In this work we have critically reviewed the processes in high-temperature sublimation growth of graphene in Ar atmosphere using enclosed graphite crucible. Special focus is put on buffer layer formation and free charge carrier properties of monolayer graphene and quasi-freestanding monolayer garphene on 4H-SiC. We show that by introducing Ar at different temperatures, TAr one can shift to higher temperatures the formation of the buffer layer for both n-type and semi-insulating substrates. A scenario explaining the observed suppresed formation of buffer layer at higher TAr is proposed and discussed. Increased TAr is also shown to reduce the sp3 hybridization content and defect densities in the buffer layer on n-type conductive substrates. Growth on semi-insulating substrates results in ordered buffer layer with significantly improved structural properties, for which TAr plays only a minor role. The free charge density and mobility parameters of monolayer graphene and quasi-freestanding monolayer graphene with different TAr and different environmental treatment conditions are determined by contactless terahertz optical Hall effect. An efficient annealing of donors on and near the SiC surface takes place in intrinsic monolayer graphene grown at 2000∘C, and which is found to be independent of TAr. Higher TAr leads to higher free charge carrier mobility parameters in both intrinsically n-type and ambient p-type doped monolayer graphene. TAr is also found to have a profound effect on the free hole parameters of quasi-freestanding monolayer graphene. These findings are discussed in view of interface and buffer layer properties in order to construct a comprehensive picture of high-temperature sublimation growth and provide guidance for growth parameters optimization depending on the targeted graphene application.

This article is devoted to Feller's diffusion equation which arises naturally in probabilities and physics (e.g. wave turbulence theory). If discretized naively, this equation may represent serious numerical difficulties since the diffusion coefficient is practically unbounded and most of its solutions are weakly divergent at the origin. In order to overcome these difficulties we reformulate this equation using some ideas from the Lagrangian fluid mechanics. This allows us to obtain a numerical scheme with a rather generous stability condition. Finally, the algorithm admits an elegant implementation and the corresponding Matlab code is provided with this article under an open source license.

Data collected at the Cascais tide gauge, located on the west coast of Portugal Mainland, have been analyzed and sea level rise rates have been updated. Based on a bootstrapping linear regression model and on polynomial adjustments, time series are used to calculate different empirical projections for the 21^st century sea level rise, by estimating the initial velocity and its corresponding acceleration. The results are consistent to an accelerated sea level rise, showing evidence of a faster rise than previous century estimates. Based on different numerical methods of second order polynomial fitting, it is possible to build a set of projection models of relative sea level rise. Appling the same methods to regional sea level anomaly from satellite altimetry, additional projections are also built with good consistency. Both data sets, tide gauge and satellite altimetry data, enabled the development of an ensemble of projection models. The relative sea level rise projections are crucial for national coastal planning and management since extreme sea level scenarios can potentially cause erosion and flooding. Based on absolute vertical velocities obtained by integrating global sea level models, neo-tectonic studies and permanent Global Positioning System (GPS) station time series, it is possible to transform relative into absolute sea level rise scenarios, and vice-versa, allowing the generation of absolute sea level rise projection curves and its comparison with already established global projections. The sea level rise observed at the Cascais tide gauge has always shown a significant correlation with global sea level rise observations, evidencing relatively low rates of composed vertical land velocity from tectonic and post-glacial isostatic adjustment, and residual synoptic regional dynamic effects rather than a trend. An ensemble of sea level projection models for the 21st century is proposed with its corresponding probability density function, both for relative and absolute sea level rise for the west coast of Portugal Mainland.

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.

Eddy current based approaches have been investigated for a wide range of inspection applications. Dodd-Deeds model and the truncated region eigenfunction expansion (TREE) method are widely applied in various occasions, mostly for the cases that the sample is relatively larger than the radius of the sensor coil. The TREE method converts the integral expressions to the summation of many terms in the truncated region. In a recent work, the impedance of the co-axial air-cored sensor due to a plate of finite radius was calculated by the modified Dodd-Deeds analytical approach proposed by authors. In this paper, combining the modified analytical solution and the TREE method, a new finite region eigenfunction expansion (FREE) method is proposed. This method involves modifying its initial summation point from the first zero of the Bessel function to a value related to the radius of the plate, therefore makes it suitable for plate with finite dimensions. Experiments and simulations have been carried out and compared for the verification of the proposed method. Further, the planar size measurements of the metallic circular plate can be achieved by utilising the measured peak frequency feature.

This paper provides a framework for the assessment of household-level risk, incorporating both a individual social risk perspective and a location-based perspective. We use this framework as a heuristic to explore the effect of social reintegration choices individuals face, which are not be addressed by current policies. For example, we explore how integrating extended family households during COVID-19 without social distancing may affect household and community risk. The goal is to aid individual decision makers, who are seeking to maintain quality-of-life while navigating local policy, with nuance relating to location-specific behavior and disease prevalence.

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.

Among the most important variables in the design of falling film microreactors (FFMRs) is the liquid film thickness as well as the gas/liquid interfacial area, which dictate the mass and heat transfer rates. In a previous work conducted in our lab the characteristics of a free-falling Newtonian liquid film have been studied and appropriate correlations have been proposed. In this work the geometrical characteristics of a non-Newtonian shear thinning liquid, flowing in an inclined open microchannel, have been experimentally investigated and design correlations that can predict with reasonable accuracy the features of a FFMR have been proposed. The test section used was an open μ-channel with square cross section (Wo=1200 μm) made of brass which can be set to various inclination angles. The liquid film characteristics were measured by a non-intrusive technique that is based on the features of a μ-PIV system. Relevant CFD simulations revealed that the volume average dynamic viscosity over the flow domain is practically the same as the corresponding asymptotic viscosity value, which can thus be used in proposed the design equations. Finally, a generalized algorithm for the design of FFMRs, containing non-Newtonian shear thinning liquids, is suggested.

In this article we explore the limiting behavior of the universal prior distribution obtained when applied over multiple meta-level hierarchy of programs and output data of a computational automata model. We were motivated to alleviate the effect of Solomonoff's assumption that all computable functions or hypotheses of the same length are equally likely, by weighing each program in turn by the algorithmic probability of their description number encoding. In the limiting case, the set of all possible program strings of a fixed-length converges to a distribution of self-replicating quines and quine-relays - having the structure of a constructor. We discuss how experimental algorithmic information theory provides insights towards understanding the fundamental metrics proposed in this work and reflect on the significance of these result in digital physics and the constructor theory of life.

This paper shows that by applying the Nyquist-Shannon sampling theorem, the spatial and temporal resolution of a simulation can be no more than half the resolution of the simulating reality. This has significant implications for not only the values of the observables in the simulation but also its physical laws. This progressive halving of nested simulations coupled with the minimum resolution compatible with the production of a simulation also sets a limit to the nestedness of a lineage of simulations (it is by no means infinite). The limit of nestedness is then used to calculate the probability that we are living in a simulation assuming a single base reality. This will be shown to be significantly lower than popular expectation. A Kardashev-like scale, with three variants, is also developed to gauge the technological advancement of a civilization in relation to the extent to which it can extract information from space and time.

In this paper, the definition of information entropy of Smoluchowski coagulation equation for Brownian motion is introduced based on coagulation probability. The expression of entropy is the function of geometric average particle volume and standard deviation with lognormal distribution assumption. The asymptotic solution with moment method shows that the entropy is a monotone increasing function of time, which is equivalence to the entropy based on particle size distribution. the result reveals that the present definition of entropy of Smoluchowski coagulation equation are inadequate because the particle average volume at equilibrium cannot be determined from the principle of maximum entropy. This provides a basis for further exploring the global properties of Smoluchowski coagulation equation.

Tobacco Free Nicotine (TFN) Electronic Nicotine Delivery Systems (ENDS) are yet to be classified as tobacco products; consequently, there is ambiguity over whether Food and Drug Administration (FDA) regulatory authority can be extended to include TFN e-cigarettes. In recent years, a more significant number of e-cigarette companies have been manufacturing TFN-containing e-cigarettes and e-liquids to circumvent FDA regulations. While studies have shown that aerosols generated from tobacco-derived nicotine-containing e-cigarettes contain significant Reactive Oxygen Species (ROS) levels, no comparison studies have been conducted using TFN e-cigarettes. This study uses a single puff aerosol generator to aerosolize TFN and tobacco-derived nicotine-containing vape-products and subsequently involves semi-quantifying ROS generated by these vape products in H2O2 equivalents. We found that the differences between ROS levels generated from TFN and tobacco-derived nicotine-containing vape products vary by flavor. TFN tobacco flavors and fruit flavors are more toxic in terms of ROS generation than menthol/ice and drink/beverage flavored products using TFN. The type of salt nicotine used in vape products, TFN or tobacco-derived nicotine, impacts the level of ROS generated from flavored vape products. Thus, a better understanding of the type of salt nicotine used in e-cigarettes (tobacco-derived or synthetic), has modulating effect on lung oxidative stress.

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.

Probability is an open question in the ontological interpretation of quantum mechanics. It has been discussed in some trajectory interpretations such as Bohmian mechanics and stochastic mechanics. New questions arise when the domain of probability extends to the complex space, including the generation of complex trajectories, the definition of the complex probability, the relation of the complex probability to the real quantum probability, and so on. The complex treatment proposed here applies the optimal quantum guidance law to derive the stochastic differential (SD) equation governing the particle’s random motions in the complex plane. The ensemble of the complex quantum random trajectories (CQRTs) solved from the complex SD equation is used to construct the probability distribution ρc(t,x,y) of the particle’s position over the complex plane z=x+iy. The correctness of the obtained complex probability is confirmed by the solution of the complex Fokker-Planck equation. The significant contribution of the complex probability is that it can be used to reconstruct both quantum probability and classical probability, and to clarify their relationship. Although quantum probability and classical probability are both defined on the real axis, they are obtained by projecting complex probability onto the real axis in different ways. This difference explains why the quantum probability cannot exactly converge to the classical probability when the quantum number is large.

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.

In public health literature the risk of death or disease associated with a dietary, environmental of behavioral factor is most commonly denoted by odds ratio (OR), hazard ratio (HR) or risk ratio (RR). The ratio indices have several desirable statistical properties. However, the most important question is whether there are some evolved innate norms of perception of risk that people use and what they are. We conducted a simple one question survey of 98 individuals with different age, sex, educational and professional backgrounds. The respondents were asked to judge the relative perceived risk of four different hypothetical habits for which data on the percentage of people affected by the disease with and without the habit was given. They were asked to rank the risks for the four habits. Results showed that the habits that had the highest difference between probability of acquiring the disease were ranked high on risk perception. The probability ratios did not affect risk perception significantly. Further age, sex, profession or formal training in statistics did not affect the response significantly. Even individuals that were formally trained to use OR and HR as risk indicators, preferred using probability differences over ratios for judging their own risk in the perceived context. This preliminary inquiry into intuitive statistical perception suggests that designing statistical indices based on people’s innate perception may be a better strategy than trying to train people to understand the indices designed by expert statisticians.

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.

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.

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.

We conducted a comparative study on the development of two synthetic methods. The solvent-free synthesis is a green chemistry method developed in a bid to ameliorate environmental adverse effects of the conventional solvent-based synthesis. The synthesis of novel dichloro and polymethoxy p-nitrophenylhydrazones through solvent free technique gave moderate to high yields which were however lower than those of the solvent-based method. The established solvent-free approach has several benefits, including universality and simplicity of the approach, catalyst-free conditions, non-use of an organic solvent, quick reaction time, fast and efficient workup, and un-solvated pure products in moderate to high yields.

While paresthesia-based spinal cord stimulation (SCS) has been proven effective to treat chronic neuropathic pain, initial benefits may lead to the development of “Failed SCS Syndrome’ (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neu-rostimulation adapters, in patients already implanted with SCS and experienced LoE. We retro-spectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before, and at 1, 3, 6 and 12-month follow-up. Outcomes included pain intensity rating with Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N=27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and Quality of Life (p=0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompa-nied by paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conver-sion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled by spatial retargeting. In light of these results, adapters could be integrated to SCS rescue algorithms or should be considered in SCS rescue.

Probabilistic inference problems have very broad practical applications. To solve this kind of problems under conditions of certainty, an effective mathematical apparatus has been developed. In real situations, obtaining deterministic estimates of relevant probabilities is often difficult; therefore, problems with handling uncertain estimates of probabilities appear. This paper examines the problem of probabilistic inference with probability trees provided that the initial probabilities are given in the form of intervals of their possible values.

Monitoring is an essential component in ecosystem management and leveraging existing data sources for multiple species of interest can be one effective way to enhance information when making management decisions. Here we analyzed juvenile Chinook Salmon (Oncorhynchus tshawytscha) bycatch data that has been collected by the recently established Enhanced Delta Smelt Monitoring program (EDSM), a survey designed to estimate the abundance and distribution of the San Francisco Estuary’s (estuary) endangered Delta Smelt (Hypomesus transpacificus). Two key aspects of the EDSM program distinguish it from other fish surveys in the estuary: a stratified random sampling design and the spatial scale of its sampling effort. We integrated the EDSM dataset with other existing surveys in the estuary and used an occupancy model to assess detection probability differences across gear types. We saw no large-scale differences in size selectivity, and while detection probability varied among gear types, cumulative detection probability for EDSM was comparable to other surveys due to the program’s use of replicate tows. Based on our occupancy model and sampling effort in the estuary during spring of 2017 and 2018, we highlighted under-sampled regions that saw improvements in monitoring coverage due to EDSM. Our analysis also revealed that each sampling method has its own benefits and constraints. Although the use of random sites with replicates as conducted by EDSM can provide more statistically robust abundance estimates relative to traditional methods, the use of fixed stations and simple methods such as beach seine may provide a more cost-effective way of monitoring salmon occurrence in certain regions of the estuary. Stronger inference on salmon abundance and distribution can be made by leveraging the strengths of each survey’s method. Careful consideration of these trade-offs is crucial as the management agencies of the estuary continue to adapt and improve their monitoring programs.

Protein import into the endoplasmic reticulum (ER) is the first step in the biogenesis of about 10,000 different soluble and membrane proteins in humans. It involves co- or post-translational targeting of precursor polypeptides to the ER and their subsequent membrane insertion or translocation. So far, three pathways for ER targeting of precursor polypeptides plus four pathways for ER targeting of mRNAs were described. Typically, these pathways deliver their substrates to the Sec61 polypeptide-conducting channel in the ER membrane. Next, the precursor polypeptides are inserted into the ER membrane or translocated into the ER lumen, which may involve auxiliary translocation components, such as the TRAP and Sec62/Sec63 complexes, or auxiliary membrane protein insertases, such as EMC and the TMCO1 complex. Recently, the PEX19/PEX3-dependent pathway, which has a well-known function in targeting and inserting various peroxisomal membrane proteins into pre-existent peroxisomal membranes, was also found to act in targeting and, putatively, inserting monotopic hairpin proteins into the ER. These either remain in the ER as resident ER membrane proteins or are pinched off from the ER as components of new lipid droplets. Therefore, the question arose if this pathway may play a more general role in ER protein targeting, i.e. represents a fourth pathway for ER targeting of precursor polypeptides. Thus, we addressed the client spectrum of the PEX19/PEX3-dependent pathway in both PEX3-depleted HeLa cells and PEX3-deficient Zellweger patient fibroblasts by an established approach, which involves label-free quantitative mass spectrometry of the total proteome of depleted or deficient cells and differential protein abundance analysis. The negatively affected proteins included twelve peroxisomal proteins and two hairpin proteins of the ER, thus confirming two previously identified classes of putative PEX19/PEX3-clients in human cells. Interestingly, fourteen collagen-related proteins with signal peptides or N-terminal transmembrane helices and belonging to the secretory pathway were also negatively affected by PEX3-deficiency, which may suggest compromised collagen biogenesis as a hitherto unknown contributor to organ failures in the respective Zellweger patients.

It is claimed that classical mechanics (CM) in terms of its equivalent Koopman-von Neumann formulation (KvN) is indeed a ’real’ quantum theory since the formalism of quantum mechanics (FQM) does not, nor need it, exclude it as a such. This claim is made manifest by suggesting a common structure of which both KvN and ordinary quantum mechanics (OQM) correspond to unitary representations of, although unitarily inequivalent such. It is shown that OQM is obtained by enforcing the extra physical condition of quantized energy levels, which by itself does not constitute the ’quantum mystery’. It is furthermore shown that KvN in a physically realizable sense contain the hallmark quantum behavior of quantum interference. It is hence concluded that both CM and OQM are subjected to the same foundational issues. As the central part of both KvN and OQM is the introduction of probabilities via FQM it is suggested that the foundational issues regarding FQM are less about FQM itself and more about the concept of probability.

Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.

The development of smart negative electrode materials with high capacitance for use in supercapacitors remains challenging. Although there have been several types of electrode materials with high capacitance used in energy storage, carbon-based materials are the most reliable electrodes due to their high conductivity, high power density and excellent stability. The most common complaint about general carbon materials is that these as-formed electrode materials can hardly ever be used as free-standing electrodes. Free-standing carbon-based electrodes are in high demand and are a passionate topic of energy storage research. Electrospun nanofibers are a potential candidate to fill this gap. However, the as-spun carbon nanofibers (ECNFs) have low capacitance and energy density on their own. To this end, several attempts have been made to improve these characteristics. In this review, we introduce negative electrode materials that have been developed. Moreover, this review places special attention to the advances of electrospun nanofiber-based negative electrode materials and their limitations. Based on the above information, we put forth a future perspective on how these limitations can be overcome to meet the demands of next-generation smart devices.

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.

Pairs of pyrrolysyl-tRNA synthetase (PylRS) and tRNAPyl from Methanosarcina mazei and Methanosarcina barkeri are widely used for site-specific incorporations of non-canonical amino acids into proteins (genetic code expansion). Previously, we achieved full productivity of cell-free protein synthesis for bulky non-canonical amino acids, including Ne-((((E)-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (TCO*Lys), by using Methanomethylophilus alvus PylRS with structure-based mutations in and around the amino acid binding pocket (first-layer and second-layer mutations, respectively). Recently, the PylRS•tRNAPyl pair from a methanogenic archaeon ISO4-G1 was used for genetic code expansion. In the present study, we determined the crystal structure of the methanogenic archaeon ISO4-G1 PylRS (ISO4-G1 PylRS) and compared it with those of structure-known PylRSs. Based on the ISO4-G1 PylRS structure, we attempted the site-specific incorporation of Ne-(p-ethynylbenzyloxycarbonyl)-L-lysine (pEtZLys) into proteins, but it was much less efficient than that of TCO*Lys with M. alvus PylRS mutants. Thus, the first-layer mutations (Y125A and M128L) of ISO4-G1 PylRS, with no additional second-layer mutations, increased the protein productivity with pEtZLys up to 578% of that with TCO*Lys, at high enzyme concentrations in the cell-free protein synthesis.

The article continues the author's publications about the matrix-tensor study of universal rules of stochastic (probabilistic) organization of long single-stranded DNA sequences in eukaryotic and prokaryotic genomes. The author reveals that corresponding matrices of probabilities of n-plets in n-textual representations of each genomic DNA are numerically interrelated each with other in such algebraic form, which has analogies with formalisms of the known tensor-matrix theory of digital antenna arrays. These arrays combine many separate antennas into a single coordinated ensemble with unique emergent properties, due to which antenna arrays are widely used in devices of medicine, astrophysics, avionics, etc. The noted analogies allow putting forward the author's hypothesis that the stochastic organization of genomic DNAs is connected with bio-antenna arrays. From the point of view of this hypothesis, many known facts about using principles of antenna arrays in inherited physiological phenomena are collected in a single grouping with genomic DNAs. This new topic about the biological meaning of profitable properties of antenna arrays includes problems of biological evolution, the origin of the genetic code, regenerative medicine, and the development of algebraic biology. These issues are discussed jointly with the author's results of quantum information analysis of stochastic features of genomic DNAs.

This article presents, for the first time, the kinetics and the general conversion features of a 3-initiator system (A/B/N), based on proposed mechanism of Mokbel et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using copper complex as the initiator. Higher FRP and CP conversion can be achieved by co-initiators concentration [B] and [N], via the dual function of (i) regeneration [A], and (ii) generation of extra radicals S' and S. The FRP and CP conversion is proportional to, respectively, the nonlinear and linear power of bI[A][B], where b and I are the absorption coefficient and the light intensity, respectively. System in air has lower conversion than in laminate due to the oxygen inhibition effects. For thick samples (with thickness z), there is an optimal concentration [A*] which is inverse proportional (bzI), in contrast with very thin sample, in which the conversion is an increasing function of [A] and [B]. The unique feature of dark polymerization in CP conversion enables the polymerization to continue in living mode, in contrasts with that of the radical-mediated pathway in most conventional FRP. The measured results of Mokbel et al are well analyzed and matching the predicted features of our modeling.

The relative operating characteristic (ROC) curve is a popular diagnostic tool in forecast verification, with the area under the ROC curve (AUC) used as a verification metric measuring the discrimination ability of a forecast. Along with calibration, discrimination is deemed as a fundamental probabilistic forecast attribute. In particular, in ensemble forecast verification, AUC provides a basis for the comparison of potential predictive skill of competing forecasts. While this approach is straightforward when dealing with forecasts of common events (e.g. probability of precipitation), the AUC interpretation can turn out to be oversimplistic or misleading when focusing on rare events (e.g. precipitation exceeding some warning criterion). How should we interpret AUC of ensemble forecasts when focusing on rare events? How can changes in the way probability forecasts are derived from the ensemble forecast affect AUC results? How can we detect a genuine improvement in terms of predictive skill? Based on verification experiments, a critical eye is cast on the AUC interpretation to answer these questions. As well as the traditional trapezoidal approximation and the well-known bi-normal fitting model, we discuss a new approach which embraces the concept of imprecise probabilities and relies on the subdivision of the lowest ensemble probability category.

Structural displacement is an important metric for assessing structural conditions because it has a direct relationship with the structural stiffness. Many bridge displacement measurement techniques have been developed, but most methods require fixed reference points in the vicinity of the target structure which limits field implementations. A promising alternative is to use reference-free measurement techniques that indirectly estimate the displacement by using measurements such as acceleration, and strain. This paper proposes novel reference-free bridge displacement estimation by the fusion of single acceleration with pseudo-static displacement derived from co-located strain measurements. First, we propose a conversion of the strain at the center of a beam into displacement based on the geometric relationship between strain and deflection curves with reference-free calibration. Second, an adaptive Kalman filter is proposed to fuse the displacement generated by strain with acceleration by recursively estimate the noise covariance of displacement from strain measurements which is vulnerable to measurement condition. Both numerical and experimental validations are presented to demonstrate the efficiency and robustness of the proposed approach.

Ischemia/reperfusion (I/R) injury results in cell death by inducing apoptosis. During I/R, early generation of mitochondrial reactive oxygen species (mtROS) can induce neighboring mitochondria to release additional ROS, a toxic cycle resulting in significant mitochondrial and cellular injury. Oxidative damage in the mitochondria contributes to various pathologies, including I/R injury. Accordingly, preventing mitochondrial oxidative damage should be therapeutically relevant for many disorders, including cardiovascular diseases. We recently discovered an Indole-Peptide-Tempo Conjugate (IPTC) that served as a novel bifunctional agent with both antioxidant and autophagy-modulating capacity. Here, we demonstrate that IPTC can protect H9C2 cardiomyocytes from hypoxia/reoxygenation (H/R) injury that results from mtROS overproduction due to impaired mitophagy and resultant mitochondrial dysfunction. We hypothesize that the mechanism of action of IPTC involves the capacity to decrease mtROS combined with induction of mitophagy.

Bacteria a Microscopic organisms are the most inexhaustible and flexible of microorganisms and constitute a huge division of the whole living earthly biomass, certain microorganisms were found to amass metallic components at a high limit Was Known as Bacterial Bio-sorption Due to their little size, capacity to become under controlled conditions, and their Accommodation to an extensive variety of ecological situations; Potent metal bio-sorbents among microorganisms, at low pH esteems, cell divider ligands are protonated and contend essentially with metals for official. With expanding pH, more ligands, such as amino and carboxyl groups, could be exposed, leading to attraction between these negative charges and the metals, and consequently increment bio-sorption onto the cell surface. Starting with Isolation and identification of heavy metal-resistant bacteria from rock Ore. Studying Factors Affecting Uranium Bio-sorption, Optimization of bacterial growth conditions and optimum for metal uptake by free and immobilized bacterial cells and Desorption ratio of uranium ions adsorbed by Coli. /alginate, All this evidence suggest that functions groups Represented in our study are responsible for metal uptake in our bacterial biomass beside change in peaks position which assigned for it's groups confirm bio-sorption of metal ions from waste due to ions charge interaction comparing with immobilized we found increase in no of binding sites indicate that immobilized bacterial have high efficiency for metal up take which also change in peaks position which assigned for its groups confirm bio-sorption of metal ions from waste due to ions charge interaction, Where the high bio-sorption yield obtained by bacteria, the Uranium & heavy metal bioremediation process expects microorganisms to be joined to a strong surface.

Pieron's and Chocholle’s seminal psychophysical work predicts that human response time to information relative to visual contrast and/or sound frequency decreases when contrast intensity or sound frequency increases. The goal of this study is to bring to the fore the ability of individuals to use visual contrast intensity and sound frequency in combination for faster perceptual decisions of relative depth (“nearer”) in planar (2D) object configurations on the basis of physical variations in luminance contrast. Computer controlled images with two abstract patterns of varying contrast intensity, one on the left and one on the right, preceded or not by a pure tone of varying frequency, were shown to healthy young humans in controlled experimental sequences. Their task (two-alternative forced-choice) was to decide as quickly as possible which of two patterns, the left or the right one, in a given image appeared to “stand out as if it were nearer” in terms of apparent (subjective) visual depth. The results show that the combinations of varying relative visual contrast with sounds of varying frequency exploited here produced an additive effect on choice response times in terms of facilitation, where a stronger visual contrast combined with a higher sound frequency produced shorter forced-choice response times. This new effect is predicted by cross-modal audio-visual probability summation.

Glutathione peroxidases (GPxs) form a broad family of antioxidant proteins essential for maintaining redox homeostasis in eukaryotic cells. In this study, we used an integrative approach that combines bioinformatics, molecular biology, and biochemistry to investigate the role of GPxs in reactive oxygen species detoxification in the unicellular eukaryotic model organism Tetrahymena thermophila. Both phylogenetic and mechanistic empirical model analyses provided indications about the evolutionary relationships among the GPXs of Tetrahymena and the orthologous enzymes of phylogenetically related species. In-silico gene characterization and text mining were used to predict the functional relationships between GPxs and other physiologically-relevant processes. The GPx genes contain conserved transcriptional regulatory elements in the promoter region, which suggest that transcription is under tight control of specialized signaling pathways. The bioinformatic findings were next experimentally validated by studying the time course of copper (Cu)-dependent regulation of gene transcription and enzymatic activity. Results emphasize the role of GPxs in the detoxification pathways that, by complex regulation of Cu-dependent GPx gene expression, enables Tetrahymena to survive in high Cu concentrations and the associated redox environment.

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.

This paper studies the goodness of fit test for the bivariate Hermite distribution. Specifically, we propose and study a Cramér-von Mises-type test based on the empirical probability generation function. The bootstrap can be used to consistently estimate the null distribution of the test statistics. A simulation study investigates the goodness of the bootstrap approach for finite sample sizes.

Abstract: Power generation using dielectric elastomer (DE) artificial muscle is attracting attention because of its light weight, low cost, and high efficiency. Since this method is a system that produces electricity without emitting carbon dioxide nor using rare earths, it would contribute to the goal of environmental sustainability. In this paper, the background of DEs, the associated high-efficient wave energy generation (WEG) systems that we developed using DEs, as well as the latest development of its material are summarized. By covering the challenges we face and the achievements that we’ve reached, we can discuss the opportunities to build the foundation of a recycled energy society through the usage of these WEGs. On the other hand, to make these possibilities commercially successful, the advantages of DEs need to be integrated with traditional technologies. To achieve this, we also consider the method of using DEs alone and a system used in combination with an oscillating water column. Finally, the current status and future of DEGs are discussed.

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.

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.

Considering that the electric refrigeration temperature range of 0.94BNT-0.06BT ceramic materials is 100~140˚C, the electric refrigeration performance of the 0.94BNT-0.06BT ceramic material system was modified by LiNbO3 doping to reduce the cooling temperature. As a result, the refrigeration temperature range of the 0.94BNT-0.06BT ceramic material system was lowered to 25~80 ˚C, achieving its cooling effect near room temperature, and in this temperature range, the adiabatic temperature changes ∆T>0.6K.

In Lagrangian dynamics, the detection of coherent clusters can help understand the organization of transport by identifying regions with coherent trajectory patterns. Many clustering algorithms, however, rely on user-input parameters, requiring a priori knowledge about the flow and making the outcome subjective. Building on the conventional spectral clustering method of Hadjighasem et al (2016), a new parameter-free spectral clustering approach is developed that automatically identifies parameters and does not require any user-input choices. A noise-based metric for quantifying the coherence of the resulting coherent clusters is also introduced. The parameter-free spectral clustering is applied to two benchmark analytical flows, the Bickley Jet and the asymmetric Duffing oscillator, and to a realistic, numerically-generated oceanic coastal flow. In the latter case, the identified model-based clusters are tested using observed trajectories of real drifters. In all examples, our approach succeeded in performing the partition of the domain into coherent clusters with minimal inter-cluster similarity and maximum intra-cluster similarity. For the coastal flow, the resulting coherent clusters are qualitatively similar over the same phase of the tide on different days and even different years, whereas coherent clusters for the opposite tidal phase are qualitatively different.

This work aimed to develop an easy-to-use smartphone-based electrochemical biosensor to quickly assess coffee blend's total polyphenol (Phs) content at industrial and individual level. The device is based on a commercial carbon-based screen-printed electrode (SPE) modified with multi-walled carbon nanotubes (CNTs) and gold nanoparticles (GNPs). At the same time, the biotransducer, Laccase from Trametes versicolor, TvLac, was immobilized on the sensor surface by using glutaraldehyde (GA) as cross-linking agent. The platform was electrochemically characterized to ascertain the influence of the SPE surface modification on its performance. The working electrode (WE) surface morphology characterization was obtained by scanning electron microscopy (SEM) and Fourier-transform infrared (FT-IR) imaging. All the measurements were carried out with a micro-potentiostat Sensit Smart by PalmSens connected to a smartphone. The developed biosensor provided a sensitivity of 0.12 μA/μM, a linear response ranging from 5 to 70 μM, and a lower detection limit (LOD) of 2.99 μM. Afterwards, the biosensor was tested for quantifying the total Phs content in coffee blends, evaluating the influence of both the variety and the roasting degree. The smartphone-based electrochemical biosensor performance has been validated though the Folin-Ciocâlteu standard method.

This article presents, for the first time, the kinetics and the general conversion features of a 3-component system, BT(BC)/iodonium/Amine, based on proposed mechanism of Liu et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using the new multi-functional initiator of benzophenone–triphenylamine (BT). The additives, iodonium and EDB, have the dual function of (i) regeneration BT and (ii) produce of extra radicals for improved FRP and CP. Analytic formulas are developed to explore the new features including: (i) the conversion efficacy (CE) of FRP is an increasing function of the light intensity, the effective absorption coefficient, and the concentration sum of each of the components, BT, Iod, amine, for transient state. However, CE at steady-state is independent to the light intensity; (ii) the trifunctional hybrid structures of BT3 leads to larger light absorption than other types of BT; it also provides more active sites for the H-abstraction in the presence of EDB, leading to high CE; (iii) the efficacy of FRP is an increasing function of the amine (EDB) concentration, in contrast to that of CP having an opposite dependence; (iv) the consumption rate of BT3 in the BT3/ Iod/EDB system is slower than that of the BT3/Iod system due to photoredox catalytic cycle, and the larger initiator regeneration (RGE)
in the three-component system. A comprehensive model is also proposed that the CE (for both FRP and CP) is governed by (N_jK_jbI), whereas more complex formulas are developed; where Kj is an effective rate constant proportional to the electron transfer quantum yield, and the combined effects of other coupling rate constants; b is an effective absorption coefficient given by the light absorption and excited state quantum yield.

In this paper, we study a generalised CIR process with externally-exciting and self-exciting jumps, and focus on the distributional properties and applications of this process and its aggregated process. The first and second moments of this jump-diffusion process are used to calculate the insurance premium based on mean-variance principle. The Laplace transform of the aggregated process is derived, and this leads to an application for pricing default-free bonds which could capture the impacts of both exogenous and endogenous shocks. Illustrative numerical examples and comparisons with other models are also provided.

Lead-free ferroelectric perovskite N-methyl-N'-diazabicyclo[2.2.2]octonium)–ammonium triio-dide, MDABCO-NH₄I₃, nanocrystals are embedded in three different polymer fibers fabricated by the electrospinning technique. The nanofibers, which are very flexible and have a high Young modulus, behave as active piezoelectric energy harvesting sources that produce a piezoelectric voltage coefficient up to geff = 3.6 VmN-1 and show a blue intense luminescence band at 325 nm. In this work, the pyroelectric coefficient is reported for the MDABCO-NH₄I₃ perovskite inserted in electrospun fibers. At the ferroelectric-paraelectric phase transition, the embedded nanocrystals display a pyroelectric coefficient as high as 194×10-6 Cm-2k-1, within the same order of magnitude as that reported for the state-of-the-art bulk ferroelectric triglycine sulfate (TGS). The perovskite nanocrystals embedded into the polymer fibers remain stable, and no degradation is caused by oxidation.

This article presents, for the first time, the kinetics and the general conversion features of free radical polymerization (FRP) in a 3-component system (A/B/N), with [A] being the initiator, and [B] and [N] are additives, based on the proposed mechanism of Rahal et al. Higher FRP can be achieved by additives [B] and [N], via the dual function of (i) regeneration [A], and (ii) generation of extra radicals (R) via the radicals (S' and S) produced by N.The initiator (coumarin) shows a dual photo-oxidation and photo-reduction character for high efficacy. The FRP conversion efficacy (CE) depends not only on the property of the initiator [A], the additives [B] and [N}, but also the types of monomers. For example, when [A]=CoumC, [A]/NPG is more efficient than [A]/Iod, but revserse trend occurs in some monomers. However, 2-component systems (with CE=0% to 80%) are always less efficient than that of 3-component systems (with CE=70% to 86%, in TMPTA). Specific systems with [A]=coumarins, [B]=Iodonium salt, and N=NPG are analyzed. Analytical formulas for the role of each component concentration, light intensity and coupling rates on the conversion efficacy are derived.

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.

In this paper, we present and analyze a compact inner-wall grating slot microring resonator (IG-SMRR) with the footprint of less than 13 μm × 13 μm on the SOI platform for label-free sensing, which comprises a slot microring resonator (SMRR) and inner-wall grating (IG). Its detection range is significantly enhanced without the limitation of the free spectral region (FSR) owing to the combination of SMRR and IG. Structural parameters of IG and SMRR are investigated and optimized for favorable transmission properties. The simulation results shows that the IG-SMRR has an ultra-large quasi-FSR of 84.6 nm, and the concentration sensitivities of sodium chloride solutions and D-glucose solutions are up to 960.61 pm/% and 933.06 pm/%, respectively. The investigation on the combination of SMRR and IG is a valuable exploration of label-free sensing application for ultra-large detection range and ultra-high sensitivity in future.

Cancer stem cells play a crucial role in tumor initiation, metastasis and therapy resistance. Cellular heterogeneity and plasticity challenge the isolation of cancer stem cells. The impact of intratumoral cellular heterogeneity in the context of treatment resistance using a label-free approach remains understudied. Here, we use the sedimentation field-flow fractionation technique to separate, without labeling, cell subpopulations of colorectal cancer cell lines and primary cultures according to their biophysical properties. One of the three cell subpopulations sorted by SdFFF exhibits cancer stem cell traits, including high tumorigenicity in vivo, and a higher frequency of tumor-initiating cells compared to the other subpopulations. In vitro two- and three-dimensional chemosensitivity assays emphasize the therapeutic relevance of this cancer stem cell-like subpopulation due to its chemoresistance. Therefore, our findings highlight a label-free cell sorting approach to reveal intratumoral cellular heterogeneity and its implication in therapy resistance. This approach enables the study of the individualized response of each sorted cell subpopulation by breaking down the tumor, thus offering new perspectives for personalized therapy.

Ageing is the strongest known risk factor for many of the neurodegenerative diseases causing cognitive decline and dementia. Identification of cognitive impairment may be a prelude to appropriate treatment, hopefully disease-modifying. Use of cognitive screening instruments may be an equitable way to identify cognitive impairment. This study examined the use of two such instruments, Free-Cog and Mini-Addenbrooke’s Cognitive Examination (MACE), in patient cohorts referred to a dedicated cognitive disorders clinic based at a tertiary neurosciences centre. Results showed that: (1) specificity and positive predictive value increased with patient age for both tests with some loss of sensitivity and negative predictive value. (2) In the oldest age groups (≥75 and ≥70 years respectively) where specificity was at maximum, a positive test result (i.e. below the specified test cut-off) rules in the diagnosis of cognitive impairment. (3) Values of an “Efficiency Index” for each test indicated qualitatively a moderate change in the probability of correct diagnosis and quantitatively an approximately 15-25% increase in the probability of correct diagnosis. These findings show that both Free-Cog and MACE may be used with confidence for the identification of cognitive impairment and dementia in older patient cohorts. These findings may have implications for public health policies directed to case-finding in clinical practice as opposed to population-based screening.

In this paper we describe and exploit a geometric framework for Gibbs probability densities and the associated concepts in statistical mechanics, which unifies several earlier works on the subject, including Souriau's symplectic model of statistical mechanics, its polysymplectic extension, Koszul model, and approaches developed in quantum information geometry. We emphasize the role of equivariance with respect to Lie group actions and the role of several concepts from geometric mechanics, such as momentum maps, Casimir functions, coadjoint orbits, and Lie-Poisson brackets with cocycles, as unifying structures appearing in various applications of this framework to information geometry and machine learning. For instance, we discuss the expression of the Fisher metric in presence of equivariance and we exploit the property of the entropy of the Souriau model as a Casimir function to apply a geometric model for energy preserving entropy production. We illustrate this framework with several examples including multivariate Gaussian probability densities, and the Bogoliubov-Kubo-Mori metric as a quantum version of the Fisher metric for quantum information on coadjoint orbits. We exploit this geometric setting and Lie group equivariance to present symplectic and multisymplectic variational Lie group integration schemes for some of the equations associated to Souriau symplectic and polysymplectic models, such as the Lie-Poisson equation with cocycle.

. This article presents, for the first time, the kinetics and the general conversion features of a 3-component system (A/B/N), based on proposed mechanism of Mau et al, for both free radical polymerization (FRP) of acrylates and the free radical promoted cationic polymerization (CP) of epoxides using various new copper complex (G2) as the initiator. Higher FRP and CP conversion can be achieved by co-additive of [B] and N, via the dual function of (i) regeneration [A], and (ii) generation of extra radicals. The FRP and CP conversion efficacy (CE) are proportional to the nonlinear power of bI[A][B], where b and I are the effective absorption coefficient and the light intensity, respectively. In the interpenetrated polymer network (IPN) capable of initiating both FRP and CP in a blend of TMPTA and EPOX, (as the monomer for FRP and CP, respectively), the synergic effects due to CP include:: (i) CP can increase viscosity limiting the diffusional oxygen replenishment, such that oxygen inhibition effects are reduced; (ii) the cationic monomer also acts as a diluting agent for the IPN network , and (iii) the exothermic property of the CP. Many new findings are explored via our analytical formuals include: (i) the CE of FRP is about twice of the CE of CP, due to the extra radicals involved in FRP; (ii) the catalytic cycle enhancing the efficacy is mainly due to the regenaration of the initiator, and (iii) the nonlinear dependence of light intensity of the CE (in both FRP and CP). For the first time, the catalytic cycle, synergic effects, and the oxygen inhibition are theoretically confirmed to support the experimental hypothesis. The measured results of Mau et al are well analyzed and matching the predicted features of our modeling. .

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.

Monitoring crown closure evolution using multi-temporal Light Detection and Ranging (LiDAR) surveys is a method that we expect to be increasingly adopted given the availability of LiDAR sensors and the accumulating survey archives. However, little attention was devoted to comparing crown closure estimates from independent surveys. Although survey parameters cannot be modified after the data collection, we speculate that the error associated to crown closure estimates comparison can be reduced by selecting optimal post-survey parameters. In this study, we compared crown closure estimates of three airborne LiDAR surveys from 2018 (40 pt/m²) used as a reference, and two lower-density surveys from 2016 (4.5 pt/m²) and 2018 (2 pt/m²). We studied the effect of the height threshold used to separate canopy points and the grid resolution, using skewness and variance of lagged difference of crown closure. Crown closure estimates using low height thresholds were more different across surveys, resulting in higher root mean squared error (RMSE), bias and more different variograms. Results show that optimal height threshold was 3 m and grid resolution was 25 m, although there was room for decision (RMSE of 7% and 5%, and bias of 4% and 0% for 2016 and 2018 low-density surveys).

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.

In this study, we investigate the performance of the saddlepoint approximation of the probability mass function and the cumulative distribution function for the weighted sum of independent Poisson random variables. The goal is to approximate the hazard rate function for this complicated model. The better performance of this method is shown by numerical simulations and comparison with a performance of other approximation methods.

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.

In this paper a high-power and propellant-free electromagnetic propulsion is proposed based on the General Relativity and nuclear fusion technology. We find that Riemann curvature vanish and geodesic motion is free from gravitational field locally in a special space-time, which demonstrates the feasibility of propellant-free electromagnetic propulsion. To achieve high-power propulsion in Schwarzschild background, we choose current loop as axisymmetric field source and obtain exact solution of Einstein-Maxwell field equation using Killing symmetry and Ernst generation technique. An implementation with superconductor shield is given according to the Meissner effect, calculation implies that the device can be sufficiently free from gravitational field with the aid of existing nuclear fusion engineering.

Post-translational modifications (PTMs) represent a cornerstone in the complexity of the proteome, significantly contributing to diversifying protein structure and function. PTMs can significantly influence protein function, stability, localization, and interactions with other molecules. Therefore, it is important when choosing a protein expression system to ensure the precise incorporation of PTMs during protein synthesis, which is paramount for producing biologically active proteins. Cell-free protein synthesis (CFPS) system has emerged as a powerful protein synthesis platform and research toolkit in synthetic biology. The open nature of the system allows the reaction environment to be tailored to any protein of interest to promote specific PTMs, thus allowing for the production of a protein with the desired modifications. This review presents various PTMs achieved in the CFPS systems, providing insights into the current challenges, successes, and future prospects.

. This article presents, for the first time, the kinetics and the general features of a photopolymerization system (under visible light) G1/ Iodonium/ TEA/gold chloride (or A/B/N/G), having initial concentrations of A0, B0, N0 and G0, based on the proposed mechanism of Tar et al. Analytic formulas are developed to explore the new features including: (i) both FRP efficacy and the production of nanogold (NG) are proportional to the relative concentration ratios of (A0+B0+N0)/G0, which may be optimized for maximum efficacy; (ii) the two competing procedure of NG production and efficacy of free radical photopolymerization (FRP) can be tailored for optimal system with nanogold in the polymer matrix;(ii) the FRP efficacy is contributed by 3 components: the coupling of the excited state of copper complex (T) with the radicals (R and S) produced by the iodonium and the amine; (iii) the production of NG is contributed by 2 components: the coupling of T and radical (S) with gold ion; (iv) NG production has a transient state value which is an increasing function of light intensity and the combined concentration ratio [(A0/G0)+(N0/(K'M0). whereas it has a steady-state independent to the light intensity.

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.

Inflammatory bowel disease (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) are chronic multifactorial disorders which affect the gastrointestinal tract with variable extent. Despite extensive research, their etiology and exact pathogenesis are still unknown. Cell-free DNAs (cfDNAs) are defined as any DNA fragments which are free from origin cell and able to circulate into bloodstream with or without microvescicles. CfDNAs are now being increasingly studied in different human diseases, like cancer or inflammatory diseases. However, to date it is unclear how IBD etiology is linked to cfDNAs in plasma. Extrachromosomal circular DNA (eccDNA) are non-plasmidic, nuclear, circular and closed DNA molecules found in all eukaryotes tested. CfDNAs appear to play an important role in autoimmune diseases, inflammatory processes, and cancer; recently, interest has also grown in IBD, and their role in the pathogenesis of IBD has been suggested. We now suggest that eccDNAs also plays a role in IBD. In this review we have comprehensively collected available knowledge in literature regarding cfDNA, eccDNA, and structures involving them such as neutrophil extracellular traps and exosomes, and their role in IBD. Finally, we focused on old and novel potential molecular therapies and drug delivery systems, such as nanoparticles, for IBD treatment.

Background: Ultrasonography’s usefulness in endometrial cancer (EC) diagnosis consists of its staging and predictive roles. Ultrasound-measured tumor-free distance from the tumor to the uterine serosa (uTFD) is a promising marker for this variable. The aim of the study was to determine the usefulness of this biomarker in locoregional staging, and thus in the prediction of lymph node metastasis (LNM). Methods: We conducted a single-institutional, prospective study on 116 consecutive patients with EC who underwent 2D transvaginal ultrasound examination. The uTFD marker was compared with the depth of ultrasound-measured myometrial invasion (uMI). Univariate and multivariate logit models were evaluated to assess the predictive power of the uTFD and uMI in regard to LNM. The reference standard was a final histopathology result. Survival was assessed by the Kaplan-Meyer method. Results: LNM was found in 17% of the patients (20/116). In the univariate analysis, uMI and uTFD were significant predictors of LNM. Accuracy was 70.7%, and NPV was 92.68% (OR 4.746, 95% CI 1.710-13.174) for uMI (p = 0.002), and 63.8%, and 89.02% (OR 0.842, 95% CI 0.736 – 0.963), respectively, for uTFD (p = 0.01). The cut-off value for uTFD in the prediction of LNM was 5.2 mm. The absence of LNM was associated more with biomarker values uMI <1/2 and uTFD >=5.2 mm than with the presence of metastases with uMI >1/2 and uTFD values <5.2 mm. In the multivariate analysis, the accuracy of the uMI-uTFD model was 74%, and NPV was 90.24% (p = NS). Neither uMI nor uTFD are surrogates for overall and recurrence-free survivals in endometrial cancer. Conclusions: Both uMI and uTFD, either alone or in combination, are valuable tools for gaining additional preoperative information on expected lymph node status. Negative lymph nodes status is better described by ultrasound biomarkers than a positive status. It is easier to use uTFD measurement as a biomarker of EC invasion than uMI, and the former still maintains a similar predictive value for lymph node metastases to the latter at diagnosis.

Meteorites represent the recoverable portions of asteroids occurring between Mars and Jupiter within the solar system that reach the surface of the Earth. Meteorites are rare extraterrestrial objects studied extensively to improve understanding of planetary evolution. In this work, calibration-free laser-induced breakdown spectroscopy (CF-LIBS) evaluates quantitative elemental and molecular analysis of the Dergaon meteorite, an H 4-5 chondrite fall sample, Assam, India. Spectral signatures of H, N, O, Na, Mg, Al, Si, P, K, Ca, Ti, Cr, Mn, Fe, Co, Ni, Ir, are measured. Along with the atomic emission, this work reports as well molecular emission from FeO molecules. The concentration of the measured elements obtained using CF-LIBS are in close agreement with earlier reports. The elements H, N and O and their concentrations are estimated using CF-LIBS for the first time. This study applies laser spectroscopy to establish presence of Ni, Cr, Co, and Ir in meteorites. Elemental analysis forms the basis for establishment of potential molecular composition of the Dergaon meteorite. Moreover, the elemental analysis approach bodes well for in-situ analyses of extraterrestrial objects including applications in planetary rover missions.

It is quite easy to stochastically distort an original count variable to obtain a new count variable with relatively more variability than in the original variable. Many popular overdispersion models (variance greater than mean) can indeed be obtained by mixtures, compounding or randomlystopped sums. There is no analogous stochastic mechanism for the construction of underdispersed count variables (variance less than mean), starting from an original count distribution of interest. This work proposes a generic method to stochastically distort an original count variable to obtain a new count variable with relatively less variability than in the original variable. The proposed mechanism, termed condensation, attracts probability masses from the quantiles in the tails of the original distribution and redirect them toward quantiles around the expected value. If the original distribution can be simulated, then the simulation of variates from a condensed distribution is straightforward. Moreover, condensed distributions have a simple mean-parametrization, a characteristic useful in a count regression context. An application to the negative binomial distribution resulted in a distribution allowing under, equi and overdispersion. In addition to graphical insights, fields of applications of special cases of condensed Poisson and condensed negative binomial distributions were pointed out as an indication of the potential of condensation for a flexible analysis of count data

Biosensors have shown great potential in realizing rapid, low cost and portable on-site detection for diseases. This work reports the development of a new bioelectronic sensor called AC electrokinetics-based capacitive (ABC) biosensor, for the detection of genomic DNA (gDNA) of methicillin-resistant Staphylococcus aureus (MRSA). The ABC sensor is based on interdigitated microelectrodes biofunctionalized with oligonucleotide probes. It uses a special AC signal for direct capacitive monitoring of topological change on nanostructured sensor surface, which simultaneously induce dieletrophoretic enrichment of target gDNAs. As a result, rapid and specific detection of gDNA/probe hybridization can be realized with high sensitivity. It requires no signal amplification such as labelling, hybridization chain reaction, or nucleic acid sequence-based amplification. This method involves only simple sample preparation. After optimization of nano-structured sensor surface and signal processing, the ABC sensor demonstrated fast turnaround of results (~10 s detection), excellent sensitivity (a detection limit of 4.7 DNA copies /µL MRSA gDNA) and high specificity, suitable for point of care diagnosis. As a bioelectronic sensor, the developed ABC sensors can be easily adapted for detection of other infectious agents.

Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focus on the potential synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HT) strategy. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HT and AFM is essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of nanomaterials with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HT enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HT is ideally suited for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology, emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools.

We define degree of dependence of two events A and B in a probability space by using Boltzmann-Shannon entropy function of an appropriate probability distribution produced by these events and depending on one parameter (the probability of intersection of A and B) varying within a closed interval I. The entropy function attains its global maximum when the events A and B are independent. The important particular case of discrete uniform probability space motivates this definition in the following way. The entropy function has a minimum at the left endpoint of I exactly when one of the events and the complement of the other are connected with the relation of inclusion (maximal negative dependence). It has a minimum at the right endpoint of I exactly when one of these events is included in the other (maximal positive dependence). Moreover, the deviation of the entropy from its maximum is equal to average information that carries one of the binary trials defined by A and B with respect to the other. As a consequence, the degree of dependence of A and B can be expressed in terms of information theory and is invariant with respect to the choice of unit of information. Using this formalism, we describe completely the screening tests and their reliability, measure efficacy of a vaccination, the impact of some events from the financial markets to other events, etc. A link is available for downloading an Excel program which calculates the degree of dependence of two events in a sample space with equally likely outcomes.

Twenty-four extensively-reared Iberian pigs were used to study the influence of fattening period length (30, 60 or 90 days) on the fatty acid profiles of intramuscular and subcutaneous fat and the relationships between both profiles. Regarding fatty acid (FA) percentage, PUFA was greater in backfat and MUFA was greater in intramuscular fat (IMF), regardless fattening period length. The longer fattening period increased MUFA content in backfat (which had a more marked change in oleic acid) and decreased PUFA content in backfat and IMF, but it did not affect SFA content. Within the 3-layers subcutaneous backfat, SFA content was greater in the inner layer, MUFA was greater in the outer layer and PUFA was greater in both of these layers. The few differences in FA composition between both adipose tissues suggest that the changes due to the feeding regime are slow and, therefore, although the length of the fattening phase was increased, the fatty acid profile did not change substantially. The strong relationship between the FA profiles of IMF and backfat might be used to predict one profile from the other one when this latter was more readily available for sampling or analytical reasons.

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.

The genus Naegleria, of free-living amoeba (FLA) group, has been investigated mainly due to its human health impact resulting in deadly infections and their worldwide distribution on freshwater systems. Naegleria fowleri, colloquially known as the “brain-eating amoeba”, is the most studied Naegleria species because it causes Primary Amoebic Meningoencephalitis (PAM) of high lethality. The assessment of FLA biodiversity is fundamental to evaluate the presence of pathogenic species and the possibility of human contamination. However, the knowledge of FLA distribution in Brazil is unknown, and to rectify this situation we present a research on identifying Naegleria spp. in the Monjolinho River, as a model study. The river is a public Brazilian freshwater source that crosses the city of São Carlos. Five distinct sampling sites were examined through limnological features, trophozoites culturing and PCR against internal transcribed spacers (ITS) regions and 5.8S rRNA sequence. The results identified N. philippinensis, N. canariensisi, N. australiensis, N.gruberi, N. dobsoni sequences, as well as a Vahlkampfia sequence. The methodology delineated here represents the first Brazilian Naegleria spp. study on a freshwater system. Our result stresses the urgency of a large scale evaluation of the presence of free-living amoebas in Brazil.

Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. However, few genera of FLA are linked to human infections. Within these genera, Acanthamoeba spp., classified by genotypes (T1-T23), being T1, T2, T4, T5, T10, T12, and T18 as capable of causing granulomatous amoebic encephalitis (GAE) in immunocompromised patients mostly and Acanthamoeba keratitis related to genotypes T2, T3, T4, T5, T6, T10, T11, T12 and T15 in apparently healthy patients. Meanwhile, Naegleria fowleri is the causative agent of an acute infection called primary amoebic meningoencephalitis (PAM), while Balamuthia mandrillaris, like some Acanthamoeba genotypes, causes GAE, differing from the latter in the description of numerous cases in patients immunocompetent. Finally, other FLA related to the pathologies mentioned above have been reported; Sappinia pedata is responsible for one case of amoebic encephalitis; Vermamoeba vermiformis has been found in cases of ocular damage, and its extraordinary capacity as endo-cytobiont for microorganisms of public health importance such as Legionella pneumophila, Bacillus anthracis, Pseudomonas aeruginosa, among others. In this review, issues related to the epidemiology of each one are addressed, updating their geographic distribution and cases reported in recent years for pathogenic FLA.

A facile and novel synthesis of thirteen 2-amino-3-cyanopyridine derivatives 5(a-m), by a one-pot multicomponent reaction (MCRs), is described for the first time, starting from aromatic aldehydes, malononitrile, methyl ketones, or cyclohexanone and ammonium acetate in the presence of the nanostructured diphosphate Na2CaP2O7 (DIPH) at 80 °C, under solvent-free conditions. These compounds were synthesized in short reaction times with good to excellent yields (84-94%). The diphosphate Na2CaP2O7 is used as an efficient catalyst, environmentally, easy handling, non-toxic, stable, and reusable. Our study was strengthened by the synthesis of five new pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) by intramolecular cyclization of 2-amino-3-cyanopyridines 5(b, c, g, h, j), with formamide. The synthesized products were characterized by FT-IR, SEM, XRD, TEM, 1H NMR, 13C NMR, TLC, and BET. The operating conditions were optimized using a model reaction in which the catalyst amount, temperature, time, and solvent effect were evaluated. The antibacterial activity was tested against Gram-positive and Gram-negative strains for the synthesized compounds.

One-Dimensional Solar Cell Capacitance Simulator (1D-SCAPS) and n-i-p planar configuration have been employed for the simulation of the caesium tin iodide (CsSnI₃)-based perovskite solar cell (PSC) with titanium (IV) oxide (TiO₂) and copper thiocyanate (CuSCN) as the electron and hole transport materials respectively. The results obtained for the initially modeled PSC compared well with similar devices in the literature but marred with high recombination rate. As such, the defect density in the CsSnI₃ absorber was varied from 10¹³ cm^-3 to 10¹⁷ cm^-3 and enriched with SnCl₂ (additive) and Br⁻(dopant) respectively. This strategy ensured a reduced concentration of Sn⁴⁺ vacancy (V_Sn) in the CsSnI₃ absorber with improved carrier lifetime and diffusion length beyond 0.05 ns and 1.1µm by a magnitude of the order of 10³ and 10² respectively for the enriched CsSnI₃ –based PSC. For the optimized PSC, we recorded V_OC=1.289 V, J_SC=32.60 mA.cm^-2, FF=83.56% and PCE=35.12%.

Among the possible improvements of Autonomous Emergency Braking (AEB) systems, reducing the intensity of the automatic braking process by studying the kinematics and general behavior of the pedestrian while crossing is crucial to determine the progressiveness of the braking, or replacing part of the braking process by an evasive maneuver when a collision is imminent. This paper proposes the integration of an autonomous avoidance system (Automatic Emergency Steering, AES) that acts directly on the steering system to generate an evasive maneuver and avoid a possible pedestrian collision (OPREVU-AES system), as well as the assessment of its effectiveness compared to a commercial AEB system. OPREVU and VULNEUREA are research projects in which INSIA and CEDINT have cooperated to improve driving assistance systems and the safety of pedestrians and cyclists through Virtual Reality (VR) techniques. The analysis of the kinematic and dynamic response of the OPREVU-AES system is conducted in CarSim© software. The effectiveness evaluation procedure is based on the reconstruction of a sample of road vehicle-to-pedestrian crashes (INSIA-UPM database), using the PCCrash® software, and taking as an indicator the probability of head injury severity (ISP). The results show that the AEB system would have prevented part of the collisions, especially after the incorporation of the OPREVU-AES system. In most of the cases where avoidance is not possible, a significant reduction of the ISP is achieved.

Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related with a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide and it is estimated that is present in up to 25% of the world's population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthetized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allow the direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight about the mechanism and drugs action in NAFLD. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical disc. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using highly specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈ 0.39 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the lipid accumulation within the cells. Moreover, we discovered that at third day from lipids challenge, the hepatocytes increased the amount of albumin secreted. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation needed to unveil the biological significance of that cell behaviour.

Background: Liquid biopsies are revolutionary tools to detect tumor-specific genetic alterations in body fluids, and cell-free DNA (cfDNA) can be used for molecular diagnosis in cancer patients. In brain tumors cerebrospinal fluid (CSF) cfDNA might be more informative than plasma cfDNA. Here, we assess the use of CSF cfDNA in pediatric embryonal brain tumors (EBT) for molecular diagnosis. Methods: CSF cfDNA of pediatric patients with medulloblastoma (n=18), ATRT (n=3), ETMR (n=1), CNS NB FOXR2 (n=2) and pediatric EBT NOS (n=1) (mean cfDNA concentration 48 ng/mL; range 4-442 ng/mL) and matched tumor genomic DNA were sequenced by WES, and/or a targeted sequencing approach, to determine single nucleotide variations (SNVs)/copy number alterations (CNA). A specific capture covering transcription start sites (TSS) of genes of interest was used for nucleosome footprinting in CSF cfDNA. Results: 15/25 CSF cfDNA samples yielded informative results, with informative CNA and SNVs in 11 and 15 cases, respectively. For cases with paired tumor and CSF cfDNA WES (n=15), a mean of 83 (range 1-160) shared SNVs was observed, including SNVs in classical medulloblastoma genes such as SMO and KMT2D. Interestingly, tumor-specific SNVs (mean 18; range 1-62) or CSF-specific SNVs (mean 5; range 0-25) were observed suggesting clonal heterogeneity. The TSS panel resulted in differential coverage profiles across all 112 studied genes in 7 cases, indicating distinct promoter accessibility. Conclusion: CSF cfDNA sequencing yielded informative results in 60% of cases (15/25), with WES feasible in 83% (15/18). These results pave the way for implementation of these novel approaches for molecular diagnosis and minimal residual disease monitoring.

This paper proposes an optimal trading algorithm based on a novel application of the conventional Control Engineering (CE). We consider a fundamental CE concept, namely, the feedback control and apply it to the Algorithmic Trading (AT). The concrete feedback control strategy is designed in a form of the celebrated Proportional-Integral-Derivative (PID) model. The highly fluctuating nature of the modern financial markets has led to the adoption of a model-free realisation of the generic PID framework. The control theoretical methodology we propose is combined with the advanced statistics for the historical market data. We obtain a specific log-normal probability distribution function (pdf) associated with the specific quantities associated with the available stock data. The empirical log-normal pdf mentioned above makes it possible the necessary PID gains optimization. For this aim, we apply the data-driven optimization approaches and consider the corresponding Monte Carlo solution procedure. The optimized PID trading algorithm we propose is also studied in the Fourier analysis framework. This equivalent frequency domain representation involves a new concept in the financial engineering, namely, the "stock market energy" concept. For the evaluation, we implement the proposed PID optimal trading algorithm and develop a Python based prototype software. We finally apply the corresponding prototype software to a dataset from the Binance BTC / USDT stock market. The experimental result illustrates the implementability of the proposed optimal PID trading scheme and also shows the effectiveness of the proposed CE methods in the modern AT.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

Understanding swash zone dynamics is of crucial importance for coastal management as the swash motion, consisting of the uprush of the wave on the beach face and the subsequent downrush, is responsible for driving changes the beach morphology trough sediment exchanges between the sub-aerial and sub-aqueous beach. Improved understanding of the probabilistic characteristics of these motions has the potential to allow coastal engineers to develop improved sediment transport models which, in turn, can be further developed into coastal management tools. In this paper, novel descriptors of swash motions are obtained by combining field data and statistical modelling. Our results indicate that the probability distribution function (PDF) of shoreline height (p(ζ)) and trough-to-peak swash heights (p(ρ)) measured at a high energy, sandy beach were both inherently multimodal. Based on the observed multimodality of these PDFs, Gaussian Mixtures are shown to be the best method to statistically model them. Further, our results show that both offshore and surf zone dynamics are responsible for driving swash zone dynamics, which indicates unsaturated swash. The novel methods and results developed in this paper, both data collection and analysis, could aid coastal managers to develop improved swash zone models in the future.

.Celiac disease (CeD) is a chronic, autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environ-mental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist de-spite apparent compliance with a GFD. That could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on GFD who expe-rience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This re-view will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

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.

Head and neck squamous cell carcinomas (HNSCCs) develop from the mucosa of the oral cavity, pharynx, and larynx. The methylation levels of Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in ccfDNA are considered pan-cancer biomarkers and have shown prognostic value in preliminary reports in HNSCC. Liquid biopsy is a non-invasive procedure that collects tumor-derived molecules including circulating cell-free DNA (ccfDNA). Here, we developed a ddPCR-based assay to detect the DNA methylation levels of plasma circulating SEPT9 and SHOX2 in patients with HNSCC. We first set up the assay on commercial methylated and un-methylated DNA. Then, the dynamic changes of the methylation levels of SEPT9 and SHOX2 were quantified in 20 patients during the follow-up. The results highlighted: i) the capability of the ddPCR-based assay in detecting very low copies of methylated molecules; ii) the significant decrease in methylation levels of SEPT9 and SHOX2 in plasma of HNSCC patients at the first time points of follow-up respect to T0; iii) a different trend of longitudinally DNA methylation variations associable to the clinicopathological features of the patients. The absolute quantification of the methylation levels of SEPT9 and SHOX2 in HNSCC may be used for risk stratification and disease monitoring.

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.

After proving, in a purely categorial way, that the inclusion functor InAlg(Σ) from Alg(Σ), the category of many-sorted Σ-algebras, to PAlg(Σ), the category of many-sorted partial Σ-algebras, has a left adjoint FΣ, the (absolutely) free completion functor, we recall, in connection with the functor FΣ, the generalized recursion theorem of Schmidt, which we will also call the Schmidt construction. Next we define a category Cmpl(Σ), of Σ-completions, and prove that FΣ, labeled with its domain category and the unit of the adjunction of which it is a part, is a weakly initial object in it. Following this we associate to an ordered pair (α,f), where α=(K,γ,α) is a morphism of Σ-completions from F=(C,F,η) to G=(D,G,ρ) and f a homomorphism in D from the partial Σ-algebra A to the partial Σ-algebra B, a homomorphism ΥαG,0(f):Schα(f)B. We then prove that there exists an endofunctor, ΥαG,0, of Mortw(D), the twisted morphism category of D, thus showing the naturalness of the previous construction. Afterwards we prove that, for every Σ-completion G=(D,G,ρ), there exists a functor ΥG from the comma category (Cmpl(Σ)↓G) to End(Mortw(D)), the category of endofunctors of Mortw(D), such that ΥG,0, the object mapping of ΥG, sends a morphism of Σ-completion in Cmpl(Σ) with codomain G, to the endofunctor ΥαG,0.

Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. Besides, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41) and FFAR4 (GPR120). FFAR2 and FFAR3are activated by short chain fatty acids like acetate, propionate and butyrate whereas FFAR1 and FFAR4 are activated by medium and long chain fatty acids like palmitate, oleate, linoleate and others. FFARs have generated considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR based therapies to treat patients with obesity and Type 2 Diabetes.

Apple replant disease is a severe problem in orchards and tree nurseries. Evidence for the involvement of a nematode-microbe disease complex was reported. To search for this complex, plots with a history of apple replanting, and control plots cultivated for the first time with apple were sampled in two fields in two years. Shoot weight drastically decreased with each replanting. Nematodes were extracted from soil samples by floatation-centrifugation, washed on a 20 µm-sieve, and used for DNA extraction. Nematode communities and co-extracted fungi and bacteria were analyzed by high-throughput sequencing of amplified ribosomal fragments. The nematode community and co-extracted fungal and bacterial communities significantly differed between replanted and control plots. Free-living nematodes of the genera Aphelenchus, Cephalenchus, and an unidentified Dorylaimida were associated with replanted plots, as indicated by linear discriminant analysis effect size. Among the co-extracted fungi and bacteria, Mortierella was most indicative of replanting. Some genera, mostly Rhabditis, indicated healthy control plots. Isolating and investigating the putative disease complexes will help to understand and alleviate stress-induced root damage of apple in replanted soil.

Nobel Prize-winning physicist Sir Roger Penrose and Stuart Hameroff, a renowned American physician and scientist, have put forward an innovative theory that the human brain has a quantum mechanism located in the microtubular protein system within neurons, known as the "Orch OR" theory. According to the researchers, this mechanism is responsible for the brain's non-computational actions such as consciousness and free will. This theory has been criticized by several researchers from both the biological and physical sides. The purpose of this paper is to examine whether there is a possible basis for this theory in the philosophy of science.

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.

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.

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.

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.

Taking a DNA-sequence, a word with letters/bases A, T, G and C, as the relation between the generators of an infinite group $\pi$, one can discriminate two important families: (i) the cardinality structure for conjugacy classes of subgroups of $\pi$ is that of a free group on $1$ to $4$ bases and the DNA word, viewed as a substitution sequence, is aperiodic. (ii) The cardinality structure for conjugacy classes of subgroups of $\pi$ is not that of a free group, the sequence is generally not aperiodic and topological properties of $\pi$ have to be determined differently. The two cases rely on DNA conformations such as A-DNA, B-DNA, Z-DNA, G-quadruplexes, etc. We found a few salient results: Z-DNA, when involved in transcription, replication and regulation in a healthy situation implies (i). The sequence of telomeric repeats comprising $3$ distinct bases, most of the time, satisfies (i). For $2$-base sequences in the free case (i) or non free case (ii), the topology of $\pi$ may be found in terms of the $SL(2,\mathbb{C})$ character variety of $\pi$ and the attached algebraic surfaces. The linking of two unknotted curves --the Hopf link-- may occur in the topology of $\pi$ in cases of biological importance, in telomeres, G-quadruplexes, hairpins and junctions, a feature we already found in the context of models of topological quantum computing. For $3$- and $4$ base sequences, other knotting configurations are noticed and a building block of the topology is the $4$-punctured sphere. Our methods have the potential to discriminate potential diseases associated to the sequences.

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.

A consistent factor in the epidemic of chronic disease is a pro-inflammatory metabolic state. The ability of clinicians to use nutrients to balance inflammation by supporting oxidant homeostasis rests on the quality of research within the field of antioxidants. Understanding the intersection of two prominent theories regarding the role of antioxidants in quelling inflammation, nutritional hormesis and oxidant scavenging, will enable the therapeutic use of antioxidants in clinical practice. This review investigates the less well-established theory, nutritional hormesis, which has not been comprehensively reviewed recently to our knowledge. To understand the state of research on the hormetic response, we conducted a comprehensive literature review describing the relationship between dietary antioxidants, hormesis, and chronic disease. We used an adaptive search strategy in PubMed and Scopus, retrieving a total of 343 articles, of which 218 were unique. Title and abstract screenings were conducted by two reviewers independently with a third as a tiebreaker, resulting in 152 articles included in this review. Most studies reviewed the hormetic response in plant and cell models (73.6%) while only 2.2% were conducted in humans. Limitations exist in translating plant/cell/animal models into the complexities of human biochemistry and physiology that warrant consideration before extrapolating such results into clinical practice. A critical hurdle in our literature review process is the lack of standardized nomenclature describing the hormetic effect in the research community that challenges the ability to comprehensively review the subject matter. Further, aA knowledge gap exists between the cell culture and animal model research that shows a biphasic, hormetic quality to the role of antioxidants and the observational human studies, which have yet to corroborate these findings. Therefore, we cannot accurately translate this research into clinical care at this time.

The closed forms of the non-resonant thermonuclear function in the Maxwell-Boltzmann and Tsallis case with depleted tail are obtained in generalized special functions. The results are written in terms of H-function of two variables. The importance of the results in this paper lies in the fact that the reaction rate probability integrals in Maxwell-Boltzmann and Tsallis cases are not obtained by the conventional method of approximation or by means of a single variable transform technique but by means of a two variable transform method. The Behaviour of the depleted non-resonant thermonuclear functions are examined using graphs. The results in the paper are of much interest to astrophysicists and statisticians in their further work in this area.

Serial femtosecond crystallography (SFX) using an X-ray free-electron laser (XFEL) enables determination of room-temperature structures without causing radiation damage. Using an optical pump-probe or mix-and-injection, SFX enables the intermediate state visualization of a molecular reaction. In SFX experiments, serial and stable microcrystal delivery to the X-ray interaction point is vital for reasonable data collection and efficient beam time. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) facility established SFX instruments at a nanocrystallography and coherent imaging (NCI) experimental station. Various sample delivery methods, including injection, fixed-target scanning, and hybrid methods, have been developed and applied to collect XFEL diffraction data. Herein, we review the currently available sample delivery methods for SFX at the NCI experimental station at the PAL-XFEL. This article will help PAL-XFEL users access the SFX system for their experiments.