Manned missions to Mars and other deep space exploration targets are expected to take place in the next 20 years. These missions will involve prolonged crew exposure to the unique space environment, increasing the risk that astronauts will experience additional physical and psychological health conditions beyond those that would be expected through normal aging on Earth. Thus, there is an acute need to develop therapeutic solutions that can withstand the harsh space environment, while maintaining astronaut health and maximizing crew capabilities to foster successful exploration-class missions. This review covers the nuanced and interdisciplinary challenge that is providing safe and effective pharmaceuticals for future deep space missions. First, the limitations of current pharmaceutical solutions are discussed; the impacts of the space environment on human health and chemical compound stability are covered, along with an evaluation of astronaut medication use on similar missions. Second, potential pharmaceutical solutions and concepts are presented for consideration. Future research should prioritize these and other potential innovations to ensure that our space programs are well equipped to maximize crew safety as astronauts explore deep space objectives.

Since 2007, highly pathogenic clade 2.3.2 H5N1 avian influenza A [A(H5N1)] viruses have evolved to clade 2.3.2.1a, b and c, and currently only 2.3.2.1c A(H5N1) viruses circulate in wild birds and poultry. During antigenic evolution, clade 2.3.2.1a and c A(H5N1) viruses acquired both S144N and V223I mutations around the receptor binding site of hemagglutinin (HA), with S144N generating an N-glycosylation sequon. We introduced single or combined reverse mutations, N144S and/or I223V, into the HA gene of clade 2.3.2.1c A(H5N1) virus and generated PR8-derived, 2 + 6 recombinant A(H5N1) viruses. When we compared replication efficiency in embryonated chicken eggs, mammalian cells and mice, the recombinant virus containing both N144S and I223V mutations showed increased replication efficiency in avian and mammalian hosts and pathogenicity in mice. The N144S mutation significantly decreased avian receptor affinity and egg white inhibition, but not all mutations increased mammalian receptor affinity. Interestingly, the combined reverse mutations dramatically increased the thermostability of HA. Therefore, the adaptive mutations possibly acquired to evade avian immunity may decrease viral thermostability as well as mammalian pathogenicity.

The fluorine-less noble-gas containing anions OBONgO- and OCNNgO-have been studied by correlated electronic structure calculation and density functional theory. The obtained energetics indicates that for Ng = Kr and Xe, these anions should be kinetically stable at low temperature. The molecular structures and electron density distribution suggests that these anions are stabilized by ion-induced dipole interactions with charges concentrated on the electronegative OBO and OCN groups. The current study shows that in additional to the fluoride ion, polyatomic groups with strong electronic affinities can also form stable noble-gas containing anions of the type X-...NgO.

Intercropping of maize (Zea mays L.) and peanuts (Arachis hypogaea L.) (M||P) significantly enhances crop yield. In a long-term M||P field experiment with two P fertilizer levels, we examined how long-term M||P affects topsoil aggregate fractions and stability, organic carbon (SOC), available phosphorus (AP), and total phosphorus (TP) in each aggregate fraction, along with crop yields. Compared to their respective monocultures, long-term M||P substantially increased the proportion of topsoil mechanical macroaggregates (7.6–16.3%) and water-stable macroaggregates (>1 mm) (13.8–36.1%), while reducing the unstable aggregate index (ELT) and the percentage of aggregation destruction (PAD). M||P significantly boosted the concentration (12.9–39.9%) and contribution rate (4.1–47.9%) of SOC in macroaggregates compared to single crops. Moreover, the concentration of TP in macroaggregates (>1 mm) and AP in each aggregate fraction of M||P exceeded that of the respective single crops (P<0.05). Furthermore, M||P significantly increased the Ca2-P, Ca8-P, Al-P, and Fe-P concentrations of intercropped maize (IM) and the Ca8-P, O-P, and Ca10-P concentrations of intercropped peanuts (IP). The land equivalent ratio (LER) of M||P was higher than one, and M||P stubble improved the yield of subsequent winter wheat (Triticum aestivum L.) compared with sole-crop maize stubble. P application augmented the concentration of SOC, TP, and AP in macroaggregates, resulting in improved crop yields. In conclusion, our findings suggest that long-term M||P combined with P application, sustains farmland productivity in the North China Plain by increasing SOC and macroaggregate fractions, improving aggregate stability, and enhancing soil P availability.

An experimental series of shearing tests with water infiltration were performed on compacted unsaturated soil to simulate the behavior of shallow slope failures. Soil samples were compacted at moisture contents from dry to wet of optimum moisture content with the degree of saturation varying from 24.0% to 59.5% while maintaining the degree of compaction at 80%. Two series of shearing with infiltration tests were performed in this study. In Series-I, just before the start of shearing, matric suction was decreased by increasing pore water pressure to start water infiltration i.e. shearing is carried simultaneously with water infiltration. In Series-II, the soil was first sheared with drained pore air and undrained pore water to pre-defined value of deviatoric stress, after which matric suction was decreased by increasing pore water pressure to start water infiltration and shearing is performed by keeping deviatoric stress constant on the specimen. The test results showed that the decrease in matric suction has an effect on the volume of infiltrated water and degree of saturation. The soil slopes compacted on the dry side of optimum moisture content showed better performance than other soils, they require more decrease in matric suction to start water infiltration and showed higher deviatoric stress. In addition to this, water infiltration alone can cause the failure of shallow slopes without having to have any further loading.

Cytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolizing cytochromes P450 located in the endoplasmic reticulum. Mutations in POR cause a broad range of metabolic disorders. The POR variant rs17853284 (P228L) identified by genome sequencing has been linked to lower testosterone levels and reduced P450 activities. We expressed POR wild type and the P228L variant in bacteria, purified the proteins, and performed protein stability and catalytic functional studies. Variant P228L affected the stability of the protein as evidenced by lower unfolding temperatures and higher sensitivity to urea denaturation. A significant reduction of small molecule metabolism was observed with POR P228L while activities of CYP3A4 were reduced by 25%, and activities of CYP3A5, and CYP2C9 were reduced by more than 40% compared to WT POR. The 17,20 lyase activity of CYP17A1 responsible for production of main androgen precursor dehydroepiandrosterone, was reduced to 27% of WT in presence of P228L variant of POR. Based on in silico and in vitro studies we predict that the change of proline to leucine may change the rigidity of the protein, causing conformational changes in POR, leading to altered electron transfer to redox partners. A single amino acid change can affect protein stability and cause a severe reduction in POR activity. Molecular characterization of individual POR mutations is crucial for a better understanding of the impact on different redox partners of POR.

Digitalization has fundamentally changed the global economy and will continue to do so. This study investigates how the US Federal Reserve and US Treasury may work together to use decentralized finance (DeFi) systems to promote economic growth in local communities. The study looks into the potential for transformation and the difficulties in incorporating DeFi into conventional financial institutions. Research shows that the use of cash as a means of payment is widely expected to decline in the future. As a result, the public’s ability to make transactions using central bank money may decline rapidly. This study's goals are to solve economic issues, promote innovation, and increase financial efficiency. The use of in-depth interviews, theme analysis, case studies, stakeholder perspectives, comparative analysis, and document analysis is suggested as part of a qualitative research methodology. The goal of these approaches is to offer a sophisticated comprehension of the dynamics of collaboration and the consequences of DeFi integration in the context of the Federal Reserve-Treasury relationship. Important data sources that are necessary to answer the research question are indicated, such as US Treasury statistics, Federal Reserve publications, DeFi platforms, and International Monetary Fund economic indicators. Informed decision-making and policy formation may pave the way for a more inclusive and efficient financial ecosystem, which will eventually drive regional economic growth in the United States and promote monetary sovereignty for the aforementioned monetary entities. This can be achieved by investigating creative collaboration tactics between the Federal Reserve and the US Treasury.

We introduce a model of a passive optical cavity based on the two-dimensional Lugiato-Lefever equation, with a localized pump carrying intrinsic vorticity S, and the cubic or cubic-quintic nonlinearity. Up to S = 5, stable vortex-ring states (vortex pixels) are produced by a variational approximation and in a numerical form. Surprisingly, vast stability areas of the vortex states are found, for both the self-focusing and defocusing signs of the nonlinearity, in the plane of the pump-strength and loss parameters. When the vortex-rings are unstable, they are destroyed by azimuthal perturbations which break the axial symmetry. The results suggest new possibilities for mode manipulations in nonlinear optical media.

The active form of fingolimod (FTY720; FT) is a sphingosine-1-phosphate receptor agonist with potential ocular applications. The goal of the present study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. FT-NE formulations were prepared with homogenization followed by probe sonication method. The lead FT-NE formulation (0.15% and 0.3% w/v loading), comprising soybean oil as lipid and Tween® 80 and Poloxamer 188 as surfactants, was further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature post-filtration through polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release, compared with the control FT solution (FT-S), over 24 h. The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

In this paper, we propose to explore a nonlinear fractional mathematical model of HFMD- Hand Foot Mouth Disease with vaccinated compartment. Firstly, we prove the non negativity and boundedness for the fractional order dynamical model. The system’s existence and uniqueness are studied using the formulation of the Caputo derivative operator. The fixed-point approach was used to get results indicating the presence of at least one solution. In numerical simulation, we obtained the approximate solution by using fractional Euler method.

Sodium-potassium (NaK) liquid alloy is a promising candidate for use as anode material in sodium batteries because of its fluidity, which effectively suppresses the growth of sodium or potassium dendrites. However, the poor wettability of the NaK liquid alloy on conventional metal substrates is unfavorable for cell fabrication due to its strong surface tension. In this paper, low-density and low-cost fluorinated aluminum foam is used as a substrate support material for NaK liquid alloy. By combining low surface tension NaK@C with fluorinated aluminum foam, we obtain a uniformly distributed and structurally stable electrode material. The composite electrode has a cycling stability of more than 3000 hours in a symmetrical cell. Furthermore, when coupled with a sulfurized polyacrylonitrile cathode in carbonate electrolyte, it maintains excellent stability even after 800 cycles, with 72% of capacity retention.

The present study aimed to evaluate the effect of the citric acid on the properties of solid pine wood, which were submitted to thermomechanical treatment. A preliminary test was performed in a previous study to evaluate the influence of different temperatures of pressing and concentrations of citric acid over the physical properties of wood. After choosing the best treatments (170°C and 5% and 10% of citric acid) it was evaluated the effect of these on the chemical properties (SEM, FTIR and pH), on the density profile using an X-ray microtomography, and on the resistance to ageing through abrasion test. The result of the chemical analysis allowed to observe an increase of the presence of ester functional groups, as well as a better coverage and higher acidity of the surface. The density profile technique allowed to observe the formation of peaks of density on the surface where the acid was applied. Lastly, it was also possible to verify an increase in the resistance to abrasion because of the application of the citric acid.

A fundamental tool in mathematical physics is the logarithmic Sobolev inequality. A quantitative version proven by Carlen with a remainder involving the Fourier-Wiener transform is equivalent to an entropic uncertainty principle more general than the Heisenberg uncertainty principle. In the stability, the remainder is in terms of an entropy, not a metric. Recently, a stability result for H¹ was obtained by Dolbeault, Esteban, Figalli, Frank, and Loss in terms of an L^p norm. Afterwards, Brigati, Dolbeault, and Simonov discussed the stability problem involving a stronger norm. A full characterization with a necessary and sufficient condition to have H¹ convergence is identified in this paper. Moreover, an explicit H¹ bound via a moment assumption is shown. Also, the L^p stability of Dolbeault, Esteban, Figalli, Frank, and Loss is proven to be sharp.

The objective of this study was to analyze the in vitro stability and toxicity of liposomes containing guarana in skin cell lines. The liposomes were produced by the reverse phase evaporation method containing 1 mg/mL guarana. The stability of the liposomes was evaluated by physical-chemical parameters for up to 90 d using three different storage conditions. The cytotoxicity of guarana (GL), liposomes (B-Lip), and guarana-loaded liposomes (G-Lip) was evaluated on spontaneously immortalized human keratinocyte cell lines (HaCaT), murine swiss albino fibroblasts (3T3), and human fibroblast (1BR.3.G). The evaluation was performed using cellular viability analysis. The techniques used were 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red capturing (NRU) and the analyses were conducted after 24, 48, and 72 h exposure of these cells to the different treatments. The G-Lip exhibited physical-chemical stability for 60 d when the samples were stored in a refrigerator. The GL, B-Lip, and G-Lip demonstrated low cytotoxicity in the three cell cultures tested since a low reduction in cell viability was only observed at the highest concentrations. In addition, greater cell damage was observed for B-Lip; however, guarana protects cells from this damage. Thus, G-Lip structures can be considered as promising systems for topical applications.

One of the challenges posed by renewable energies is the stabilization of parameters related to the quality of electrical energy. This study demonstrates the existence of a relationship between input blocks of hydropower and the variation of the fundamental frequency of the electricity grid. By mapping production data provided by Spanish Electric Network with frequency measured in the laboratory, it is shown that gradients of hydropower are correlated with frequency fluctuations for certain characteristic times. Considering hourly instances of energy input, the study compares two methods for calculating hydropower gradients (linear regression and pseudo-linear regression); and two methods for calculating local frequency extremes (the "specular inertia" method and analysis by comparison with the moving average), in order to corroborate the results.

Tagetes genus of Composite family consider one of the most favorite floriculture plant. Therefore, of particular interest examine the salt tolerance of this bedding and coloring agent plant. In this research, was report the role of glycinebetaine (GB) in attenuating the adverse impacts of salt stress in African marigold plant, along with their anti-oxidative capacities and biochemical attributes. The salt stressed African marigold (100 and 150 mM NaCl) was treated with GB at 200 mM, beside untreated control plants. According to the obtained results, the growth characters were negatively in salt stressed plants but a mitigate impact of GB were observed in this respect. Obviously, the morphological as well as some physiological characters were reduced with salinity treatments while GB treatment reverses these effects. Overall, the alleviate impact of GB on the negative impact of salt stress was enhanced through improving total phenolic and antioxidant enzyme activity. Further, it is concluded that GB concentration induces the activities of antioxidative enzymes which scavenged ROS increased under saline conditions.

In this paper, we investigate the dynamics of following higher order difference equation x_{n+1}=A+B((x_{n})/(x_{n-m}²)) with A,B and initial conditions are positive numbers, and m∈{2,3,⋯}. Especially we study the boundedness, periodicity, semi-cycles, global asymptotically stability and rate of convergence of solutions of related higher order difference equations.

Hybrid lead halide perovskites have been revolutionary in the photovoltaic research field, reaching efficiencies comparable with the most established photovoltaic technologies, although they do not yet reach their competitor stability. The search for a stable configuration required the engineering of the charge extraction layers; in this work, molecular doping is used as an efficient method for small molecule and polymer, employed as hole transport materials in planar heterojunction configuration on compact-TiO2. We proved the viability of this approach, obtaining significantly increased performances and reduced hysteresis on compact titania-based devices. We investigated the photovoltaic performance, correlating to the hole transport material structure. We have demonstrated that the molecular doping mechanism is more reliable than the oxidative doping, and verified that molecular doping in polymeric hole transport materials leads to highly efficient perovskite solar cell, with long-term stability.

We investigate the flow structure and dynamics of moderate-Rayleigh-number ($Ra$) thermal convection in a two-dimensional inclined porous layer. Direct numerical simulations (DNS) confirm the emergence of $\mathit{O}(1)$ aspect-ratio large-scale convective rolls, with one `natural' roll rotating in the counterclockwise direction and one `antinatural' roll rotating in the clockwise direction. As the inclination angle $\phi$ is increased, the background mean shear flow intensifies the natural-roll motion, while suppressing the antinatural-roll motion. Moreover, our DNS reveal---for the first time in single-species porous medium convection---the existence of \emph{spatially-localized} convective states at large $\phi$, which we suggest are enabled by subcritical instability of the base state at sufficiently large inclination angles. To better understand the physics of inclined porous medium convection at different $\phi$, we numerically compute steady convective solutions using Newton iteration and then perform secondary stability analysis of these nonlinear states using Floquet theory. Our analysis indicates that the inclination of the porous layer stabilizes the boundary layers of the natural roll, but intensifies the boundary-layer instability of the antinatural roll. These results facilitate physical understanding of the large-scale cellular flows observed in the DNS at different values of $\phi$.

L-glutamate is one the most important excitatory neurotransmitter at central nervous system level and it is implicated in several pathologies. So, it is very important to monitor its variations, in real time in animal models’ brain. Amperometric biosensors have been used because of their very high temporal and spatial resolution, and because suitable for a short to mid-term implantation. The present study aimed to develop and characterize a new glutamate biosensor design that exploits the selectivity of Glutamate Oxidase (GluOx) for l-glutamate, and the capability of a small molecule as propylene glycol (PG) to influence and extend the stability and the activity of enzyme. Different designs were evaluated by modifying the main components in their concentrations to find the most suitable design. Moreover, enzyme concentrations from 100 U/ml up to 200 U/ml were verified and different PG concentrations (1%, 0.1% and 0.05%) were tested. The most suitable selected design was Pt_c/PPD/PEI(1%)₂/GlutOx₅/PG(0.1%) and it was compared to the same already described design loading PEDGE, instead of PG, in terms of over-time performances. PG has proved to be capable of determining an over-time stability of the glutamate biosensor in particular in terms of linear region slope (LRS) up to 21 days.

Over the past decade, the credit quality of loan portfolios across most countries in the world remained relatively stable until the financial crises hit the global economy in 2007–2008. In this paper I discuss, the relationship between non-performing loans and economic landscape. Since 2008, nonperforming loans have been an increasingly hot topic in the international scene, due to their important and rising volume and their impact on the economy as a whole, on the banking system and on its credit supply. Since then, average bank asset quality deteriorated sharply due to the global economic recession. Yet the deterioration of loan performance was very uneven across countries. I am interested in explaining these differences in bank asset quality across countries and over time. In this paper, I therefore study the empirical determinants of non-performing loan (NPL) ratios using a data set for EU countries covering the past decade. The paper assumes that the spatial organization of banking systems and the geographical distribution of comercial banks branches, ATMs and GDP growth are major factors influencing the effectiveness in credit system. The aim of this paper is to construct a continuous and quantifiable model, which will demonstrate a role of economic condition, technology, competition, policy, business climate in Financial Stability. Main hypotheses suggests, that GDP growth, interest rate, new business, FDI, ATMs and geographical distribution of branches have an influences on NPL (non-performing loans).

In its prefusion state, the SARS-CoV-2 Spike protein (similarly to other class I viral fusion proteins) is metastable, which is considered to be an important feature for optimizing or regulating their functions. After the binding process of its S1 subunit (S1) with the ACE2, the Spike protein (S) suffers a dramatic conformational change where S1 splits from the S2 subunit, which then penetrates the membrane of the host cell, promoting the fusion of the viral and cell membranes. This results in the infection of the host cell. In a previous work, we showed -using large scale molecular dynamics simulations- that the application of external electric fields (EF) induces drastic changes and damage in the receptor-binding domain (RBD) of the wild type Spike protein, as well of the Alpha, Beta and Gamma variants, leaving a structure which cannot be recognized any more by ACE2. In this work, we first extend the study to the Delta and Omicron variants and confirm the high sensitivity and extreme vulnerability of S to moderate EF (as weak as 104 V m-1), but, more importantly, we also show that, in contrast, the postfusion state of the spike protein does not suffer structural damage even if electric field intensities four orders of magnitude higher are applied. These results provide a solid scientific basis to confirm the prefusion state metastability roots of the SARS-CoV-2 Spike protein susceptibility to be damaged by EF. After the virus docks to the ACE2 receptor, the stable and robust postfusion conformation develops, which exhibits a similar resistance to EF (damage threshold higher than 108 V m-1) like most globular proteins.

Global economy, financial markets and technology are on the verge of moving to a new stage of development – information society. Three major world countries the US, Russia and China will play a leading role in this process. However, the specific development path will depend on many factors, including the stability of legal systems, security of computer and financial technologies, the effectiveness of legislation. The focus of this article is to assess the current condition of the economy the major countries, to identify trends and methods of stabilization of legal systems on the basis of balance of rights and obligations of the business, suggest some methods of objective evaluation of the impact factors of the total taxes, fixed costs and the legal system dynamics on financial indicators.

Malaria is a critical fevered illness caused by Plasmodium parasites transmitted among people through the bites of infected female Anopheles mosquitoes. Public awareness about the disease is important for the control of disease. This article proposes a mathematical model to study the dynamics of malaria disease transmission with the influence of awareness-based control interventions. We found two equilibria of the model, namely the disease-free and endemic equilibrium. Disease-free equilibrium is stable globally if basic reproduction number (R0) is less than unity (R0&lt;1). Some basic mathematical properties of the proposed model, such as nonnegativity and boundedness of solutions, the feasibility of the equilibrium points and their stability properties, have been studied. Finally, we adopted optimal control to minimize the cost of disease control and solve the problem by formulating Hamiltonian functional. The optimal use of insecticides for controlling the mosquito population is determined. Numerical simulations have been provided for the confirmation of the analytical results. We conclude that media awareness with optimal control approach is best for cost-effective malaria disease management.

The stick-free flight stability is an old-fashioned and non-progressive issue; nevertheless, it is still existent, and of significant importance to the design of aircraft whose control system is reversible. The problem’s existence necessitates a deep assessment of stick-free flight stability throughout the aircraft design. Up to now, this problem has been addressed using either analytical approaches, which are only related to the static stability evaluation, or performing flight tests. In this study, the problem is handled in its entirety, from static and dynamic flight stability assessment to design criteria with a comprehensive perspective. Moreover, it is also exhibited that contrary to what has been generally proposed in the literature, limiting the problem of stick-free flight stability through static stability assessment is far from the main challenge. As a brief scope, the derivation of the control surface dynamics, a stick-free trim algorithm, and assessment rationale of the stick-free static and dynamic flight stability using a simulation approach are proposed. As a consequence, the aim is to set a broad understanding for designers related to this phenomenon and add adjunct design criteria in the design optimization process by approaching it in terms of modeling, simulation, and flight test perspective.

Hip dysplasia is a prevalent hereditary condition affecting dogs and cats, characterized by inadequate development of the hip joint. This condition leads to pain due to capsular distension, microfractures, and joint incongruity in young animals, ultimately progressing to osteoarthritis in adult and elderly animals. The pursuit of pain relief and improved quality of life for individuals with osteoarthritis has been a focal point in several studies. In this context, veterinary physiotherapy has gained prominence in small animal practice, serving as both palliative care and a supportive modality in the clinical or post-surgical management of degenerative joint diseases. Laser therapy and hydrotherapy, recognized for their analgesic effects and capacity to promote muscle mass gain, have garnered attention for their potential efficacy in treating joint diseases. This study aims to evaluate the therapeutic effects of super pulsed laser therapy and controlled low-impact exercises (water treadmill) on a patient recovering from surgery involving bilateral femoral head and forehead resection. We observed positive outcomes, including pain resolution, improved muscle mass, and enhanced range of motion, contributing to the patient's overall recovery.

Hip dysplasia is a prevalent hereditary condition affecting dogs and cats, characterized by inadequate development of the hip joint. This condition leads to pain due to capsular distension, microfractures, and joint incongruity in young animals, ultimately progressing to osteoarthritis in adult and elderly animals. The pursuit of pain relief and improved quality of life for individuals with osteoarthritis has been a focal point in several studies. In this context, veterinary physiotherapy has gained prominence in small animal practice, serving as both palliative care and a supportive modality in the clinical or post-surgical management of degenerative joint diseases. Laser therapy and hydrotherapy, recognized for their analgesic effects and capacity to promote muscle mass gain, have garnered attention for their potential efficacy in treating joint diseases. This study aims to evaluate the therapeutic effects of super pulsed laser therapy and controlled low-impact exercises (water treadmill) on a patient recovering from surgery involving bilateral femoral head and forehead resection. We observed positive outcomes, including pain resolution, improved muscle mass, and enhanced range of motion, contributing to the patient's overall recovery.

Derivatives products have become essential in portfolio diversification, price discovery and risk hedging. Derivatives are complex instruments; their role is twofold, risk management and speculation, and their actual Impact on the underlying assets’ behaviours are not well understood. Little is documented empirically on how these instruments’ two-edged roles influence firms’ financing decisions, firm risk exposures, and stability. Given the growing interest in using derivatives in risk management and portfolio engineering, this study examines the practical impact of derivatives usage on the underlying firm’s financing policy and stability. The paper uses data from South African listed non-financial firms for the period 2000 to 2019. The study employs a dynamic panel model estimated with System Generalised Methods of Moments (GMM). The initial analysis shows that derivatives use reduces the cost of capital and increases firm stability. However, further in-depth analysis provides evidence that extensive use of derivatives increases firms’ capital costs and negatively impacts financial stability. These findings imply that the risk embedded in derivatives’ speculation dominates their risk management function. The results are subjected to numerous controls for robustness, including financial leverage, firm size, cashflows and asset tangibility.

A mathematical model given by a two - dimensional differential system is introduced in order to understand the transition process from the normal hematopoiesis to the chronic and accelerated acute stages in chronic myeloid leukemia. A previous model of Dingli and Michor is refined by introducing a new parameter in order to differentiate the bone marrow microenvironment sensitivities of normal and mutant stem cells. In the light of the new parameter, the system now has three distinct equilibria corresponding to the normal hematopoietic state, to the chronic state, and to the accelerated acute phase of the disease. A characterization of the three hematopoietic states is obtained based on the stability analysis. Numerical simulations are included to illustrate the theoretical results.

The synchronous generator, as the main component of power systems, plays a key role in these system’s stability. Therefore, utilizing the most effective control strategy for modeling and control the synchronous generator results in the best outcomes in power systems’ performances. The advantage of using a powerful controller is to have the synchronous generator modeled and controlled as well as its main task i.e. stabilizing power systems. Since the synchronous generator is known as a complicated nonlinear system, modeling and control of it is a difficult task. This paper presents a sum of squares (SOS) approach to modeling and control the synchronous generator using polynomial fuzzy systems. This method as an efficacious control strategy has numerous superiorities to the well-known T–S fuzzy controller, due to the control framework is a polynomial fuzzy model, which is more general and effectual than the well-known T–S fuzzy model. In this case, a polynomial Lyapunov function is used for analyzing the stability of the polynomial fuzzy system. Then, the number of rules in a polynomial fuzzy model is less than in a T-S fuzzy model. Besides, derived stability conditions are represented in terms of the SOS approach, which can be numerically solved via the recently developed SOSTOOLS. This approach avoids the difficulty of solving LMI (Linear Matrix Inequality). The Effectiveness of the proposed control strategy is verified by using the third-part Matlab toolbox, SOSTOOLS.

Rapid draw-down in an earthfill dam has serious implications for dam safety regarding slope stability. The evaluation of reservoir draw-down impact on slope stability was carried out considering the case study of 8 hours of rapid draw-down of the Middle Marsyangdi Hydroelectric Power Project (MMHPP) rock-fill dam using the Limit Equilibrium Method (LEM) and stress-based Finite Element Method (FEM). The time-dependent factor of safety (FOS) was evaluated and found that the 8 hours of rapid draw-down undertaken in October 2012 for reservoir flushing was unsafe with a draw-down rate of 1.91m/h. The resulting FOS of 1.28 and 1.27 using LEM and FEM was classified as unsafe as per the US Army Corps of Engineers’ guideline, the minimum required factors of safety should be greater than 1.3. The minimum safe allowable draw-down rate of 0.76m/h for 20 hours was identified. Applying three layers of horizontal filter materials and increasing the upstream dam’s permeability provided adequate FOS results for all cases by increasing seepage discharge to reduce the destabilizing excess pore water pressure. Several gradual draw-down rates were also tested and found that FOS increases with decreased draw-down rates, as it reduces the excess pore water pressure controlled with stabilizing existing water load.

Internet of things (IoT) is a network of smart things. This indicates the ability of these physical things to transfer information with other physical things. The characteristics of these networks, such as topology dynamicity and energy constraint, challenges the routing problem in these networks. Previous routing methods could not achieve the required performance in this type of network. Therefore, developers of this network designed and developed specific methods in order to satisfy the requirements of these networks. One of the routing methods is utilization of multi-path protocols which send data to its destination using routes with separate links. One of such protocols is AOMDV routing protocol. In this paper, this method is improved using gray system theory which chooses the best paths used for separate routes to send packets. To do this, AOMDV packet format is altered and some fields are added to it so that energy criteria, link expiration time, and signal to noise ratio can also be considered while selecting the best route. The proposed method named RMPGST-IoT is introduced which chooses the routes with highest rank for concurrent transmission of data, using a specific routine based on the gray system theory. In order to evaluate and report the results, the proposed RMPGST-IoT method is compared to the ERGID and ADRM-IoT approaches with regard to throughput, packet receiving rate, packet loss rate, average remaining energy, and network lifetime. The results demonstrate the superior performance of the proposed RMPGST-IoT compared to the ERGID and ADRM-IoT approaches.

By defining a constant probabilistic orbit of and iterated functions, the stability dynamics of these functions in possible interactions through connectivity provides the formation of a dynamic fixed point as a metric space between both iterated functions. The presence of a dynamic fixed point identifies qualitatively phases of iteration time lengths and interaction orbits of the event. Qualitative results show that the greater the average distance from one of the functions to the fixed point of the other (all possible solutions), the higher the iteration expression on time (false asymptotic effect) of one of the functions and in the opposite hand, the lower the average distance, the higher orbit’s interactions proximity between iterated functions (stability). This feature reveals asymptotic (well-defined) behavior between functions f and g within a well-defined Lyapunov stability.

Wind power generation is one of the mainstream renewable energy resources. Voltage stability is as important as the frequency stability of a power system with a high penetration of wind power generation. The advantages of high-voltage direct current (HVDC) transmission systems become more significant with the increase of both installed capacity and transmission distance in offshore wind farms. Therefore, this study discusses about various voltage control methods for wind turbines and HVDC transmission systems. First, various voltage control methods of a wind farm were introduced, and they include QV control and voltage droop control. The reactive power of a wind turbine varies with active power, while the active power from each wind turbine may be different owing to wake effects. Thus, QV and voltage droop control with varying gain values were also discussed in this paper. Next, the voltage control methods for a HVDC transmission system, such as power factor control, voltage control, and Vac-Q control, are also summarized and tested in this study. When a three-phase short circuit fault occurs or a suddan reactive power load increases, the system voltage would drop immediately. Thus, various voltage control methods for wind turbines or HVDC can make the system's transient response more stable. Therefore, this study implemented the simulation scenarios, including a three-phase short circuit fault at the point of common coupling (PCC) or a sudden increase of reactive power load, and adopted various voltage control methods, which aims to verify whether additional voltage control methods are effective to improve the performance of transient voltage.

Abstract: Due to their rapid evolution and their impact on health care, be-ta-lactamases, protein degrading beta-lactam antibiotics, are used as generic model of protein evolution. Therefore, we investigated the mutation effects in two distant beta-lactamases TEM-1 and CTX-M-15. Interestingly we found a site with a complex pattern of genetic interactions. Mutation G251W in TEM-1 is in-activating the protein’s function just as the reciprocal mutation W251G in CTXM-15. Phylogenetic analysis revealed that mutation G has been entrenched in TEM-1 background: while rarely observed throughout the phylogeny it is es-sential in TEM-1. Using a rescue experiment in TEM-1 G251W mutant, we could identify sites that alleviates the deviation from G to W. While few of these muta-tions could potentially involve local interactions, most of them were found on distant residues in the 3D structure. Many well-known mutations having an impact on protein stability, such as M182T, were recovered. Our results there-fore suggest that entrenchment of an amino acid may rely on diffuse interactions among multiple sites with a major impact on protein stability.

In this work, a xylan-based antimicrobial additive agent was prepared and aimed for uses in paper products against Escherichia coli bacteria. The derived Cationic-Xylan-grafted-PHGH (CX-g-PHGH) was successfully synthesized by graft copolymerization of cationic-xylan with guanidine polymer (PHGH) using ceric ammonium nitrate as initiator. The obtained CX-g-PHGH had maximum PHGH grafting ratio of 18.45% and efficiency of 58.45%, and showed good viscosity and thermal stability. Furthermore, the paper samples prepared in this work were reinforced obviously with the addition of CX-g-PHGH by improved mechanical properties. Compared to the reference paper without any of the xylan-derivatives, the index of tensile, tear, burst and folding endurance of the paper had increases up to 20.07%, 25.31%, 30.20% and 77.78%, respectively. Moreover, the prepared CX-g-PHGH paper exhibited an efficient antimicrobial activity against E. coli bacterial, by which a lot of applications based on the new xylan-derived additive agent obtained in this work could be found, especially in field of antimicrobial paper products against E. Coli bacteria from contaminated food.

City marathons have evolved and grown exponentially in type and popularity, managerial complexity, for their financial impact on their host cities and for the attraction of corporate sponsors. Much research has focused on evaluating the broad economic, urban, tourist, social, sporting, and symbolic effects of city marathons on host cities. Research have not examined the importance of the contribution of sponsors to the financial stability and its implications to the overall management and further success of marathons. This article focuses on the cases of the Bank of America Chicago Marathon and the Marathon Valencia Trinidad Alfonso and examines how effective has been the contribution of their sponsors to the financial stability and its implications for the management and success of both races over time. Results show that the international success of both events –in terms of sporting participation, performance and economic impact– is closely related to the design and management of the event; the synergies between the political, business and sporting spheres that the organizational leadership of the event has made it possible to implement and, as a consequence, the support received from sponsors, which has not only provided both races with financial stability, but also has contributed to improve the management of the race.

Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies de-scribing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonautes proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases and an atypical ribonuclease III (RNaseIII). NCRIP regulates the expression of mRNAs by degrading them in a specific manner. Its mechanism binds dsRNA but only cuts ssRNA. NCRIP exhibits a diversity of functional roles. It represses the epimutational pathway and the lack of NCRIP increases the generation of drug resistant strains. NCRIP also regulates the control of retrotransposons expression, playing an essential role in genome stability. Finally, NCRIP regulates the response during phagocytosis, affecting the multifactorial process of virulence. These critical NCRIP roles in virulence and antifungal drug resistance, along with its exclusive presence in Mucorales, mark this pathway as a promising target to fight against mucormycosis.

A multi-environment evaluation of sorghum genotypes was conducted across six environments in the 2021 main growing season in a randomized complete block design with three replications. The objectives of the study were to estimate the magnitude of genotypes by environment interaction (GEI) and grain yield stability of drought-tolerant sorghum genotypes across different environments. Data were subjected to analysis of variance, Additive Main Effects and Multiplicative Interaction (AMMI), and GGE biplot analysis. Combined analysis of variance revealed significant variations among genotypes, environments, and GEI for yield and yield-related traits, indicating that these factors significantly affected grain yield. The maximum mean grain yield value of genotypes due to the mean effect of the environment was obtained from G1 (5119.93kg ha-1), followed by G14 (4834.57 kg ha-1), and G18 (4801.20 ha-1), while the least mean grain yield was obtained from G3 (3314.50 kg ha-1). The multiplicative variance of the treatment sum of squares due to GEI was partitioned into four principal component axes (PCA). Sum squares of the first and second interaction principal component axis (IPCA) explained 71.07% and 17.50% of the GEI variation, respectively. The IPCA1&2 mean squares were highly significant (P≤0.01), indicating the adequacy of the AMMI model with the first two IPCAs for cross-validation of grain yield variation. The magnitude of the GEI sum squares was 3.9 times that of the genotype sum squares for grain yield, indicating the presence of substantial differences in genotypic responses across environments. The results of cultivar superiority measure (Pi), yield stability index (YSI), AMMI stability value (ASV), regression coefficient (bi), and deviation from regression (S2di) depicted that genotypes G18, G22, G31, and 32 were the most stable genotypes for grain yield and biomass yield, respectively. AMMI2 biplot showed Jinka, Alduba, and Kako were the most discriminating environments as indicated by the long distance from the origin; whereas testing locations Meioso and Gato with short vector length indicated that these locations had less discriminating power on the genotypes' performance. The study has provided precious information on the yield stability status of the sorghum genotypes and the best environments for future improvement programs in Ethiopia.

This research work presents the nonlinear control framework to estimate and reject the mismatched lumped disturbances acting on the nonlinear uncertain system. It is an unfortunate fact that the conventional Extended State Observer (ESO) is not capable to estimate the mismatched lumped disturbance and its derivative simultaneously for the systems. Also, the basic ESO is only suitable for systems with Integral Chain Form (ICF) structure. Similarly, the conventional Feedback Linearizing Control (FLC) approach is not robust for stabilizing the systems in the presence of disturbances and uncertainties. Hence, the nonlinear control framework is proposed to overcome the above issues which are composed of, (a) Dual Extended State Observer (DESO), and (b) DESO based FLC. The DESO provides information on the unmeasured state, mismatched disturbance, and its derivative. While the DESO-FLC utilizes the information from DESO to counter the effect of such disturbances and to stabilize the nonlinear systems around the reference point. The detailed closed-loop analysis is presented for the proposed control framework in the presence of lumped disturbances. The performance robustness of the presented design has been validated for the third order, nonlinear, unstable, and disturbed Magnetic Levitation System (MLS). The results of the DESO-FLC approach are compared with the most popular Linear Quadratic Regulator (LQR) and nonlinear FLC approaches based on the integral error criterion and the average electrical energy consumption.

To gain insight into the differences between onshore and offshore atmospheric turbulence, 2 pressure fluctuations were measured for offshore wind under different environmental conditions. 3 A durable piezo-electric sensor was used to sample turbulent pressure data at 50 kHz. Offshore 4 measurements were performed at 100 m height on Germany’s FINO3 offshore platform in the 5 German Bight together with additional meteorological data provided by Deutscher Wetterdienst 6 (DWD). The statistical evaluation revealed that the stability state in the atmospheric boundary has a 7 large impact on turbulent fluctuations. Therefore, we used higher statistical properties (described 8 by so-called shape factors) to the stability state. Data was classified to be either within the unstable, 9 neutral or stable stratification. We found that in case of stable stratification, the shape factor is 10 mostly close to zero, indicating that a thermally stable environment produces closer-to Gaussian 11 distributions. Non-Gaussian distributions were found in unstable and neutral boundary layer states 12 and an occurrence probability was estimated. Possible impact on laminar-turbulent transition on the 13 blade is discussed with application of so-called laminar aerofoils on wind turbine blades. Use of a 14 cut-off frequency to separate load and aerodynamic turbulence is proposed.

In this work, we introduce a new and generalized concept (herein referred to as Caputo fractional delta derivative and Caputo fractional delta dini derivative of order $\alpha\in(0,1)$) for Caputo fractional derivatives on an arbitrary time domain $\mathbb{T}$ which is a closed subset of $\mathbb{R}$. Combining the continuous and discrete time domains, we create a unified framework for stability analysis on time scales. Comparison results and stability criteria for the considered Caputo fractional dynamic equations are presented based on a new definition for Caputo fractional delta derivative of a Lyapunov function, contributing to the broader understanding of fractional calculus on time scales. The work also incorporates an illustrative example to demonstrate the relevance, effectiveness and applicability of the established stability results over that of the integer order.

Flexible electronics have revolutionized the field by overcoming the rigid limitations of traditional devices, offering superior flexibility and adaptability. Conductive ink performance is crucial, directly impacting the stability of flexible electronics. While metal filler-based inks exhibit excellent conductivity, they often lack mechanical stability. To address this challenge, we present a novel conductive ink utilizing a ternary composite filler system: liquid metal and two micron-sized silver morphologies (particles and flakes). We systematically investigated the influence of filler type, mass ratio, and sintering process parameters on the composite ink's conductivity and mechanical stability. Our results demonstrate that flexible wires fabricated with the liquid metal/micron silver particle/micron silver flake composite filler exhibit remarkable conductivity and exceptional bending stability. Interestingly, increasing the liquid metal content results in a trade-off, compromising conductivity while enhancing mechanical performance. After enduring 5000 bending cycles, the resistance change in wires formulated with a 4:1 mass ratio of micron silver particles to flakes is only half that of wires with a 1:1 ratio. This study further investigates the mechanism governing resistance variation during flexible wire bending. Additionally, we observed a positive correlation between sintering temperature and pressure with the conductivity of flexible wires. The significance of sintering parameters on conductivity follows a descending order: sintering temperature, sintering pressure, and sintering time. Finally, we demonstrate the practical application of this technology by integrating the composite ink-based flexible wires with conductive polymer-based strain sensors. This combination successfully achieved the detection of human movements, including finger and wrist bending.

Abstract Background: Hypochlorous acid (HA) is a potent disinfectant with broad-spectrum antimicrobial activity against bacteria, fungi, and viruses. Aim: This study aimed to investigate the factors that influence the stability of hypochlorous acid (HOCl) and their impact on its disinfectant properties Methods: This study explored the stability of hypochlorous acid, emphasizing factors that affect its disinfectant efficiency, such as pH level, temperature, and the presence of organic materials. Findings: Our investigation revealed that HOCl is the most stable and effective disinfectant under weakly acidic conditions, where the undissociated form of hypochlorous acid is predominant. Although it is stable under various conditions, its efficacy is compromised by the presence of heavy metals, organic matter, and UV radiation. Conclusions: This comprehensive analysis concludes that, while hypochlorous acid is a highly effective disinfectant, understanding and maintaining the optimal conditions for its stability is crucial for maximizing its disinfection potential. Implications: The findings can be used to formulate new guidelines and regulations to guide the proper formulation, storage, and use of stable HOCL as disinfectants.

With the application of high-precision, enormous rotating equipment and the addition of harsh working conditions, the advantages of dry gas sealing technology are increasingly obvious. Herein, research on the dynamic stability of dry gas seals is reviewed based on their operating mechanism. The influence of the dry gas seal structure, vibration response, and dynamic followability on the reliability of the shaft end sealing system of rotating machinery is the focus of current dry gas sealing technology. This work reviews the research history; analyzes the key coefficient of instability of the sealing system under external disturbances and the existing research on stability models; discusses the influence of starting and stopping characteristics, working conditions, and groove parameters on the stability of dry gas seals; and points out the shortcomings in the existing research. In addition, potential developments in dynamic stability are proposed, including improving model accuracy, improving experimental techniques, or applying intelligent control and optimization methods to enhance the dynamic stability of the sealing system. Finally, the development prospects for dry gas sealing technology in intelligent monitoring and wide temperature range adaptations are discussed, and theoretical guidance for improving the dry gas seal system is provided.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, represents a serious threat to public health. The spike (S) glycoprotein of SARS-CoV-2 mediates viral entry into host cells and is heavily glycosylated. In this study, we systemically analyzed the roles of 22 putative N-linked glycans in SARS-CoV-2 S protein expression, membrane fusion, viral entry, and stability. Using α-glycosidase inhibitors, castanospermine and NB-DNJ, we confirmed that disrupting the N-linked glycosylation process blocked the maturation of the S protein, leading to impairment of S protein-mediated membrane fusion. Single substitution of each of the 22 N-linked glycosylation sites with glutamine revealed that 9 out of the 22 N-linked glycosylation sites were critical for S protein folding and maturation, resulting in reduced S protein-mediated cell-cell fusion and viral entry. Of note, N1074Q mutation markedly affected S protein stability and induced significant receptor-independent syncytium (RIS) formation in HEK293T/hACE2-KO cells, and removal of the furin-cleavage site partially compensated instability of N1074Q mutation. Although the corresponding mutation in the SARS-CoV S protein (N1056Q) did not induce RIS in HEK293T cells, the mutants N669Q and N1080Q exhibited increased fusogenic activity and induced syncytia formation in HEK293T cells. Therefore, N-glycans on the SARS-CoV and SARS-CoV-2 S2 subunits are of great importance in maintaining the prefusion state of the S protein. The study revealed the critical roles of N-glycans in S protein maturation and stability, which have implications for the design of vaccines and anti-viral strategies.

This study assessed the impacts of genotypes, environments, and their interaction on the performance of elite cowpea lines for key adaptive, grain yield, and associated traits across different locations. A total of 42 elite genotypes were evaluated in five Nigerian environments, representing various savanna ecologies during the 2021 growing season. The experimental design employed was an alpha lattice arrangement, replicating each genotype three times. The results revealed significant differences among genotypes, environments, and genotype-by-environment interaction for most traits, including days to maturity, 100 seed weight, and grain yield. GGE biplot showed G21 (IT14K-2111-2) and G25 (IT15K-2386-1) as the most stable genotypes across the five environments, G41(IT1K-61-82) was best adapted to Ibadan and Shika, G5 (245-1) was best adapted to Bagauda and Gumel while G30 (IT16K-2365-1) was best adapted to Bauchi. G21 and G25 could be recommended across the five test environments while G41, G30 and G5 are specific to the adapted environments.

In recent years, the use of solid waste fillers to partially replace natural fillers in asphalt mixtures to produce high-performance asphalt mixtures has received widespread attention. However, differences in the material properties of solid waste fillers remain a problem for this recycling method. To address this issue, limestone powder in asphalt mixtures was replaced by three solid waste fillers (steel slag powder, tailings powder and calcium carbide slag powder) in this study. The chemical composition of the fillers was first characterized to assess the homogeneity of the material. Then, AC and SMA asphalt mixtures were designed and produced and characterized for wet stability. The results showed that asphalt mixtures with solid waste fillers were superior to LP asphalt mixtures in terms of resistance to water damage, and steel slag powder showed the best improvement in moisture stability of asphalt mixtures. The optimum substitution of solid waste filler for limestone filler was 25%. In addition, the moisture stability of asphalt mixture with limestone filler was significantly improved with the addition of anti-stripping agents. In contrast, the moisture stability of asphalt mixtures with solid waste filler was slightly improved. Solid waste fillers could be used in asphalt mixtures and have a similar function as the anti-stripping agent. In summary, the use of solid waste fillers to replace mineral fillers in asphalt mixtures is a reliable, value-added, recycling option.

This study proposes a nonlinear mathematical model of virus transmission based on the SEIR model. In this study, the interaction between viruses and immune cells is investigated using phase-space analysis of a mathematical model. Specifically, it is focused on the dynamics and stability behavior of the mathematical model of a virus spread in a population and its interaction with human immune systems cells. The endemic equilibrium points are found and local stability analysis of all equilibria points of the related model is obtained. Further, the global stability analysis either, at disease-free equilibria, or in endemic equilibria is discussed by constructing the Lyapunov function which shows the validity of the concern model exists. Finally, a simulated solution is achieved and the relationship between viruses and immune cells is highlighted.

To describe the hysteresis nonlinearities in smart actuators, numerous models have been presented in the literature, among which the Preisach operator would be the most effective one due to its capability in capturing multi-loop or sophisticated hysteresis curves. When such an operator is coupled with uncertain nonlinear dynamics, especially in noncanonical form, it is a challenging problem to develop techniques to cancel out the hysteresis effects, and at the same time achieve asymptotic tracking performance. To resolve this problem, in this paper, we investigate the problem of iterative inverse-based adaptive control for an uncertain noncanonical nonlinear systems with unknown input Preiasch hysteresis, and a new adaptive version of the closest match algorithm is proposed to compensate for the Preisach hysteresis. With our scheme, the stability and convergence of the closed-loop system can be established. The effectiveness of the proposed control scheme is illustrated by simulation and experiment results.

Proliferating cell nuclear antigen (PCNA) is the key regulator of human DNA metabolism. One important interaction partner is p15, involved in DNA replication and repair. Targeting the PCNA-p15 interaction is a promising therapeutic strategy against cancer. Here, a Förster resonance energy transfer (FRET)-based assay for the analysis of PCNA-p15 interaction was developed. Next to the application as screening tool for the identification and characterization of PCNA-p15 interaction inhibitors, the assay is also suitable for the investigation of mutation-induced changes in their affinity. This is particularly useful for analysing disease associated PCNA or p15 variants at the molecular level. Recently, the PCNA variant C148S has been associated with Ataxia-telangiectasia-like disorder type 2 (ATLD2). ATLD2 is a neurodegenerative disease based on defects in DNA repair due to an impaired PCNA. Incubation time dependent FRET measurements indicated no effect on PCNAC148S-p15 affinity, but on PCNA stability. The impaired stability and increased aggregation behaviour of PCNAC148S was confirmed by intrinsic tryptophan fluorescence, DSF and AF4 measurements. The analysis of the disease associated PCNA variant demonstrated the versatility of the interaction assay as developed.

In recent years, graphene has received so much attention because of its superlative properties and its potential to revolutionize electronics especially in VLSI. This study analyzes the effect of single event upset (SEU) in SRAM cell which employs metal-oxide semiconductor type graphene nano-ribbon field effect transistor (MOS-GNRFET) and compares the results respectively with another SRAM cell designed in PTM 10nm FinFET node. Our simulation show there is a change in data stored in the SRAM after heavy ion strike. However, it recovers from radiation effects after 0.46 ns for GNRFET and 0.51 ns for FinFET. Since the degradation observed in Q and Qb of GNRFET SRAM are 2.7X and 2.16X as compared to PTM nano-MOSFET, we can conclude that GNRFET is less robust to single effect upset. In addition, the stability of SRAM can be improved by increasing the supply voltage VDD.

This work is devoted to the study of active and stable nickel catalysts for methane dry reforming based on Pr-doped ceria-zirconia obtained by solvothermal continuous method. The studies of physicochemical and catalytic properties of the 5%Ni\Ce0.75Zr0.25-xPrxO2 series showed that Pr introduction leads to an increase in the amount of highly reactive oxygen of the oxide lattice. Praseodymium-based catalysts showed significantly higher reactant conversions. In addition to the nature of support, the method of nickel introduction was also studied - Ni was added both by impregnation and one-pot with mixed oxide preparation. The method of Ni addition was shown to have significant effect on the morphology of the supported active component and, respectively, on the catalytic activity. The 5%Ni/Ce0.75Zr0.15Pr0.1O2 catalyst prepared by one-pot method showed stable operation in the MDR reaction for 30 hours at CO2 and CH4 conversions of ~40% and an H2 yield of ~18% (Т=700°С, τ=10ms).

In this work, we consider two SIR patterns with demography: the classical pattern and a modified pattern with a linear transmission coefficient of the infection. By reformulating of each first order differential systems as a system with two second-order differential equations, we investigate the nonlinear dynamics of the system from the Jacobi stability point of view by using the KCC geometric theory. We will study the intrinsic geometric properties of the systems by determining the geometric associated objects: the zero-connection curvature tensor, the nonlinear connection, the Berwald connection, and the five KCC invariants: the first invariant - the external force εi, the second invariant - the deviation curvature tensor Pji, the third invariant - the torsion tensor Pjki, the fourth invariant - the Riemann-Christoffel curvature tensor Pjkli, and the fifth invariant - the Douglas tensor Djkli. In order to obtain necessary and sufficient conditions for the Jacobi stability near the equilibrium points, the deviation curvature tensor will be determined at each equilibrium points. Furthermore, we will compare the Jacobi stability with the classical linear stability, inclusive by diagrams related to the values of parameters of the system.

For embankment slope stability, soil cohesivity is one of the most important shear strength parameters. The effect of cohesiveness on the slope stability of a homogeneous embankment dam under rapid drawdown loading conditions was examined in this study. With the use of numerical modeling in GeoStudio, different situations were explored based on cohesiveness (0 kN/m², 5 kN/m², 10 kN/m^2, and 15 kN/m²) under a 1 m per day drawdown rate. The factor of safety value obtained from the long-term steady-state condition under 15 kN/m² cohesion was equivalent to a 116.8% increase from the one obtained under 0 kN/m² cohesion. The factor of safety values obtained after subjecting the embankment to different soil cohesion levels yielded a p-value of 1.91 x 10^-41, according to the Analysis of Variance. The calculated p-value (alpha value) is less than 0.05, suggesting that the differences between the examined cohesiveness values based on the list of the factor of safety values are statistically significant. The findings derived in this study show that it is significant to capture the effect of material characteristics during the design phase of an embankment dam.

In this paper we investigate the global asymptotic stability of following system ofhigher order difference equations with quadratic terms:xn+1=A+Byn/yn−m^2, yn+1=A+Bxn/xn−m^2, where A and B are positive numbers and the initial values are positive numbers.We also study the boundedness, rate of convergence and oscillation behaviour of thesolutions of related system.

Nanographene oxide (GOn) constitutes a nanomaterial of high value in the biomedical field. However, large scale production of highly stable aqueous dispersions of GOn is yet to be achieved. In this work, we explored high-power ultrasonication as a method to reduce particle size of GO and characterized the impact of the process in the physico-chemical properties of the material. GOn was obtained with lateral dimensions of 99 ±43 nm and surface charge of −39.9 ± 2.2 mV. High-power ultrasonication enabled an improvement of stability features, particularly by resulting in a decrease of the average particle size, as well as zeta potential, in comparison to GO obtained by low-power exfoliation and centrifugation (287 ± 139 nm; −29.7 ± 1.2 mV). Re-markably, GOn aqueous dispersions were stable for up to 6 months of shelf-time, with a global process yield of 74%. This novel method enabled the production of large volumes of highly con-centrated (7.5 mg mL-1) GOn aqueous dispersions. Chemical characterization of GOn allowed the identification of characteristic oxygen functional groups, supporting high-power ultrasonication as a fast, efficient and productive process for reducing GO lateral size, while maintaining the material’s chemical features.

Wave is a common environmental load that often causes serious damages to offshore structures. In addition, the stability for the submarine artificial slope is also affected by the wave loading. Although the landslide of submarine slopes induced by the waves has received wide attention, the research on the influence of solitary-wave is rare. In this study, a 2-D integrated numerical model is developed to investigate the stability of the foundation trench under the solitary wave loading. The Reynolds-Averaged-Stokes (RANS) equations are used to simulate the propagation of a solitary wave, while the current is realized by setting boundary inlet/outlet velocity. The pore pressure induced by the solitary wave is calculated by Darcy’s law and the seabed is characterized by Mohr-Coulomb constitutive model. Firstly, the wave model is validated through the comparison between analytical solution and experimental data. The initial consolidation state of slope under hydrostatic pressure is achieved as the initial state. Then, the factor of stability (FOS) for the slope corresponding to different distance between wave crest and slope top is calculated with the strength reduction method. The minimum of FOS is defined as the stability index for the slope with specific slope ratio during the process of dynamic wave loading. The parametric study is conducted to examine the effects of soil strength parameters, slope ratio and current direction. At last, the influence of upper slope ratio in a two-stage slope is also discussed.

Black poplar (Populus nigra L.) was thermally modified in nitrogen atmosphere. Treatment in nitrogen atmosphere can improve the dimensional stability of black poplar. The effects of the modification process on poplar wood were evaluated for temperatures: 160 °C, 190 °C, and 220 °C applied for 2 h; and 160 °C and 190 °C for 6 h. The percentual impact of temperature and time of modification on the properties of modified wood was analysed. The study permitted to identify correlations between the chemical composition and selected physical properties of thermally modified poplar wood. The dimensional stability of poplar wood improves after thermal modification in nitrogen. The higher the temperature of modification, the lower the equilibrium moisture content (EMC) of black poplar. At the temperature of 220 °C, EMC was two times lower than the EMC of non-modified black poplar. It is also possible to reduce the dimensional changes of wood two-fold (at the modification temperature of 220 °C), both in radial and tangential directions, independently of the acclimatisation conditions (from 34% to 98% RH). Similar correlations have been found for wood that has been soaked in water. Higher modification temperatures and longer processing times contributed to a lower swelling anisotropy (SA).

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

This paper aims to investigate the global asymptotic stability of following system of higher order difference equations with quadratic terms: x_{n+1}=A+B((y_{n})/(y_{n-m}²)),y_{n+1}=A+B((x_{n})/(x_{n-m}²)) where A and B are positive numbers and the initial values are positive numbers. We also study the rate of convergence and oscillation behaviour of the solutions of related system.

Background: Outbreak of the Covid-19 is now an ongoing global health emergency. At the end of December 2019, the first infection was reported in Wuhan and the world did not pay attention to this extremely contaminated disease and plucked to react rapidly. The World is in an vulnerable state in disease spreading, facing a great loss of lives and socio-economic aspects also. That is why we have proposed a potential mathematical model with data analysis to predict and control the outcome of this pandemic. Methods: The model presented the epidemic dynamics of multiple compartments. We collected available online data of Spain. In primary step, we estimated the parameters using either the data analysis or reference papers. Then we did the data fitting analysis in comparison with the outcome of our mathematical results. The results of the system depended not only the parameters also on social consciousness. Results: It is found that disease progression in this model is determined by the basic reproductive ratio, $R_0$, the actual epidemic of $R_0$ and effective $R(t)$ of each day. If $R_0>1$, the number of latently infected individuals grows exponentially; endemic solution is stable while infection rate decays if $R_0<1$. The optimal control theory stated that vaccination and treatment strategies are highly effective for reducing both susceptible and infected population and to increase the recover rate high. In Spain, after state of alarm (quarantine) on 14 March 2020, reported cases increasing for 13 days only and from the 14th day, daily reported cases started to decline albeit with small fluctuation. Our proposed model approximates that the disease in Spain could be fully under control by after July 2020. Conclusion: Outbreak will be in control of health care system, reduce the death rate and will ensure social-economic stability.

A second order rational difference equation $$x_{n+1}=px_{n}+\frac{q}{x_{n-1}^2}$$ with the parameters $p$ and $q$ which lies in $(0,1)$, is studied. The dynamics of the equilibrium is characterized through the trichotomy of the parameter $p<\frac{1}{2}$, $p=\frac{1}{2}$ and $p>\frac{1}{2}$. It is found that there is no periodic solution of period $2$ and $3$ but there exists periodic solutions with only periodic solution $5$ and $10$ are achieved computationally.

This Letter revisits the instability of jet produced by shaped charge. Scaling laws for shaped charge jet are derived by dimensional analysis. It shows that the scaling laws are universal when cross-sectional shrinkage rate is not included in the formulation.

In this study, we investigate the form of solutions, stability character and asymptotic behavior of the following four rational difference equations x_{n+1} = (1/(x_{n}(x_{n-1}±1)±1)), x_{n+1} = ((-1)/(x_{n}(x_{n-1}±1)∓1)), such that their solutions are associated with Tribonacci numbers.

Polydimethylsiloxane with hydroxy groups was functionalized to form functionalized polydimethylsiloxane, which subsequently underwent an addition reaction with isophorone diisocyanate to form the prepolymer. Next, 3-aminopropyltriethoxysilane (APTS) reacted with 3-glycidoxypropyltrimethoxysilane (GPTS) to produce bridged polysilsesquioxanes, and the sol–gel technology was employed to form hyperbranched polysiloxane nanoparticles with hydroxy groups, which was used as the additive. The hyperbranched polysiloxane and the prepolymer containing NCO functional groups then underwent an addition reaction to produce the hybrid materials. Fourier-transform infrared spectroscopy and 29Si nuclear magnetic resonance were used to characterize the structure of the polyurethane hybrid. Regarding thermal stability, after the hyperbranched polysiloxane nanoparticles was introduced, the integral procedural decomposition temperature increased from 348 ºC for polyurethane matrix to 859 ºC for the hybrid material. The results revealed that the thermal stability of the hybrid material substantially increased by approximately 247%.

In this study, a parameter of volume stability was proposed for the first time to design polymorph zirconia ceramics used for special components. A series of heterogeneous polymorph zirconia ceramics with various amounts of monoclinic (M) phase were fabricated by two-step sintering. Samples with about 27%, 31%, and 51% M phase content were selected to study the properties. The thermal shock durability was found to be associated with thermal expansion behavior and noncritical micro cracks, which both based on M phase initial content. In good agreement with experimental results, the correlation of normalized K versus M phase initial content was established. It could provide a repeatable reference to prepare special zirconia components without loss of density.

Reliable and robust control of power converters is a key issue in the performance of numerous technological devices. In this paper we show a design technique for the control of a DC-DC buck converter with a switching technique that guarantees not only good performance but also global stability. We show that making use of the contraction theorem in the Jordan canonical form of the buck converter, it is possible to find a switching surface that guarantees stability but it is incapable of rejecting load perturbations. To overcome this, we expand the system to include the dynamics of the voltage error and we demonstrate that the same design procedure is not only able to stabilize the system to the desired operation point but also to reject load, input voltage and reference voltage perturbations.

The earth infrastructure is the backbone of the global economy, connecting people, enhancing quality of life, and promoting health and safety. However, its vulnerabilities are becoming apparent due to climate change, mainly through frequent wetting and drying (wd) cycles. This study aimed to assess the impact of controlled w-d cycles on the hydromechanical properties of clayey and silty sand soils and its implications for the performance of a typical flood embankment. Volumetric changes were monitored during the w-d cycles. Soil water characteristic curve (SWCC), saturated hydraulic conductivity (ksat), effective cohesion (c’) and effective angle of internal friction (ϕ’) were measured at 1 and 10 w-d cycles. The results indicated that the 10 w-d cycles decreased the saturated moisture content and a flatter SWCC compared to the 1 w-d cycle for clayey soil. The ksat was also significantly higher at 10 w-d cycles than the 1 w-d cycle for clayey soil. An insignificant difference was found in both SWCC and ksat at 1 and 10 w-d cycles for silty sand soil. The ϕ’ for the clayey soil decreased from 28.5 to 20.1 as the wd cycles increased from 1 to 10, while the c’ remained unchanged at 10 kN/m2. On the other hand, for the silty sand soil, the ϕ’ increased from 34.6 to 37.5 with an increase in w-d cycles from 1 to 10, and the c’ remained constant at 1 kN/m2. Numerical modelling of transient water flow coupled with slope stability analysis revealed the dependence of flood embankment performance on the soil's hydromechanical properties and the flooding duration. These findings underscore the need for proactive measures to mitigate landslide risks in regions prone to frequent w-d cycles, thereby ensuring the safety and resilience of slopes and associated infrastructure.

Since the first case of 2019 novel coronavirus disease (COVID-19) detected on Jan 30, 2020, in India, the number of cases rapidly increased to 3819 cases including 106 deaths as of 5 April 2020. Taking this into account, in the present work, we are studying a Bats-Hosts-Reservoir-People transmission fractional-order COVID-19 model for simulating the potential transmission with the thought of individual social response and control measures by the government. The real data available about infectious cases from $14^{th}$ March to $26^{th}$ March 2020 is analysed and accordingly various parameters of the model are estimated or fitted. The Picard successive approximation technique and Banach's fixed point theory have been used for verification of the existence and stability criteria of the model. Numerical computations are done utilizing the iterative Laplace transform method. In the end, we illustrate the obtained results graphically. The purpose of this study is to estimate the effectiveness of preventive measures, predicting future outbreaks and potential control strategies using the mathematical model.

Although natural products are an important source of drugs and drug leads, identification and validation of their target proteins have proven difficult. Here, we report the development of a systematic strategy for target identification and validation employing drug affinity responsive target stability (DARTS) and mass spectrometry imaging (MSI) without modifying or labeling natural compounds. Through a validation step using curcumin, which targets aminopeptidase N (APN), we successfully standardized the systematic strategy. Using label-free voacangine, an antiangiogenic alkaloid molecule as the model natural compound, DARTS analysis revealed vascular endothelial growth factor receptor 2 (VEGFR2) as a target protein. Voacangine inhibits VEGFR2 kinase activity and its downstream signaling by binding to the kinase domain of VEGFR2, as was revealed by docking simulation. Through cell culture assays, voacangine was found to inhibit the growth of glioblastoma cells expressing high levels of VEGFR2. Specific localization of voacangine to tumor compartments in a glioblastoma xenograft mouse was revealed by MSI analysis. The overlap of histological images with the MSI signals for voacangine was intense in the tumor regions and showed colocalization of voacangine and VEGFR2 in the tumor tissues by immunofluorescence analysis of VEGFR2. The strategy employing DARTS and MSI to identify and validate the targets of a natural compound as demonstrated for voacangine in this study is expected to streamline the general approach of drug discovery and validation using other biomolecules including natural products.

40 years of cloud observations are available globally from satellites allowing derivation of climate data records (CDRs) for climate change studies. The aim of this study is to investigate how stable these cloud CDRs are and whether they qualify stability requirements recommended by the WMO’s Global Climate Observing System (GCOS). We also investigate robust trends in global total cloud amount (CA) and cloud top temperature (CTT) that are significant and common across all CDRs. The latest versions of four global cloud CDRs, namely CLARA-A3, ESA Cloud CCI, PATMOS-x and ISCCP-HGM, are analysed. This assessment finds that all three AVHRR based cloud CDRs satisfy even the strictest GCOS stability requirements for CA and CTT when averaged globally. While CLARA-A3 is most stable in global averages, PATMOS-x offers the most stable CDR spatially. While we find these results highly encouraging, there however remain large spatial differences in the stability of and across the CDRs. All four CDRs continue to agree on the statistically significant decrease in global cloud amount over the last four decades, although this decrease is now weaker compared to the previous assessments. This decreasing trend is stabilizing or even reversing in the last two decades; the latter is seen also in MODIS-Aqua and CALIPSO GEWEX datasets. Statistically significant trends in CTT are observed in global averages in the AVHRR-based CDRs, but the spatial agreement in the sign and the magnitude of the trends is weaker compared to those in CA. We also present maps of Common Stability Coverage and Common Trend Coverage that could provide a valuable metric to carry out an ensemble-based analysis of the CDRs.

Elastic properties of materials and their changes with temperature are important for their applications in engineering. A study on the influence of phase composition of AISI 4130 alloy on Young's modulus (Ed), shear modulus (Gd), and damping (Q-1) was carried out by Impulse Excitation Technique (IET). The material characterization was carried out using confocal microscopy, XRD, MET, HV, and dilatometry. A stable structure, composed of ferrite (BCC) and pearlite (α-Fe+Fe3C), was obtained by annealing. Metastable structure of martensite (BCT) was obtained by quenching. The Ed, Gd, and Q-1 were measured, varying the temperature from RT to 900 °C. The values of Ed and Gd, at RT, were determined as 201.5 and 79.2 GPa (annealed), and 190.13 and 76.5 GPa (quenched), respectively. In the annealed steel, the values Ed and Gd decrease linearly on heating up to 650 °C, with the thermal expansion. In the quenched steel, weak changes in the dilatometric curve, Ed, Gd, and Q-1, in the range of 350-450 °C, indicated decompositions of the martensitic phase. Sharp decrease in the moduli and high peak of Q-1, was observed for both samples around 650-900 °C, revealing low lattice elastic stability of the phases during transformations α(BCC)+Fe3C↔γ(FCC).

Tunnel-interchange connecting sections pose significant safety challenges on mountainous expressways due to their high incidence of accidents. Improving road safety necessitates a comprehensive understanding of driver behavior in such areas. This study explores the influences of road characteristics, signage information volume, and traffic conditions on drivers' car-following and lane-changing behavior in tunnel-interchange diverging areas. Utilizing driving data from 25 subjects of 72 simulated road models, driving performance is assessed using Friedman rank test and multivariate variance analysis. The results highlight the significant influence of both connection distance and signage information load on driving behavior. In tunnel-interchange scenarios, the reduction of velocity increased by 62.61%, and speed variability surged by 61.11%, indicating potential adverse effects on driving stability due to the environmental transitions. Decreased connection distances are associated with reduced lane-changing durations, larger steering angles, and increased failure rates. Furthermore, every two units increase in signage information leads to a 13.16% rise in maximum deceleration and a 5% increase in time headway. Notably, the signage information volume shows a significant interaction with connection distance (F=1.60, P=0.045) for most car-following indicators. Hence, the study recommends a maximum connection distance of 700 m and signage information not exceeding nine units for optimal safety and stability.

Voltage sags can cause the interruption of power supply and can negatively affect operations of customers. In this paper, the authors study the impact of battery energy storage systems (BESS) on voltage sags. A stochastic method of fault positions is used. Faults of various types are simulated and voltages are recorded. Firstly, with the BESS integrated into the network, there are higher residual voltages, fewer voltage sags and less expected critical voltage loss. Secondly, if the BESS converter power factor is reduced, recorded residual voltages are higher, voltage sags are fewer, and the number of expected critical voltage sags is lower. Finally, when three BESS converter control modes, namely constant voltage, constant power factor, and constant reactive power, were assessed, results showed similar voltage sag performances for constant power factor and constant reactive power modes. Furthermore, operating in constant voltage control outperformed the other two modes as it resulted in higher residual voltages, a lower number of voltage sags, and fewer expected critical voltage sags. The paper has demonstrated that the BESS can improve voltage sag performance. In addition, the power factor of the BESS converter and the mode of operation of the converter can influence the magnitude of the voltage sag performance improvement.

The instability of traveling pulses in nonlinear diffusion problems is inspected on the example of Gunn domains in semiconductors. Mathematically the problem is reduced to the calculation of the "energy" of the ground state in Schrödinger equation with a complicated potential. A general method to obtain the bottom-part spectrum of such equations based on the approximation of the potential by square wells is proposed and applied. Possible generalization of the approach to other types of nonlinear diffusion equations is discussed.

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer-small molecule drug combinations for which stability data is available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in-silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

Ni-Al alloys have good corrosion-resistant properties making them preferable as a material of choice compared to ordinary metals. A good understanding of the phase diagram and thermodynamic properties of the Ni-Al alloy binary system is essential in determining relevant industrial applications of the system. The Ni-Al phase diagram is being reassessed since those found in the literatures are based on very old experimental studies. The phase diagram and thermodynamic properties of the Ni-Al alloy is determined using the Thermo-Calc 2022b software over a temperature range of 200 K to 2000 K and 1 atm of pressure. A total of nineteen fields (including elemental Al and Ni) comprising of five single solid phases, one liquid phase, and twelve double regions was obtained from the equilibrium calculation. The thermodynamic calculation has six invariant reactions comprising of two eutectic reactions (914.83 ± 0.025 K and 1641.80 ± 0.025 K), three peritectic reactions (1123.55 ± 0.025 K, 1400.72 ± 0.025 K and 1642.65 ± 0.025 K), and one peritectoid reaction (913.96 ± 0.025 K). The solubility of Al in Ni is also determined. The Thermo-Calc temperature – composition of the Ni-Al alloy is compared with the existing experimental studies to identify the physical properties of the different thermodynamic properties of the Ni-Al alloy binary system.

Alkenyl Succinic Anhydride (ASA) is a sizing agent used in papermaking to increase the water repellency of paper. Almost 60 years after the introduction of the chemical in papermaking, scientists still have differing views on how ASA interacts with cellulose. Several experiments were conducted to bring more clarity to the ASA sizing mechanism, especially on the contentious question of ASA-cellulose covalent bonding or the esterification reaction between ASA and cellulose during papermaking. Herein, research papers and patents, including experiments and results, from the1960’s to 2020 were reviewed. Our investigation revealed that the ester bond formation between ASA and cellulose is insignificant and is not a prerequisite for sizing effectiveness; the main ASA related material found in sized paper is hydrolyzed ASA or both hydrolyzed ASA and ASA salt. In addition, ASA emulsion stability and ASA emulsion retention are important for sizing efficiency improvement.

Titanium dioxide (TiO₂) micro and nano architectures have been intensively studied in the past years because of many varied applications in environmental, energy conversion, and storage fields, such as heterogeneous catalysis, dye-sensitized solar cells, lithium/sodium ion batteries, lithium-sulfur (Li-S) batteries, and bio-nanotechnology, etc. Especially the surface and interface structures in the TiO₂ structures play important roles in those applications. This mini review article focuses on TiO₂ micro and nano architectures with the prevalent crystal structures (anatase, rutile, brookite, and TiO₂(B)), and summarizes major advances in the surface and interface engineering and applications in environmental and electrochemical applications. We present the principles and growth mechanisms of TiO₂ nanostructures via different strategies, with an emphasis on rational control of the surface and interface structures. We further discuss the applications of TiO₂ micro and nano architectures in photocatalysis, lithium/sodium ion batteries, and Li-S batteries. Throughout the discussion, the relationship between the device performance and the surface structures of TiO₂ micro/nano structures will be highlighted. Then we discuss the phase transitions of TiO₂ nanostructures and possible strategies of improving the phase stability. The review concludes with a perspective on the current challenges and future research directions.

This work explores state-of-the-art approaches for stabilizing an inverted pendulum on a cart system, which has been used for over a century to demonstrate ideas in nonlinear and linear control theory, owing to its simple practical implementation yet complex system dynamics. We introduce energy-based control methods and propose a simple linear controller to quickly force the system to the downward equilibrium before swing-up. By constraining the system to start from a stable equilibrium configuration, the problem of global stability is reduced to ensuring that the system can follow all heteroclinic orbits that start very close to the downward equilibrium. Multiple Lyapunov functions are employed to ensure non-zero tracking, increasing the system's domain of attraction than is achieved by traditional controllers based on a single Lyapunov function. We stabilize our inverted pendulum system in the upright configuration through pole placement using a linear quadratic regulator known for fast settling times and smooth system response and through sliding mode controllers known for their robustness to disturbances and model uncertainties. While sliding mode controllers exhibit faster stabilization of the pendulum angle, they fail to stabilize the cart position in a reasonable amount of time. The paper concludes by suggesting various controller techniques that can enhance the swing-up and stabilization controller architectures, leaving room for future exploration. To facilitate further research and education, an open-source MATLAB simulation code is provided, encapsulating the system dynamics and controller designs. This resource offers flexibility for customization, making it a valuable tool for both researchers and educators working with inverted pendulum systems.

In this study, an analysis was conducted on 16 durum wheat genotypes cultivated under seven different crop management systems. The purpose was to investigate the influence of Genotype (G), Environment (E), and Genotype by Environment interactions (GxE) on the content of total free phenolic compounds (TPC) and the antioxidant capacity (AC) of durum wheat in Mediterranean environments and identify their adaptability in climatic change. Additionally, possible correlations between TPC and AC with protein content (PC), and vitreous-kernel percentage (VKP) of the samples were examined. The results indicated significant impacts from E, G, and GxE on both TPC and AC. Among the E, the mean values for TPC, ABTS, DPPH, and FRAP values were recorded at 48.8 mg TE/100 g dw, 121.3 mg TE/100 g dw, 23.0 mg TE/100 g dw, and 88.4 mg TE/100 g dw, respectively. Environments subjected to splitting topdressing N fertilization consistently showed low values, while the late sowing ones possessed high values. The Organic environment maintained a stable position in the middle across all measurements. The predominant influence was attributed to GxE, as indicated by the order GxE &gt;E&gt;G for ABTS, DPPH, and FRAP while for TPC was E&gt;GxE&gt;G. A comprehensive exploration of GxE interaction holds the potential to improve the total free phenolics content and antioxidant capacity of durum wheat within wheat farming systems. Achieving this enhancement involves the meticulous selection of cultivars that not only display high values but also exhibit stability across diverse conditions. Noteworthy genotypes for TPC include G5, G7 and G10, for ABTS include G3, G5 and G7, and for protein include G1, G9, and G16. G7 and G5 had high presence of frequency with G7 being the closest genotype to the ideal for both TPC and ABTS. These results suggest that the cultivation period as well as the nitrogen fertilization and its application method have a significant impact on the various antioxidant properties of durum wheat. This study holds significant importance as it represents the first comprehensive exploration of the impact of various E on the TPC and AC in durum wheat, with a special emphasis on the crop management. Notably, the significance of several statistical tools is also highlighted, such as the GGE biplot, Pi, and KR, in identifying superior genotypes, with the GGE biplot being highly valuable since it offers a visual representation of the study's outcomes.

Transition metal alloys have emerged as promising electrocatalysts due to their ability to modulate key parameters such as d-band electron filling, Fermi level energy, and interatomic spacing, thereby influencing their affinity towards reaction intermediates. However, the structural stability of alloy electrocatalysts during alkaline hydrogen evolution reaction (HER) remains a subject of debate. In this study, we systematically investigate the structural evolution and catalytic activity of the c-Co/Co3Mo electrocatalyst under alkaline HER conditions. We reveal that the instability of the Co3Mo alloy and H0.9MoO3 during alkaline HER leads to the destruction of the crystal structure, resulting in the formation of hexagonal cobalt (h-Co) from hexagonal Co(OH)2 as an intermediate species. Furthermore, we explore the re-adsorption and surface coordination of the Mo element, which enhances the catalytic activity for alkaline HER. This work provides valuable insights into the dynamic behavior of alloy-based electrocatalysts, shedding light on their structural stability and catalytic activity during electrochemical reduction processes

As there exist no repulsive forces in strong interaction, in a hypothetical approach, strong interaction can be assumed to be equivalent to a large gravitational coupling. Based on this concept, strong coupling constant can be defined as a ratio of the electromagnetic force and the gravitational force associated with proton, neutron, up quark and down quark. With respect to the product of strong coupling constant and fine structure ratio, we review our recently proposed two semi empirical relations and coefficients 0.00189 and 0.00642 connected with nuclear stability and binding energy. We wish to emphasize that- by classifying nucleons as ‘free nucleons’ and ‘active nucleons’, nuclear binding energy can be fitted with a new class of ‘three term’ formula having one unique energy coefficient. Based on the geometry and quantum nature, currently believed harmonic oscillator and spin orbit magic numbers can be considered as the lower and upper “mass limits” of quark clusters.

The use of biolubricants as an alternative for petroleum-based products has played an important role in the last decade. Thus, due to the encouragement of global policies, which mainly support green chemistry and circular economy, there has been an increasing interest in bio-based products, including biolubricants, from scientific and industrial points of view. Due to the different applications of biolubricants for a wide range of practical uses, the raw materials, production, and characteristics might vary, making this field a continuously changing subject of study by researchers. The aim of this research work was to focus on biolubricant production from vegetable oil crops in a bio-refinery perspective, paying attention to the main raw materials used, the corresponding production methods (with special focus on double transesterification), the role of catalysts and techno-economic studies. Thus, the main factors affecting quality parameters such as viscosity or oxidative stability have been covered, including catalyst addition, reaction temperature or the use of raw materials, reagents or additives were also analyzed. The latest research trends were included, updating previous studies about this matter, considering current conclusions and future research.

Mineral wool made from basalt fibers is frequently used as an insulating material in construction systems. In this study, both unused mineral wool, and wool obtained from the softened roofing area, were comprehensively analyzed in a laboratory using different characterization techniques. Firstly, the amount of initial water content and compressive strength at 10% deformation were determined. Secondly, microstructure and surface chemical composition were analysed by Scanning electron microscopy (SEM) equipped with energy dispersive x-ray spectroscopy (EDX). To study heterogeneities near the fiber surface and to examine cross-sectional composition, a Scanning transmission electron microscope (STEM) was used. Finally, to verify possible reasons for resin degradation, Thermogravimetry analysis and differential scanning colometry (TGA-DSC) were simultaneously carried out. The results show that natural aging under high humidity and thermal fluctuations greatly affects the surface morphology and chemical composition of fibrous composite. Phenol-formaldehyde and other hydrophobic compounds that protect fibers against moisture and give compressive resistance were found to be degraded.

In the modern power grid, characterized by the increased penetration of power electronics and extensive utilization of renewable energy, inverters-based power plants play a pivotal role as the principal interface of renewable energy sources (RESs) and the grid. Considering the stability characteristics of grid-following (GFL) inverters when the grid is relatively weak, the application of grid-forming (GFM) controls becomes imperative to enhance the stability of the entire power plant. Thus, there is an urgent need for suitable and effective models to study the interaction and stability of the paralleled inverters employing GFL and GFM controls. Thus, the small-signal modeling with full-order state space model and eigenvalues analysis is presented in this paper. First, the small-signal state-space model of the individual GFL and GFM inverters is obtained considering the control loop, interaction, reference frame, transmissions, and time delays. Then, the models of the individual inverter are extended to the hybrid inverters to study the effects of the GFM inverters on the small- signal stability of the entire system. And, the impacts of the inertia and damping are analyzed by the eigenvalues of the state-transition matrix. Case comprising three parallel GFL inverters and two GFL inverters with one GFM inverter, respectively, are studied to examine the effectiveness and accuracy of the model. Finally, the stability margin obtained from the eigenvalue analysis of the entire system is verified by time-domain simulations.

Metal halide perovskites have shown excellent optoelectronic properties, including high photoluminescence quantum yield, tunable emission wavelength, narrow full-width at half-maximum and low-cost solution-processed fabrication, which make it exhibit great potential as the emission layer materials of light emitting diodes. With the joint efforts of researchers from different disciplines, there has been a significant progress in the improvement of external quantum efficiency (EQE) and stability of perovskite light emitting diodes (PeLEDs) in recent few years, especially in green PeLEDs with EQE over 30%. In this review, we firstly introduce the basic device structure of PeLEDs, as well as the factors influencing EQE and stability of PeLEDs. Secondly, the development of lead-based and lead-free PeLEDs are summarized systematically. Thirdly, challenges of PeLEDs are discussed in detail, including low EQE of blue PeLEDs, poor device stability and EQE roll-off. Finally, some suggestions and perspectives of the future research directions for PeLEDs are proposed.

Stratified Taylor Couette Flow (STCF) undergoes transient growth. Recent studies have shown that there exists transient amplification in the linear regime of counter-rotating STCF. It is reported that as Gr increases, the maximum amplification factor ($G_0$) initially decays before it eventually starts growing after reaching a certain critical value Gr$_{c}$. Assuming other parameters of the model are kept constant, the value Gr$_{c}$ changes with respect to different speed ratios of the cylinders. The observed decay/growth pattern of $G_0$ is attributed to the interplay between the induced shear and buoyancy. In this study, the mechanism that triggers this observed pattern is investigated. The kinetic budget of the optimal transient perturbation is analysed numerically to simulate the interaction of the shear production (SP), buoyancy production (BP) and other energy components that contributes to the total optimal transient kinetic energy. These contributions affect the total energy by influencing the perturbation to extract kinetic energy (KE) from the mean flow. The decay of $G_0$ resulted from the positive amplification of both BP and SP, while the growth is attributed to the negative and positive amplification of BP and SP, respectively. The optimal SP is positively amplified, implying that there is the possibility of constant linear growth. These findings agree with the linear growth rate for increasing values of Gr.

This article introduces a new physically based Lyapunov function difinition, which can be used as acoustic energy for finite amplitude pressure oscillations in reacting systems especially in combustion chambers. Reacting flow is seen as an open, non-equilibrium (parameters are distributed unevenly locally) thermodynamic system. This Lyapunov function is defined as the maximum mechanical work, which could be extracted by a heat engine from studied system, if this system would be disconnected from inlet and outlet and from any other surrounding environment, and the engine could transfer to the surrounding environment only mechanical work.

Magnesium, as one of the most abundant cation in the human body, plays an important role in both physiological and pathological processes. In this study, it was shown that a promising biomedical material Mg-substituted hydroxyapatite (Mg-HA) can be synthesized via fast mechanochemical method. For this method, the nature of magnesium-contained carriers was shown to be important. When using magnesium oxide as a source of magnesium, the partial insertion of magnesium cations into the apatite structure occurs. In contrast, when magnesium hydroxide or monomagnesium phosphate is used, a single-phase Mg-HA is formed. Both experimental and theoretical investigations showed that an increase in the Mg content leads to a decrease in the lattice parameters and unit cell volume of Mg-HA. Density functional theory calculations showed the high sensitivity of the lattice parameters towards the crystallographic position of the calcium site substituted by magnesium. It was shown experimentally that insertion of magnesium cations decreases the thermal stability of the hydroxyapatite. The thermal decomposition of Mg-HA leads to the formation of a mixture of stoichiometric HA, magnesium oxide and Mg-substituted tricalcium phosphate phases.

Melittin, a natural antimicrobial peptide, displays a broad-spectrum antimicrobial activity, which has caused increasing attention as a potential antibiotic alternative. However, melittin has not been used widely at present due to its high hemolysis and low proteolytic stability. In this study, N-terminal fatty acid was conjugated to melittin to develop new melittin-derived lipopep-tides (MDLs) for improving the limitation of melittin. Our results showed that, the antimicrobial activity of MDLs was increased by 2 to 16 times compared with native melittin, and the stability of these MDLs against trypsin and pepsin degradation was increased by 50 to 80%. Besides, the hemolytic of the MDLs decreased when the length of the carbon chain of fatty acids exceeded 10. Among them, the newly designed analog Mel-C8 showed optimal antimicrobial activity and protease stability. The antimicrobial mechanism studied revealed that the MDLs showed a rapid bactericidal effect by interacting with LPS or LTA and penetrating the bacterial cell membrane. In conclusion, we designed and synthesized a new class of MDLs with potent antimicrobial activity, high proteolytic stability, and low hemolysis through N-terminal fatty acid conjugation.

The current deformation and stable state of slopes with historical shatter signs is a concern for engineering construction. Suspected landslide scarps were discovered at the rear edge of the slope of the Genie in the Sichuan-Tibet transportation corridor during a field investigation. In order to qualitatively determine the current status of the surface deformation of this slope, this paper uses high-resolution optical remote sensing, airborne LiDAR and InSAR technologies for comprehensive analysis. The interpretation of high-resolution optical and airborne LiDAR data revealed that the rear edge of the slope exhibits three levels of scarps. However, no deformation was detected with the D-InSAR analysis of ALOS-1 radar images from 2007 to 2008 or with the Stacking-InSAR and SBAS-InSAR processing of Sentinel-1A radar images from 2017 to 2020. A geological model of the slope was established in combination with field investigation stipulating that the slope is composed of steep anti-dip layered dolomite limestone and that the scarps at the rear edge of the slope were caused by historical shallow toppling. Further research is recommended to determine the extent of toppling deformation and evaluate the slope stability under the disturbance of tunnel excavation.

Bi0.5Na0.5TiO3-0.06BaTiO3 (BNT-BT) thin films were prepared by both chemical solution (CSD) and pulsed laser deposition (PLD). The microstructure, dielectric, and ferroelectric properties were investigated. High stability of the dielectric permittivity (∆ɛ/ɛ(150 °C) ≤ ± 15%) over a wide temperature range from room temperature to 300 °C was obtained. Distinctly, the CSD film showed high TCC stability with variation of ± 5% up to 250°C. Furthermore, the CSD film showed an unsaturated ferroelectric hysteresis loop characteristic of the ergodic relaxor phase, however the PLD one exhibited almost saturated loop signature of the coexistence of both ergodic and non-ergodic states. The energy storage properties of the prepared films were determined using the P–E loops obtained at different temperatures. The results showed that these films exhibit stable and improved energy storage density comparable to the ceramic capacitors. Moreover, the CSD film exhibited more rigidity and better energy storage density that exceeds 1.3 J/cm3 under low applied field of 317 KV/cm as well as interesting efficiency in a large temperature range. The obtained results are very promising for energy storage capacitors operating at high temperatures.

In current work, we illustrate the effect of adding small amount of Carbon to very common Co2MnSi Heusler alloy based-glass coated microwires. A significant change in the magnetic and structure structural properties has observed for the new alloy Co2MnSiC compared to the Co2MnSi alloy. The magneto-structural investigations have performed to clarify the main phys-ical parameters i.e., structural & magnetic at a wide range of measuring temperature. The XRD analysis illustrated the well-defined crystalline structure with average grain size (Dg = 29.16 nm) and a uniform cubic structure with A2-type compared to the mixed L21 and B2 cubic structures for Co2MnSi-based glass coated microwires. The magnetic behaviour has investigated at a tem-perature range (5 to 300 K) and an external applied magnetic field (50 Oe to 20 kOe). The adding of small amount of Carbon to the Co2MnSi matrix enhance the magnetic thermal stability, where the thermomagnetic behaviour of Co2MnSiC glass-coated microwires show a perfect stable be-haviour for a temperature range from 300 K to 5 k, the differences between the coercivity value is only 0.3 Oe compared to 4 Oe for Co2MnSi-sample. In addition, M-H loops measured at tempera-ture below 50 K show unsaturated loops; meanwhile the Co2MnSi loops shows a strong antifer-romagnetic coupling for the loops measured below 50 K. By studying the field cooling (FC) and field heating (FH) magnetizations curves at a wide range of external applied magnetic field we detected a critical magnetic field (H = 1 kOe) where FC and FH curves have a stable magnetic behavior for Co2MnSiC sample, such stability does not find in Co2MnSi sample. We proposed a phenomenal expression to estimate the magnetization thermal stability, ΔM (%), of FC and FH magnetization curves and the maximum value is detected at the critical magnetic field where ΔM (%) ≈ 98 %. The promising magnetic stability of Co2MnSiC glass-coated microwires with tem-perature is due to the changing of the microstructure induced by adding Carbon, as the A2-type structure show a unique stability by variation the temperature and the external magnetic field. In addition, a unique internal mechanical stress, which induced during the fabrication process and plays on controlling magnetic behavior with temperature and external magnetic field. The ob-tained results make Co2MnSiC promising candidate for magnetic sensing devices based Heusler glass-coated microwires.

Converting biowaste into biochar and subsequently putting it into the soil are considered to be an effective approach to sequestrate carbon (C). However, biochar will inevitably undergo the aging process in soil, which influences its stability, and ultimately threatens its carbon sequestration ability. This study selected CaCl2 as exogenous additive of sewage sludge and bone dreg to quantify both surface C and bulk C stability in Ca-rich biochars under three aging processes (dry-wet aging, freeze-thaw aging, and natural aging in farmland soil), and revealed the influence mechanisms of exogenous Ca on biochar stability. Results showed that after dry-wet aging (25 rounds), freeze-thaw aging (25 rounds), and natural aging in different farmland soils (5 months), oxidized surface C in Ca-rich biochar decreased by 10~23%, 28~41%, and 0~74%, respectively, compared to that in pristine biochar, while oxidized bulk C decreased by 6~10%, 0~1%, and 0~35%, respectively. Under three aging processes, the surface C and bulk C stability in Ca-rich biochar were superior to that in corresponding pristine biochar, which was attributed to the “protective effect” of Ca-containing crystals on biochar surface, including CaO, Ca5(PO4)3Cl, Ca5(PO4)3(OH), Ca8H2(PO4)6·H2O and Ca10(PO4)6(OH)2. These Ca-containing crystals could block the connection between biochar-C and the external oxidizing environment, intervening the oxidation of C-C/C=C in biochar, but also prevented aging from damaging C structure of biochar, reducing the generation of fragmented structure. By comprehensively assessing surface C and bulk C stability under three aging processes, final C sequestration in Ca-rich biochar increased to 27~80%, compared to that in pristine biochar (23~74%). Therefore, Ca-rich biochar is more dominant than pristine biochar, considering C sequestration potential during long-term aging in soil.

The system identification problem with multiple nonlinearities is relevant. Its decision depends on many factors. These include: feedbacks, the method of connecting nonlinear links, signal properties. They affect the identifiability of the system parameters. We introduced a condition for the excitation constancy for state variables, which considers the S-identifiability of the system. We propose system decomposition by measuring input to identify parameters. Each subsystem has an implicit identification representation. It guarantees obtaining estimates of subsystem parameters based on experimental data. The trajectories boundedness of adaptive system proved in parametric and coordinate spaces. Conditions guaranteeing exponential stability of the system obtained. Systems of self-oscillation generation and nonlinear correction of a nonlinear system consider. Conditions for the trajectories boundedness of the adaptive system obtained for these cases. The influence of nonlinearity and feedback on the system performance estimated.

Objective: To evaluate the physical and chemical stability of the antibiotic temocillin at the recommended dose for severe infections and contained in infusion bags or elastomeric devices at different temperatures for its use in Outpatient Parenteral Antimicrobial Therapy (OPAT) programs.Method: Solutions of temocillin 12 g/L diluted in 0.9% sodium chloride were stored at 4ºC ± 2ºC, 25°C ± 2°C, 32°C ± 2°C and 37°C ± 2°C for 72 h both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated at 12, 24, 30 48 and 72 h after manufacturing. The solutions were considered stable if color, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%. Results: There were no observed changes in color or clarity in any of the refrigerated (4°C) samples or in the samples incubated at 25ºC and 32ºC. At 37ºC, an increase in intensity of yellow color was observed at 30, 48 and 72 h in both infusion bags and elastomeric pumps samples. All samples remained within the pH range 6.84–6.06. At 4ºC, 25ºC and 32°C ± 2°C, temocillin attained the stability criteria of ≥90% of the original concentration for the whole experiment in both devices. At 37ºC, temocillin was stable for 24 h but its concentration dropped below 90% from that time point both in the infusion bags and in the elastomeric pumps.Conclusions: According to the data provided in this stability study, temocillin administrated by continuous infusion would be an appropriate candidate for the treatment of patients that can be discharge to complete therapy in an OPAT program.

Abstract: Remarkably, the p53 transcription factor, referred to as “the guardian of the genome”, is not essential for mammalian development. Moreover, efforts to identify p53‑dependent developmental events have produced contradictory conclusions. Given the importance of pluripotent stem cells as models of mammalian development, and their applications in regenerative medicine and disease, resolving these conflicts is essential. Here we attempt to reconcile disparate data into justifiable conclusions predicated on reports that p53‑dependent transcription is first detected in late mouse blastocysts, that p53 activity first becomes potentially lethal during gastrulation, and that apoptosis does not depend on p53. Furthermore, p53 does not regulate expression of genes required for pluripotency in embryonic stem cells (ESCs); it contributes to ESC genomic stability and differentiation. Depending on conditions, p53 accelerates initiation of apoptosis in ESCs in response to DNA damage, but cell cycle arrest as well as the rate and extent of apoptosis in ESCs are p53-independent. In embryonic fibroblasts, p53 induces cell cycle arrest to allow repair of DNA damage, and cell senescence to prevent proliferation of cells with extensive damage.

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