A unified critical state model has been developed for both clean sand and silty sand using the modified Cam-clay model (MCC). The main feature of the proposed model is a new critical state line equation in the e-ln(p) plane that is capable of handling both straight and curved test results. With this feature, the error in calculating plastic volumetric strain is eliminated in theory. Another crucial feature of the model is the transformed stress tensor based on the SMP (spatially mobilized plane) criterion, which takes into account the proper shear yield and failure of soil under three-dimensional stresses. Additionally, the proposed model applies the intergranular void ratio with the fines influence factor for silty sand. Only eight soil parameters are required for clean sand, and a total number of twelve soil parameters are needed for silty sand.

Considering the negative impacts of climate changes along with the rapid increase in population in Islamic dominated states, e.g., the Middle East, water tension among upstream and downstream states is increasing. Despite the importance of water management in Islamic culture, the role of religion has been under-valued and under-emphasized by the scholars. The paper has sought to compare and contrast Islamic water management principles (IWMP) with international water law principles (IWLP). The findings from this analysis show not only that IWMP are in conformity with IWLP, but that in many cases, IWMP can be more effective. For instance, where international water accords between riparian states of a shared river basin are poorly developed and lack enforcement mechanisms under IWLP, those upstream states can abuse their geographical locations depriving those downstream-ers. In contrast, IWMPs stress the equitable and reasonable use of water resources among upstream and downstream users of a shared watercourse. Moreover, although IWLPs emphasize the conservation and preservation of ecosystems and the environment at the basin level, the inter-basin states especially those upstream can pose significant harm to the ecosystems. On the other side, Islam as the religion of peace, has placed much emphasis on the preservation of nature. For example, the verse, “.... And waste not by excess, for Allah loves not the wasters” [Quran, 7:31], illustrates the importance of the sustainable use of water and the environment. It is argued that if Islamic Water Management Principles are incorporated into the management instrument of Islamic States, the issue of equitable and sustainable use of water among Muslim-dominated riparian states (e.g., Iran, Afghanistan, etc.) will be solved.

This paper seeks to explain the rapid growth of the Islamic State of Iraq & Syria (ISIS) and approach the question of “what is” the Islamic State? The paper offers several contributions. First is the proposal of a dynamic hypothesis that ISIS is an emerging-state actor and differs notably from traditional non-state actors and insurgencies. The theory consists of both a causal loop diagram and key propositions. A detailed system dynamics simulation (E-SAM) was constructed to test the theory. The propositions of emerging-state actor theory are constructed as synthetic experiments within the simulation and confirm evidence of emerging-state actor behavior. E-SAM’s novelty is its combination of combat simulation with endogenous geospatial feedback, ethnographic behavior in choosing sides in conflict, and details internal simulation of key actor mechanisms such as financing, recruiting and governance. E-SAM can be loaded with scenarios to simulate non-state actors in different geospatial domains: ISIS in Libya, Boko Haram in Nigeria, Taliban in Afghanistan and even expatriated ISIS fighters returning to pursue new conflicts such as in Indonesia.

Bridges enable communications and transportation of goods nationally and internationally, underpinning economic and social activities, thus they are pylons of our prosperity and mobility. Bridges worldwide are constantly subjected to physical wear, ageing, deterioration, hazards, environmental influences, and increased loading. Loss of performance and functionality of bridge structures would have a crucial impact on overall infrastructural resilience and would cause significant negative economic and social consequences. Monitoring their behaviour for different loading conditions relies on accurate estimations of the stress-strain state of various critical components and remaining capacities. These activities are of high importance for better planning and lifespan prolongation, that is the extension of their service life and prevention of unforeseen collapses, in line with sustainability principles of well-informed maintenance. In many cases, access to the structure is limited or even impossible, which causes the need for the deployment of remote and contactless methods. One such innovative technique, which has recently attracted attention in scientific and practical applications is the digital image correlation (DIC). DIC is a contactless approach applicable for obtaining the full field of strains and deformations of full-scale real structures. Although the DIC approach has been widely used in world engineering practice for monitoring bridges and has proved to be a reliable and accurate method, there is a lack of systematic integral review on previous practical applications, revealing limitations and perspectives. This is the main motivation and novelty of this study, which will describe selected case studies, in which DIC was used on real full-scale bridge structures and propose improvements for the method.

This paper describes an entropy equation that can be used for measuring energy. It originated from measuring economy in AI models, where the assumption would be that any organic system makes use of energy efficiency to form its structures. Looking at clustering and cohesion resulted in the equation E = (mean * variance). It was apparent however, that it was a very generic type of equation and it could be adjusted so that distance represents mean. This new version was applied to the domain of physics and the universe, when the equation can support the idea that work is done through the energy released by the 'change' in entropy. A comparison with Einstein's relativity equation is made and also the audacious suggestion that a black hole has only potential energy inside, which converts to kinetic energy after a Big Bang, for example. From that suggestion, a universal theory about state change can be made.

Based on the dynamic strength variation mechanism of concrete under complex loading conditions, two approaches were devised: numerical testing and CT scanning, guided by the principle of minimizing energy dissipation. A methodology for calculating concrete's failure area and measuring its strength was developed. The analysis delves into the mechanisms behind failure patterns and variations in concrete specimen strength, focusing on crack initiation, development, and the resultant failure surface formed by crack propagation, along with the stress distribution in concrete specimens subjected to diverse loading conditions. Through evaluating the strength and computed failure area of concrete specimens, it is evident that the loading method influences both the strength and failure area of concrete specimens. In general, a larger failure area correlates with a higher measured strength.

The equation of state of asymmetric nuclear matter as well as the neutron and proton effective masses and their partial-wave and spin-isospin decomposition are analyzed within the Brueckner–Hartree–Fock approach. Theoretical uncertainties for all these quantities are estimated by using several phase-shift-equivalent nucleon-nucleon forces together with two types of three-nucleon forces, phenomenological and microscopic. It is shown that the choice of the three-nucleon force plays an important role above saturation density, leading to different density dependencies of the energy per particle. These results are compared to the standard form of the Skyrme energy-density functional and we find that it is not possible to reproduce the BHF predictions in the (S,T) channels in symmetric and neutron matter above saturation density, already at the level of the two-body interaction, and even more including the three-body interaction.

Partially state-owned firms are common in both developed and developing countries and contribute around 10% of the world's GDP. This has led to a rich literature exploring various aspects of competition between such “mixed”-ownership firms. This paper contributes to the existing literature by studying the effects of mixed ownership on the intensity of competition in oligopoly markets. Our findings indicate that state ownership exerts an anti-competitive influence, with a higher state ownership share resulting in less aggressive behavior by firms in the product market. This result implies that industries with a higher proportion of state ownership yield lower total surplus. Further, when considering factors such as taxes, soft budget constraints, and weak property rights, the anti-competitive effects of state ownership are accentuated.

In recent times, there has been significant enthusiasm for the development of all solid state batteries. This interest stems from a dual focus on safety—addressing concerns related to toxic and flammable organic liquid electrolytes—and the pursuit of high energy density. \cite{SCHNELL2018160,Zheng2018}. While liquid electrolyte batteries constitute for now the vast majority of commercial cells, solid electrolyte batteries show great promise. In parallel with experimental research, computational models \cite{GrazioliEtAlCM2016} clarify the several fundamental physics \cite{LiMonroeARCBM2020} that take place throughout battery operations. We review some classical models, emphasizing the conceptual advancements documented in the most recent works.

This review provides an extensive overview of the developments in the field of polymer science, focusing on the solid-state modification (SSM) of thermoplastic materials. The background of the study places thermoplastics within the context of their increased use over the past century, highlighting their versatility in various applications and the associated environmental and health concerns due to certain additives. The methods section delves into the specifics of SSM, a technique that involves the incorporation of monomers or oligomers into the amorphous phase of polymers through multiple exchange reactions, distinguishing it from traditional melt polymer modification methods. The results section outlines the unique aspects of SSM and its increasing recognition for its potential to enhance material performance in areas such as catalysts and composites. It also discusses the application of SSM in modifying different thermoplastic polymers, highlighting various studies demonstrating the method's effectiveness in altering polymer properties. Finally, this work emphasizes SSM's importance in environmental sustainability and its potential in the recycling and upcycling of plastic materials. It acknowledges the challenges and future perspectives in the field, particularly regarding the scalability of SSM techniques for industrial applications and their role in advancing a circular economy in the polymer industry.

There is a continuous interest in cannabinoids like Δ9-tetrahydro cannabinol (Δ9-THC) and cannabidiol (CBD). A patent of Webster et al., described the conversion of CBD to either D8-THC or D9-THC, depending on the acid catalyst applied. The use of para-toluene sulfonic acid (pTSA) led to the formation of D8-THC, while boron trifluoride etherate (BF3·Et2O) yielded mainly D9-THC. The enormous difference in product selectivity between these two catalysts was investigated with Molecular Modeling. It was found that pTSA leads to fast isomerization of Δ9-CBD to Δ8-CBD and subsequent ring closure to Δ8-THC. BF3·Et2O catalysis leads to the formation of tertiary carbenium ions in the Transition States which yield D9-THC and some iso D8-THC. Under dry conditions in refluxing toluene, it was found that pTSA is predominantly present as a dimer, and only a small fraction is available as monomeric catalyst. Applying the computationally derived activation barriers in Transition State theory yielded reaction rates predicting amounts of cannabinoids that are in close agreement with the experimental findings.

Karate is a martial art that originated in Japan It is characterized by its diverse techniques, including punches, kicks, strikes, and open hand techniques. Generally, karate practitioners shall execute techniques fast, with an impactful finishing towards the target. The present study aims to examine the effectiveness of customized gym sessions in enhancing the athletes’ general performance with a duration of 3-months’time. A total of 7 tests were monitored, i.e., anthropometric measurement, sit and reach test, stork balance stand test, T-test, counter movement jump, 20m sprint, and Yo-Yo endurance test. 4 male amateur athletes (state representative) that has practiced karate for at least 6 years, with at least 5 days training per week, were selected. The age ranges from 15 to 20 years old. The athletes were requested to have a proper rest (at least 7 hours sleeping time) five days before the actual test day. The results show that all athletes have at least maintained or improved stork balance for both legs. The balance improvement ranges from 0% up to 134.69%. However, both the T-test and 20m sprint test demonstrated a negative outcome. The time consumed to complete 20m is increased, which deteriorated the linear speed capability by 1.89% up to 8.93%. Also, 3 out of 4 athletes show that the T-test performance does not provide a satisfactory achievement. The agility of athletes was found to drop by 3.58% up to 10.60%. Interestingly, the athletes’ stamina was found to improve based on the VO2 max prediction and Yo-Yo test. The enhancement of VO2 max prediction and Yo-Yo test recorded as 0% - 7.53% and 9.09% - 20%, respectively. So far, there is no clear indicator on the flexibility of the athletes’ spine and length of the hamstring muscles, based on the sit and reach test. Short-term gym sessions with a duration of 3 months might improve the strength and body balance of athletes. However, the impact on the responsiveness and agility of athletes did not show any significant breakthrough. In future study, it is recommended that a large sample of participants should be included in the analysis.

This paper proposes a metaphysical framework for distinguishing between human and machine intelligence. By drawing an analogy from Kant’s incongruent counterparts, it posits two identical deterministic worlds -- one comprising a human agent and the other comprising a machine agent. These agents exhibit different types of information processing mechanisms despite their apparent sameness in a causal sense. By postulating the distinctiveness of human over machine intelligence, this paper resolves what it refers to as “the vantage point problem” – namely, how to legitimize a determinist’s assertion of determinism by placing the determinist within the universe.

As the global community shifts away from fossil fuels towards more environmentally friendly energy alternatives, there is an escalating demand for sophisticated energy storage solutions. Solid-State Batteries (SSBs) have emerged as a promising advancement, presenting a superior substitute to conventional lithium-ion batteries. This review provides an in-depth examination of SSBs, emphasizing their enhanced energy density, safety, and longevity. We evaluate conventional cathode materials, including lithium cobalt oxide (LiCoO2), lithium manganese oxide (LiMn2O4), and lithium iron phosphate (LiFePO4). Additionally, we introduce emerging materials such as sulfides, oxides, and air-based cathodes, discussing their benefits, limitations, and their congruence with solid electrolytes. Special attention is devoted to the structural fine-tuning of cathode ma-terials, investigating approaches like nanostructuring, surface coatings, and composite strategies to counteract issues such as restricted conductivity and structural volatility. The review critically analyzes the electrical and thermal properties of these materials, which are essential for battery safety and efficacy. Moreover, we present a comparative assessment of cathode materials based on performance indicators and identify prevailing research voids and hurdles in the commerciali-zation of SSB cathodes. Concluding, we suggest prospective research directions and innovations, underscoring the revolutionary potential of SSB technologies in paving the way for a sustainable energy horizon.

The fact that quantum gravity does not admit a co-variant vacuum state has far-reaching consequences for all physics. It points out that space could not be empty, and we return to the notion of an ether . Such a concept requires a preferred reference frame for, e.g., universe expansion and black holes. Here, we intend to discuss vacuum and quantum gravity from three essential viewpoints: universe expansion, black holes existence, and quantum decoherence.

Covid-19 has become a non-natural national disaster that affects the national resilience of the Indonesian state. In maintaining national resilience, the implementation of state defense is needed. This research aims to describe the awareness of defending the state of millennials during the current situation of the Covid-19 pandemic in Indonesia by using a quantitative approach with descriptive analysis methods with survey techniques. The results of this study indicate that most millennials are aware of the obligation to defend the state amid the current Covid-19 pandemic, namely by implementing health protocols such as preparing cleaning equipment, conducting social distancing, and working from home. However, there are still millennials who cannot run it for some reason. Based on the results of this study, it concluded that most millennials are aware of the obligation to defend the state during a pandemic by complying with health protocols as a form of state defense character.

The exact dynamics of emergence remains one of the most prominent outstanding questions for the field of complexity science. I first discuss various perspectives on emergence in various contexts, then offer a different perspective on understanding emergence in a graph-theoretic representation. From the discussion, an observer’s choice in state space seems to have an effect for that observer to detect emergent behavior. To test these ideas, I analyze the dynamics of all possible spatial state spaces near the critical temperature in an Ising model. As a result, state space topologies that appear more deterministic flip more bits than topologies that appear more random, which is contrary to our intuitions about randomness. In addition, the size of different state spaces constrain a system’s ability to explore various states within the same time frame. These results are important to understanding emergent phenomena in biological systems, which are layered with various state spaces and observational perspectives.

Multipartite entanglement is a resource for application in disparate protocols, of computing, communication and cryptography. Nested entanglement provides resource-states for quantum information processing. In this paper, Matryoshka quantum resource-states, which contain nested entanglement patterns, has been studied. A novel scheme for the generation of such quantum states has been proposed using an anisotropic XY spin-spin interaction-based model. The application of the Matryoshka GHZ-Bell states for n-qubit teleportation is reviewed and an extension to more general Matryoshka ExhS-Bell states is posited. An example of Matryoshka ExhS-Bell states is given in the form of the genuinely entangled seven-qubit Xin-Wei Zha state. Generation, characterisation and application of this seven-qubit resource state in theoretical schemes for quantum teleportation of arbitrary one, two and three qubits states, bidirectional teleportation of arbitrary two qubit states and probabilistic circular controlled teleportation are presented.

Multipartite entanglement is a resource for application in disparate protocols, of computing, communication and cryptography. In this paper, generation, characterisation and application of a genuine genuinely entangled seven-qubit resource state is studied. Theoretical schemes for quantum teleportation of arbitrary one, two and three qubits states, bidirectional teleportation of arbitrary two qubit states and probabilistic circular controlled teleportation as well as three schemes for undertaking tripartite quantum state sharing are presented.

New proposals for the equation of state of four- and five-dimensional hard-hypersphere mixtures in terms of the equation of state of the corresponding monocomponent hard-hypersphere fluid are introduced. Such proposals (which are constructed in such a way so as to yield the exact third virial coefficient) extend, on the one hand, recent similar formulations for hard-disk and (three-dimensional) hard-sphere mixtures and, on the other hand, two of our previous proposals also linking the mixture equation of state and the one of the monocomponent fluid but unable to reproduce the exact third virial coefficient. The old and new proposals are tested by comparison with published molecular dynamics and Monte Carlo simulation results and their relative merit is evaluated.

A methodological similarity between Thomas Hobbes and Pëtr Kropotkin is the intention to spread a theoretical foundation to everyone, in the sense that they are willing to give to all the people a clear description of the reality and a subsequent political view. To do so, they use a scientific method, deductive (starting from empirical observations) in the case of Hobbes, inductive-deductive in the case of Kropotkin. Kropotkin underlines the educational value of the scientific method.In this work we want to highlight that, although they both start their argumentations from a materialist ontology, Hobbes and Kropotkin conjecture two completely different states of nature. Hobbes describes the state of nature through the two famous metaphors homo homini lupus (citing Plautus) and bellum omnium contra omnes, while Kropotkin introduced the theory of mutual aid. Both the theory of a state of war by Hobbes and the theory of mutual aid by Kropotkin have been revolutionary. Hobbes has been influenced by the scientific revolution initiated by Francis Bacon, one of his mentors, and Galileo Galilei, together with a criticism towards the ancient Greece philosophers, in particular Aristotle. Kropotkin has been influenced by the ground-breaking writings of Charles Darwin together with a very fruitful Russian scientific environment.We want to stress here that the disenchanted view of the human nature in Hobbes, a state of war due to the fact that everyone has rights on everything, helps him to legitimate sovereignty, while the positive view of human nature in Kropotkin, a spontaneous mutual aid among people in a community, helps him to legitimate anarchy. Therefore, the fascinating scientific methods of the two materialists Hobbes and Kropotkin to structure a solid political theory cannot neglect different views on human nature due to their historical contexts.

Solid state fermentation (SSF) is considered more sustainable than traditional fermentation because it uses low amounts of water and transforms agro-industrial residues into value added products. Enzymes, biofuels, nanoparticles and bioactive compounds can be obtained from SSF. The key factor in SSF processes is the choice of microorganisms and their substrates. Many fungal species can be used and are mainly used due their lower requirements of water, O2 and light. Residues rich in soluble and insoluble fiber are utilized by lignocellulolytic fungi because they have the enzymes that break fiber hard structure (lignases, celullases or hemicelullases). During the hydrolysis of lignin, some phenolic compounds are released but fungi also synthetize compounds such as mycophenolic acid, dicerandrol C, phenylacetates, anthraquinones, benzofurans and alkenyl phenols that have health beneficial effects such as antitumoral, antimicrobial, antioxidant and antiviral activities. Another important group of compounds synthetized by fungi during fermentation are polysaccharides that also have important health promoting properties. Fungal biofermentation has also proved to be a process which can release high contents of phenolics and it also increases the bioactivity of these compounds.

It is shown that quantum entanglement is the only force able to maintain the fourth state of matter, possessing fixed shape at an arbitrary volume. Accordingly, a new relativistic Schrödinger equation is derived and transformed further to the relativistic Bohmian mechanics via the Madelung transformation. Three dissipative models are proposed as extensions of the quantum relativistic Hamilton-Jacobi equation. The corresponding dispersion relations are obtained.

Open source software such as OpenDSS has given a lot of help to distribution network researchers and educators. With high penetration of distributed renewable energy resources into distribution network, tradition distribution steady state analysis software such as OpenDSS is faced with difficulty in handling distributed generators. Three-phase distributed generators are often modeled in sequence frame while unbalanced distribution network are usually modeled in phase frame. So a load flow in sequence-phase coupled frame is proposed to handle models described in both frames. Voltage controlled DGs which are difficult to cope with in OpenDSS are handled in proposed program. The steady state analysis platform is programmed with open source Modelica language and the main aim of this paper is to introduce an open source platform for active distribution network steady analysis include load flow and short circuit analysis which can be easily adopted and improved by other educators and researchers.

Transportation contributes significantly to greenhouse gas emissions, with electrification offering a promising solution. This study evaluates the degradation of State of Health (SOH) over 2.5 years for electrified buses under different charging protocols: DC Fast charging and Flash charging. The vehicles’ models, charging protocols, and financial implications are discussed. High-level simulations reveal that after 2.5 years, the Flash charging vehicle’s SOH reaches 88.93%, while the DC fast charging vehicle reaches 89.46%, showing a 0.47% difference. This slight variance is attributed to Flash charging vehicles avoiding full charge/discharge cycles, reducing battery aging impact. Considering this minimal SOH degradation difference, the choice between DC Fast charging and Flash charging primarily hinges on capital expenditure disparities. Flash charging, with its lower initial battery capacity and reduced capital costs, presents a compelling alternative for city busoperators seeking to electrify their fleets.

In this paper a full state feedback control of a double inverted pendulum on a cart (DIPC) are designed and compared. Modeling is based on Euler-Lagrange equations derived by specifying a Lagrangian, difference between kinetic and potential energy of the DIPC system. A full state feedback control with H infinity and H 2 is addressed. Two approaches are tested: open loop impulse response and a double inverted pendulum on a cart with full state feedback H infinity and H 2 controllers. Simulations reveal superior performance of the double inverted pendulum on a cart with full state feedback H infinity controller.

A difficult open problem that has never been fully resolved in the literature to date is the behaviour of the (TDCDP) third approximation. As a giant step towards modern control theory, this cutting-edge paper will advance control theory and other relevant inter-disciplinary subjects. Because control theory is important in industry and engineering, this study will be especially beneficial to anyone working in these disciplines who wish to understand more about recent advances in control theory settings. In contrast, the wealth of applications of Fokker Planck Kolmogorov (FPK) equations numerous disciplines As a result, the study instantly gains more taste and credibility. At the end of the paper, there are several challenging open problems, some concluding remarks, and recommendations for further investigation.

Neuronal timing is critical for many brain functions such as perception and learning. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). Depolarization-induced analogue-digital facilitation (d-ADF) is a form of context-dependent synaptic facilitation that is induced by constant depolarization of the presynaptic neuron and is mediated by voltage inactivation of presynaptic Kv1 channels. Whether synaptic delay is modulated during d-ADF remains unclear. We show here that despite Pr is elevated during d-ADF at L5-L5 synapses, the synaptic delay is surprisingly unchanged, suggesting that both Pr- and AP-dependent changes in synaptic delay compensate for each other. We conclude that in contrast with other short- or long-term modulation of presynaptic release, timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

Drought stress imposes substantial constraints on the growth and production of wheat (Triticum aestivum L.), a globally important cereal crop that is essential for food security. To mitigate these adverse effects, researchers are intensifying their efforts to comprehend how different genotypes respond to drought stress, aiding in the development of sustainable breeding and management strategies. This review summarized past and recent research on genotype-dependent responses of wheat to drought stress, encompassing morphological, physiological, biochemical, molecular, genetic, and epigenetic reactions in plants. Screening of drought-affected features at early developmental stages can provide valuable insights into the adult growth stages that are closely linked to plant productivity. The review underscores the importance of identifying key traits associated with drought resistance, and the potential of leveraging wheat diversity to select cultivars with desirable agronomic characteristics. It also highlights recent advancements in investigating Bulgarian wheat genotypes with varying levels of drought tolerance, specifically in detecting essential features contributing to drought tolerance. Cultivating drought-resistant wheat genotypes and understanding stress stability determinants could markedly contribute to enhancing wheat production and ensuring stable yields under changing climate conditions.

The dynamic response of a Bell-and-Bloom magnetometer to a parallel (to the bias field) time-dependent field is modelled beyond the commonly assumed quasi-static regime. The results unveil features that are related to the parametric nature of the considered system. It is shown that a for low-amplitude time-dependent field different operating conditions are possible and that, beside the commonly reported low-pass-filter behaviour, a band-pass response emerges. Moreover, we numerically show that for larger field amplitude the system, due to its parametric nature, has a kind of ``non-linear'' response.

Natural gas hydrate has gained significant attention in recent years. To safely and sustainably exploit the natural gas from gas hydrate-bearing sediments, it is crucial to understand the long-term mechanical characteristics of the hydrate reservoir. In this study, the influence of hydrate and fine particles on the strain rate dependence of hydrate-bearing sediments under plane strain conditions has been studied. The experimental results show that the strain rate dependency of the mechanical properties of hydrate-bearing sediments is positively correlated with hydrate saturation instead of the morphology of hydrate in sediments. The residual strength of hydrate-bearing sediments is primarily controlled by the hydrate saturation and is independent of the strain rate. Changes in hydrate saturation, and fines content, can affect the relationship between the strain rate and shear band angle. Finally, the local volumetric expansion effect of hydrate-bearing sediments without fines content is more significant and shows a strong strain rate dependence characteristic. Overall, this study provides valuable insights into the long-term mechanical characteristics of hydrate reservoirs. These insights can contribute to the development of a constitutive model of hydrate-bearing sediments with time-dependence in the future, and which is meaningful to the exploitation of natural gas hydrate.

Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) is the most common chemotherapy used for GBM patients. Recently, combination chemotherapy strategies have more effective antitumor effects and focus on slowing down the development of chemotherapy resistance. A combination of TMZ and cholesterol lowering medications (statins) is currently under investigation in in vivo and clinical trials. In our current investigation, we have used a triple combination therapy of TMZ, Simvastatin (Simva), and Acetylshikonin (ASH) and investigated its apoptotic mechanism in GBM cell lines (U87 and U251). We used viability, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) and immunoblotting autophagy assays. Our results showed that TMZ/Simva/ASH combination therapy significantly induced more apoptosis compared to TMZ, Simva, ASH, and TMZ/Simva treatments in GBM cells. Apoptosis via TMZ/Simva/ASH treatment induced mitochondrial damage (increase of ROS, decrease of MMP) and induced caspase-3/7 activation in both GBM cell lines. Compared to all single treatments and the TMZ/Simva treatment, TMZ/Simva/ASH significantly increased positive acidic vacuole organelles. We further confirmed that the increase of AVOs during the TMZ/Simva/ASH treatment was due to partial inhibition of autophagy flux (accumulation of LC3β-II and decrease in p62 degradation) in GBM cells. Our investigation also showed that TMZ/Simva/ASH-induced cell death was depended on autophagy flux as further inhibition of autophagy flux increased TMZ/Simva/ASH-induced cell death in GBM cells. Finally, our results showed that TMZ/Simva/ASH treatment potentially depends on an increase of Bax expression in GBM cells. Our current investigation might open new avenues for more effective treatment of GBM but further investigations are required for better identification of the mechanisms.

Human metapneumovirus is one of major causes of common cold among children, especially infants. Its key enzyme is RNA-dependent RNA-polymerase, which performs both replication and transcription, including capping and cap methylation. The goal of the work is to find possible inhibitors of RNA-dependent RNA-polymerase across the active compounds of Rosaceae plants. The candidates were selected by molecular docking to cap-transferring domain of RNA-polymerase (PDB ID: 4UCZ) in Autodock VINA. Among all the substances tested by docking, ellagic acid derivatives showed the most promising results (affinity values below -10 kcal/mol). Hence, they could be treated as possible candidate drugs against metapneumoviral infection after experimental examination. The main advantage of using these substances should be their low toxicity, which is quite uncommon for selective RNA polymerase inhibitors used in clinical practice. Occurrence of ellagic acid derivatives among the plants from Rosaceae family like raspberry could explain their effect during common cold.

The lateral pressure generated by liquefied soil on pile is a critical parameter in the analysis of soil-pile interaction in liquefaction-susceptible sites. Previous studies have shown that liquefied sand behaves like a non-Newton fluid, and its effect on piles has rate-dependent properties. In this study, a simplified pseudo-static method for liquefiable soil-pile interaction analysis is proposed by treating the liquefied soil as a thixotropic fluid, which considers the rate-dependent behavior. The viscous shear force generated by the relative movement between the viscous fluid (whose viscosity coefficient varies with excess pore pressure and shear strain rate) and the pile was assumed to be the lateral load on the pile. The results from the simplified analysis show that the distribution of bending moment is in good agreement with experiments data. Besides, the effects of various parameters, including relative density, thickness ratio of non-liquefiable layer to liquefiable layer, and frequency of input ground motion, on the pile-soil rate-dependent interaction were discussed in detail.

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

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

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

Cranioplasty (CP) is the main surgical procedure aimed at reproducing a structural or morphological defect of the skull. It has been shown that cranioplasty can be useful for patients with traumatic brain injury (TBI) to achieve functional cognitive and motor improvements. Here, we describe a patient with long-term severe TBI who recovered consciousness following delayed CP. We found that a delayed CP may result in a meaningful functional recovery with emergence from a minimally conscious state and recovery of functional communication, even more than a year after decompressive craniectomy. Delayed intervention is equally successful in promoting functional recovery in long-term TBI patients, as early CP has already shown.

We propose a theoretical method for the deterministic shaping of quantum light via photon number state selective interactions. Nonclassical states of light are an essential resource for high precision optical techniques that rely on photon correlations and noise reshaping. Notable techniques include quantum enhanced interferometry, ghost imaging, and generating fault tolerant codes for continuous variable optical quantum computing. We show that a class of nonlinear-optical resonators can transform many-photon wavefunctions to produce structured states of light with nonclassical noise statistics. The devices, based on parametric down conversion, utilize the Kerr effect to tune photon number dependent frequency matching, inducing photon number selective interactions. With a high amplitude coherent pump, the number selective interaction shapes the noise of a two-mode squeezed cavity state with minimal dephasing, illustrated with simulations. We specify the requisite material properties to build the device and highlight the remaining material degrees of freedom which offer flexible material design.

Modern development of high-intensity and high-resolution X-ray technology allows detailed studies of the multiphoton absorption and scattering of X-ray photons by deep and subvalent shells of molecular systems on a wide energy range. The interpretation of experimental data requires the improvement of computational methods for obtaining excited and ionized electron states of molecular systems with one or several vacancies. The specificity of solving these problems requires the use of molecular orbitals obtained in one-center representation. Slow convergence of one-center expansions is a significant disadvantage of this approach; it affects the accuracy of the calculation of spectroscopic quantities. We offer a method of including higher harmonics in one-center expansion of a molecular orbital with the use of wave functions of electrons of deep shells of a ligand (off-center atom of a molecule). The method allows one to take into account correctly electron density of a linear molecule near the ligand when describing vacancies created in a molecular core leading to radial relaxation of electron density. The analysis of the parameters of one-center expansion of the ligand functions depending on ligand’s charge is performed. The criteria for the inclusion of higher harmonics of one-center decomposition of the ligand functions in the molecular orbital are determined. The efficiency of the method is demonstrated by the example of diatomic molecules HF, LiF, and BF by estimating energy characteristics of their ground and ionized states.

This paper offers a novel geometric and visual approach to the renowned Four Color Map Theorem and K5 non-planarity problem while unveiling their profound connection to the "kissing number" problem in 2D. We represent planar graphs through circles and tangents, simplifying complex structures and shedding light on these classic problems. Our proofs by contradiction, rooted in the kissing number concept, reveal that both the Four Color Map Theorem and K5 non-planarity are fundamentally linked, as they pivot around the concept of coloring. This study bridges the realms of geometry and graph theory, providing fresh insights and emphasizing the significance of the kissing number problem in various fields.

A spike-timing-dependent-plasticity (STDP) device with a Ga-Sn-O (GTO) conductance change layer deposited by a mist-CVD method has been developed. First, the memristive characteristic is analyzed. Next, based on it, spike waveforms are determined. Finally, the STDP characteristic is successfully confirmed. This is the first report on the realization of a STDP characteristic using a thin film deposited by the mist-CVD method, which is achieved by the GTO properties and a well-designed clear methodology to realize a STDP characteristic from a memristive characteristic.

This study investigates the impact of Government Consumption (GC) on Saudi Arabia’s GDP during major economic crises from 1969 to 2022, with a focus on periods marked by fluctuations in oil and non-oil revenues. By integrating these revenue streams, the research provides a more comprehensive analysis of fiscal policy effectiveness during economic downturns. Using an Autoregressive Distributed Lag (ARDL) model, the study reveals the complex role of Government Consumption (GC) in stabilizing and stimulating the Saudi economy amidst revenue volatility.Key findings indicate that while GC does not significantly influence GDP in the short term, its long-term effectiveness varies across different crises. Specifically, GC has acted as a buffer against immediate economic shocks during certain crises while providing a stimulus for economic recovery in others. For instance, during the 2020 COVID-19 pandemic, timely fiscal measures significantly boosted GDP, underscoring the importance of adaptive and proactive fiscal policies. Conversely, the 2014-2016 oil price collapse demonstrated that GC alone was insufficient to counteract economic downturns, emphasizing the need for diversified revenue strategies.These findings underscore the dual role of GC in economic stabilization and recovery. During the COVID-19 pandemic, GC played a crucial role in both mitigating negative economic impacts and supporting recovery efforts, showcasing its effectiveness in times of global disruptions. This demonstrates GC's capability as an immediate buffer against economic shocks and a stimulus for economic recovery. In contrast, during the 2014-2016 oil price collapse, GC was less effective, indicating the limitations of relying solely on government spending without broader economic diversification. This highlights the necessity of diversified revenue strategies to complement fiscal measures for long-term economic resilience.The robustness of the findings was ensured through various diagnostic tests, including checks for autocorrelation, heteroskedasticity, and stationarity of residuals. The absence of significant autocorrelation and heteroskedasticity, along with the stationarity of differenced variables, confirms the validity of the econometric models used.The study contributes to the discourse on fiscal policy in oil-dependent economies by illustrating the critical role of diversified revenue strategies and adaptive fiscal measures in enhancing economic resilience. Recommendations are offered for policymakers to optimize fiscal strategies, ensuring robust economic recovery and long-term stability in volatile markets. This research highlights the necessity for Saudi Arabia to refine its fiscal policies towards greater economic diversification and stability.

Epilepsy is a non-communicable neurological disease characterized by abnormal brain activity with conceivable peripheral implications. Few studies examine the role of peripheral and brain inflammation in the relationship between seizure predisposition and nonalcoholic fatty liver disease. Severe early-life infections leading to sepsis results in increased inflammation that can aggravate epilepsy and hepatic damage progression both associated with increased odds for hospital admissions in epileptic patients. Here, we examined the effect of early LPS challenge (1 mg/kg, i.p. at post-natal day3, PND3) in inducing hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45), evaluating the intra- and inter-gender differences on systemic and liver inflammation, hepatic lipid dysmetabolism and oxidative damage associated to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Early LPS challenge induced a major inflammatory and immune response in male epileptic rats than females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-insulted females showed a marked alteration in hepatic metabolic and lipid profile and the reduction in mitochondrial fatty acid oxidation. The two different gender-related mechanisms of LPS-induced liver injury converge in mitochondrial oxidative damage with intensified ROS production in both sexes, that notably induced a compensatory increase in antioxidant defense only in females. Our study with a translational potential points out that early postnatal infections predispose epileptic rats to develop or worsen hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

A two-qubit Hamiltonian model exhibiting an SU(2) symmetry is considered. The related dynamical problem results to be then exactly solvable both in the time-independent and in the time-dependent case. Basing on the formal, general form of the related time evolution operator, the time-dependence of the level of entanglement of some initial conditions is studied within both the Rabi and the Landau-Majorana-Stückelber-Zener scenarios.

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence of protective capacity. Yet, within the field there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, nAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bnAbs). More recently, a focus on non-neutralising antibodies (nnAbs), or neutralisation-independent effects of nAbs, has emerged. These can have additive effects on protection or in some cases, be a major correlate of protection. As their name suggests, nnAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nnAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nnAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nnAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nnAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

This article deals with a finite-source stock-dependent stochastic inventory system with heterogeneous servers and retrial facility. The system can store up to S number of items, and the lifetime of each item follows an exponential distribution. The primary customers arrive in a finite waiting hall from a finite source and get service from the multi-channel (c-heterogeneous servers). The customer’s arrival rate depends on the present stock level. Those customers who arrive while the waiting hall is full enter into the finite orbit. Also, customers in the waiting hall can become impatient and enter the orbit. The (s,Q) ordering policy is adopted for the replenishment of stocks. In the steady state, the joint probability distribution of a number of items in the inventory, busy servers, customers in the waiting hall, and orbit is computed. The comparative numerical analysis of heterogeneous and homogeneous servers on the expected total cost, the average number of customers in the waiting hall and orbit, the fraction of successful retrial rate, and the average impatient customer rate are also carried out.

Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision of replication for fast proliferation and increased genomic instability. To overcome the consequences of improper replication control malignant cells frequently inactivate parts of their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other pathways which help to maintain replication fork stability (ATR-CHK1). This creates a dependency on the remaining DDR pathways, vulnerability to further destabilization of replication and synthetic lethality of DDR inhibitors with common oncogenic alterations such as mutations of TP53, RB1, ATM, amplifications of MYC, CCNE1 and others. The response to RS is normally limited by coordination of cell cycle, transcription and replication. Inhibition of WEE1 and PKMYT1 kinases, which prevent unscheduled mitosis entry, leads to fragility of under-replicated sites. Recent evi-dence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets – ATR, CHK1, PARP and their inhibitors.

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

Creep is a fundamental property naturally exists in some types of rock, which is significant for the long-term stability of roadways during the mining process. In this paper, the long-term strength of coal and rock were obtained via laboratory experiments, and a Cvisc elasto-viscoplastic model was adopted and introduced in FLAC3D, based on the 3101 transport roadway in Hongqinghe Coal Mine, to investigate the influence of creep on the stability of deep-high stress roadway. The test results show that the long-term strength of 3-1 coal and sandy mudstone, respectively, is 18.65 MPa, 39.95 MPa. The plastic zone, the deformation, and the damage of roadway surrounding rock behave an obvious increase after being excavated for 720d as the creep model was chosen. The plastic zone failure with models shear-p (1090.7 m3), shear-n (381.7 m3), tension-n (98.4 m3), and tension-p (30.8 m3), the damage value has an obvious increment of increased 21.2% (0.053), the deformation increases in the order is two-sidewalls (1978 mm), roof (907 mm), floor (101 mm). The creep of the roadway can be divided into three stages: the accelerating stage, the decaying stage, and the stable stage. The creep speed of each stage is greatly affected by the presence or absence of anchor spray support: the creep speed of the bare roadway roof, roadway side, and floor stability, respectively, is 1.01, 1.02, and 0.12 mm/d; After anchor spray support, the creep velocity, correspondingly, decreased to 0.69, 0.37, and 0.12 mm/d, and the amount of surrounding rock damage decreased from 0.302 to 0.243. This indicates that the anchor spray support can significantly reduce the creep effect of the roadway. The Cvisc creep model was verified reliable and can provide guidance for deep high-stress coal roadway support.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) lymphocytes eliminates cells infected with viruses. Antiviral ADCC requires three components: 1) antibody; 2) effector lymphocytes with the Fc-IgG receptor CD16A; and 3) viral proteins in infected cell membranes. Fc-afucosylated antibodies bind with greater affinity to CD16A than fucosylated antibodies; individuals’ variation in afucosylation contributes to differences in ADCC. Current assays for afucosylated antibodies involve expensive methods. We report an improved bioassay for antibodies that support ADCC which encompasses afucosylation. This assay utilizes externalization of CD107a by NK-92-CD16A cells after antibody recognition. We used anti-CD20 monoclonal antibodies, GA101 WT or glycoengineered (GE), 10% or ~50% afucosylated, and CD20-positive Raji target cells. CD107a increased detection 7-fold compared to flow cytometry to detect Raji-bound antibodies. WT and GE antibody effective concentrations (EC50s) for CD107a externalization differed by 20-fold, with afucosylated GA101-GE more detectable. The EC50s for CD107a-externalization vs. 51Cr cell death were similar for NK-92 CD16A and blood NK cells. Notably, the %CD107a-positive cells negatively correlated with dead Raji cells and was nearly undetectable at high NK:Raji ratios required for cytotoxicity. This bioassay is very sensitive and adaptable to assess anti-viral antibodies but unsuitable as a surrogate assay to monitor cell death after ADCC.

Potential dependent special relativity and Gauss's law for the electric field have been used for gravity by assuming vacuum energy to be generated when the energy is a minimum useful expression for vacuum energy has been found. This expression shows that elementary particles are generated by gravity vacuum filling their hollow balls; using Schrödinger equation for spherically symmetric particles vacuum energy is quantized. Treating mass as vibrating spheres thus solving Schrödinger, coordinate harmonic oscillator energy relation has been found.

Regression models are mostly used in all fields of sciences for modelling the relationship between a dependent variable and independent variable(s). The least square method is often used to estimate the parameters in a linear model because it is the best linear unbiased estimator. These estimates can only be reliable if the assumption of normality is satisfied. In some cases the dependent variable might be bimodal and shows a non-linear relationship with the independent variable(s). In this case, a non-linear model should be used. In non-linear model, the standard errors are often obtained by linearizing the nonlinear function around the parameter, assuming central limit theorem. After the linearization, the least square parameter estimates are obtained. It should be noted that the error of the non-linear model is different from that of the transformed linear model. Thus, there is a need to transform back to the original non-linear model. In this note, a novel non-linear function was developed into a non-linear regression model, called Normal-Power model. The least square method was used to estimate the parameter of the transformed model. Its usefulness in regression model was demonstrated using real data of Nigeria Economy-Tourism model.

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

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

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.

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

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

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

The finite volume method (FVM) is a kind of numerical analysis method that can take into account topography and apply local subdivision cells as the finite element method (FEM). The adjoint state method (ASM) can easily calculate the gradient vector of the objective function for the inversion. The author developed a program that applied these methods to 3-D Magnetotelluric (MT) inversion and verified it using test models. As a result, it was confirmed that the program can perform analysis properly and efficiently considering topography and subsurface resistivity heterogeneity.

A framework for analysis that focusses on options for structuring and funding the State Owned Enterprises (SOEs) is required in order to apply concepts and information more effectively to policy analysis and program creation. Regardless of the political or economic driving reason for SOE organisation, the requirements of the people must be met in developing countries necessitate that the strategy be viewed from this angle. The types of SOEs and the applicability of fiscal federalism are examined in this article. There are certain lessons to be learnt from the past, and a bad policy can have unintended repercussions. Strategies must be developed for the organisation of SOEs while taking into account the various starting situations.

The primary aim of this study was to investigate the variations in cognitive load as self-efficacy gradually increases and examine the potential within-mediating effect of state anxiety between self-efficacy and cognitive load. The experiment manipulated the self-efficacy of 49 adult participants through the false feedback paradigm, employing a within-subject experimental design and using facial expression recognition as the experimental task. The data were analyzed using Hierarchical Linear Modeling. The results revealed that self-efficacy negatively predicted state anxiety and cognitive load, while state anxiety positively predicted cognitive load. Moreover, state anxiety played a complete mediating role at multiple levels in this process.

Naomi Goldenberg’s model of religion as a “vestigial state” is an excellent interrogation of how religion interacts with the state. To Goldenberg, religions traditionally functioned in the same manner as nation-states before being conquered and delineated as semi-autonomous institutions under the larger secular apparatus. However, I argue in this paper that Goldenberg’s “vestigial state” fails to account for the dynamism that religions have in their relationships to the state. I propose seeing religions as “alternative authorities,” which can be subordinate, cooperative, or hostile to the secular state. These perspectives as an alternative authority are seen best in the evolution of American fundamentalism and Christian nationalism, whose adherents have historically distinguished themselves from the state while simultaneously engaging in the effort to reshape it. In looking at how these movements develop, we understand that religions are constantly evolving in how to achieve and maintain power.

This article investigates hydraulic percolation in saturated porous media, focusing on containment systems using sheet pile walls and gravity concrete dams. The Laplace equation, which governs hydraulic flow in porous media, is solved using the Finite Element Method through the ANSYS software. The modeling of the porous media employs a planar quadratic element called Plane 55, originally used for thermal problems, composed of four nodes and one hydraulic degree of freedom per node. The numerical results of the water pressure acting on the hydraulic structure, flow rate, and hydraulic gradient at the outlet of the porous media are compared with results obtained in the technical-scientific literature using flow nets. Two different methodologies are used to obtain the rate of seepage: by using the average hydraulic velocity or by calculating the integral of the hydraulic gradient perpendicular to the flow area. Both methodologies are compared and validated in the numerical simulations. This work also demonstrates the importance of mesh refinement for obtaining the flow rate in the studied hydraulic systems.

This study focuses on the synthesis, characterization and study of a new perovskite-type materials as cathode in SOFC. The synthesized doped perovskites have been successfully synthesized with high purity. The electrochemical performance of these materials was extensively examined through the characterization of I-V-P and EIS curves at the three temperatures: 750, 800 and 850 °C. Where it is revealing a substantial reduction of total resistances by approximately 50% and 70%, accom-panied by an impressive increase in power densities by around 200% and 300%, respectively. The cell featuring Sm0.01Sr0.99Fe0.5Co0.5O3 exhibited the most commendable electrochemical properties at each temperature, following closely were Pr0.01Sr0.99Fe0.5Co0.5O3 and La0.01Sr0.99Fe0.5Co0.5O3.

In our discipline, some numbers, facts and methods are established and unquestionable. Still, a credible source is hard to find. Likewise, some state-of-the-art papers do not have the right focus, or they do not point at current research trends and future mission statements. Lastly, reliable resources for claims and statements that are arguable are not always found in the typical journals of our field. The paper at hand solves this issue for our field. Through critical review of a vast amount of journal papers, monographs, handbooks, conference proceedings and theses as well as manuals, textbooks and tutorials, numbers, facts, methods, claims statements, state-of-the-art, research and application trends are reflected and substantiated.

Many bacteria have the ability to survive in challenging environments; however, they cannot grow on standard culture media, a phenomenon known as the Viable but Non-Culturable (VBNC) state. Bacteria commonly go into the VBNC state under nutrient-poor environments or under stressful conditions. This review explores the concept of the VBNC state, providing insights into the beneficial bacteria known to employ this strategy. The investigation covers different chemical and physical factors that can induce the latency state, cell features, and gene expression observed in cells in the VBNC state. The revision also covered the significance and applications of beneficial bacteria, methods for evaluating bacterial viability, the ability of bacteria to persist in environments associated with higher organisms, and the factors that facilitate the return to the culturable state. Knowledge about beneficial bacteria capable of entering the VBNC state remains limited, however, beneficial bacteria in this state could face adverse environmental conditions, and return to culturable state when conditions become suitable and continue to exert their beneficial effects. Likewise, this unique feature positions them as potential candidates for healthcare applications, such as the use of probiotic bacteria to enhance human health, applications in industrial microbiology for the production of prebiotics, functional foods, and in the beer and wine industry. Moreover, their use in formulations to increase crop yield and for bacterial bioremediation offers an alternative pathway to harness their beneficial attributes.

Approximately 6 million youth aged 12 to 20 consume alcohol monthly in the United States. The effect of alcohol consumption in adolescence on behavior and cognition is heavily researched, however, little is known about how alcohol consumption in adolescence may alter brain function, leading to long-term developmental detriments. In order to investigate differences in brain connectivity associated with alcohol use in adolescents, brain networks were constructed using resting state functional magnetic resonance imaging data collected by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) from 698 youth (12-21 years, 117 hazardous drinkers and 581 no/low drinkers). Analyses assessed differences in brain network topology based on alcohol consumption in eight pre-defined brain networks, as well as in whole-brain connectivity. Within the central executive network (CEN), basal ganglia network (BGN), and sensorimotor network (SMN), no/low drinkers demonstrated stronger and more frequent connections between highly globally efficient nodes, with fewer and weaker connections between highly clustered nodes. Inverse results were observed within the dorsal attention network (DAN), visual network (VN), and frontotemporal network (FTN), with no/low drinkers demonstrating weaker connections between nodes with high efficiency and increased frequency of clustered nodes compared to hazardous drinkers. Results from this study show clear organizational differences between adolescents with no/low or hazardous alcohol use, suggesting that aberrant connectivity in these brain networks is associated with risky drinking behaviors.

To reduce environmental impacts from sodium silicate synthesis it was suggested the use of sugarcane bagasse ash (SCBA) as a source of silicon dioxide and sodium carbonate using the ceramic method. Although the production of sodium silicate is carried out on a large scale, it should be noted that its process requires temperatures above 1000 °C or the use of highly corrosive agents such as sodium hydroxide and chlorine gas used to neutralize the remaining sodium hydroxide. In the present work, the synthesis temperatures were reduced to 800 °C with a reaction time of 3 hours by pressing equimolar mixtures of previously purified SCBA and sodium carbonate, then heat treatment was carried out under the indicated conditions. The resulting materials were analyzed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Among the crystalline phases, calcium disodium silicate was identified, in addition to sodium silicate, so it was inferred that the other components of the ash can interfere with the synthesis of silicate. Therefore, to obtain the highest composition of sodium silicate, a leaching treatment of the SCBA is required.

Transparent conductive electrodes (TCEs) are of enormous significance to the emergence of flexible and wearable electronics and continued growth of modern devices. Versatile and tunable TCEs, featuring with not only high optical transmittance but also intriguing features of electrochemical energy-storage capability, remain a significant challenge. Here we develop capacitive active films comprised of graphene-conjugated V2O5@poly (3,4-ethylene dioxythiophene) ternary composite (V2O5@PEDOT/rGO) on silver nanowire coated substrates as solid-state super/pseudocapacitors. The constructed electrodes exhibit improved electrolyte ions interaction with effective graphene layer, achieving high areal capacitance 0.6-1.2 mF.cm−2 with 0.5M LiCl electrolytes at optical transparency >60% with record durability. As demonstrated, the kinetic blocking of PEDOT layer and anchoring capability of graphene upon amphoteric soluble vanadium ions from layered V2O5 nanoribbons/nanobelts contribute synergistically to the unusual electrochemical stability, also shown using scanning electrochemical microscopy (SECM) providing electroactivity sites and ion transportation rates. As-fabricated symmetric solid-state supercapacitors delivered broad potential window >1.4 V under two different electrolyte environments (aqueous LiCl and LiCl/PVA gel) and demonstrated higher power and energy density (0.27 μWh.cm−2) outperforming previously reported devices at <0.1 μWh.cm−2. The electrochemical properties are also discussed in terms of solvation in polymer gel electrolyte ions.

Background: World Health Organization (WHO) estimates that there were 558000 new cases with resistance to Rifampicin, of which 82% had multidrug-resistant tuberculosis (MDR-TB). Objectives: We aimed to identify the prevalence of MDR-TB in River Nile state, Sudan, and the risk factors contributing to its occurrence. Methods: This was a descriptive cross-sectional hospital-based study involved 200 specimens taken from patients suspected of having MDR-TB tested using an automated GeneXpert assay. Results: Results of GeneXpert assay showed that the presence of Mycobacterium tuberculosis in 81 (40.5%), and out of 81 positive test results there were 13 (16%) had MDR-TB. Additionally, 7 cases of MDR-TB were previously treated which represented about (53%) of MDR patients, the remaining 6 MDR-TB patients were new cases and represented (47%) of MDR-TB patients. Moreover, there were 4 MDR-TB patients who had a history of contact with MDR-TB patients. Conclusion: Prevalence of MDR-TB in River Nile State, Sudan was 16%, which is greater than WHO estimation for Sudan (10.1%). The results revealed that the main risk factor to develop MDR-TB was a history of contact with MDR-TB, so adherence to treatment and social awareness about the spread of MDR-TB are crucial preventive measures.

In the paper is described the control electronics for an industrial pneumatic – hydraulic system based on a low-cost PLC. The developed system is a hydraulic pulse system and it generates series of high pressure hydraulic pulses (max. 200 bar). We describe requirements, an overall concept of the embedded control system, user interface, security features and network connectivity. In the description of the software solution we describe implementation of hierarchical ordered program threads (multithreaded program) and main control state machine. At the conclusion, we describe the calibration method of the system and calibration curves and we present the schematic diagram and a photo of a functional prototype of the system.

In this article we derive a closed form expression for the symmetric logarithmic derivative of Fermionic Gaussian states. This provides a direct way of computing the quantum Fisher Information for Fermionic Gaussian states. Applications range from quantum Metrology with thermal states to non-equilibrium steady states with Fermionic many-body systems.

This paper discusses the management of public expenditures in Indonesia in State Budget 2017. The data collected from fiscal policy documents, especially about government spending plans in 2017, and then be reviewed by policy analysis, the theory of public expenditures, and the theory of public goods, and compared with the theory of public expenditure in Islamic economics. Public expenditure management in Indonesia has implemented a distribution system that divided public expenditure for central government expenditures, transfers to the regions, and the village fund. In terms of fiscal policy, public expenditure priorities to support the achievement of sustainable economic growth, job creation, poverty reduction, and the reduction of gaps in the welfare of the whole community. In Islamic economics, public expenditure is used to meet the needs of the community based on the principles of general interest derived from the shari'a. Public expenditure on Indonesia's government as an effective tool to divert economic resources and increase the income of society as a whole, and focused on the embodiment of the people's welfare.

The current state-of-the-art does not provide a universal and rapid method of determining the state of health (SOH) of a battery or a supercapacitor without carefully examining the degradation of hundreds of full charge/discharge cycles. Lithium-ion batteries, sodium-ion batteries and supercapacitors of different cell chemistries were studied by impedance spectroscopy during lifetime tests. Faradaic and capacitive charge storage are distinguished by the relationships between stored electric charge and capacitance. For batteries, impedance spectroscopy is best applicable in the flat region of the voltage-charge curve. An approximately linear correlation between pseudocapacitance and Ah capacity is observed as long as overcharge and deep discharge are avoided. The correct calculation of quantities related to complex impedance and differential capacitance is outlined – which may also be useful as an introductory text and tutorial for newcomers to the field. Novel diagram types are proposed for the purpose of instant performance and failure diagnosis of batteries and supercapacitors.

Hydroperoxides (ROOH) are known as damaging agents capable of mediating mutation, while a role as signaling agents through oxidation of protein sulfhydryls that can alter cancer-related pathways has gained traction. Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme that reduces ROOH at the expense of glutathione (GSH). GPX2 is noted for a tendency of large in-creases or decreases in expression levels during tumorigenesis that leads to investigators focusing on its role in cancer. However, GPX2 is only one component of multiple enzyme families that metabolize ROOH and GPX2 levels are often very low in the context of these other ROOH reducing activities. Colorectal cancer (CRC) was selected as a case study for examining GPX2 function as colorectal tissues and cancers are sites where GPX2 is highly expressed. A case can be made for a significant impact of changes in expression levels. There is also a link between GPX2 and NADPH oxidase 1 (NOX1) from earlier studies that is seldom addressed and is discussed, presenting data on a unique association in colon and CRC. Tumor-derived cell lines are quite commonly used for pre-clinical studies involving the role of GPX2 in CRC. Generally, selection for this type of work is limited to identifying cell lines based on high and low GPX2 expression with the standard re-search scheme of overexpression in low expressing lines and suppression in high expressing lines to identify impacted pathways. This overlooks CRC subtypes among cell lines involving a wide range of gene expression profiles and a variety of driver mutation differences along with a large difference in GPX2 expression levels. A trend for low and high GPX2 expressing cell lines to segregate into different CRC subclasses, indicated in this report, suggests that choices based solely on GPX2 levels may provide misleading and conflicting results by disregarding other properties of cell lines and failing to factor in differences in potential protein targets of ROOH. CRC and cell line classification schemes are presented here that were intended to assist workers in performing pre-clinical studies but are largely unnoted in work on GPX2 and CRC. Studies are often initiated on the premise that the transition from normal to CRC is associated with up-regulation of GPX2. This is probably correct. However, the source normal cells for CRC could be almost any colon cell type, some with very high GPX2 levels. These factors are addressed in this study.

Gradients of smooth functions with non-independent variables are relevant for exploring complex models and for the optimization of functions subjected to constraints. In this paper, we investigate new and simple approximations and computations of such gradients by making use of independent, central and symmetric variables. Such approximations are well-suited for applications in which the computations of the gradients are too expansive or impossible. The derived upper-bounds of the biases of our approximations do not suffer from the curse of dimensionality for any $2$-smooth function, and theoretically improve the known results. Also, our estimators of such gradients reach the optimal (mean squared error) rate of convergence (i.e., $\mathcal{O}(N^{-1})$) for the same class of functions. Numerical comparisons based on a test case and a high-dimensional PDE model show the efficiency of our approach.

Assessing observation noise is a critical step in the development of a stochastic model for GNSS navigation and positioning. This process ensures that the statistical properties of the observational data are accurately characterized, leading to more reliable and precise positioning results. Traditionally, the one sigma values for observation noise, 0.3 m for code and 3 mm for carrier phase, alongside elevation-dependent weighting schemes, have been standard. However, these may no longer be suitable due to significant advancements in GNSS systems, receivers, and antennas. Previous research predominantly focused on code type and PPP techniques, often limited by the inability to separately assess observation types across different frequency bands due to ionospheric delay. Furthermore, these studies were generally constrained by limited experimental data. This research advocates for the use of ultra-short baselines to eliminate atmospheric delay and other error sources, providing a detailed assessment of observation noise for various frequency bands, GNSS systems, and receiver & antenna types over an extensive period and across multiple baselines. The findings suggest a need to reconsider traditional one sigma values and elevation-dependent weighting schemes for current applications.

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

We consider a Cauchy problem for differential equations in a Hilbert space $X$. The problem is stated in a time interval $I$, which can be finite or infinite. Weuse a fixed point argument for history-dependent operators to prove the unique solvability of the problem. Then, we state and prove convergence criteria for both a general fixed point problem and thecorresponding Cauchy problem. These criteria provide necessary and sufficient conditions on a sequence $\{u_n\}$ which guarantee its convergence to the solution of the corresponding problem, in the space of both continuous and continuously differentiable functions. We then specify our results in the study of a particular differential equation governed by two nonlinear operators. Finally, we provide an application in viscoelasticity and give a mechanical interpretation of the corresponding convergence result.

From the first isolation of the cystovirus bacteriophage Φ6 from Pseudomonas syringae 50 years ago, we have progressed to a better understanding of the structure and transformations of the many parts of the virion. The three-layered virion encapsulating the tripartite double stranded RNA (dsRNA) genome, breaches the cell envelope on infection, generates its own transcripts, and coopts the bacterial machinery to produce its proteins. The generation of new virions starts with a procapsid with a contracted shape, followed by packaging single stranded RNA segments with concurrent expansion of the capsid, and finally replication to reconstitute the dsRNA genome. The outer two layers are then added, and the fully formed virions released by cell lysis. Most of the procapsid structure composed of the proteins P1, P2, P4 and P7 is now known, as well as its transformations to the mature, packaged nucleocapsid. The outer two layers are less well studied. One additional study investigated the binding of the host protein YajQ to the infecting nucleocapsid, where it enhances the transcription of the large RNA segment that codes for the capsid proteins. Finally, we relate the structural aspects of bacteriophage Φ6 top those of other dsRNA viruses, noting the similarities and differences.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

This paper discusses a passive control issue for Nonlinear Time-Varying (NTV) systems subject to stability and attenuation performance. Based on the modeling approaches of Takagi-Sugeno (T-S) fuzzy model and the Linear Parameter-Varying (LPV) model, a Parameter-Dependent Polynomial Fuzzy (PDPF) model is constructed to represent the NTV systems. According to Parallel Distributed Compensation (PDC) concept, a parameter-dependent polynomial fuzzy controller is built to achieve robust stability and passivity of PDPF model. Furthermore, the passive theory is applied to achieve the performance constraining the disturbance effect on the PDPF systems. To develop the stability criteria, by introducing a parameter-dependent polynomial Lyapunov function, one can derive some stability conditions which belong to the term of Sum-Of-Squares (SOS) form. Based on the Lyapunov function, two stability criteria are proposed to design the corresponding PDPF controller such that the NTV system is robustly stable and passive. Finally, a numerical example is applied to demonstrate the effectiveness of the proposed stability criterion.

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

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

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

Neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. Analysis of ZIKV epidemic strains showed that glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS.

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

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

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

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

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

This paper explores the dynamics of political competition, resource availability, and conflict through a simulation-based approach. Utilizing agent-based models (ABMs) within an evolutionary game theoretical framework, we investigate how individual behaviors and motivations influence collective outcomes in civil conflicts. Our study builds on the theoretical model developed by Basuchoudhary et al. (2023), which integrates factors such as resource availability, state capacity, and political entrepreneurship to explain the evolution of civil conflict. By simulating boundedly rational agents, we demonstrate how changes in resource availability and state capacity can alter the nature of civil conflict, leading to different equilibrium outcomes. The findings highlight the importance of understanding individual motivations and adaptive behaviors in predicting the stability and resolution of conflicts. This research contributes to the growing body of literature on the use of agent-based models in evolutionary game theory and provides valuable insights into the complex interactions that drive civil violence.

By sinking and storing carbon from the atmosphere via photosynthesis, forests play a significant role in combating climate change. Global warming is currently the most pressing global issue. Forests play an important role in the global carbon cycle, covering 30% of the world's terrestrial land area and conserving 81% of the earth's terrestrial carbon biomass. The aim of the study was to quantify and map the Carbon Sink and Stock Values of the Yeraba state forest ecosystem. Primary and secondary data sources were used in this study. Primary data such as plot length and width, DBH (diameter at breast height), soil data, and ground control point (GCP) were obtained in the field using a Garmin 72 GPS, a clinometer, and a diameter tape. Diameter tape, caliper and Soil ogre materials. Beside from this sentimental 2 satellite image, there was also another important primary data. In addition to the primary data source, secondary data sources were used. It includes published books, journals and studies, reports, website sources, and other materials that are publicly available. The systematic sampling technique for identifying each intersection point in the area at regular intervals was the most appropriate sampling design for this study. The study used data from four forest carbon pools, including AGB, BGB, soil, and litter, to calculate the carbon sink and stock values of the Yeraba state forest ecosystem. A total of 17 quadrats, each measuring 20m x 20m and spaced 428 m apart, were used to collect vegetation data. For litter and soil sample collection, five 1 m x 1 m sub-quadrats were established at each quadrat's four corners and center. This data was correlated with five Sentinel 2A level 1c imagery data derived vegetation indices of 2023 to obtain a model and estimate of AGB and AGC at the study site. The total mean carbon stock density of Yeraba state Forest was 404.895 t/ha, with 223.656t/ha, 58.15t/ha, 3.41t/ha, and 119.679 t/ha in the above ground carbon, below ground carbon, litter carbon, and soil carbon pools, respectively. The three environmental factors that influence the distribution of different carbon pools in the forest are altitudinal gradient, slope, and aspect. Standing from the result and inputs the researcher recommended that, Future research may find that using LiDAR and Radar imageries, which can address the saturation and canopy penetration issues, will increase the accuracy of carbon stock estimation.

This paper presents a comparative study of heat transfer performance of lattice structured heat sinks. 20 different unit cells were chosen and heat sinks were modelled in nTop with constant unit cell size. Al 6061 alloy was chosen for analysis due to its good thermal conductivity, low weight, low cost, and high strength. Steady state thermal analysis was performed using ANSYS with constant input parameters for all samples. Heat flux and temperature distribution within the heat sinks were analysed. The study aims to provide a comprehensive understanding of the thermal performance of lattice heat sink designs.

In the paper the new, fractional order, state space model of a heat transfer in a one- 1 dimensional metallic rod is addressed. The fractional orders of derivative along space and time 2 are not exactly known and they are described by intervals. The proposed model is the interval 3 expanding of the state space fractional model of the one dimensional heat transfer. It is expected to 4 better describe the reality because interval order of each real process is hard to estimate. Elementary 5 properties of the proposed model are analysed. Theoretical results are experimentally validated using 6 data from real experimental laboratory system.

Solid-state batteries (SSBs) have emerged as a promising alternative to conventional lithium-ion batteries, with notable advantages in safety, energy density, and longevity, yet the environmental implications of their lifecycle, from manufacturing to disposal, remain a critical concern. This review paper examines the environmental impacts associated with the production, use, and end-of-life management of SSBs, starting with the extraction and processing of raw materials which highlights significant natural resource consumption, energy use, and emissions. A comparative analysis with traditional battery manufacturing underscores the environmental hazards of novel materials specific to SSBs. The review also assesses the operational environmental impact of SSBs by evaluating their energy efficiency and carbon footprint in comparison to conventional batteries, followed by an exploration of end-of-life challenges including disposal risks, regulatory frameworks, and the shortcomings of existing waste management practices. A significant focus is placed on recycling and reuse strategies, reviewing current methodologies like mechanical, pyrometallurgical, and hydrometallurgical processes, along with emerging technologies that aim to overcome recycling barriers, while also analyzing the economic and technological challenges of these processes. Additionally, real-world case studies are presented, serving as benchmarks for best practices and highlighting lessons learned in the field. In conclusion, the paper identifies research gaps and future directions for reducing the environmental footprint of SSBs, underscoring the need for interdisciplinary collaboration to advance sustainable SSB technologies and contribute to balancing technological advancements with environmental stewardship, thereby supporting the transition to a more sustainable energy future.

Depression, anxiety, and pain are part of a common phenomenon that requires to be studied together when evaluating patients with chronic pain. The aim of the study was to examine the correlations between depression, anxiety and pain intensity in patients with chronic pain and how they change when a depressive episode was added. A sample of 120 patients with chronic pain (age: 51.90±11.94; 81.7% female; 18.3% male) was studied in two stages with a three-month period between them. Patients with a depressive episode (n=61) were treated with antidepressants and analgesics, while a patient without depression (n=59) was treated only with analgesics. The scales used to achieve the objectives were: HAM-D-17, Spielberger‘s STAI and VAS. Insignificant correlations were found between depression, state and trait anxiety, and pain intensity (p&lt;0,05) in the group without depression, except for a significant one between depression and state anxiety (p&lt;0,01) in the second stage. Significant correlations were identified between all indicators (p&lt;0,01) in the group with depression at the two stages. Those in the second stage were stronger. The interrelations between sensory and affective aspects of pain were stronger when a depressive episode occurs, the severity of which determines their dynamics.

Time series forecasting has been a challenging area in the field of Artificial Intel-ligence. Various approaches such as linear Neural Networks, Recurrent Linear Neural Networks, Convolutional Neural Networks and recently Transformers have been attempted for the time series forecasting domain. Although, Trans-former-based architectures have been outstanding in the Natural Language Pro-cessing domain, especially in autoregressive language modeling, the initial at-tempts to use transformers in the time series arena have met with mixed success. One of the recent papers demonstrated that modeling the multi-variate time se-ries problem as independent channels on a transformer architecture produced lower mean square and mean absolute errors on benchmarks, however, another recent paper claimed that a simple linear neural network out-performs previous approaches including transformer-based designs. We investigate this paradox in detail comparing the linear Neural Network and Transformer based designs, provide insights to why a certain approach may be better for a particular type of problem. We also improve upon the recently proposed simple linear Neural Network based architecture by using dual pipelines with batch normalization and reversible instance normalization. Our enhanced architecture outperforms all existing architectures for time series forecasting on majority of the popular benchmarks.