent RNA synthesis. These processes, both potentially leading to protein production, were initially described only in viral systems, and although RNA-dependent RNA polymerase activity was shown to be present, and RNA-dependent RNA synthesisfound to occur, in mammalian cells, its function was presumed to be restricted to regulatory. However, recent results, obtained with multiple mRNA species in several mammalian systems, strongly indicate the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. It can result in the rapid production of the extraordinary quantities of specific proteins as was seen in cases of terminal cellular differentiation and during cellular deposition of extracellular matrix molecules. A malfunction of this process may be involved in pathologies associated either with the deficiency of a protein normally produced by this mechanism or with the abnormal abundanceof a protein or of its C-terminal fragment. It seems to be responsible for some types of familial thalassemia and may underlie the overproduction of beta amyloid in sporadic Alzheimer’s disease. The aim of the present article is to systematize the current knowledge and understanding of this pathway. The outlined framework introduces unexpected features of the mRNA amplification such as its ability to generate polypeptides non-contiguously encoded in the genome, its second Tier, a physiologically occurring intracellular polymerase chain reaction, iPCR, a Two-Tier Paradox and RNA Dark Matter. RNA-dependent mRNA amplification represents a new mode of genomic protein-encoding information transfer in mammalian cells. Its potential physiological impact is substantial, it appears relevant to multiple pathologies and its understanding opens new venues of therapeutic interference, it suggests powerful novel bioengineering approaches and its further rigorous investigations are highly warranted.

In this paper, mean-field type games between two players with backward stochastic dynamics are defined and studied. They make up a class of non-zero-sum differential games where the players' state dynamics solve backward stochastic differential equations (BSDEs) that depend on the marginal distributions of player states. Players try to minimize their individual cost functionals, also depending on the marginal state distributions. Under some regularity conditions, we derive necessary and sufficient conditions for existence of Nash equilibria. Player behavior is illustrated by numerical examples, and is compared to a centrally planned solution where the social cost, the sum of player costs, is minimized. The inefficiency of a Nash equilibrium, compared to socially optimal behavior, is quantified by the so-called price of anarchy. Numerical simulations of the price of anarchy indicate how the improvement in social cost achievable by a central planner depends on problem parameters.

Transfusion dependent thalassemia (TDT) patients are treated with continued blood transfusions and show a higher prevalence of depression. TDT with consequent iron overload and inflammation is associated with increased severity of depressive symptoms in TDT children.Aim of the study: To construct a pathway-phenotype which combines iron overload and neuro-immune biomarkers with depressive symptom subdomains in TDT children.Methods: We measured iron status parameters (iron, ferritin, transferrin saturation percentage) and inflammatory (interleukin-1β and tumour necrosis factor-α) biomarkers in TDT (n=111) and healthy (n=53) children and analyzed the results using machine learning.Results: Cluster analysis separated TDT children with depression from those without depression and revealed two depressive subgroups one with low self-esteem and another with increased social-irritability scores. Exploratory factor analysis validated four depressive symptom dimensions as reliable constructs, namely key depressive, physiosomatic, lowered self-esteem and social-irritability dimensions. Partial Least Squares showed that 73.0% of the variance in a latent vector extracted from those four clinical subdomains, immune-inflammatory and iron overload biomarkers was explained by exposure variables including the number of blood transfusions and hospitalizations and use of deferoxamine. The exposure data, iron and immune biomarkers, and symptom subdomains are reflective manifestations of a single latent trait, which shows internal consistency reliability and predictive relevance.Conclusions: The nomological network combining exposure, pathways and behavioral phenome manifestations provides an index of overall severity and disease risk and, therefore, constitutes a new drug target, indicating that iron overload and immune activation should be targeted to treat depression due to TDT.

Increasing distributed generation and intermittency, along with the increasing frequency of extreme weather events, impose a serious challenge for the electric power supply security. Understanding the costs of interruption is vital in terms of enhancing the power system infrastructure and planning the distribution grid. On the other hand, customer rights and demand response techniques are further reasons to study the worth of power reliability. In this paper, the authors make use of directional distance function and shadow pricing method for a case study from Finland. The aim is to calculate the cost of one minute of power interruption from the distribution network operator perspective. The sample consists of 78 distribution network operators from Finland with cost and network information between 2013 and 2015.

The In this paper, a universal method has been developed, which is a combination of an optimization method and a method for assessing the marginal utility. At present, the problem of optimal load distribution in the power system between a hydropower plant (HPP) and thermal power plants (TPP) is solved using the equality of the differential incremental rate characteristics of fuel consumption at TPP and water consumption at HPP by the Lagrangian multiplier method. In this case, the number of iterations can be five or more. The proposed approach is based, first of all, on the correct representation of the differential characteristics and calculation of a hydro resource price for the operational control of the HPP. Based on the comparison of water volume at a HPP and fuel amount at combined heat and power plants (CHPP) used for generation of 1 kW power, it is possible to determine a water price for a HPP. As a result of implementing the developed method for the HPP, a price of sold electricity in the flexible energy market will be comparable with the price for sold electricity produced at CHPPs, being equal to approximately 120 rubles/MW∙h.

Aiming at the current optimization problem of electric vehicle charging path planning, a charging path optimization strategy for electric vehicles under the "Traffic-Price-Distribution" mode is proposed. This strategy builds an electric vehicle charging and navigation system based on road traffic network model, real-time electricity price model and distribution network model. Based on Dijkstra shortest path algorithm and Monte Carlo time-space prediction method, the goal is to minimize the charging cost of electric vehicles. Optimal charging path. The simulation results of MATLAB and MATPOWER show that the electric vehicle charging path optimization strategy can better solve the local traffic congestion problem and improve the safety and stability of the distribution network on the basic of fully considering the convenience of electric vehicle charging.

A theoretical nonlocal thermoelastic model for studying the effects of the thermal conductivity variability on a rotating nanobeam has been described in the present article. The theory of thermal stress is employed using the Euler–Bernoulli beam model and generalized heat conduction with phase lags. It is believed that the thermal conductivity of the current model varies linearly according to temperature. Due to variable harmonic heat, the considered nanobeam excited and was subjected to a time-varying exponential decay load. Using the Laplace transform process, the analytical solutions for displacement, deflection, thermodynamic temperature and bending moment of rotating nanobeams are provided in final forms and a numerical example has been taken to address the problem. A comparison of the stated results was displayed and additionally, the influences of non-local parameters and varying load were analyzed and examined. We also investigate how the linear changes in the temperature of physical properties can influence both the static and dynamic responses to the rotating nanobeam.

Risk attitudes are relevant factors affecting the production and investment decisions at farm level. They are key factors that are related to farmers’ attitudes towards environment and climate change. Several methodological approaches are available to measure the level of stated risk of an economic agent. The Multiple Price List (MPL) method is one of the methods that is gaining relevance. In this study we apply the MPL and relate the risk outcomes with farmers’ characteristics and their perception towards environment and climate change. Data was collected using a face to face survey carried out for a group of 370 agricultural producers of the irrigation district located in northwest of Mexico. Results showed an average risk of about 0.32, locating the agricultural producers of the region in a group with risk aversion, according to the MPL scale. The heterogeneity analysis showed that the socioeconomic factors and the perceptions towards climate change are related to the farmers´ stated risk level. Farmers who are young women with propensity to use public support to invest were shown to be greater risk lovers. Farmers in the region have perceived climate change to a greater extent like floods, hail, diseases and pests, and changing vegetation.

Sustainability in material purchasing is a growing area of research. Goods purchasing decisions strongly affect transportation path flows, vehicle consolidation, inventory levels and related obsolescence costs. Within a global sourcing context, companies experience the need of new decision making approaches capable to consider a large variety of factors, also linked with society and environment. Environmental impact assessment has become a key requirement for materials purchasing and transportation decisions since global warming is a rising concern both in academic and industrial researches. In fact, it is well known that the freight transport industry is responsible for large amounts of carbon emissions contributing to global warming. In this paper, we initially analyse and compare the environmental economic policies established by the International Governments in relation to the carbon trading systems adopted. Then, we develop a multi-objective lot sizing approach useful in practice to define the sustainable quantity to purchase when a Cap and Trade mitigation policy is present. We further analyse the model behaviour according to different carbon price values by demonstrating that carbon prices are still far too low to motivate managers towards sustainable purchasing choices.

This paper identifies a dilemma in the relationship between R^2 and price efficiency: After comprehensively studying the R^2 change around 7 well-known corporate events, neither the traditional understanding of R^2 as price inefficiency, nor the behavioral way of R^2 as price efficiency can explain the observed R^2 change around the events. We adopt an alternative methodology to replace the standard difference-in-difference regression and directly decompose the R^2 change. We find that, due to the endogeneity of events, the changes of R^2 are over-estimated. We further propose that in the event study setting, the R^2 change may be simply the consequence of the inflow/outflow of some trend-chasing investors, and it may be detached from price (in) efficiency. Empirical evidences are consistent with this hypothesis.

Land price sustainability issues have been addressed by many authors in the past. Most of these researchers used land prices (from land price maps) as the primary data source in their studies. Only a few papers analysed official land price maps, which are available very rarely. For this reason, we studied the spatial and temporal changes of land prices in the city of Olomouc based on an analysis of official land price maps from 1993 to 2017. We proposed several research hypotheses to confirm some general statements about land price development. We concluded that some macroeconomic indicators had a significant impact on changes in land prices. In the residential and commercial areas and historical centre, land prices are significantly higher than in other monitored aspects (land-use types). We also concluded that no link existed between land-use stability and land price stability. Surprisingly, no long-term stable areas were found in the area of interest. The analysis also confirmed that land price and its change over time varied in different spatial aspects. Surprisingly, the smallest influence was reflected in the economic aspect. Regarding natural events in recent decades, we observed a significant drop in land prices in the vicinity of watercourses threatened by flooding. These findings can assist in better understanding local development and changes in land price.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

China is one of the world’s most important countries for waterfowl because of the large amount of potential habitat and its position along major migratory routes. Waterfowl poaching in China is a serious threat, and for over twenty years colleagues and I have tracked waterfowl poaching in China including hunting methods, trade routes and prices involved. According to the latest survey of a NGO, 11.8% of Chinese people have participated in wildlife consumption, and about 32.0% of people have seen wildlife consumption (Not necessarily involved in killing and eating the wildlife). The survey results come from 100 000 internet questionnaires. The current report provides an update focusing on waterfowl poaching in Xinjiang Province of the northwest China, where is highly pathogenic area on the avian influenza, SARS and the Wuhan coronavirus pneumonia (such as COVID-19). The cases in 2011, 2012, and 2014 involved about 1816 to 2760 birds of more than 20 species, with an estimated total of 200 000 wild birds being hunted by a group per year in Xinjiang. Strangely, the poacher was not punished by any law. We know a few waterfowl species are protected as a list of Key Protected Species in China, and hopefully this report will draw attention to the scope of waterfowl poaching in China. China has made great progress with protecting other wildlife, and hopefully more can be done to protect migrating waterfowl.

Background: Clinical cases reports with snake accidents show that venom bite induces increased oxidative stress including several markers of lipid peroxidation and other oxidative stress marker in plasma. Methods: The main findings of this work were performed with BthTx-II on paw edema of animals treated with the toxin and biochemical measurement of COX-2, PGE2, MDA and the effects of peroxiredoxin inhibitors on edema and myotoxicity were also evaluated. Results: The results show that edema and myotoxocity induced by PLA2 (BthTx-II) induces a strong mobilization of arachidonic acid and an increase in cellular oxidative stress as measured by increased malondialdehydo (MDA) concentration and protein carbonylation. Thus, these findings establish the strong link between oxidative stress, arachidonic acid mobilization and that these events may explain the presence of oxidative stress markers in snake-bitten patients. Experiments performed with animals previously treated with commercially purchased inhibitors showed enzymes such as thioredoxin (TXN), thioredoxin reductase (TXNRD) and other glutathione (GSH)-related antioxidant defenses could play an essential role controlling and defining the end of edema on the late phase of PLA2 BthTx-II-induced process. Conclusion. This study showed that thioate-dependent antioxidant enzymes play an important role in resolving the edema induced by BthTx-II.

Predicting copper price is essential for making decisions that can affect companies and governments dependent on the copper mining industry. Copper prices follow a time series that is non-linear, non-stationary, and which have periods that change as a result of potential growth, cyclical fluctuation and errors. Sometimes the trend and cyclical components together are referred to as a trend-cycle. In order to make predictions, it is necessary to consider the different characteristics of trend-cycle. In this paper, we study a copper price prediction method using Support Vector Regression. This work explores the potential of the Support Vector Regression with external recurrences to make predictions at 5, 10, 15, 20 and 30 days into the future in the copper closing price at the London Metal Exchanges. The best model for each forecast interval is performed using a grid search and balanced cross-validation. In experiments on real data-sets, our results obtained indicate that the parameters (C, ε, γ) of the model Support Vector Regression do not differ between the different prediction intervals. Additionally, the amount of preceding values used to make the estimates does not vary according to the predicted interval. Results show that the support vector regression model has a lower prediction error and is more robust. Our results show that the presented model is able to predict copper price volatilities near reality, being the RMSE equal or less than the 2.2% for prediction periods of 5 and 10 days.

In this paper, we consider a manufacturer who produces and sells a kind of innovative product in the monopoly market environment. Because the life cycle of innovative product is usually shorter than its procurement lead time, one unique demand quantity (scenario) will occur in the selling season, thus there is only one chance for the manufacturer to determine both optimal production quantity and optimal sale price. Considering this one-time feature of such a decision problem, a price-setting newsvendor model for innovative products is proposed. Different to the existing price-setting newsvendor models, the proposed models determine the optimal production quantity and sale price based on some specific state (scenario) which is most applicable for the manufacturer. The theoretical analysis provides managerial insights into the manufacturers’ behaviors in a monopoly market of an innovative product and several phenomena in the luxury goods market are well explained.

Based on the Expected Utility Theory and Regret Theory, the Extended Regret Theory (ERT) is proposed in this paper to study the optimal pricing strategy of retailers in e-commerce environment. Taking the diversity of sales channels and the uncertainty of consumers in e-commerce environment into consideration, author of the paper designs an extended regret utility function which comprehensively considers both pessimistic and optimistic attitudes of decision makers in retailing industry to describe their regret-avoidance behavior. According to the sensitivity analysis, it is found that the optimal retail price decreases as the consumer price sensitivity coefficient increases, yet does not show variation with changes of the consumers pessimism degree. Moreover, the optimal retail price(s) obtained under EUT, ERT and combination of EUT and ERT represent the same.

The open communication is an exigent need for future power system where the time delay is unavoidable. In order to secure the stability of the grid, the frequency must remain within its limited range which is achieved through the load frequency control. The load frequency control signals are transmitted through communication networks which induces time delay that could destabilize the power systems. So, in order to guarantee the stability the delay margin should be computed. In this paper, we present a new method for calculating the delay margin in load frequency control systems. The transcendental time delay characteristics equation is transformed to frequency dependant equation. The spectral radius is used to find the frequencies at which the roots crosses the imaginary axis. The crossing frequencies are determined through the sweeping test and the binary iteration algorithm. A one-area load frequency control system is chosen as case study. The effectiveness of the proposed method has been proved through comparing with the most recent published methods. The method shows its merit with less conservativeness and less computations. The PI controller gains are preferable to be chosen large to reduce the damping, however, the delay margin decreases with increasing the PI controller gains.

This article discusses the outcomes of a quantitative analysis of the competitiveness of grain and its recycling in the countries-members of the Eurasian Economic Union (EEU) through econometric panel data models. The analysis is based on the data of public authorities’ statistics of the countries-members of the EEU, as well as the United Nations Comtrade Database which is a repository of official international trade statistics. The results of the analysis allow to assess the level of competitiveness of produced agro-food products in the countries-members of the EEU and determine the extent to which various factors affect it. The research conclusions can be used to develop and adjust the agreed with the agro-food policy in the EEU.

: Following the phenomenal growth of and competition among coffee chain retailers, the coffee chain market has expanded substantially thanks to rising income levels, the increasing young population, and rapidly changing lifestyles. Attracting consumers’ attention and enhancing their loyalty behaviors have become very difficult for coffee chain retailers. This study seeks to understand the mechanisms through which emotions and the dedication-constraint model lead to brand loyalty and willingness to pay more to certain coffee chain retailers. Emotions and the dedication-constraint model are major factors in the research, but few studies have combined them to examine the formation of loyalty behaviors. This study synthesizes emotional responses and the dedication-constraint model to develop a theoretical model. Based on the ambivalent view of emotions, it also examines how positive and negative emotions affect the combination of brand loyalty and willingness to pay more to certain coffee chain retailers. Moreover, it identifies the antecedents of affective and calculative commitments in the context of coffee chain retailers. Our findings indicate that loyalty behaviors (dedication- and constraint-based mechanisms from brand loyalty and willingness to pay more to certain coffee chain retailers), emotional responses, and affective and calculative commitments significantly affect brand loyalty directly and indirectly through both positive and negative emotions. Furthermore, service quality, physical environment quality, and price fairness significantly affect affective commitments, while price fairness significantly affects both affective and calculative commitments. Finally, affective and calculative commitments significantly affect willingness to pay more, both directly and indirectly, through positive emotions and affect it directly through negative emotions. The results’ theoretical and managerial implications and possible future research directions are discussed.

The deepening of electricity reform results in increasingly frequent auctions and the surge of generators, it becomes difficult to analyze generators’ behaviors. Since it’s hard to find analytical market equilibriums, approximate equilibriums were obtained instead in previous studies by market simulations, which are strict to initial estimations and simulation results are chaotic in some cases. In this paper, a multi-unit power bidding model is proposed to reveal the bidding mechanism under clearing pricing rule by employing auction approach, for which initial estimations are non-essential. Normalized bidding price is introduced to construct generator's price-related bidding strategy. Nash equilibriums are derived depend on the marginal cost and the winning probability which are computed from bidding quantity, transmission cost and demand distribution. Furthermore, we propose a comparative analysis to explore the impact of uncertain elastic demand on the performance of the electricity market. The result indicates that, there exists market power among generators leading to social welfare decreases even under competitive conditions but elastic demand is an effective way to restrain generators’ market power. The feasibility of the models is verified by a case study. Our work provides decision support for generators and a direction for improving market efficiency.

This work presents a novel approach to construct surrogate models of parametric Differential Algebraic Equations based on a tensor representation of the solutions. The procedure consists in building simultaneously, for every output of the reference model, an approximation given in tensor-train format. A parsimonious exploration of the parameter space coupled with a compact data representation allows to alleviate the curse of dimensionality. The approach is thus appropriate when many parameters with large domains of variation are involved. The numerical results obtained for a nonlinear elasto-viscoplastic constitutive law show that the constructed surrogate model is sufficiently accurate to enable parametric studies such as the calibration of material coefficients.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

The paper examines the effects of crude oil price shocks on the Indian economy development and GDP Growth for the period of 2010 till 2018. The present Indian economy growth has been facing the identical issues of escalating the trade disparity and continuing inflation. In this connection, the study focused on the determine relationship between the speculation and crude oil price impact on the Indian economic development activity and GDP growth and the paper investigated the how oil price variations effect on the Indian economy development through different networks, viz. WPI, CP, IIP, GDP, Monetary policy, trade and investment. The paper used methods an GARCH model and description to tool the volatility on both the oil and stock markets and then developed an extension of the vector auto-regression (VAR) models are also applied to determine the oil price shocks effect on macroeconomic indicators and the outcomes of co-integration model propose that crude oil is pro‐cyclical to output, and the paper used VAR investigation to the discrepancy decomposition to capture the linear inter‐dependencies among the variables.

The purpose of this paper is to analyze market reflexivity in agricultural futures contracts with different maturities. To this end, we apply a four-dimensional Hawkes model to storable and non-storable agricultural commodities. We find market reflexivity for both storable and non-storable commodities. Reflexivity accounts for about 50 to 70 percent of the total trading activity. Differences between nearby and deferred contracts are less pronounced for non-storable than for storable commodities. We conclude that the co-existence of exogenous and endogenous price dynamics does not change qualitative characteristics of the price discovery process that have been observed earlier without consideration of market reflexivity.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

We propose an iterative scheme for feature-based positioning using a new weighted dissimilarity measure with the goal of reducing the impact of large errors among the measured or modeled features. The weights are computed from the location-dependent standard deviations of the features and stored as part of the reference fingerprint map (RFM). Spatial filtering and kernel smoothing of the kinematically collected raw data allow efficiently estimating the standard deviations during RFM generation. In the positioning stage, the weights control the contribution of each feature to the dissimilarity measure, which in turn quantifies the difference between the set of online measured features and the fingerprints stored in the RFM. Features with little variability contribute more to the estimated position than features with high variability. Iterations are necessary because the variability depends on the location, and the location is initially unknown when estimating the position. Using real WiFi signal strength data from extended test measurements with ground truth in an office building, we show that the standard deviations of these features vary considerably within the region of interest and are neither simple functions of the signal strength nor of the distances from the corresponding access points. This is the motivation to include the empirical standard deviations in the RFM. We then analyze the deviations of the estimated positions with and without the location-dependent weighting. In the present example the maximum radial positioning error from ground truth are reduced by 40% comparing to kNN without the weighted dissimilarity measure.

RNA interference (RNAi) is one of the main mechanisms for disease resistance and small RNA production in plants. The main proteins involved in RNAi include Dicer-like (DCL), RNA-dependent RNA polymerase (RDR), double-stranded RNA-binding (DRB), and Argonaute (AGO). Juglandaceae contains a variety of important woody plants, and walnuts are one of the four major woody plant groups and one of the four major dried fruits in the world. To clarify the evolution and functional differentiation of RNAi-related proteins in the walnut (Juglans regia) genome, this study integrated various web resources from gene family acquisition to structural analysis and transcriptome data to correlate walnuts and their congeners. The walnut genome has 5 DCL, 13 RDR, 15 DRB and 15 AGO genes, similar genes encoding conserved protein structural domains and conserved motifs with similar subcellular localization. Walnut AGO proteins are classified into three classes and seven subclasses. The DCL is divided into four categories, while RDR is mainly divided into four categories, and DRB can be divided into six categories. The exception is that the copy number of walnut RDR1 is 9, in which seven RDR1 are distributed in clusters on chromosome 16. Purifying selection drove the formation of walnut genes, but protein classes were subjected to varying degrees of purifying selection. Additionally, these results showed some similarity in other plants of the walnut family. Moreover, different RNAi-related genes of walnut produced abundant selective expression in response to different tissues and stresses. In this study, DCL, RDR, DRB and AGO gene families were identified and analysed in the genome of the walnut family for the first time and preliminarily examined the evolution, structure and expression characteristics of these families to provide a preliminary basis for the evolution of the walnut RNAi pathway and breeding research.

In order to evaluate the economy of superhighway, on the basis of the analysis of the cost of the ordinary expressway and high speed railway, the cost of superhighway is estimated. On this basis, the standard of the toll of superhighway at all levels is determined by reference to the standard of the construction cost and the toll collection standard of the ordinary expressway. According to the toll collection standard of superhighway and the fuel consumption cost of superhighway at all levels, the cost of single car and the single person cost of superhighway are calculated. Based on the analysis of highway passenger transport, railway passenger transport and civil aviation ticket price, the single person cost per kilometer of the above travel modes is calculated and compared with the single person travel cost per kilometer of superhighway. The results show that the single person cost of superhighway is between 0.29 and 0.47 yuan /km, which is 0.28 yuan /km higher than the highway bus, 0.18 yuan /km higher than the ordinary expressway self driving and 0.23 yuan /km higher than the express train, but 0.78 yuan/km lower than that of the first class seat of high-speed train, and is 0.92 yuan/km far lower than that of civil aviation flight economy class and 2.42 yuan/km lower than the business class. Therefore, the superhighway trip has certain advantages in economy.

Understanding the detailed timing of crop phenology and their variability enhances grain yield and quality by providing precise scheduling of irrigation, fertilization, and crop protection mechanisms. Advances in information and communication technology (ICT) provide a unique opportunity to develop agriculture-related tools that enhance wall-to-wall upscaling of data outputs from point-location data to wide-area spatial scales. Because of the heterogeneity of the worldwide agro-ecological zones where crops are cultivated, it is unproductive to perform plant phenology research without providing means to upscale results to landscape-level while safeguarding field-scale relevance. This paper presents an advanced, reproducible, and open-source software for plant phenology prediction and mapping (PPMaP) that inputs data obtained from multi-location field experiments to derive models for any crop variety. This information can then be applied consecutively at a localized grid within a spatial framework to produce plant phenology predictions at the landscape level. This software supports the development of process-oriented and temperature-driven plant phenology models by intuitively and interactively leading the user through a step-by-step progression to the production of spatial maps for any region of interest. Maize (Zea mays L.) was used to demonstrate the robustness, versatility, and high computing efficiency of the resulting modeling outputs of the PPMaP. The framework is implemented in R, providing a flexible and easy‐to‐use GUI interface. Since this allows appropriate scaling to the larger spatial domain, the software can effectively be used to determine the spatially explicit length of growing period (LGP) of any variety.

Here, I introduce a concept called autonomous selection to refer to a source of selection that is part of the individuals upon which it acts. The concept is motivated by a set of phenomena with the following characteristics: Natural selection shaped a variant (e.g., gene, epigenetic mark, or combination thereof) to act in a manner that reduces the frequency of one or more heritable traits of the individual in which it is located if those traits are detrimental to individual or group fitness. Phenomena with these characteristics are peculiar to traditional evolutionary theory but have been identified rather frequently in recent decades. They are also relevant to adaptive evolution: By reducing the frequency of a trait detrimental to fitness, the variant accelerates the evolution of adaptations, which allows its holders to adapt better to constantly changing environments. The variant is shaped by (natural) selection, but also does (autonomous) selection. Several phenomena with these characteristics have been invoked by proponents of the extended evolutionary synthesis (EES). The concept of autonomous selection helps resolve some of the controversy surrounding the EES: EES proponents call attention to the incompleteness of contemporary theory, emphasizing individuals’ processes that influence which adaptations those individuals evolve. I argue for the special importance of individuals’ processes that do not just influence those individuals’ adaptations, but also accelerate the adaptive evolution of those individuals. All known phenomena that fit this description are examples of autonomous selection. Other phenomena raised by EES proponents do not meet this threshold.

To understand the evolution of the human norovirus GII.P6-GII.6 and GII.P7-GII.6 strains, we analyzed both the RdRp region and VP1 gene in globally collected strains using authentic bioinformatics technologies. A common ancestor of the P6- and P7-type RdRp region emerged approximately 50 years ago and a common ancestor of the P6- and P7-type VP1 gene emerged approximately 110 years ago. Subsequently, the RdRp region and VP1 gene evolved. Moreover, the evolutionary rates were significantly faster for the P6-type RdRp region and VP1 gene than the P7-type RdRp region and VP1 genes. Large genetic divergence was observed in the P7-type RdRp region and VP1 gene compared with the P6-type RdRp region and VP1 gene. The phylodynamics of the RdRp region and VP1 gene fluctuated after the year 2000. Positive selection sites in VP1 proteins were located in the antigenicity-related protruding 2 domain, and these sites overlapped with conformational epitopes. These results suggest that the GII.6 VP1 gene and VP1 proteins evolved uniquely due to recombination between the P6- and P7-type RdRp regions in the HuNoV GII.P6-GII.6 and GII.P7-GII.6 virus strains.

Time evolution operators of a strongly ionizing medium are calculated by a time-dependent unitary transformation (TDUT) method. The TDUT method has been employed in quantum mechanical system composed of discrete states. This method is especially helpful for solving molecular rotational dynamics in quasi-adiabatic regimes because the strict unitary nature of the propagation operator allows us to set the temporal step size large; a tight limitation on the temporal step size ($\delta t <<1$) can be circumvented by the strict unitary nature. On the other hand, in a strongly ionizing system where the Hamiltonian is not Hermitian, the same approach cannot be directly applied because it is demanding to define a set of field-dressed eigenstates. In this study, the TDUT method was applied to the ionizing regime using the Kramers-Henneberger frame, in which the strong-field-dressed discrete eigenstates are given by the field-free discrete eigenstates in a moving frame. Although the present work verifies the method for a one-dimensional atom as a prototype, the method can be applied to three-dimensional atoms, and molecules exposed to strong laser fields.

We study in this paper the time evolution of stock markets using a statistical physics approach. We consider an ensemble of agents who sell or buy a good according to several factors acting on them: the majority of the neighbors, the market ambiance, the variation of the price and some specific measure applied at a given time. Each agent is represented by a spin having a number of discrete states q or continuous states, describing the tendency of the agent for buying or selling. The market ambiance is represented by a parameter T which plays the role of the temperature in physics: low T corresponds to a calm market, high T to a turbulent one. We show that there is a critical value of T, say T_c, where strong fluctuations between individual states lead to a disordered situation in which there is no majority: the numbers of sellers and buyers are equal, namely the market clearing. The specific measure, by the government or by economic organisms, is parameterized by $H$ applied on the market at the time t₁ and removed at the time t₂. We have used Monte Carlo simulations to study the time evolution of the price as functions of those parameters. In particular we show that the price strongly fluctuates near T_c and there exists a critical value H_c above which the boosting effect remains after H is removed. Our model replicates the stylized facts in finance (time-independent price variation), volatility clustering (time-dependent dynamics) and persistent effect of a temporary shock. The second party of the paper deals with the price variation using a time-dependent mean-field theory. By supposing that the sellers and the buyers belong to two distinct communities with their characteristics different in both intra-group and inter-group interactions, we find the price oscillation with time. Results are shown and discussed.

Dengue fever is a viral mosquito-borne infection, a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called Antibody-Dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: i) primary dengue infection, ii) secondary dengue infection with the same (homologous) dengue virus and iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production, and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights on the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.

Objective: To investigate the protein expression levels of cyclin‑dependent kinase subunit 2 (CKS2) and cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significances. Methods: A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumor, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analyzed the clinical significance of the expression of the two factors. Results: (1) The positivity rates for CKS2 in benign gastric tumor tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, i.e., 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumor diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=0.625, P=0.000). (3) The median follow-up time of 126 patients was 46.5 months, and the overall survival rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the overall survival rate for patients in the CKS2 (+) group was significantly worse (25.0% vs 64.0%, 2=15.67, P=0.000) and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse overall survival (30.1% vs 60.5%, 2=15.67, P=0.000). (4) The overall survival rates of CKS2(+)CD47(+) group, CKS2(+)CD47(-) group, CKS2(-)CD47(+) group, and CKS2 (-)CD47 (-) group were 20.0%(13/65), 58.3%(7/12), 57.1%(8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2(+)CD47(+) group was significantly poor. Conclusion: High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

In recent years, the photophysical properties of crystalline metal-organic frameworks (MOFs) have become increasingly relevant for their potential application in light-emitting devices, photovoltaics, nonlinear optics and sensing. The availability of high-quality experimental data for such systems makes them ideally suited for a validation of quantum mechanical simulations, aiming at an in-depth atomistic understanding of photophysical phenomena. Here we present a computational DFT study of the absorption and emission characteristics of a Zn-based surface-anchored metal-organic framework (Zn-SURMOF-2) containing anthracenedibenzoic acid (ADB) as linker. Combining band-structure and cluster-based simulations on ADB chromophores in various conformations and aggregation states, we are able to provide a detailed explanation of the experimentally observed photophysical properties of Zn-ADB SURMOF-2: The unexpected (weak) red-shift of the absorption maxima upon incorporating ADB chromophores into SURMOF-2 can be explained by a combination of excitonic coupling effects with conformational changes of the chromophores already in their ground state. As far as the unusually large red-shift of the emission of Zn-ADB SURMOF-2 is concerned, based on our simulations, we attribute it to a modification of the exciton coupling compared to conventional H-aggregates, which results from a relative slip of the centers of neighboring chromophores upon incorporation in Zn-ADB SURMOF-2.

This paper presents sufficient conditions for almost global stability of nonlinear switched systems consisting of both stable and unstable subsystems. Techniques from the stability analysis of switched systems have been combined with the multiple Lyapunov density approach - recently proposed by the authors for the almost global stability of nonlinear switched systems composed of stable subsystems. By using slow switching for stable subsystems and fast switching for unstable subsystems lower and upper bounds for mode-dependent average dwell times are obtained. In addition to that, by allowing each subsystem to perform slow switching and using some restrictions on total operation time of unstable subsystems and stable subsystems, we have obtained a lower bound for an average dwell time.

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

RNA silencing serves key roles in a multitude of cellular processes, including development, stress responses, metabolism, and maintenance of genome integrity. Dicer, Argonaute (AGO), double-stranded RNA binding (DRB), RNA-dependent RNA polymerase (RDR) and DNA-dependent RNA polymerases known as Pol IV and Pol V form core components to trigger RNA silencing. Common bean (Phaseolus vulgaris) is an important staple crop worldwide. In this study, we aimed to unravel the components of the RNA-guided silencing pathway in this non-model plant taking advantage of the availability of two genome assemblies of Andean and Meso-American origin. We identified six PvDCLs, thirteen PvAGOs, 10 PvDRB, 5 PvRDR, in both genotypes, suggesting no recent gene amplification or deletion after the gene pool separation. In addition, we identified one PvNRPD1 and one PvNRPE1 encoding the largest subunits of Pol IV and Pol V, respectively. These genes were categorized into subgroups based on phylogenetic analyses. Comprehensive analyses of gene structure, genomic localization and similarity among these genes were performed. Their expression patterns were investigated by means of expression models in different organs using online data and quantitative RT-PCR after pathogen infection. Several of the candidate genes were up-regulated after infection with the fungus Colletotrichum lindemuthianum.

This paper shows the influence of CCP’s collateralization on the pricing of the Credit Default Swaps (CDS). A narrowly variant in the way the CDS seller decides over the resources in the settlement comes with a substantial change on the elements that determine the price of the CDS.

A new type of ordinary differential equation is introduced and discussed, namely, the time-dependent order ordinary differential equations. These equations can be solved via fractional calculus and are mapped into Volterra integral equations of second kind with singular integrable kernel. The solutions of the time-dependent order differential equations smoothly deforms solutions of the classical integer order ordinary differential equations into one-another, and can generate or remove singularities. An interesting symmetry of the solution in relation to the Riemann zeta function and Harmonic numbers was also proved.

Achieving sustainable management of forests in China is becoming increasingly important with more awareness and realization of the importance of forests in environmental protection. Forest certification, a market-based instrument to promote sustainable forest management, has been recognized by many countries including China. While landowners’ perception and perspective regarding this voluntary program have been well-documented in literature, how to motivate and incentivize landowners to participate in forest certification remained under-studied questions. With the face-to-face survey of landowners in Shandong, China, this study analyzed landowners’ willingness to accept compensation for participating in forest certification. Results indicated that landowners average accepted compensation, in terms of increased timber price, was about RMB120 (~$17.2)/m3 to have their forests certified. Results from multiple regression showed that the level of such compensation required for certification adoption was influenced by ownership size, owners’ demographics, certification program requirements, as well as importance placed on timber sale. These findings would inform policy-makers in designing compensation-related polices and establish incentive-based mechanisms to motivate landowners participate in forest certification programs in China.

The rural population percentage decreased from 82.7% to 68.9% in 2011, even though there is an increase in the total rural population, which stands at 833.7 million, and the rural population were now more than three times compared to the population seven decades ago. Another observation is the decrease in cultivators percentage from 71.9% to 45.1 %, while agriculture labour increase from 28.1% to 54.9% during the same period. Despite the increase in irrigated land and net area sown, the average holdings' size under the farmers is continuously decreasing, and it requires a study to look into the reasons. The research probes the role of Minimum Support Price (MSP) in supporting farmers and measuring market price above MSP needed to help marginal and small farmers remain above the poverty level. It explains how different market rates above MSP have a different impact on different categories of agriculture landholding. The study works on developing a common model that relates the impact of MSP on different farmers categories. The model can be generalized to all crops and regions and useful in designing policies that focus on uplifting the income of agricultural farmers.

Changes in crude oil price affect the shipping freight market in three different channels. This study explores the dependence structure between oil prices and maritime freight rates to identify the strongest channel. Therefore, it investigates the relationship between oil prices and three major maritime freight rates; the Baltic Dry Index (BDI), the Baltic Dirty Tanker Index (BDTI), and the Baltic Clean Tanker Index (BCTI). We employ the decomposition method, not studied in the existing literature. The copula approach identifies the time-varying effects and asymmetry in the tail dependence structure between oil prices and freight rates. The main results of this analysis are as follows. The decomposed components display different conditional dependence patterns, and asymmetry is revealed in the upper and lower tail dependence. In the long run, we find more dependence in extreme periods like the financial crises. In short-run fluctuations, we find the dependence increases in an economic boom. The implications of the results suggest that dependence can vary over time and may change depending on extreme events, implying that the complementary strategies of the long run and short run should be different.

ccJE+Advax is an inactivated cell culture Japanese encephalitis (JE) vaccine formulated with Advax™, a novel polysaccharide adjuvant based on delta inulin. This vaccine has previously shown promise in murine and equine studies and the current study sought to better understand its mechanism of action and assess the feasibility of single dose vaccine protection. Mice immunised with ccJE-Advax had higher serum neutralisation titres than those immunised with ccJE alone or with alum adjuvant. ccJE+Advax induced extraordinarily broad cross-neutralising antibodies against multiple flaviviruses including West Nile virus (WNV), Murray Valley Encephalitis Virus (MVEV), St Louis Encephalitis virus (SLE) and Dengue-1 and -2 viruses. Notably, the DENV-2 cross-neutralising antibodies from ccJE+Advax immunised mice uniquely had no DENV-2 antibody dependent enhancement (ADE) activity, by contrast to high ADE activity seen with DENV-1 cross-reactive antibodies induced by mbJE or ccJE alone or with alum adjuvant. JEV-stimulated splenocytes from ccJE+Advax immunised mice showed increased IL-17 and IFN-γ production, consistent with a mixed Th1 and Th17 response, whereas ccJE-alum was associated with production of mainly Th2 cytokines. There is an ongoing lack of human vaccines against particular flaviviruses, including WNV, SLE and MVEV. Given its ability to provide single-dose JEV protection as well as to induce broadly neutralising antibodies free of ADE activity, ccJE+Advax vaccine could be highly useful in all situations where rapid protection is desirable but ADE needs to be avoided, e.g. during a local outbreak or for use in travellers or the military requiring rapid travel to JEV endemic regions.

In this paper, we address the energy eigenvalues of two-dimensional Dirac oscillator perturbed by dynamical noncommutative space. We derived the relativistic Hamiltonian of Dirac oscillator in dynamical noncommutative space ($\tau$-space), in which the space-space Heisenberg–like commutation relations and noncommutative parameter are position-dependent. Then used this Hamiltonian to calculate the first-order correction to the eigenvalues and eigenvectors, based on the second quantization and using the perturbation theory. It is shown that the energy shift depends on the dynamical noncommutative parameter $\tau$. Knowing that with a set of two-dimensional Bopp-shift transformation, we mapped the noncommutative problem to the standard commutative one.

Real-time evolution of the electron densities under excitations in La₂CuO₄ was calculated by the time-dependent density functional theory (TDDFT). The author found, for the first time, under excitations, the electron cloud of Cu²⁺ changes obviously and the characteristic frequencies are 83 meV and 36 meV, respectively, for two different modes. The results are unexpected and close to that of lattice vibrations. The results show that the electron cloud of Cu²⁺ (just like the lattice) can be the electron-pairing medium in high temperature copper oxide superconductors.

This paper focuses on the physical attributes of land that intrinsically limit land use and possibly affect land values. In particular, we investigate if the slope of a land does decrease its price and investigate the role of land slope in forming more reliable constant-quality land price indices and aggregate house price indices. We find that, while land slopes do decrease the land price per unit, they have a small effect on the quality-adjusted land price indices in selected neighborhoods in Auckland, New Zealand, where sloped terrain is common.

Corn is the main agricultural product and has been produced in Kazakhstan as important nutrition in human and animal food. The research results shown in the article, the fact of increasing the sustainability of corn production is formulated, methodological approaches to assessing the level of sustainability are developed, and criteria are defined for the main indicators of sustainability and efficiency of corn production. The world's corn production was 1,223 million tons in the 2021/22 season. Kazakhstan's corn production average was 1,1 million tons and the production area are 206,870 in the 2021/22 season. The yield per hectare was 5,985 kg in the 2021/22 season. Corn consumption was 1170.5 million tons and exported was 180.1 m.tons of corn in the 2021/22 season in Kazakhstan. The purpose of this study is a determination of sustainable developments of corn consumption and production in Kazakhstan and worldwide between the 2011/12 and 2021/22 seasons. Statistical data have been obtained from the International Grain Council, FAOSTAT, USDA, PhD diploma thesis of the article's author, Bureau of National Statistics. Data obtained have been shown in the tables issued by the use of percentage and index calculations. The study analyzed a major factor affecting supply and demand, sustainable development of corn production and market prices.