Explaining the emergence of behavior and understanding on the basis of neuronal mechanisms is still elusive. One renowned proposal is the Free Energy Principle (FEP), which uses an information-theoretic framework derived from thermodynamic considerations to describe how behavior and understanding would emerge. FEP starts from a whole organism approach, based on mental states and phenomena, mapping them into the neuronal substrate. An alternative approach, the Energy Homeostasis Principle (EHP), initiates a similar explanatory effort, but starting from single neuron phenomena and building up to the whole organism’s behavior and understanding. In this work, we develop the EHP as an alternative but complementary vision to FEP and try to explain how behavior and understanding would emerge from the local requirements of the neurons. Based on EHP and a strict naturalist approach that sees living beings as physical and deterministic systems, we explain scenarios where learning would emerge without the need for volition or goals. Given these starting points, we state several considerations of how we see the nervous system, particularly the role of function, purpose, and the conception of goal-oriented behaviors. We problematize these conceptions, giving an alternative teleology-free framework in which behavior and, ultimately, understanding would still emerge. We reinterpret neural processing explaining basic learning situations up to simple anticipatory behavior. Finally, we end the work with an evolutionary perspective of how this non-goal-oriented behavior appears. We acknowledge that in the current form of our proposal, we are still far from explaining the emergence of understanding. Still, we set the ground for an alternative neuron-based framework to ultimately explain understanding.

The free energy principle states that self-organization occurs through minimization of free energy, which is a measure of potential thermodynamic work. By minimizing free energy, the organism happens to also minimize surprise over its boundary, promoting chances of survival. We discuss the ethical implications of the cognitive goal in detail from an empirical point of view, highlighting the principle of least action as a physical basis of Occam's razor, the universality of the free energy principle, and its explanation of natural selection. We explain that the free energy principle extends to groups of organisms and helps us understand group-scale adaptations and selection in biology. The free energy principle applies to all scales of organization in the organism from single cells to the entire nervous system. When this principle is taken to its logical extremes of modeling groups, populations and ecosystems, we uncover a new, evolutionarily sensible path at explaining puzzling aspects of human motivation and judgement, including ethical decisions. To minimize free energy, populations have to act to maximize gathering of information, while building effective models at mitigating changes to its dynamic structure. The free energy principle thus provides a naturalistic explanation of some of our deepest ethical intuitions, and valuable principles of social behavior. We interpret the cognitive goal that corresponds to the principle as seeking a dynamic, fruitful, yet peaceful activity that sustains the organism. This state of mind is interestingly similar to the Buddhist intuition of mental equanimity; the organism's final goal is to be at peace and harmony with the environment. Another immediately relevant aspect is that assemblies must form to promote symbiotic, synergistic, positive feedback loops, which coincides with the findings of ecologists. Therefore, ethics naturally emerges in self-organizing systems. Assemblies of organisms must ultimately unite in macro-minds to achieve the greatest reduction in free energy, as well as building technological extensions of themselves to improve their capacity to do such, therefore the principle also predicts a post-singularity world-mind composed mostly of artificial intelligence.

The retrospective noninterventional study investigated the kinetic energy of video images of 18 fertilized eggs (7 were normal and 11 were abnormal) recorded by a time-lapse device leading up to the beginning of the first cleavage. The norm values of cytoplasmic particles were measured by the optical flow method. Three phases profile for normal cases were found regarding the kinetic energy that were 2.199×10⁻²⁴±2.076×10⁻²⁴, 2.369×10⁻²⁴±1.255×10⁻²⁴, and 1.078×10⁻²⁴±4.720×10⁻²⁵ (J) for the phases 1, 2, and 3, respectively. In phase 2, the energies were 2.369 × 10⁻²⁴ ± 1.255 × 10⁻²⁴ and 4.694 × 10⁻²⁴ ± 2.996 × 10⁻²⁴ (J) (mean ± SD, P = 0.0372), and the time required was 8.114 ± 2.937 and 6.018 ± 5.685 (H) (P = 0.0413) for the normal and abnormal cases, respectively. The kinetic energy change was considered a condition for applying the free energy principle that states that, for any self-organized system to be in equilibrium in its environment, it must minimize its informational free energy. The kinetic energy while interpreting it in terms of the free energy principle suggesting clinical usefulness would further our understanding of the phenomenon of fertilized egg development with respect to the birth of human life.

Gedanken experiments illustrating exemplifications of the Landauer principle in the free falling Einstein elevator are treated. Double-well simplest information system embedded into the free falling elevator is addressed. Infinitesimal horizontal force applied to the particle m transfers it from position “0” to position “1”, emerging from the free falling double-well system confining mass m. When thermal noise is considered, the potential barrier of kBT should be surmounted for the erasing of one bit of information. Entropic forces arising in the free falling elevator are considered. The maximal change in the entropy of free-joint polymer chain attached to the free falling elevator is estimated as ΔSmax≅kB, and it is remarkably independent of the mass attached to the chain and the parameters of the chain itself. Free falling minimal Szilard engine is treated. The informational re-interpretation of the minimal Szilard process is shaped as follows: the energy kBTln2 necessary for erasing of 1 bit of information is spent for lifting up mass, whatever, is the value of this mass. Appropriate choice of frames enables elimination of gravity in the considered system; however elimination of the thermal noise (dissipation processes) by the same procedure is impossible.

Despite their obvious differences, biological systems at different scales tend to exhibit common organizational patterns. Unfortunately, these commonalities are usually obscured by the parcelled terminology employed by various scientific sub-disciplines. To explore these commonalities, this papers a comparative study of diverse applications of the maximum entropy principle, ranging from amino acids up to societies. By presenting these studies under a common language, this paper establishes a unified view over seemingly highly heterogeneous biological scenarios.

Phenomenon of vacuum fluctuations of virtual particles in high energy physics has been mathematically modeled by a third order differential equation. Aim of present theory is to unravel underlying mathematical equation capable of explaining microscopic phenomenon of vacuum fluctuations. Solution of such a differential equation after applying appropriate boundary conditions gives an acceptable wave function i.e. . Operation of energy and time operator on this wave function proves that these operators do not hold commutative property. Time energy uncertainty principle has been derived by calculating variance of energy and time for the same wave function.

Synergy, emerges from synchronized reciprocal positive feedback loops between a network of diverse actors. For this process to proceed, compatible information from different sources synchronically coordinates the actions of the actors resulting in a nonlinear increase in the useful work or potential energy the system can manage. In contrast noise is produced when incompatible information is mixed. This synergy produced from the coordination of different agents achieves non-linear gains in free energy and in information (negentropy) that are greater than the sum of the parts. The final product of new synergies is an increase in individual autonomy of an organism that achieves increased emancipation from the environment with increases in productivity, efficiency, capacity for flexibility, self-regulation and self-control of behavior through a synchronized division of ever more specialized labor. Examples that provide quantitative data for this phenomenon are presented. Results show that increases in free energy density require decreases in entropy density. This is proposed as a law of thermodynamics.

Development of methods and algorithms to predict the effect of mutations on protein stability, protein-protein, and protein-DNA/RNA binding is necessitated by the needs of protein engineering and for understanding the molecular mechanism of disease-causing variants. The vast majority of the leading methods are either methods with adjustable parameters or machine learning algorithms, both requiring a database of experimentally measured folding and binding free energy changes. These databases are collections of experimental data taken from scientific investigations typically aimed at probing the role of particular residue on the above-mentioned thermodynamics characteristics, i.e., the mutations are not introduced at random and do not necessarily represent mutations originating from single nucleotide variant (SNV). Thus, the reported performance of the leading algorithms assessed on these databases or other limited cases, may not be applicable for predicting the effect of SNVs seen in the human population. Indeed, we demonstrate that the SNVs and non-SNVs are not equally presented in the corresponding databases and the distribution of the free energy changes are not the same. Furthermore, the Pearson correlation coefficients (PCCs) obtained on cases involving SNVs are less impressive than for non-SNVs, indicating that caution should be used in applying them to reveal the effect of human SNVs. All methods are found to underestimate the energy changes by roughly a factor of 2.

It has been recognized for some time that even for perfect conductors, the interaction Casimir entropy, due to quantum/thermal fluctuations, can be negative. This result was not considered problematic because it was thought that the self-entropies of the bodies would cancel this negative interaction entropy, yielding a total entropy that was positive. In fact, this cancellation seems not to occur. The positive self entropy of a perfectly conducting sphere does indeed just cancel the negative interaction entropy of a system consisting of a perfectly conducting sphere and plate, but a model with weaker coupling in general possesses a regime where negative self-entropy appears. The physical meaning of this surprising result remains obscure. In this paper we re-examine these issues, using improved physical and mathematical techniques, partly based on the Abel-Plana formula, and present numerical results for arbitrary temperatures and couplings, which exhibit the same remarkable features.

A major goal of neuroscience is understanding how neurons arrange themselves into neural networks that result in behavior. Most theoretical and experimental efforts have focused on a top-down approach which seeks to identify neuronal correlates of behaviors. This has been accomplished by effectively mapping specific behaviors to distinct neural patterns, or by creating computational models that produce a desired behavioral outcome. Nonetheless, these approaches have only implicitly considered the fact that neural tissue, like any other physical system, is subjected to several restrictions and boundaries of operations.Here, we propose a new, bottom-up conceptual paradigm: The Energy Homeostasis Principle, where the balance between energy income, expenditure, and availability are the key parameters in determining the dynamics of the found neuronal phenomena from molecular to behavioral levels. Neurons display high energy consumption relative to other cells, with metabolic consumption of the brain representing 20% of the whole-body oxygen uptake, contrasting with this organ representing only 2% of the body weight. Also, neurons have specialized surrounding tissue providing the necessary energy which, in the case of the brain, is provided by astrocytes. Moreover, and unlike other cell types with high energy demands such as muscle cells, neurons have strict aerobic metabolism. These facts indicate that neurons are highly sensitive to energy limitations, with Gibb’s free energy dictating the direction of all cellular metabolic processes. From this activity, the largest energy, by far, is expended by action potentials and post-synaptic potentials; therefore, plasticity can be reinterpreted in terms of their energy context. Consequently, neurons, through their synapses, impose energy demands over post-synaptic neurons in a close loop-manner, modulating the dynamics of local circuits. Subsequently, the energy dynamics end up impacting the homeostatic mechanisms of neuronal networks. Furthermore, local energy management also emerges as a neural population property, where most of the energy expenses are triggered by sensory or other modulatory inputs. Local energy management in neurons may be sufficient to explain the emergence of behavior, enabling the assessment of which properties arise in neural circuits and how. Essentially, the proposal of the Energy Homeostasis Principle is also readily testable for simple neuronal networks.

We present software on total energy calculation by quantum mechanics first principle method with a graphic user interface (GUI). Total energy calculation in this software is based on numerical analysis of time-dependent density functional (the used numerical method is finite difference time domain). QUMEC package has been equipped by common exchange-correlation energy terms with electron spin polarization calculation. With this package, users can calculate the total energy of the free particle, bulk materials, and materials with free surfaces at the atomic scale. The package is tested by several physical subjects, i.e., the surface energy of nano-LiCoO₂ and diffusion constant of lithium atoms in LiNi­_0.5Mn_1.5O₄.

The classical uncertainty principle inequalities were imposed as a mathematical constraint over the general relativity geodesic equation. In this way, the uncertainty principle was reformulated in terms of the proper space-time length element, Planck length and a geodesic-derived scalar, leading to a geometric expression for the uncertainty principle (GeUP). This re-formulation confirmed the necessity for a minimum length for the space-time line element in the geodesic, dependent on a geodesic-derived scalar which made the expression Lorentz-covariant. In agreement with quantum gravity theories, GeUP required the imposition of a perturbation over the background Minkowski metric unrelated to classical gravity. When applied to the Schwarzschild metric, a geodesic exclusion zone was found around the singularity where uncertainty in space-time diverged to infinity.

Molecular modeling is widely utilized in subjects including but not limited to physics, chemistry, biology, materials science and engineering. Impressive progress has been made in development of theories, algorithms and software packages. To divide and conquer, and to cache intermediate results have been long standing principles in development of algorithms. Not surprisingly, Most of important methodological advancements in more than half century of molecule modeling are various implementations of these two fundamental principles. In the mainstream classical computational molecular science based on force fields parameterization by coarse graining, tremendous efforts have been invested on two lines of algorithm development. The first is coarse graining, which is to represent multiple basic particles in higher resolution modeling as a single larger and softer particle in lower resolution counterpart, with resulting force fields of partial transferability at the expense of some information loss. The second is enhanced sampling, which realizes "dividing and conquering" and/or "caching" in configurational space with focus either on reaction coordinates and collective variables as in metadynamics and related algorithms, or on the transition matrix and state discretization as in Markov state models. For this line of algorithms, spatial resolution is maintained but no transferability is available. Deep learning has been utilized to realize more efficient and accurate ways of "dividing and conquering" and "caching" along these two lines of algorithmic research. We proposed and demonstrated the local free energy landscape approach, a new framework for classical computational molecular science and a third class of algorithm that facilitates molecular modeling through partially transferable in resolution "caching" of distributions for local clusters of molecular degrees of freedom. Differences, connections and potential interactions among these three algorithmic directions are discussed, with the hope to stimulate development of more elegant, efficient and reliable formulations and algorithms for "dividing and conquering" and "caching" in complex molecular systems.

Structural information of biological macromolecules is crucial and necessary to deliver predictions about the effects of mutations—whether polymorphic or deleterious (i.e., disease causing), wherein, thermodynamic parameters, namely, folding and binding free energies potentially serve as effective biomarkers. It may be emphasized that the effect of a mutation depends on various factors, including the type of protein (globular, membrane or intrinsically disordered protein) and the structural context to which it occurs. Such information may positively aid drug-design. Furthermore, due to the intrinsic plasticity of proteins, even mutations involving radical change of the structural and physico-chemical properties of the amino acids (native vs. mutant) can still have minimal effects of protein thermodynamics. However, if a mutation causes significant perturbation of either folding or binding free energies, it is quite likely to be deleterious. Mitigating such effects is a promising alternative to the traditional approaches of designing inhibitors. This can be done by structure-based in silico screening of small molecules for which binding to the dysfunctional protein restores its wild type thermodynamics. In this review we emphasize on the effects of mutations on two important biophysical characteristics, stability and binding affinity, and how structures can be used for structure-based drug design to mitigate the effects of disease-causing variants on the above biophysical characteristics.

The antioxidant activity of molecules constitutes an important factor for the regulation of redox homeostasis and reduction of oxidative stress. Cells affected by oxidative stress can undergo genetic alteration, causing structural changes and promoting the onset of chronic diseases, such as cancer. The in silico study performed here was developed to evaluate the antioxidant potential of two molecules, ZINC08706191 (Z91) and ZINC08992920 (Z20), with recognized epithelial anticancer potential. Molecular docking, chemical-quantum calculations and Pearson's correlation were performed. The Z91 and Z20 molecules showed lower binding free energy (ΔG) values for the receptor-ligand interaction than the reference molecules (caffeine – CAF and ascorbic acid – AA), and better results for values of molecular descriptors correlated with ΔG, resulting in a decrease of ΔG. Strong correlations were observed between ΔG values for the five receptors evaluated and ΔG values of the potential epithelial anticancer activity available in literature. These results attest to the significant antioxidant potential of the Z91 and Z20 molecules and their strong relation with the potential epithelial anticancer activity and may be indicated for further analysis in relation to the control of oxidative stress and epithelial anticancer activity.

In the paper, a fully discrete compact difference scheme with $O(\tau^{2}+h^{4})$ precision is established by considering the numerical approximation of the one-dimensional Allen-Cahn equation. The numerical solutions satisfy discrete maximum principle under reasonable step ratio and time step constraint is proved. And the energy stability for the fully discrete scheme is investigated. An example is finally presented to show the effectiveness of scheme.

A high-performance Lead-free Piezoelectric Energy Harvester (LPEH) based on a Ba0.85Ca0.15Ti0.90Zr0.10O3 + CuO 0.3 wt% (BCTZC0.3) composite was fabricated by sintering at 1450℃. The BCTZC0.3 composite, which has an enhanced high-energy-conversion constant (〖d_33×g〗_33), shows improved piezoelectric power-generation performance when compared with conventional piezoelectric energy harvesters. The BCTZC0.3-based LPEH produces instantaneous maximum power of 8.2 mW and an energy density of 107.9 mW/cm3 in a weak magnetic field of 250 μT. This energy harvester can be used to charge a capacitor and operate a wireless sensor network (WSN) system to provide temperature sensing and radio-frequency (RF) transmission in a 250 μT magnetic field. The proposed LPEH is a promising green-energy device for potentially self-powering WSN systems when applied.

Studies involving vortex in hybrid superconducting devices and their interaction with different components inside the sample are an important issue to reach higher values of their critical parameters in superconducting materials. The vortex distribution on each side of sample with different fundamental parameters, such as temperature T, penetration depth λ, coherence length ξ, electron mass m and the order parameter Ψ, may help to improve the superconducting properties. Thus, in this work, we used the modified Ginzburg-Landau theory to investigate hybrid superconductor (HS), but also to provide a highly tunable and adjustable theoretical tool to theoretically explain the experimental results involving HS, in order to study the vortex behaviour in superconductors of mesoscopic dimensions with extremely differences among their fundamentals parameters. Therefore, we evaluated the influence of HS on vortex configuration and their effects in the field-dependent magnetization. The results show that the during the increment of applied magnetic field H the diamagnetic response of HS, Meissner effect, include additional jumps of magnetization while diamagnetism continues its increase in the sample. In addition, the differences among parameters, create an interface between both components, two different magnitudes of supercurrent and vortex sizes producing a lower degradation of local superconductivity, which increase the upper critical field. On the other hand, this type HS with differences of parameters on both sides can be used to control the vortex movement in the selected superconducting region sample with more accuracy.

Nonequilibrium work switching simulations and Jarzynski’s equation are a reliable method to compute free energy differences, ΔAlow→high, between two levels of theory, such as a pure molecular mechanical (MM) and a quantum mechanical/molecular mechanical (QM/MM) description of a system of interest. Despite the inherent parallelism, the computational cost of this approach can quickly get very high. This is particularly true for systems where the core region, the part of the system to be described at different levels of theory, is embedded in an environment, such as explicit solvent water. We find that even for relatively simple solute–water systems, switching lengths of at least 5 ps are necessary to compute ΔAlow→high reliably. In this study, we investigate two approaches towards an affordable protocol, with emphasis on keeping the switching length well below 5 ps. Inserting a hybrid charge intermediate state with modified partial charges which resembles the charge distribution of the desired high level makes it possible to obtain reliable calculations with 2 ps switches. Attempts using step-wise linear switching paths, on the other hand, did not lead to improvement, i.e., faster convergence for all systems. To understand these findings, we analyzed the solutes’ properties as a function of partial charges used, the number of waters in direct contact with the solute, and studied the time needed for water molecules to reorient themselves upon a change in the solute’s charge distribution.

A novel method proposed in the production of Calophyllum inophyllum biodiesel has been investigated experimentally. In this study, we report the results of biodiesel processing with electromagnetic induction technology. The method used is to compare the results of Calophyllum inophyllum biodiesel processing between conventional, microwave and electromagnetic induction. The degumming, transesterification, and esterification process of the 3 methods are measured by stopwatch to obtain time comparison data. Characteristics of viscosity, density, and Fatty Acid Metil Ester (FAME) were obtained from testing of a Gas Chromatography-mass Spectrometry (GCMS) at the Polytechnic Chemistry Laboratory of the State of Malang. The results show that the biodiesel produced by this method satisfies the biodiesel standards and their characteristics are better than the biodiesel produced by conventional and microwave methods. The electromagnetic induction method also offers a fast and easy route to produce biodiesel with the advantage of increasing the reaction rate and improving the separation process compared to other methods. This advanced technology has the potential to significantly increase biodiesel production with considerable potential to reduce production time and costs.

The growing adoption of distributed energy production technologies, and the potential of energy underutilization when it is produced by non-connected groups, has raised interest in ‘sharing economy’ concepts in the electricity sector. We suggest that mechanisms, such as peer-to-peer (P2P) energy trading, will allow users to exchange their surplus energy for mutual benefits, stimulate the adoption of renewable energy, encourage communities to ‘democratically’ control their own energy supplies for local development, and improved energy efficiency, and create many other benefits This approach is receiving increasing attention across the world, particularly in Germany, the Netherlands and Australia. Nevertheless, the actual development and implementation of these platforms is slow and mostly limited to trial activities. This study investigates the challenges and barriers facing P2P energy trading developments based on previous academic and industry studies. We provide a comprehensive multidimensional barrier analysis through a PESTLE approach to assess the barriers from a variety of perspectives, including the political (P), economic (E), social (S), technological (T), legal (L), and environmental (E) aspects. This approach clarifies the many intersecting problem fields of P2P trading in renewable energy, and the paper identifies a list of such barriers, and discusses the prospects for addressing these issues. We also elaborate on the importance of incentive-based P2P market design.

Polymer materials are increasingly being used for sliding machine elements due to their numerous advantages. They are used even where they are deformed and in such a state they interact frictionally e.g. in machine hydraulics or lip seals. Few publications deal with the influence of deformation, which is the effect of e.g. assembly on tribological properties of polymeric material. This deformation can reach up to ε ≈ 20% and is achieved without increasing the temperature of the polymer material. The paper presents the results of investigations in which high-density polyethylene (PE-HD) was maintained in deformation by means of a special grip (holder). The wear of the sample was significantly higher than that of the undeformed sample. This effect persisted even after partial relaxation of the stress in the sample after 24 hours. Additional investigations were carried out to explain the obtained results. There were the microscopic observations of the surface after friction, measurements of microhardness and free surface energy. Changes in the value of surface free energy and a significant decrease in microhardness with deformation under tension were observed. Strained material had a different surface appearance after friction and a different size and form of wear products. It was indicated that it is probable that the cohesion of the material will decrease and that the character of the wear process will change as a result of tension. Tension without heating of polymeric material (PE-HD), e.g. as a result of assembly, has been qualified as a hazard to be taken into account when designing and analysing polymeric sliding elements.

The Simulation analogy presented in this work enhances the accessibility of abstract quantum theories, specifically the stochastic hydrodyanimc model (SQHM), by relating them to our daily experiences. The SQHM incorporates the influence of fluctuating gravitational background, resembling dark energy, into quantum equations. This model successfully addresses key aspects of Objective-Collapse Theories, including resolving the 'tails' problem through the definition of quantum potential length in addition to the De Broglie length, beyond which coherent Schrödinger quantum behavior and wavefunction tails cannot be maintained. The SQHM emphasizes that an external environment is unnecessary, asserting that the quantum stochastic behavior leading to wave-function collapse can be an inherent property of a system in a spacetime with fluctuating metrics. Embedded in relativistic quantum mechanics, the theory establishes a coherent link between the uncertainty principle and the constancy of light speed, aligning seamlessly with finite information transmission speed. Within a fluctuating quantum system, the SQHM derives the indeterminacy relation between energy and time, offering insights into measurement processes impossible within a finite time interval in a truly quantum global system. Experimental validation is found in confirming the Lindemann constant for solid lattice melting points and the transition from fluid to superfluid states. The SQHM's self-consistency lies in its ability to describe wavefunction collapse and the measure process. Additionally, the theory resolves the Pre-existing Reality problem by showing that large-scale systems naturally decay into decoherent states stable in time. Continuing, the paper demonstrates that the physical dynamics of SQHM can be analogized to a computer simulation employing optimization procedures for realization. This perspective elucidates the concept of time in contemporary reality and enriches our comprehension of free will. The overall framework introduces an irreversible process impacting the manifestation of macroscopic reality at the present time, asserting that the multiverse exists solely in future states, with the past comprising the formed universe after the current moment. Decoherence at the present time functions as a reduction of the multiverse to a single universe. The macroscopic reality, characterized by fractal consistency where microscopic domains with quantum properties coexist, provides insights into how our consciousness apprehends dynamic reality, the spontaneous emergence of gravity in discrete spacetime evolution, and the attainment of the classical General Relativity limit in Quantum Loop Gravity and Causal Dynamical Triangulation. The Simulation Analogy highlights a strategy focused on minimizing information processing, facilitating the universal simulation in solving its predetermined problem. From within, reality becomes the manifestation of specific physical laws emerging from the inherent structure of the simulation devised to address its particular issue. In this context, the reality simulation appears to employ an entropic optimization strategy, minimizing information loss while efficiently compressing data in line with the simulation's intended purpose.

One of the biggest challenges in characterizing 2-D image topographies is finding a low-dimensional parameter set that can succinctly describe, not so much image patterns themselves, but the nature of these patterns. The 2-D Cluster Variation Method (CVM), introduced by Kikuchi in 1951, can characterize very local image pattern distributions using configuration variables, identifying nearest-neighbor, next-nearest-neighbor, and triplet configurations. Using the 2-D CVM, we can characterize 2-D topographies using just two parameters; the activation enthalpy and the interaction enthalpy. Initial investigations with two different representative topographies (``scale-free-like'' and ``rich club-like'') produce interesting results when brought to a CVM free energy minimum. Additional phase space investigations, where one of these two parameters has been set to zero, identify useful parameter ranges. Careful comparison of the analytically-predicted configuration variables versus those obtained when performing computational free energy minimization on a 2-D grid show that the computational results differ significantly from the analytic solution. The 2-D CVM can potentially function as a secondary free energy minimization within the hidden layer of a neural network, providing a basis for extending node activations over time and allowing temporal correlation of patterns.

Our purpose is to address the biological problem of finding foundations of the organization in the collective activity among cell networks in the nervous system, at the meso/macroscale, giving rise to cognition and consciousness. But in doing so, we encounter another problem related to the interpretation of methods to assess the neural interactions and organization of the neurodynamics, because thermodynamic notions, which have precise meaning only under specific conditions, have been widely employed in these studies. The consequence is that apparently contradictory results appear in the literature, but these contradictions diminish upon the considerations of the specific circumstances of each experiment. After clarifying some of these controversial points and surveying some experimental results, we propose that a necessary condition for cognition/consciousness to emerge is to have available enough energy, or cellular activity; and a sufficient condition is the multiplicity of configurations in which cell networks can communicate, resulting in non-uniform energy distribution, the generation and dissipation of energy gradients due to the constant activity. These ideas may reveal possible fundamental principles of brain organization and how healthy activity may derive to pathological states.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in-silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physiological conditions. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in-silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared to the pertuzumab-HER2 complex.

Naltrexone (NTX) is a potent opioid antagonist with good blood-brain barrier permeability, targeting different endogenous opioid receptors, particularly the mu-opioid receptor (MOR). Therefore, it represents a promising candidate for drug development against drug addiction. However, the details of the molecular interactions of NTX and its derivatives with MOR are not fully understood, hindering ligand-based drug discovery. In the present study, taking advantage of the high-resolution X-ray crystal structure of the murine MOR (mMOR), we constructed a homology model of the human MOR (hMOR). A solvated phospholipid bilayer was built around the hMOR and submitted to microsecond (µs) molecular dynamics (MD) simulations to obtain an optimized hMOR model. NTX and its derivatives were docked into the optimized hMOR model and submitted to µs MD simulations in an aqueous membrane system. The MD simulation results were submitted to Molecular Mechanics Generalized-Born surface area (MMGBSA) binding free energy calculations and principal component analysis. Our results revealed that NTX and its derivatives showed differences in protein-ligand interactions; however, they shared contact with residues at TM2, TM3, H6, and TM7. The binding free energy and principal component analysis revealed the structural and energetic effects responsible for the higher potency of NTX compared to its derivatives.

The principles of causality and unitarity are studied within rational nonlinear electrodynamics proposed earlier. We investigate dyonic and magnetized black holes and show that in the self-dual case, when the electric charge equals the magnetic charge, corrections to Coulomb's law and Reissner-Nordstrom solutions are absent. In the case of the magnetic black hole, the Hawking temperature, the heat capacity and the Helmholtz free energy are calculated. It is shown that there are second-order phase transitions and it was demonstrated that at some range of parameters the black holes are stable.

Proteins in biological systems function at the interface of single molecule and bulk chemistry and thus provide novel insights into the basic physical chemistry of scaling and emergent phenomena. For example, a binary mechanical model based on the chemistry of muscle contraction unifies molecular mechanics and thermodynamics and provides an explicit solution to the Gibbs paradox. Using the same model system, here I show that chemical activities of molecular states have no effect on chemical kinetics or energetics. Specifically, while the concentration or number of molecules in a molecular state is widely thought to contribute to reaction free energies, here I show that it is not the physical presence of molecules that pushes a reaction forward but the number of microstates, , accessible in a chemical state that pulls a reaction toward equilibrium with an entropic force down an entropic funnel. With the derivation of an entropic contribution to chemical kinetics, I develop a novel chemical kinetic formulation that fully describes the chemical thermodynamics of both equilibrium and non-equilibrium reactions in terms of an a priori system reaction energy landscape.

In thermodynamic theory, free energy (i.e., available energy) is the concept facilitating the combined applications of the theory’s two fundamental laws, the first and the second laws of thermodynamics. The critical step was taken by Kelvin, then by Helmholtz and Gibbs— that in natural processes, free energy dissipates spontaneously. With the formulation of the second law of entropy growth, this may be referred to as the dissymmetry proposition manifested in the spontaneous increase of system/environment-entropy towards equilibrium. Because of Kelvin’s pre-entropy-law formulation of free energy, our concept of free energy is still defined, energy-centrally, as body’s internal energy or enthalpy, subtracted by energy that is not available within a framework on the premise of primacy of energy, in which free energy dissipates spontaneously and universally. This primacy of energy is called into question because the driving force to cause a system’s change is the purview of the second law. This paper makes a case for an engineering thermodynamics framework, instead, to be based on the premise of the primacy of dissymmetry over free energy. With Gibbsian thermodynamics undergirded with dissymmetry proposition and engineering thermodynamics with the dissymmetry premise, the two branches of thermodynamics are unified to become classical thermodynamics.

We take a heterodox approach to the ΛFRW Cosmology starting from the modification of Newtonian gravity by explicitly incorporating Mach's Principle through an additional term a great scale in the gravitation. The results show that at the after of the matter-radiation decoupling, the distribution of matter at scales greater than 10Mpc contributes with an inverse Yukawa-like field, which verifies the observations: resulting null in the inner solar system, weakly attractive in ranges of interstellar comoving distances, very attractive in comoving distance ranges comparable to the clusters of galaxies, and repulsive in cosmic scales. This additional term explains dark energy, removes the incompatibility between the density of matter and the flatness of the universe; and also allows the theoretical deduction of the Hubble-Lemaitre Law. Additionally, Birkhoff Theorem, Virial Theorem, the missing mass of Zwicky, the BAO, gravitational redshift are discussed. It is concluded that the dark energy and the missing mass can be approached with the usual physics if a classical, large-scale modification of the Inverse Square Law.

The free energy principle (FEP) is a mathematical and scientific principle that describes the relationship between the physical behavior of a dynamical system and the interpretation of such behavior as carrying out inference. It blurs the boundary between the ontological mode of the system of interest and the epistemological significance it acquires through its dynamic interaction with the environment. New materialism (or neo-materialism), despite lacking a single definition, refers to a range of emerging perspectives that attempt to dismantle the long-held divisions between ontology, epistemology, and even ethics, with the aim of achieving a comprehensive transformation of naturalized thinking. In this context, new materialism provides powerful tools to reframe some of the conceptual foundations of the FEP. This paper is the first in a series that aims to systematically construct a neo-materialistic perspective for the FEP, exploring its wide-ranging implications. It serves as an introduction to the series, arguing for the justification of deploying new materialism to reframe the FEP and introducing some essential concepts to be utilized in developing a neo-materialistic account of the FEP.

In this work we report recent theoretical calculations of a superconducting island in a strong vortex confinement regime. The obtained results reveal the evolution of superconducting condensate as a function of electron mean-free path (l) with the evolution of an applied magnetic field H0. The results of this study provide an insight about the emergent superconducting properties under such conditions, using the Ginzburg-Landau numerical simulations where spatial variation of thickness d on island, omnipresent in these kind of structures grown on Si (111), is taken into account. These results offer a new route to tailor superconducting circuits by using the controlled bombardment, in order to explore the impact on vortex distribution, phase of order parameter, number of vortices, free energy and the first H1 and second critical field H2.

In this work, we report the electric energy storage properties of (1-x)Bi0.5(Na0.8K0.2)0.5TiO3-xBi0.2Sr0.7TiO3 (BNKT-BST; x = 0.15-0.50) relaxor ferroelectric ceramics enhanced via a domain engineering method. A rhombohedral–tetragonal phase, the formation of highly dynamic PNRs, and a dense microstructure are confirmed from XRD, Raman vibrational spectra, and microscopic investigations. The relative dielectric permittivity (2664 at 1 kHz) and loss factor (0.058) were gradually improved with BST (x=0.45). The incorporation of BST into BNKT can disturb the long-range ferroelectric order, lowering the dielectric maximum temperature Tm and inducing the formation of highly dynamic polar nano-regions. In addition, the Tm shifts toward high temperature with frequency and a diffuse phase transition, indicating relaxor ferroelectric characteristics of BNKT-BST ceramics, which is confirmed by the modified Curie Weiss law (γ=1.83). The rhombohedral–tetragonal phase, fine grain size, and lowered Tm with relaxor properties synergistically contribute to a high recoverable energy density Wrec of 0.81 J/cm3 and a high energy efficiency η of 86.95% at 90 kV/cm for x = 0.45.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

We study the effect of the generation of the mechanical transverse wave (MTW)　travelling in the opposite direction (OD) to a moving medium (MM) on the relativistic energy conservation law (RECL). From the viewpoint of the relativity of simultaneity (RS), the time on the coordinate coinciding with the advance end of the wave (AEW) travelling toward the rear of the MM passes faster than that on the coordinate coinciding with the wave source (WS). Then the AEW in the MM travels forward compared to that in the rest frame of reference (RFR) which is stationary relative to the medium when the time on the coordinate coinciding with the WS is same for each inertial frame of reference (IFR). Hence, the coordinate interval (CI) between the AEW and WS in the MM is observed to be larger than that between them in the RFR. We show that this difference holds true for the CI of any portion having transverse velocities mutually converted by the Lorentz transformation (LT). This difference in the CI leads to that in the rest mass (RM). We demonstrate that the RM included in wave motion (WM) in the MM is larger than one included in WM in the RFR when comparing the portions having transverse velocities mutually converted by the LT. This relation holds true for all portions in WM. Therefore, the total coordinate interval of the portion (CIP) and total RM (TRM) included in WM in the MM (WMMM) are large compared to them included in WM in the RFR. Furthermore, we compare the relativistic kinetic energy (RKE) of the MTW travelling in the OD to the MM (ODMM) with that of the MTW propagating in the direction vertical to the moving direction of the medium. We prove that the CIP and RM included in the former MTW are larger than them included in the latter MTW when comparing each portion with the same transverse velocity (TV). Moreover, the total CIP and TRM included in the former MTW are also large compared to them included in the latter MTW. The reason for these is that the latter CIP and RM are equal to them in the RFR when comparing the portions having transverse velocities mutually converted by the LT. On the other hand, the energy supplied to generate each MTW is the same. From these, we demonstrate that the RKE of the MTW travelling in the ODMM can be larger than the total relativistic energy (TRE) of the MTW propagating in the direction vertical to the moving direction of the medium. Consequently, we propose a violation of the RECL and Einstein’s principle of relativity (EPR) because the TRE is not necessarily conserved in the IFR in which the medium is moving.

Clausius’ virial theorem set a basis for relating kinetic energy in a body of independent material particles to its potential energy, pointing to their complementary role with respect to the second law of maximum entropy. In action mechanics, expressing the entropy of ideal gases as a capacity factor for sensible heat or enthalpy plus the configurational work to sustain the relative translational, rotational and vibrational action yields algorithms for estimating chemical reaction rates and positions of equilibrium. All properties of state including entropy, work potential as Helmholtz and Gibbs energies and activated transition state reaction rates can be estimated, using easily accessible molecular properties, such as atomic weights, bond lengths, moments of inertia and vibrational frequencies. Understanding how Clausius’ virial theorem balances the internal kinetic energy with field potential energy justifies partitioning between thermal and statistical properties of entropy, yielding a more complete view of the evolutionary nature of the second law of thermodynamics. The ease of performing these operations is illustrated by three important chemical gas phase reactions, the reversible dissociation of the hydrogen molecules, lysis of water to hydrogen and oxygen and the reversible formation of ammonia from nitrogen and hydrogen. Employing the ergal also introduced by Clausius to define the reversible internal work to overcome molecular interactions plus the configurational internal work of negative Gibbs energy as a function of volume or pressure may provide a practical guide for managing risk in industrial processes and climate change at the global scale.

This paper is devoted to an accurate determination of the London dispersive and polar free energy of adsorption, the two Lewis acid γs+ and base γs- components of polar surface energy γsAB of 2D single-crystalline and polycrystalline covalent organic frameworks such as TAPPy-TPA-COFs. Inverse gas chromatography (IGC) at infinite dilution was used to quantify the different surface parameters of the different materials. From IGC measurements, one determined the net retention time of the adsorption of n-alkanes and several polar solvents on single-crystalline and polycrystalline covalent organic frameworks. The free surface Gibbs energy of adsorption was obtained for the various organic molecules at different temperatures from their net retention volume values. The separation between the London dispersive energy and the polar energy of adsorbed molecules was carried out by using a new thermodynamic parameter PSX chosen as new indicator variable and taken into account the deformation polarizability and the harmonic mean of the ionization energies of solvents and solid materials, derived from London dispersion equation. The obtained results are very promising for the accurate determination of the surface thermodynamic parameters of adsorption of organic solvents on solid surfaces.

A modified free-wake vortex ring model is proposed to compute the dynamics of a floating horizontal-axis wind turbine. The model is divided into two parts. The near wake model uses a blade bound vortex model and trailed vortex model, which is developed based on vortex filament method. By contrast, the far wake model is based on the vortex ring method. The proposed model is a good compromise between accuracy and computational cost, for example when compared with more complex vortex methods. The present model is used to assess the influence of floating platform motions on the performance of a horizontal-axis wind turbine rotor. The results are validated on the 5MW NREL rotor and compared with other aerodynamic models for the same rotor subjected to different platform motions. It was found that the results from the proposed method are more reliable than the results from BEM theory especially at small angles of attack in the region of low wind speeds, on the one hand, and high wind speeds with blade pitch motions, on the other hand. And also the proposed method is less time consuming and has similar accuracy when comparing with more advanced vortex based methods.

Precise binding affinity predictions are essential for structure-based drug discovery (SBDD). Focal adhesion kinase (FAK) is a member of the tyrosine kinase protein family and is overexpressed in a variety of human malignancies. Inhibition of FAK using small molecules is a promising therapeutic option for several types of cancer. Here, we conducted computational modeling of FAK targeting inhibitors using 3-dimensional structure-activity relationship (3D-QSAR), molecular dynamics (MD), and hybrid topology-based free energy perturbation (FEP) methods. The structure-activity relationship (SAR) studies between the physicochemical descriptors and inhibitory activities of the chemical compounds were performed with reasonable statistical accuracy using CoMFA and CoMSIA. These are two well-known 3D-QSAR methods based on the principle of supervised machine learning (ML). Essential information regarding residue-specific binding interactions was determined using the MD and MM-PB/GBSA methods. Finally, physics-based relative binding free energy (〖∆∆G〗_RBFE^(A→B)) values of analogous ligands were estimated using the alchemical FEP simulation. An acceptable agreement was observed between the experimental and computed relative binding free energies. The overall results using ML and physics-based hybrid approaches could be useful for the rational optimization of accessible lead compounds with similar scaffolds targeting the FAK receptor.

Zika virus (ZIKV) has been characterized as one of the potential pathogens and placed under future epidemic outbreaks by the WHO. However, lack of potential therapeutics can result in uncontrolled pandemic like other human pandemic viruses; therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted the strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the ZIKVpro and ZIKVRdRp proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of top four common bioflavonoids, viz. rutin, nicotiflorin, isoquercitrin, and hyperoside. These compounds showed substantial docking energy (-7.9 to -11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (His51, Asp74, and Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals the stability of respective docked complexes contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp for further experimental assessment.

The calculation of the vapour pressure of organic molecules at 298.15K is presented using a commonly applicable computer algorithm based on the group-additivity method. The basic principle of this method rests on the complete breakdown of the molecules into their constituting atoms, further characterized by their immediate neighbour atoms. The group contributions are calculated by means of a fast Gauss-Seidel fitting algorithm using the experimental data of 2036 molecules from literature. A ten-fold cross-validation procedure has been carried out to test the applicability of this method, which confirmed excellent quality for the prediction of the vapour pressure, expressed in log(pa), with a cross-validated correlation coefficient Q2 of 0.9938 and a standard deviation  of 0.26. Based on these data, the molecules' standard Gibbs free energy G°vap has been calculated. Furthermore, using their enthalpies of vaporization, predicted by an analogous group-additivity approach published earlier, the standard entropy of vaporization S°vap has been determined and compared with experimental data of 1129 molecules, exhibiting excellent conformance with a correlation coefficient R2 of 0.9598, a standard error  of 8.14 J/mol/K and a medium absolute deviation of 4.68%.

What is the function of cognition? On one influential account, cognition evolved to co-ordinate behaviour with environmental change or complexity (Godfrey-Smith 1996). Liberal interpretations of this view ascribe cognition to an extraordinarily broad set of biological systems – even bacteria, which modulate their activity in response to salient external cues, would seem to qualify as cognitive agents. However, equating cognition with adaptive flexibility per se glosses over important distinctions in the way biological organisms deal with environmental complexity. Drawing on contemporary advances in theoretical biology and computational neuroscience, we cash these distinctions out in terms of different kinds of generative models, and the representational and uncertainty-resolving capacities they afford. This analysis leads us to propose a formal criterion for delineating cognition from other, more pervasive forms of adaptive plasticity. On this view, biological cognition is rooted in a particular kind of functional organisation; namely, that which enables the agent to detach from the present and engage in counterfactual (active) inference.

The mechanisms of natural oscillations and resonance are described, considering the peculiarities of the transformation of elastic and kinetic energy in the implementation of the law of conservation of energy in local and integral volumes of the body, using the concept of mechanics based on the concepts of space, time and energy. When describing the motion in the Lagrange form, the elastic deformation energy of the particles is determined by the quadratic invariant of the tensor, whose components are the partial derivatives of Euler variables with respect to Lagrange variables. The increment of the invariant due to elastic deformation is represented as the sum of two scalars, one of which depends on the average value of the relative lengths of the edges of the particles in the form of an infinitesimal parallelepiped, the second is equal to the standard deviation of these lengths from the average value. It is shown that each of the scalars can be represented in the form of two dimensionless kinematic parameters of elastic energy, which participate in different ways in the implementation of the law of conservation of energy. One part of the elastic energy passes into kinetic energy and participates in the implementation of the law of conservation of energy for the body as a whole, considering external forces. The second part is not converted into kinetic energy but changes the deformed state of the particles in accordance with the equations of motion while maintaining the same level of the part of the elastic energy of the particles used for this. The kinematic parameters differ from the volume density of the corresponding types of energy by a factor equal to the elastic modulus, which is directly proportional to the density and heat capacity of the material and inversely proportional to the volume compression coefficient. Transverse, torsional, and longitudinal vibrations are considered free and under resonance conditions. The mechanisms of transformation of forced vibrations into their own after the termination of external influences and resonance at the superposition of free and forced vibrations with the same or similar frequency are considered. The formation of a new free wave at each cycle with an increase in the amplitude, which occurs mainly due to internal energy sources, and not external forces, is justified.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

We study Einstein's gravity coupled to nonlinear electrodynamics with two parameters in Anti-de Sitter spacetime. Magnetically charged black holes in an extended phase space is investigated. We obtain the mass and metric functions, their asymptotic and corrections to the Reissner--Nordstr\"{o}m metric function when the cosmological constant vanishes. The first law of black hole thermodynamics in extended phase space is formulated and the magnetic potential and the thermodynamic conjugate to the coupling are obtained. We proved the generalized Smarr relation. The heat capacity and the Gibbs free energy are computed and phase transitions are studied. It was shown that the electric field of charged objects at the origin and electrostatic self-energy are finite within the nonlinear electrodynamics proposed.

In this paper, we consider the one-dimensional Ising model (shortly, 1D-MSIM) having mixed spin-(s,(2t−1)/2) with nearest neighbors and the external magnetic field. We establish the partition function of the model by means of the transfer matrix. Under a null boundary condition, we compute certain thermodynamic quantities for the 1D-MSIM. We find some precise formulas to determine the model’s free energy, entropy, magnetization, and susceptibility. By examining the model’s associated iterative equations, we use the cavity approach to investigate the phase transition problem. We numerically determine the model’s periodicity.

The application of warm-mixing technology brings considerable economical and environment benefits by decreasing the mixing temperature during warm asphalt mixture(WMA) production. However, the possible water residue also generates concerns in moisture susceptibility. For deep investigation on the influencing factors and mechanism of the moisture susceptibility of WMA, surface free energy(SFE) test and laboratory tests are applied in this research. A novel indicator based on SFE namely effective adhesion work is proposed to assess the asphalt-aggregate adhesion with different moisture contents. Then, given the mixing procedure of dry mixing method, an advanced three-phase model as form of asphalt-aggregate-warm mixing additive is introduced improving from the conventional two-phase asphalt-aggregate model for better reflecting the separate addition of warm mixing additive during mixing. Afterwards, the influence of aggregate types, asphalt type, aggregate moisture contents, warm-mixing agent types and warm-mixing process on the moisture susceptibility of WMA is analyzed utilizing the models and indicators proposed. Finally, the validity of the SFE indicator is verified by comparing the calculation of effective adhesion work with freeze-thaw splitting test result. The results show that all of the above factors impact the moisture susceptibility of WMA by influencing the interfacial adhesion, with the effect of moisture content being the most significant. Meanwhile, effective adhesion work and the three-phase model brought out in this research are proven to be feasible to characterize the adhesion properties of WMA, offering theoretical support to the research on warm mixing technology.

About a century ago, in the spirit of ancient atomism, the quantum of light was renamed the photon to suggest its primacy as the fundamental element of everything. Since the photon carries energy in its period of time, a flux of photons inexorably embodies a flow of time. Time comprises periods as a trek comprises legs. The flows of quanta naturally select optimal paths, i.e., geodesics, to level out energy differences in the least time. While the flow equation can be written, it cannot be solved because the flows affect their driving forces, affecting the flows, and so on. As the forces, i.e., causes, and changes in motions, i.e., consequences, cannot be separated, the future remains unpredictable, however not all arbitrary but bounded by free energy. Eventually, when the system has attained a stationary state, where forces tally, there are no causes and no consequences. Then time does not advance as the quanta only orbit on and on.

The QBIT theory is an attempt toward solving the problem of consciousness based on empirical evidence provided by various scientific disciplines including quantum mechanics, biology, information theory, and thermodynamics. This theory formulates the problem of consciousness in the following four questions: (1) What is the nature of qualia? (2) How are qualia generated? (3) Why are qualia subjective? (4) Why does a quale have a particular quality or meaning?In sum, the QBIT theory proposes that (1) when a pack of quantum information is compressed beyond a certain threshold, a quale is generated; (2) a quale is a superdense pack of maximally entangled qubits in a pure state; (3) when information-theoretic certainty of a system about an external stimulus exceeds a particular level, the system becomes conscious of that stimulus; (4) subjectivity of consciousness is due to the fact that maximally entangled pure states are private and unshareable.

Dispersed silver nanoparticles (AgNPs) on the surface of titanium alloy (Ti6Al4V) and titanium alloy modified by titania nanotube layer (Ti6Al4V/TNT) substrates were produced by chemical vapor deposition method (CVD) using novel precursor of the formula [Ag₅(O₂CC₂F₅)₅(H₂O)₃]. The structure and volatile properties of this compound were determined using single crystal X-ray diffractometry, variable temperature IR spectrophotometry (VT IR), and electron inducted mass spectrometry (EI MS). The morphology and the structure of the produced Ti6Al4V/AgNPs, and Ti6Al4V/TNT/AgNPs composites were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Moreover, measurements of hardness, Young’s modulus, adhesion, and surface free energy have been carried out. The ability to release silver ions from the surface of produced nanocomposite materials immersed in PBS solution has been estimated using inductively coupled plasma mass spectrometry (ICP MS). The wettability and the surface free energy of samples were estimated on the base of contact angle studies with the use of water and diiodomethane. Among the studied surface-modified titanium alloy implants, the best nano-mechanical properties were noticed for the Ti6Al4V/TNT15/AgNPs composite. The location of silver nanoparticles inside of titania nanotubes caused their lowest release rate, which may indicate on suitable properties above mentioned type of the composite for the construction of implants with a long term of antimicrobial activity.

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

Diamidophosphate has been identified as a possible prebiotic compound used in the precursor membranes of the first ‘life’. Compounds such as these will be helpful in developing novel biomimetic approaches in synthetic chemistry. Thermochemical data for this type of compounds are not available. Hess’ law and estimates from calorimetric measurements used by Wakefield in the 1970s for other amido phosphates have been used to estimate the thermochemical values for the diamido and monoamido-phosphoric acid. Enthalpy of formation at 298.15 ^oC is calculated as – 821.9 kJ/mol and the free energy of formation calculated as -813.5 kJ/mol for the diamidophosphoric acid. The calculated enthalpy of formation of monoamidic phosphoric acid is -1117.1 kJ/mol and its free energy of formation is - -1105 kJ/mol.

The relationship of the animal with its environment has been of longstanding interest in philosophy and science. Here I provide a brief introduction to concepts that place an emphasis on mutualism as the basis of organism - environment interaction, in contrast to the long standing view that the environment exerts an instrumental role in shaping the organism. Two influential theories have been von Uexküll’s theory of umwelt and Gibson’s theory of affordances. The former envisioned the animal as immersed in its surroundings (umwelt) to form a functional unit. In a similar manner, the latter theory describes a unity between 1) environmental information that provides the animal with opportunities for action (affordances) and 2) the ability of the animal to perceive and engage with those affordances. These views have influenced more recent ecological models of the organism as the functional unit of biology and have also influenced models of immune function. In ecological models, agency is seen as the ability of the organism to predict and control its engagement with the environment in order to maintain its integrity. The predominant contemporary model of neural function in which perception and action are understood to operate through Bayes-like active inference complements the concept of agency as proposed by the mutualism models. However, it is suggested that rather than a constant mutualism, encounters between organism and environment range over a dynamic spectrum from dualism to mutualism. It is also suggested that along this spectrum, agency emerges when the balance of instrumentality shifts from the environment to the organism, and that the balance of this relationship can further progress towards a felicitous mutualism. Meaning emerges between environmental information and an agent as opportunity for action. Implications for opportunities to foster agency in animals within our care is noted.

In this paper we investigate some properties of square-free numbers. In particular, we study a function that counts the number of square-free numbers no larger than the given number n. We show that this function has asymptotics consistent with the predictions of the Riemann hypothesis and use this to obtain new and better estimates of the density of square-free numbers. Finally, we present a well-known generalization of the concept of a square-free number to monoids and research on square-free factorizations.

This paper explores the suppression of ideas within academic scholarship by academics, either by self-suppression or because of the efforts of other academics. Legal, moral, and social issues distinguishing freedom of speech, freedom of inquiry, and academic freedom are reviewed. How these freedoms and protections can come into tension is then explored by an analysis of denunciation mobs who exercise their legal free speech rights to call for punishing scholars who express ideas they disapprove of and condemn. When successful, these efforts, which constitute legally protected speech, will suppress certain ideas. Real-world examples over the past five years of academics who have been sanctioned or terminated for scholarship targeted by a denunciation mob are then explored.

The study of the surface thermodynamic properties of solid materials is primordial for the determination of the dispersive surface energy, polar enthalpy of adsorption and Lewis’s acid base properties of solid particles. Inverse gas chromatography technique (IGC) at infinite dilution is the best surface technique for the determination of the surface physicochemical properties of materials. (1) Background: This paper was devoted to study the surface properties of solid materials such as alumina particles by using IGC technique. (2) Methods: Different methods and molecular models such as spherical, cylindrical, van der Waals, Redlich-Kwong, Kiselev and geometric models, were used to determine the London dispersive surface energy of solid surfaces. Hamieh model was also used and highlighted the thermal effect on the surface area of solvents. (3) Results: The variations of the dispersive surface energy and the free energy of adsorption were determined for alumina particles as a function of the temperature as well as their Lewis’s acid base constants. Alumina surfaces were proved to exhibit a strong Lewis amphoteric character three time more basic than acidic (4) Conclusions: The new methodology based on Hamieh model gave the more accurate results of the physicochemical properties of the particle surfaces.

A theoretical account of development in mesocortical anatomy is derived from the free energy principle, operating in a neural field with both Hebbian and anti-Hebbian neural plasticity. An elementary structural unit is proposed, in which synaptic connections at mesoscale are arranged in paired patterns with mirror symmetry. Exchanges of synaptic flux in each pattern form coupled spatial eigenmodes, and the line of mirror reflection between the paired patterns operates as a Markov blanket, so that prediction errors in exchanges between the pairs are minimized. The theoretical analysis is then compared to the outcomes from a biological model of cortical neurodevelopment, in which neuron precursors are selected by apoptosis for cell body and synaptic connections maximizing synchrony and also minimizing axonal length. It is shown that this model results in patterns of connection with the anticipated mirror symmetries, at micro-, meso- and inter-arial scales, among lateral connections, and in cortical depth, explaining the spatial organization and functional significance of neuron response preferences, and compatible with features of both columnar and noncolumnar cortex. Multi-way interactions of mirrored representations provide a preliminary anatomically realistic model of cortical information processing.

Tapping panel dryness (TPD) syndrome is a complex disease of Rubber tree (Hevea brasiliensis L.) which causes cessation of latex drainage upon tapping of rubber tree. Rubber tree virus (RTV1) was identified as a novel pathogen associated with rubber tree and a potential causal agent of TPD. RTV1 is a monopartite RNA virus that is linear, non-enveloped and has a single-stranded (ss) positive RNA genome of approximately 6081 nucleotides and is composed of two major open reading frames (ORFs), ORF1 (polyprotein), and ORF2 (movement protein. This study aimed to investigate the possibility of rubber genome encoded tree microRNAs (miRNAs) as novel therapeutic targets against RTV1 using in silico algorithms. Mature rubber tree miRNAs are retrieved from the miRBase database and are used for hybridization of RTV1 using five different five different computational algorithms including miRanda, RNA22, RNAhybrid and psRNATarget. A total of eleven common rubber tree miRNAs were identified based on consensus genomic positions. The consensus of four algorithms predicted the hybridization sites of hbr-miR396a and hbr-miR398 at common locus positions 6676, 1840 respectively. To validate the prediction, secondary structures of the consensual rubber tree miRNAs and free energy of duplex binding were calculated using the RNAfold and RNAcofold algorithms respectively. We created a plot between rubber tree miRNAs and RTV1 ORFs by using Circos algorithm. In this study, we predicted eleven consensual rubber tree miRNAs. Among these miRNAs, hbr-miR398 was identified as the most effectual miRNA that may target the ORF1 gene of the RTV1 genome. The predicted data will be important in the development of rubber trees resistant to RTV1.

This review covers some of the central relationships between artificial intelligence, psychology, and economics through the lens of information theory, specifically focusing on formal models of decision-theory. In doing so we look at a particular approach that each field has adopted and how information theory has informed the development of the ideas of each field. A key theme is expected utility theory, its connection to information theory, and the Bayesian approach to decision-making and forms of (bounded) rationality. What emerges from this review is a broadly unified formal perspective derived from three very different starting points that reflect the unique principles of each field. Each of the three approaches reviewed can, in principle at least, be implemented in a computational model in such a way that, with sufficient computational power, they could be compared with human abilities in complex tasks. However, a central critique that can be applied to all three approaches was first put forward by Savage in {\it The Foundations of Statistics} and recently brought to the fore by the economist Binmore: Bayesian approaches to decision-making work in what Savage called `small worlds' but cannot work in `large worlds'. This point, in various different guises, is central to some of the current debates about the power of artificial intelligence and its relationship to human-like learning and decision-making. Recent work on artificial intelligence has gone some way to bridging this gap but significant questions still need to be answered in all three fields in order to make progress on these problems.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assisted. It is especially relevant for sensor nodes location in UWSNs. Global Positioning System (GPS) is not suitable for using in UWSNs because of the underwater propagation problems. Hence some localization algorithms based on the precise time synchronization between sensor nodes have been proposed which are not feasible for UWSNs. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme base on the Particle Swarm Optimization (PSO) algorithm to decrease the localization error. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence in this algorithm, we use a small number of mobile beacons to help achieve location without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.

In the framework of mean field approximation, we consider a spin system consisting of two interacting sub-ensembles: spins interactions with in each sub-ensemble are ferromagnetic, while the inter-ensemble interactions are antiferromagnetic. We define the effective number of the nearest neighbors, and show that if the two sub-ensembles have the same effective number of the nearest neighbors, the classical form of critical exponents (, , , ) gives way to the non-classical form (, , , ), and the scaling function changes simultaneously. We demonstrate that this system allows for two second-order phase transitions and two first-order phase transitions. We observe that an external magnetic field does not destroy the phase transitions, but only shifts their critical points, allowing for control of the system’s parameters. We discuss the regime when the magnetization as a function of the magnetic field develops a low-magnetization plateau, and show that the height of this plateau abruptly rises to the value of one when the magnetic field reaches a critical value. Our analytical results are supported by a Monte Carlo simulation of a three-dimensional layered model.

Alzheimer’s disease is the most common neurodegenerative disease and affects persons of all races, ethnic groups, and sexes. The disease is characterized by neuronal loss leading to cognitive decline and memory loss. There is no cure and the effectiveness of existing treatments is limited and depends on the time of diagnosis. The long prodromal period, during which patients’ ability to live a normal life is not affected despite neuronal loss, often leads to a delayed diagnosis because it can be mistaken for normal aging of the brain. In order to make a substantial impact on AD patients, early diagnosis may provide a greater therapeutic window for future therapies to slow AD-associated neurodegeneration. Current gold standards for disease detection include magnetic resonance imaging and positron emission tomography scans, which visualize amyloid β and phosphorylated tau depositions and aggregates. Liquid biopsies, already an active field of research in precision oncology, are hypothesized to provide early disease detection through minimally or non-invasive sample collection techniques. Liquid biopsies in Alzheimer’s disease have been studied in cerebrospinal fluid, blood, ocular, oral, and olfactory fluids. However, most of the focus has been on blood and cerebrospinal fluid due to biomarker specificity and sensitivity attributed to the effects of the blood-brain barrier and inter-laboratory variation during sample collection. Many studies have identified amyloid β and phosphorylated tau levels as putative biomarkers, however, advances in next-generation sequencing-based liquid biopsy methods have led to significant interest in identifying nucleic acids species associated with Alzheimer’s disease from liquid tissues. Differences in cell-free RNAs and DNAs have been described as potential biomarkers for AD and hold the potential to affect disease diagnosis, treatment, and future research avenues.

Raw materials used for producing concrete, such as sand and gravel, are in short supply worldwide. It has been reported that the production of cement, one of the main constituents of concrete, results in the emission of a large amount of CO₂, accounting for 8% of total global CO₂ emissions. In this study, we developed a method to produce a construction material using only sand as the solid raw material. By utilizing a technique to produce organic silicon material from sand, we placed sand, alcohol, and catalyst in a closed vessel and heated it to 240 °C. After 24 h, the sand particles were bonded to each other, and a hardened body was formed. A tradeoff in production conditions, such as temperature, time, and the amount of sand, was confirmed.

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.

Bioenergetics, genetic coding, and catalysis are all difficult to imagine emerging without pre-existing historical context. That context is often posed as a “Chicken and Egg” problem; its resolution is concisely described by de Grasse Tyson: “the egg was laid by a bird that was not a chicken”. The concision and generality of that answer furnish no details—only an appropriate framework from which to examine detailed paradigms that might illuminate paradoxes underlying these three life-defining biomolecular processes. We examine experimental aspects here of five examples that all conform to the same paradigm. The paradox in each example is resolved by coupling if, and only if, conditions for two related transitions between levels. One drives, and each restricts fluxes through, or “gates” the other. That reciprocally-coupled gating, in which two gated processes constrain one another, maps onto the formal structure of “strange loops”. That mapping may help unite the axiomatic foundations of genetics, bioenergetics, and catalysis. As a physical analog for Gödel’s logic, biomolecular strange-loops provide a natural metaphor around which to organize these data, linking biology to the physics of information, free energy, and the second law of thermodynamics.

The Thermodynamic Formalism provides a rigorous mathematical framework to study quantitative and qualitative aspects of dynamical systems. At its core there is a variational principle and corresponding, in its simplest form, to the Maximum Entropy principle, used as a statistical inference procedure to represent, by specific probability measures (Gibbs measures), the collective behaviour of complex systems. This framework has found applications in different domains of scienThe Thermodynamic Formalism provides a rigorous mathematical framework to study quantitative and qualitative aspects of dynamical systems. At its core there is a variational principle and corresponding, in its simplest form, to the Maximum Entropy principle, used as a statistical inference procedure to represent, by specific probability measures (Gibbs measures), the collective behaviour of complex systems. This framework has found applications in different domains of science, in particular, has been fruitful and influential in neurosciences. In this article, we review how the Thermodynamic Formalism can be exploited in the field of theoretical neuroscience, as a conceptual and operational tool, to link the dynamics of interacting neurons and the statistics of action potentials from either experimental data or mathematical models. We comment on perspectives and open problems in theoretical neuroscience that could be addressed within this formalism.ce, in particular, has been fruitful and influential in neurosciences. In this article, we review how the Thermodynamic Formalism can be exploited in the field of theoretical neuroscience, as a conceptual and operational tool, to link the dynamics of interacting neurons and the statistics of action potentials from either experimental data or mathematical models. We comment on perspectives and open problems in theoretical neuroscience that could be addressed within this formalism.

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

Facebook (FB) is the most popular online networking platform. There are several FB pages dedicated to spreading awareness about the Celiac disease (CD). To get the latest information, a huge number of CD patients follow Celiac disease Facebook (CD-FB) pages. Such pages frequently post beneficial information. However, very less is known if they provide appropriate information to CD patients. We conducted this study to know if CD-FB pages spread misleading information to CD patients. CD-FB pages from three celiac-influenced countries were explored using the FB platform and Google search engine. From October 2021 to April 2022, a total of 147 CD-FB, Italy (n=63), the USA (n=46), and India (n=38), were found eligible. Of them, 13% of pages (followers Mean±SD; Italy 2478±2011; USA 12635±12486; India 667±313) shared misleading information, particularly about gluten-free ingredients, and treatment of CD. In total,16% of CD-FB pages discussed alternative treatments option. Surprisingly, 7% of pages (followers Mean±SD; USA 23800±10465; India 628±333) supported alternative treatments for CD. CD-FB pages are useful for disseminating celiac-related information. While most of such pages provide useful information, a few pages sometimes contain misleading information. CD patients must consult their treating unit before following any uncertain information posted on CD-FB pages.

In this paper, we look at how Artificial Swarm Intelligence can evolve using evolutionary algorithms that try to minimize the sensory surprise of the system. We will show how to apply the free-energy principle, borrowed from statistical physics, to quantitatively describe the optimization method (sensory surprise minimization), which can be used to support lifelong learning. We provide our ideas about how to combine this optimization method with evolutionary algorithms in order to boost the development of specialized Artificial Neural Networks, which define the proprioceptive configuration of particular robotic units that are part of a swarm. We consider how optimization of the free-energy can promote the homeostasis of the swarm system, i.e. ensures that the system remains within its sensory boundaries throughout its active lifetime. We will show how complex distributed cognitive systems can be build in the form of hierarchical modular system, which consists of specialized micro-intelligent agents connected through information channels. We will also consider the co-evolution of various robotic swarm units, which can result in development of proprioception and a comprehensive awareness of the properties of the environment. And finally, we will give a brief outline of how this system can be implemented in practice and of our progress in this area.

The mutual information between the state of a neural network and the state of the external world represents the amount of information stored in the neural network that is associated with the external world. In contrast, the surprise of the sensory input indicates the unpredictability of the current input. In other words, this is a measure of inference ability, and an upper bound of the surprise is known as the variational free energy. According to the free-energy principle (FEP), a neural network continuously minimizes the free energy to perceive the external world. For the survival of animals, inference ability is considered to be more important than simply memorized information. In this study, the free energy is shown to represent the gap between the amount of information stored in the neural network and that available for inference. This concept involves both the FEP and the infomax principle, and will be a useful measure for quantifying the amount of information available for inference.

Lead halide perovskite has become a promising candidate for high-performance photodetector (PD) applications due to its attractive optical and electrical properties such as high optical absorption coefficient, high carrier mobility, and long carrier diffusion length. However, the presence of highly toxic lead in these devices has limited their practical applications and even hindered their progress toward commercialization. Therefore, the scientific community has been committed to searching for low-toxic and stable perovskite-type alternative materials. Lead-free double perovskite materials, which are still in the preliminary stage of exploration, have achieved inspiring results in recent years. In this review, we mainly focused on two types of lead-free double perovskite based on different Pb substitution strategies, including A2M(I)M(Ⅲ)X6 and A2M(IV)X6. We reviewed the research progress and prospects of lead-free double perovskite photodetectors in the past three years. And more importantly, from the perspective of optimizing inherent defects in materials and improving device performance, we proposed some feasible pathways and made an encouraging perspective for the future development of lead-free double perovskite photodetectors.

In cancer, the lymphatic system is hijacked by tumor cells to escape from primary tumor and to metastasize to the sentinel lymph nodes. Tumor lymphangiogenesis is stimulated by the vascular endothelial growth factors-C (VEGFC) after binding to its receptor VEGFR-3. However, how VEGFC cooperates with other molecules to promote lymphatic neovessels growth is not fully determined. Here, we found that tumor lymphangiogenesis developed in tumoral lesions and in their surrounding adipose tissue (AT). Interestingly, lymphatic vessel density correlated with an increase of circulating free fatty acids (FFA) in the lymph from tumor-bearing mice. We found that adipocyte-released FFA are uploaded by lymphatic endothelial cells (LEC) to stimulate their sprouting. Lipidomic analysis identified the monounsaturated oleic acid (OA) as the major circulating FFA in the lymph in tumoral context. OA transporters FATP-3, -6 and CD36 were only upregulated on LEC in the presence of VEGFC showing a collaborative effect of these molecules. OA released from adipocytes is taken up by LECs to stimulate the fatty acid β-oxidation, leading to increase adipose tissue lymphangiogenesis. Our results provide new insights on the dialogue between tumors and adipocytes via the lymphatic system and identify a key role for adipocyte-derived FFA in the promotion of lymphangiogenesis, revealing novel therapeutic opportunities for inhibitors of lymphangiogenesis in cancer.

In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has ac-cumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 848 reconstructed patients, 9 trials were analyzed. The survival data from these trials were pooled into three types of treatments: i) treatments based on ty-rosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs as-sociated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. This multi-treatment Kaplan-Meier graph, generated through the Shiny method, summarized the current evidence on these treatments in both qualitative and quantitative terms.

This manuscript employs a surface stress-driven nonlocal model to explore the combined effects of long-range interaction and surface energy on higher vibration modes of functionally graded nanobeams. The nanobeam theory, based on Bernoulli-Euler kinematics, incorporates surface effects such as surface elasticity, surface residual stresses, surface density, and rotary inertia. Hamilton's principle is applied to derive the governing equation with size-dependent considerations. The main outcomes of a parametric investigation, considering four different kinematic boundary conditions (Cantilever, Simply-Supported, Clamped-Pinned, and Doubly-Clamped) while varying the nonlocal parameter and material gradient index, are presented and discussed. Additionally, the normalized natural frequencies for the second, third, fourth and fifth modes of vibrations are provided and analyzed for each case under study. The results underscore the model's effectiveness in capturing surface energy effects on the overall dynamic behavior of functionally graded Bernoulli-Euler nanobeams, offering a cost-effective approach for designing and optimizing nano-scaled structures.

The strength of laser joined metal and plastic hybrids is based purely on adhesion. Unpolar plastics like polypropylene depend solely on the mechanical adhesion while polar plastics like polyamide 6.6 develop covalent bonds with the metal. In this research the influence of different surface metallizations on the lap shear strength of laser joined hybrids was investigated. Sandblasted AISI 304 was used as base metal and reference. Aluminum and titanium coatings were deposited by the means of Arc-PVD. Polypropylene and polyamide 6.6 were utilized as polar und unpolar plastics. The lap shear strength of all hybrids with polyamide 6.6 was higher than the polypropylene samples. For all investigated variations of the laser power, scanning speed and the cohesive and adhesive failure modes, the samples joined with the sandblasted AISI 304 showed the highest lap shear strength. The reduction in lap shear strength for the coated samples was due to the increased difference in thermal conductivity between the plastics and the coating materials. This lead to increased warping and residual stresses. It can be concluded that the thermal properties of the metallization in laser joined metal and plastic hybrids has a high impact on the lap shear strength.

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

: In Philadelphia chromosome positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated about the efficacy of low-intensity and chemo-free regimens. Our objective was to analyse all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyse Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 562 reconstructed patients, 8 trials were analyzed. The survival data from these trials were pooled into three types of treatment: i) treatments based on tyrosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); ii) TKIs associated to steroids with no chemotherapy (TKISTE); iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. In conclusion, the multi-treatment Kaplan-Meier graph generated in this study has effectively summarized the current evidence on these treatments in comparative terms.

An attempt is made to model the atomic nucleus as a combination of bound and free or unbound nucleons. Due to strong interaction, bound nucleons help in increasing nuclear binding energy and due to electroweak interaction, free or unbound nucleons help in decreasing nuclear binding energy. In this context, with reference to proposed 4G model of final unification and strong interaction, recently we have developed a unified nuclear binding energy scheme with four simple terms, one energy coefficient of 10.1 MeV and two small numbers 0.0016 and 0.0019. In this paper, by eliminating the number 0.0019, we try to fine tune the estimation procedure of number of free or unbound nucleons pertaining to the second term with an energy coefficient of 11.9 MeV. It seems that, some kind of electroweak interaction is playing a strange role in maintaining free or unbound nucleons within the nucleus. It is possible to say that, strong interaction plays a vital role in increasing nuclear binding energy and electroweak interaction plays a vital role in reducing nuclear binding energy. Interesting observation is that, Z can be considered as a characteristic representation of range of number of bound isotopes of Z. For medium, heavy and super heavy atoms, beginning and ending mass numbers pertaining to bound states can be understood with 2Z+0.004Z^2 and 3Z+0.004Z^2 respectively. With further study, neutron drip lines can be understood. Based on this kind of data fitting procedure and by considering the mass ratio of pions and electroweak bosons, existence of our 4G model of electroweak fermion of rest energy 584.725 GeV can be confirmed confidently.

Wastewater contaminated with antibiotics is a major environmental challenge. We developed here the green synthesis of bio-graphenes by using natural precursors (Xanthan, Chitosan, Boswellia, Tragacanth). The use of these precursors can act as templates to create 3D doped graphene structures with special morphology. Also, this method is a simple method for in-situ synthesis of doped graphenes. The elements present in the natural polymers (N) and other elements in the natural composition (P, S) are easily placed in the graphene structure and improve the catalytic activity due to the structural defects, surface charges, increased electron transfers, and the high absorption. In this mechanism, O2 dissolved in water absorbs onto the positive charged C in doped graphenes to create oxygenated radicals, which enables the degradation of antibiotic molecules. Light irradiation increases the amounts of radicals and rate of antibiotic removal. The results have shown that the hollow cubic Chitosan-derived graphene has shown the best performance due to the doping of N, S, and P. The Boswellia-derived grapheme shows the highest surface area, but lower catalytic performance, which indicates the more effective role of doping in the catalytic activity. The effect of oxygen and light were also studied to accelerate the degradation process.

An imbalance in any metabolic system can be traced to its homeostasis. When homeostatic environment is not attainable then there will be a response from the body. A new shift has emerged, “the negative feedback effect of high fructose consumption;” more pain than gain. The human metabolic system daily combat fructose sugar metabolism which emanates from high consumption. This inadvently lead to a chronological series of complications arising from the feedback. These feedbacks play pivotal roles in skeletal muscle damage and other body frameworks, it also fosters toxic advanced glycation end products (AGEs), factors that impose and inflict damaging effects to the body`s energy currency and serious threat to health. These damages are missed or overlooked because of early nonspecific physiological symptoms. High level of fructose has both long- and short-term effects on human metabolic processes. These effects which are majorly through the production of reactive oxygen species (ROS) and other free radicals, are felt in the disruption of biomolecules such as causing DNA mutation, lipid peroxidation etc. these effects in turn lead to various diseases such as cancer, diabetes, atherosclerosis, and other health issues. In this review, we will focus on the damaging effects this sugar has on human health and the present solutions being applied. We will also look at the next step in combatting and controlling these negative feedbacks.

Background: Traditional omic analysis relies on p-value and fold change as selection criteria. There is an ongoing debate on their effectiveness in delivering systemic and robust interpretation, due to their dependence on assumptions of conformity with various parametric distributions.Here, we propose a threshold-free selection method based on robust, non-parametric statistics, ensuring independence from the statistical distribution properties and broad applicability. Such methods could adapt to different initial data distributions, contrary to statistical techniques based on fixed thresholds. Methods: Our work extends the Rank Products methodology with a neutral selection method of high information-extraction capacity. We introduce the calculation of the RP distribution’s entropy to isolate the features of interest by their contribution to the distribution’s information content. The aim is a methodology performing threshold-free identification of the differentially expressed features, which are highly informative about the phenomenon under scrutiny. Conclusions: Applying the proposed method on microarray (transcriptomic and DNA methylation) and RNAseq count data of varying sizes and noise presence, we observe robust convergence for the different parameterisations to stable cutoff points. Functional analysis through BioInfoMiner and EnrichR was used to evaluate the information potency of the resulting feature lists. Overall, the derived functional terms provide a systemic description highly compatible with the results of traditional statistical hypothesis testing techniques. The methodology behaves consistently across different data types. The feature lists are compact and information-rich, indicating phenotypic aspects specific to the tissue and biological phenomenon i nvestigated. Selection by information content measures efficiently addresses problems, emerging from arbitrary thresholding, thus facilitating the full automation of the analysis.

Considering Games with the broad definition proposed by Juul (Juul, 2010), consequences outside of the magic circle can be negotiated. This definition opens up the possibility to define serious games, games developed with an utilitarian goal in mind, in addition to fun. The entertaining and utilitarian objectives may however be contradictory, leading serious games to be, more often than not, less than optimal in at least one of the two dimensions. Another way to play with the boundaries of games is to consider pervasive games, which include alternate reality games, and crossmedia games (Montola, 2005). We question here the limit between game, play and toy in the context of a mixed reality serious game. ‘Pangu’ is a game designed for bachelor students, with biochemistry as the utilitarian objective, and the origin of life as a game theme. The students are asked to play the game on their smartphone, which in turn ask them to build molecules with a tangible balls-and-sticks model typically used in chemistry classes. Pictures taken from the models allow users to ‘scan’ these models and progress in the game. The use of the game was observed in four opportunities. An unanticipated observation is that, in addition to expected behaviors, some students used briefly the models like a toy rather than in the context of the game. It is therefore tempting to speculate that the pervasive nature of the game is blurring the game/non game boundary and, in the context of this serious game, opens a door for fun.

Despite the uptake of tobacco smoking declining in the UK, smoking is still the leading cause of preventable poor health and premature death. While improved approaches to smoking cessation are necessary, encouraging and assisting smokers to switch by using substantially less toxic non-tobacco nicotine products may be a possible option. To date few studies have investigated the rates of smoking cessation and smoking reduction associated with the free provision of electronic-cigarettes (e-cigarette) to smokers. In this study the Blu Pro e-cigarette was given to smokers for use in place of tobacco for 90 days. The rates of smoking abstinence and daily smoking patterns were assessed at baseline 30 days, 60 days and 90 days. The response rate was 87%. After 90 days, the complete abstinence rate was 36.5% from 0% at baseline. Frequency of daily smoking reduced from 88.7% to 17.5% (P<0.001) and median consumption of cigarettes/day from 15 to 5 (P<0.001). Median days per month participants smoked also dropped from 30 to 13 after 90-days (P<0.001). On the basis of these results there may be value in smoking cessation services and other services ensuring that smokers are provided with e-cigarettes at zero or minimal costs for at least a short period of time.

This paper investigates if the polar groups induced by a plasma treatment can increase the lap shear strength of laser joined metal and plastic hybrids. Optimal laser joining parameters for cold-rolled AISI304 – Polyamide 6.6 and sandblasted AISI304 - Polypropylene hybrids are developed. The OWRK-method was utilized to identify the change in surface free energy of a low-pressure plasma treatment. Plasma treated samples were joined and tested. The fractured surfaces were investigated via light microscopy and SEM. The arithmetic means of the plasma treated hybrids lap shear strength with polyamide 6.6 varied slightly but all measured values were within the range of the untreated samples. The lap shear strengths of the polypropylene hybrids were significantly reduced. This was attributed to an overaging and the development of low molecular weight oxidized materials which lead to a weak boundary layer. No correlation between surface free energy and the lap shear strength could be found.

Humanity faces serious social and environmental problems, including climate change and biodiversity loss. Risks are increasing and conditions deteriorating. Increasingly, scientists, global policy experts, and the general public conclude that incremental approaches are insufficient and transformative change is needed across all sectors of society. However, the meaning of transformation is still unsettled in the literature, as is the proper role of science in fostering it. This paper is the first in a three-part series that adds to the discussion by proposing a novel science-driven research-and-development program aimed at societal transformation. More than a proposal, it offers a perspective and conceptual framework from which societal transformation might be approached and understood. While acknowledging the necessity of reform to existing societal systems (e.g., governance, economic, and financial systems), the focus of the series is on transformation understood as systems change or systems migration—the de novo development of and migration to new societal systems. The series provides definitions, aims, reasoning, worldview, and a theory of change, and discusses fitness metrics and design principles for new systems. This first paper proposes a worldview built using ideas from evolutionary biology, complex systems science, cognitive sciences, and information theory that is intended to serve as the foundation for the R&amp;D program.

Issues related to safe and abundant energy production have been prominent in recent years. This is particularly tr ue when society considers how to increase the quality of life by providing low-cost energy to citizens. A significant concern of the Gulf Cooperation Council (GCC) relates to the environmental effects of energy production and energy use associated with climate change. Efforts to reduce fossil fuel use and increase the use of renewable energy, together with the price volatility of fossil fuels, have seriously impacted the economics of many of the oil-producing countries, particularly the Gulf States, which has led to efforts to make their economies more diverse and less dependent on oil production.

The world is facing an energy crisis. Governments are seeking to provide universal energy access and guarantee energy security while trying to mitigate climate change. One possible solution is energy transitions towards low carbon energy systems. Among other things (physical infrastructure, public policy and regulatory enablers and knowledge and capacities) changes in the energy systems require a well informed and participative citizenship. Within this context the concept of energy literacy appears. Energy literacy is the understanding of how energy is generated, transported, stored, distributed and used, awareness about its environmental and social impacts and the knowledge to use it efficiently in the different sectors of the economy. This paper provides a systematic literature review in the Web of Science’s Core Collection. Most of the work done around energy literacy addresses its evaluation among different groups, particularly students at different levels, and the construction, application and evaluation of tools for improving energy literacy. Other frequently studied issues are the influence of energy literacy in decision making, its drivers and conceptual research about the topic. Energy enables citizens to effectively contribute to energy efficiency and sustainable development, nevertheless energy literacy is not strongly correlated to energy consumption habits.

Quercetin is a flavonoid with a low molecular weight that belongs to the human diet's phenolic phytochemicals and non-energy constituents. Quercetin has a potent antioxidant capacity, being able to capture Reactive Oxygen Species (ROS), reactive nitro-gen species (RNS), and Reactive Chlorine Species (ROC), which act as reducing agents by chelating transition metal ions. Its structure has five functional hydroxyl groups, which work as electron donors and are responsible for capturing free radicals. In addition to its antioxidant capacity, it was described different pharmacological properties of Quercetin, such as carcinostatic properties, antiviral, antihypertensive, anti-inflammatory, protection of Low-Density Lipoprotein (LDL) oxidation, and inhibi-tion of angiogenesis are developed in this review.

Pancakes are fast food snacks that are generally made with the basic ingredients of wheat flour, which is an imported commodity and detrimental for people who are allergic to gluten. To reduce the use of wheat, alternative raw materials derived from local commodities are used, such as modified cassava flour (mocaf), arrowroot flour, and suweg flour. The experiment was carried out by mixing mocaf flour, arrowroot flour, and suweg flour to produce composite flour with a ratio of 70:15:15 (CF1), 70:20:10 (CF2), and 70:20:5 (CF3). The result showed that the ratio of mocaf flour, arrowroot flour, and suweg flour had a significant effect on pasting temperature, peak viscosity, hold viscosity, breakdown viscosity, setback, L*, a*, hue, whiteness, ∆E, as well as swelling volume and solubility on the characteristics of the composite flour It also had a significant effect on the texture characteristics of hardness, adhesiveness, chewiness, color characteristics L*, a*, whiteness, ∆E, and preference for the flavor of gluten-free pancake products. It is known that the best formulation for the resulting pancake product is P1, with the addition of a 70% ratio of mocaf flour, 15% ratio of arrowroot tuber flour, and 15% ratio of suweg flour.

Background: Free-living amoebas (FLA), also amebas, are eukaryotic and mitochondrial microorganisms that are capable of growing in any environment, aquatic or terrestrial. These free-living amoebas are mostly non-pathogenic to humans. However, there exist some highly pathogenic species, such as Acanthamoeba — mainly T-4 genotype —, Naegleria fowleri (known as brain-eating amoeba), and Balamuthia mandrillaris. They can be called "brain-eating amoebas” because of their ability to cause substantial destruction of brain tissue. There is no standard treatment; immunological processes which predispose humans to acquire and infection and, then, a disease are unknown. In addition, there are other species of free-living amoebas such as, Sappinea pedata, Vermamoeba vermiformes, Vanellas sp,Vahlkampfia sp., and, more recently, Paravahlkampfia francinae, which is less virulent and aggressive than the first three mentioned above. Methods: All CSF samples were evaluated in our laboratory under the microscope. Monoxenic and axenic cultures were negative as well as the presence of cysts or exponential growth. PCR was negative using the FLA primers. Results: Under close observation of sterile CSF, we can see mobile forms of non-human cells. None of the observed forms has the morphotype of Acanthamoeba, Naegleria sp. or Balamuthia mandrillaris. Conclusions: Due to these findings, we know these structures can be observed in the CSF and many of them do not form cysts as others do. In addition, these microorganisms are uncultivable in conventional medium culture to FLA and impossible to detect even when using molecular tools such as PCR, using the primers for EUK A/B or 18s RNAr gene as a target.

Consciousness is usually perceived as a state of being aware of one’s environment as well as self. Despite its omnipresence in our life, understanding this concept is challenging. This has given rise to several theories attempting to explain the nature of consciousness, as well as hard and soft problems of consciousness. In fact, the boundaries of consciousness defined by these theories are a topic of continued discussion, particularly in light of the recent advances in artificial intelligence (AI). Some of these theories consider consciousness as a simple integration of information while others purport the need for an agency in the process of integration for an entity to be considered conscious. Some theories consider consciousness as a graded entity and some equate consciousness with content of awareness. In this work, major theories of consciousness are reviewed and compared, focusing on awareness, attention, and sense of self. These findings are interpreted in relation to AI in order to ascertain what makes AI distinct from natural intelligence.

Consciousness is usually interpreted as a state of being aware of one’s environment as well as self, while awareness is understood as knowledge of something. Despite their semantic differences, in philosophy, these terms are often used interchangeably, as is the case of the hard problem of consciousness proposed by Chalmers, which in fact is the hard problem of awareness. Trilogy paradigm of consciousness (or simply “trilogy”) offers a new paradigm where consciousness is the result of a unique interaction between awareness and the decision-making process. By conferring the input of awareness to the decision-making process, a new mental function of awareness-based choice selection (ABCS) or true free will emerges. Likewise, application of the power of decision-making to the process of awareness gives rise to discretionary selection of information for awareness (DSIA) or intentional attention. The intertwined actions of ABCS and DSIA comprise “I” which is the faculty of our consciousness and is what sets natural intelligence (NI) apart from artificial intelligence (AI). Based on trilogy, mind is an unconscious compilation of all mental function excluding ABCS and DSIA that are the essence of consciousness. As humans, we are a union of “I,” our minds, and our bodies.

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be a specific diameter (~500 m), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNF stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

The term sustainable energy is very familiar to all of us yet its exact definition or meaning has so far been vague. To date the widely adopted definition of sustainable energy has been inspired by the definition of sustainable development formulated more than 30 years ago in the Our Common Future - the UN’s Report of the World Commission on Environment and Development. The current definition conceals the true spirit of the Report and this has some ramifications. It raises the question as to whether we have put too much emphasis on attaining the future dimension of sustainability in the middle of the situation where the energy survivability is in fact the real issue in many parts of the world. In this paper the role of energy in sustaining livelihoods of low income communities is discussed. Existing definition of sustainable energy that the whole world seems to have embraced is looked at critically and its downsides exposed. The identified pillars of sustainable energy and the associated issues is discussed and the need for an additional pillar, i.e. affordability is discussed and called for. This paper will argue that global definition of sustainable energy seems inappropriate and should be jettisoned and a more realistic definition should be formulated, adopted and embraced at local (i.e. national or regional) level taking into account local attributes and factors. The current push for a transition from the reliance on conventional energy sources to ‘cleaner’ energy sources (generally associated with renewable energy) has further exacerbated the issue of energy affordability that has made the conditions even more dire for so many groups of the world population. In the midst of this situation, those who push for a rushed energy transition seem to be those who also produce unsustainably high carbon footprint but who can easily offset their carbon foot-print through the ‘net-zero’ concept.

Earth’s climate cannot be ignored any longer. Policies are vital in order to mitigate the negative effects of climate change. The energy crisis created by the Russo-Ukrainian war and pandemic affected the EU and its member states. The focus is more than ever on its energy policies and independence. The EU revised the energy strategy in response to Russia’s blackmail, and it sped up all the processes for energetic independence from Russia. This benefited the climate change policies the most, as all the measures involved reducing energy consumption and increasing renewables, thus contributing to reducing greenhouse gas emissions. As a member state of the EU, Romania is committed to complying with EU regulations. With a high degree of energy independence compared with the other EU members, Romania plans to become a regional energy provider and modernize the energy infrastructure internally as a response to Russia’s unprovoked aggression. The measures that the EU and Romania implemented after the war started in 2022 have come to fruition, and the effects are becoming visible a year later. This study aims to study the energy strategy of Romania in correlation with the EU strategy in the turbulent period of pandemics and war between 2019 and 2023, with the latest available data.

Pteridine reductase 1 is a trypanosomatid multifunctional enzyme that provides a mechanism for escape of Dihydrofolate reductase (DHFR) inhibition. This is because PTR1 can reduce pterins and folates. Trypanosomes require folates and pterins for survival and are unable to synthesize them de novo. Currently there are no anti-folate based Human African Trypanosomiasis (HAT) chemotherapeutics in use. Thus, successful dual inhibition of TbDHFR and TbPTR1 has implications in the exploitation of anti-folates. We carried out molecular docking of a ligand library of 5742 compounds against TbPTR1 and identified 18 compounds showing promising binding modes. The protein-ligand complexes were subjected to Molecular dynamics to characterize their molecular interactions and energetics followed by in vitro testing. In this study, we identified five potential TbPTR1 inhibitors that showed low micromolar Trypanosome growth inhibition in in vitro experiments with no significant human cell cytotoxicity. Compounds RUBi004, RUBi007, RUBi014, and RUBi018 displayed moderate to strong antagonism when used in combination with the known TbDHFR inhibitor, WR99210. This gave an indication that the compounds might inhibit both TbPTR1 and TbDHFR. RUBi016 showed an additive effect in the isobologram assay. Our results provide a basis for scaffold optimization for further studies in the development of HAT antifolates.