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

Usually, the vector control of the induction machine (IM) is done by using cascade control structures with conventional linear PI controllers, the inner loop being designed for current control, and the outer loop for rotor flux and speed control. In this paper, starting from the dq model of the IM with the rotor magnetic flux space vector aligned along the d axis, advanced control algorithms are proposed for the two control loops of the cascade structure. For the current inner loop, after the decoupling control of the two dq currents, predictive algorithms with constraints are used to control and limit the currents. Since the outer loop has a nonlinear affine multivariable plant model, a homotopy-based variant of feedback linearization is used to obtain a non-singular decoupling matrix of the feedback transformation even when the rotor flux is zero at the start-up of the motor. During the continuous variation of the homotopy parameter, the model of the plant is variable, in which case the model free algorithms are properly used to control the flux and speed of the IM. The comparative analysis obtained for the cascade structure with conventional PI controllers and advanced algorithms, respectively, shows that the last lead to improve the dynamical performance of the IM.

Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicated its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 38-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. Not only does the heightened specificity of E380Q/S387L improve the hydrolytic activity against pro-immunogenic peptides, but also holds this version of the enzyme as a promising candidate as an oral therapy enzyme for celiac disease.

Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p < 0,0001), CE-PTV < 15 cm³ (p=0,03), surgical resection > 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.

Caries are lesions caused by acidic compounds derived from the metabolism of bacteria such as streptococci. It is not merely the presence of acidogenic bacteria that causes caries but an imbalance in the oral biofilm microhabitat and its behavior. One factor underlying biofilm formation is quorum sensing (QS), that in gram-positives relies on peptidic molecules, whereas in gram-negatives is driven by small diffusible signals. Strategies based on QS inhibition have been proposed as alter-natives to antimicrobial therapies. Here, we investigate the antibiofilm potential of the lactonase enzyme Aii20J, previously reported as effective against biofilms of periodontal disease origin. We generated in vitro polymicrobial biofilms dominated by gram-positive taxa using supragingival samples from caries-free and caries-active children. The effect of Aii20J on the biofilms was evalu-ated regarding its biomass-reducing ability, as assessed with crystal violet assay, and its effects on the bacterial composition of the polymicrobial biofilms, as assessed by 16S community profiling. We describe significant biomass reductions upon Aii20J exposure without significant changes in bac-terial composition at the genus level. Our results support the use of Aii20J to prevent oral biofilm formation while highlighting the influence of the polymicrobial environment on bacterial commu-nities and their response to antibiofilm treatments.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

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.

A method is proposed for describing the dynamics of systems of interacting particles in terms of an auxiliary field, which in the static mode is equivalent to given interatomic potentials, and in the dynamic mode is a classical relativistic composite field. It is established that for interatomic potentials, the Fourier transform of which is a rational algebraic function of the wave vector, the auxiliary field is a composition of elementary fields that satisfy the Klein-Gordon equation with complex masses. The interaction between particles carried by the auxiliary field is nonlocal both in space variables and in time. The temporal non-locality is due to the dynamic nature of the auxiliary field and can be described in terms of functional-differential equations of retarded type. Due to the finiteness mass of the auxiliary field, the delay in interactions between particles can be arbitrarily large. A qualitative analysis of the dynamics of few-body and many-body systems with retarded interactions has been carried out, and a non-statistical mechanisms for both the thermodynamic behavior of systems and synergistic effects has been established.

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.

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.

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.

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.

Paenibacillus sp. tmac-D7 was isolated from coastline growing Trifolium macraei (double-head clover) root nodules from Bodega Bay, California. The draft genome is 5,567,337 bp with a G+C% of 52.4%, an N50 of 114,261 bp, and 5,282 predicted protein-coding genes. Paenibacillus, while found in many other environments, is frequently isolated from root nodules, with many acting as plant pathogen antagonists. Paenibacillus sp. tmac-D7 is the first genome of a non-rhizobial endophyte isolate from wild Trifolium macraei (double-head clover).

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

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

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Einstein was skeptical of part of quantum mechanics, and he believed that Heisenberg’s uncertainty principle did not reflected the full depth of reality. He famously stated, ”God does not play dice with the universe.” However, since quantum mechanics has passed so many experimental tests, most physicists today assume that Einstein was wrong. Nevertheless, we will demonstrate that Heisenberg’s uncertainty principle must be modified to unify gravity with quantum mechanics. This modification leads to the Certainty-Uncertainty principle where the certainty part is strongly linked to gravity. This means Einstein likely was right in his intuition also on this point. The key is to understand that the de Broglie wavelength is not the actual wavelength of matter but merely a derivative of the true matter wavelength, namely the Compton wavelength. Furthermore, one must understand that the gravitational constant, first introduced in 1873, is simply a composite constant needed to rectify the incomplete definition of kilogram mass introduced into Newtonian gravity in 1873.

We present a data-driven, in situ proximal multi-sensor digital soil mapping approach to develop digital twins for multiple agricultural fields. A novel Digital Soil CoreTM (DSC) Probe was engineered that contains seven sensors, each of a distinct modality, including sleeve friction, tip force, dielectric permittivity, electrical resistivity, soil imagery, acoustics, and visible and near-infrared spectroscopy. The DSC System integrates components the DSC Probe, DSC software, and deployment equipment to sense soil characteristics at a high vertical spatial resolution (mm scale) along in situ soil profiles up to a depth of 120 cm in about 60 sec. The DSC Probe in situ proximal data are harmonized into a data cube providing vertical high-density knowledge associated with physical-chemical-biological soil conditions. In contrast, conventional ex situ soil samples derived from soil cores, soil pits, or surface samples analyzed using laboratory and other methods are bound by substantially coarser spatial resolution and multiple compounding errors. Our objective was to investigate the effects of mismatched scale between high-resolution in situ proximal sensor data and coarser resolution ex situ soil laboratory measurements to develop soil prediction models. Our study was conducted in central California soil in almond orchards. We collected DSC sensor data and spatially co-located soil cores that were sliced into narrow layers for laboratory-based soil measurements. Partial Least Squares Regression (PLSR) cross-validation was used to compare results testing four data integration methods. Method A reduced the high-resolution sensor data to discrete values paired with layer-based soil laboratory measurements. Method B used stochastic distributions of sensor data paired with layer-based soil laboratory measurements. Method C allocated the same soil analytical data to each one of the high-resolution multi-sensor data within a soil layer. Method D linked the high-density multi-sensor soil data directly to crop responses (crop performance and behavior metrics) bypassing costly laboratory soil analysis. Overall, the soil models derived from Method C outperformed Methods A and B. Soil predictions derived using Method D were most cost-effective for directly assessing soil-crop relationships, making this method well-suited for industrial-scale precision agriculture applications.

The rapid development and integration of Autonomous Mobile Robots (AMRs) have 1 revolutionized industries by enhancing automation capabilities. A critical challenge in this evolution 2 is achieving effective navigation and obstacle avoidance, which are essential for deploying AMRs 3 seamlessly in varied environments. This paper presents a detailed exploration of AMR navigation 4 and obstacle avoidance advancements through the application of reinforcement learning, specifically 5 focusing on small-scale Sri Lankan manufacturing facilities. The study demonstrates the effectiveness 6 of Q-learning in managing dynamic obstacles within a factory environment. The AMR successfully 7 avoided obstacles in 36 out of 50 test runs, achieving a 72% success rate, and maintained an average 8 distance of 12 cm from each obstacle, underscoring the algorithm’s precision in maintaining safe nav- 9 igation paths while dynamically adapting to environmental changes. The continuous monitoring by 10 ultrasonic sensors, combined with iterative learning, enabled the robot to refine its decision-making 11 process and efficiently navigate through the environment. This paper also provides a comprehensive 12 examination of conventional methods, tracing their historical development and assessing their role in 13 addressing real-world challenges. The results highlight the significant improvements brought by rein- 14 forcement learning, particularly when integrated with sensor fusion and motor control technologies, 15 to enhance navigation and dynamic object collision avoidance. The study involves developing an 16 AMR prototype, refining algorithms, and assessing system performance in controlled environments. 17 By automating material transportation and addressing operational constraints in manufacturing 18 settings that predominantly rely on manual labor, this paper advances the practical deployment of 19 AMRs. Additionally, it discusses ethical considerations, potential limitations, and the importance 20 of real-world validation, offering valuable insights for the future development and integration of 21 autonomous mobile robotics in dynamic industrial environments.

Several studies in computer vision have examined specular removal, which is crucial for object detection and recognition. This research has traditionally been divided into two tasks: specular highlight removal, which focuses on removing specular highlights on object surfaces, and reflection removal, which deals with specular reflections occurring on glass surfaces. In reality, however, both types of specular effects often coexist, making it a fundamental challenge that has not been adequately addressed. Recognizing the necessity of integrating specular components handled in both tasks, we constructed a Specular-Light (S-Light) DB for training single-image-based deep learning models. Moreover, considering the absence of benchmark datasets for quantitative evaluation, the Multi-Scale Normalized Cross Correlation (MS-NCC) metric, which considers the correlation between specular and diffuse components, was introduced to assess the learning outcomes.

The DNS of film boiling requires strong computational resources that are difficult to obtain for a daily CFD use by the practitioners of the industrial R&D experts. On the other hand, the film boiling experiments are associated with the usage of the expensive and highly sophisticated apparatus, and the research to this end is found to be relatively difficult due to high heat flow rates that are present in the process itself. When combined with a transient heat conduction in a solid, the problem becomes significantly difficult. Therefore, a novel method in computation of conjugate heat transfer during film boiling in a quiescent liquid has been proposed in this paper. The method relies on the solution of mass, momentum and energy conservation equations in a two-fluid framework, supplemented with the appropriate closures. Furthermore, the turbulent flow has been found as an important parameter in obtaining the accurate solution of the temperature field evolution in a solid specimen, via the proper modeling of turbulent kinetic energy (TKE) value, that has been imposed as a constant value, i.e., the frozen turbulence approach. It was found, in addition, that the appropriate TKE value can be obtained by use of Kelvin-Helmholtz instability theory in conjunction with the boundary layer theory. The obtained results show excellent agreement with the experimental data within the first 15 s of the experiment, i.e., the first ca. 10 % of the total duration of the film boiling mode of heat transfer. Furthermore, the heat transfer coefficient has matched the error bands prescribed by the authors of the paper that has presented the correlations, whilst the averaged values are far beyond this band, i.e., are slightly more than 30 % higher. The further inspection has revealed a measure of similarity between the computational result of the volume fraction field distribution and the experiment, thus confirming the capability of the method to obtain realistic interface evolution in time. The method has shown full capability for further pursuing the industrial-scale film boiling problems that involve turbulent flow and the conjugate heat transfer approach.

Mechanization is an important factor to improve the green total factor productivity of planting industry, which is the key way to realize the sustainable development and high-quality development of agriculture. Using the panel data of 30 provinces in China from 2001 to 2019, this paper uses the stochastic frontier analysis method of output oriented distance function to measure the green total factor productivity of planting industry based on net carbon sink, and empirically studies the impact of mechanization on the planting green total factor productivity. The empirical analysis finds that mechanization can significantly promote the planting green total factor productivity, and this basic conclusion is still robust after using instrumental variables, sub sample regression. Further research found that the path of mechanization on planting green total factor productivity is mainly reflected in technology progress and spatial spillover. The mechanism of operation scale expansion, factor allocation optimization and technical efficiency change is not significant. Given these findings, the paper adds considerable value to the empirical literature and also provides various policy- and practical implications.

Global climate change requires urgent solutions. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon, partly compensating for the anthropogenic CO₂ emissions that are a major cause of rising global temperatures. However, poorly planned and executed tree-planting could actually increase CO₂ emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose ten golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery, while simultaneously improving livelihoods. These are: i) Protect existing forest first; ii) Work together (involving all stakeholders); iii) Maximize biodiversity recovery to meet multiple goals; iv) Select appropriate areas; v) Use natural regeneration wherever possible; vi) Select species to maximise biodiversity; vii) Use resilient plant material (with appropriate genetic variability and provenance); viii) Plan ahead for infrastructure, capacity and seed supply; ix) Learn by doing (using an adaptive management approach); and x) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities and their dependence on benefits from successful reforestation programmes that restore ecosystem functioning and deliver a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is now crucial to build on the public and private interest in this topic to ensure interventions provide effective, long-term carbon sinks and maximise benefits for biodiversity and people.

We present a Machian model of Quantum Cosmology with full dark matter and light speed expansion and rotation. During galaxy formation and evolution, fraction of dark matter transforms to visual matter with a relation of the form, m_vis = constant * (m_dark)^2/3. Using this relation and replacing MOND’s ‘critical acceleration’ with “current cosmic maximum angular acceleration”, galactic flat rotation speed range of (50 to 500) km/sec can be fitted well. Estimated flat rotation speeds of DD168, Milky Way and UGC12591 are 49.96 km/sec, 199.66 km/sec and 521.75 km/sec respectively. Based on these striking coincidences, it is possible to say that, MOND’s approach is implicitly connected with cosmological estimation of 95% invisible matter. Considering galactic total matter and current cosmic maximum angular acceleration, galactic working radii, angular velocity and visual matter density can be estimated. Even though, this model is free from ‘big bang’, ‘inflation’, ‘dark energy’, ‘flatness’ and ‘red shift’ issues, at 2.722 K, estimated present Hubble parameter is 66.24 km/sec/Mpc, cosmic radius is 146.3 times the Hubble radius, angular velocity is 146.3 times lower than the Hubble parameter and cosmic age is 146.3 times the Hubble age. With future observations and advanced telescopes, it may be possible to see far distant galaxies and very old stars far beyond the current observable cosmic radius.

In article questions of development low-waste technologies of processing of steel-smelting slag are considered, gland allowing by extraction and its connections from steel-smelting slag to receive additional raw materials for production became, and the remains to use in building industry. Studying of gravitational methods of enrichment of steel-smelting slag and heat treatment the ore-fuel of pellets is the basis for work. Proceeding from it, in work modern physic-mechanical, chemical and physical and chemical methods of researches (UV-spectroscopy, electronic microscopy, the granulometric analysis) are used.

Into the frame of the French TANDEM project (Tsunamis in the Atlantic and the English ChaNnel: Definition of the Effects through numerical Modelling) Principia has been working on the development and qualification of two in-house CFD software’s: the 2D EOLE-SV (Saint Venant) model for simulation of large scale tsunami propagation from the source up to coastal scale and the 3D EOLE-NS (Navier-Stokes) model dedicated to tsunami coastal impact modelling. This paper presents a large range of test cases carried out into the frame of the project and dedicated to the validation of numerical codes in various tsunami wave conditions. The main aspects of phenomena such as wave generation, propagation and coastal impact are investigated on academic situations. A real case simulation is concerned as well, the devastating 2011 Tohoku event which is compared with in-situ data.

In the introductory part of this review, the relevant results of mostly the latest experimental studies on carotenoid absorption and availability in the human body are briefly presented. The subsequent parts summarise such topics as carotenoid carriers, body transport and tissue delivery, before finally reporting on molecular-level studies of carotenoid binding by membrane receptors. The main message of the review is contained in the section describing computational investigations of carotenoid intercalation and dynamic behaviour in lipid bilayers. The relevance of these computational studies lies in showing the direct link between the microscopic behaviour of molecules and the characteristics of their macroscopic ensembles. Furthermore, studying the interactions between carotenoids and lipid bilayers, and certainly proteins, on the molecular- and atomic-level using computational methods facilitates interpretation and explanation of the macroscopic properties of these systems and, hopefully, helps to better understand the biological functions of carotenoids.

A three-dimensional vector field model is proposed, whose dimensions are the Hansen Solubility Parameters: dispersion parameter (δD), polarity parameter (δP), and hydrogen bonding parameter (δH). The vector space that defines the field has the peculiarity of having the dispersion vector with a magnitude of 2, as its base vector, while polarity and hydrogen bonding vectors have a magnitude of 1. A substance is characterised as a position vector, and the interaction between two substances is determined by calculating the vector difference of both, known as the interaction vector. Interaction among substances may involve solubility, swelling, cracking, surface tension, interface tension, and any physical phenomena where intermolecular energies of dispersion, polarity or hydrogen bonding come into play. This paper studies free surface energy (surface and interfacial tension). It has been found that free surface energy is directly proportional to the square of the magnitude of the interaction vector. The proportionality constant, τ, is expressed in length units, has a value of 0.025 nm, and does not depend on the chemical nature of the substance or state of matter (solid, liquid or gas). Constant value τ appears universal and aligns with the thickness of interfaces, thereby supporting Guggenheim's hypothesis. This hypothesis asserts that interfaces possess actual thickness and are not merely mathematical surfaces, as originally postulated by Gibbs. Moreover, it also has been found that interface thickness, τ, is approximately equal to half of the Bohr radius, a0, which is defined by universal constants. Because the solubility parameters of thousands of substances are known and can be easily determined from molecular structure, a good approximation of the surface and interfacial tension of any given substance can now be calculated. It has also been found that contact angles of sessile droplets in three-phased systems can be calculated from the interaction vectors of the implicated substances.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

Reactive oxygen species (ROS) play a pivotal role in cellular function, and their overproduction contributes to oxidative stress, fatigue, aging, and diseases. To counteract these effects, incorpo-rating antioxidant-rich nutrients is recommended. Functional waters, including electrolyzed hydrogen water (EHW), are gaining attention for potential antioxidant effects through daily in-take. This study employs aquaphotomics and near-infrared spectroscopy (NIRS) to elucidate the molecular mechanisms behind the antioxidant activity of EHW. Previous investigation reported a 100% loss in antioxidant functionality through autoclaving, and a 40% decrease with hydrogen gas removal, prompting the current investigation into the mechanisms of antioxidant effects and especially the role of water molecular structure in it. Aquaphotomics analysis of near infrared (NIR) spectral data revealed that the primary characteristic of EHW associated with anti-radical function is presence of water solvation shells. Autoclaving and degassing led to loss of these water molecular species and a significant increase in free water molecules. The study suggests that water shells (solvation shells) in EHW play a crucial role in neutralizing ROS, although the specific ions or nanoparticles responsible for creating these shells remain unidentified. This concept aligns well with existing proposals of the crucial role of water solvation shells in ROS neutralization.

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

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

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

With the intensive development of data transmitting and processing devices of the terahertz (THz) frequency range, an important part of which are integrated plasmonic components and communication lines, it becomes necessary to measure correctly the optical constants of their conductive surfaces. In the paper we describe a reliable method for determining the effective permittivity εm of a metal surface from the measured characteristics (refractive and absorption indices) of THz surface plasmon polaritons (SPPs). The novelty of the method is the conduction of measurements on a metal surface with a dielectric layer of subwavelength thickness, suppressing the radiative losses of SPPs, which are not taken into account by the SPP dispersion equation. The method was tested on a number of flat "gold sputtering - zinc sulfide layer - air" structures with the use of the THz radiation (λ0 = 141 μm) of the Novosibirsk free electron laser (NovoFEL). The SPP characteristics were determined from interferograms measured with a plasmon Michelson interferometer. It was found that the method allowed a significant increase in the accuracy of εm in comparison with measurements on the same metal surface without a dielectric layer.

Biosensors detect specific bio-analytes by generating a measurable signal from the interaction between the sensing element and the target molecule. Surface acoustic wave (SAW) biosensors offer unique advantages due to their high sensitivity, real-time response capability, and label-free detection. The typical SAW modes are the Rayleigh mode and the shear-horizontal mode. Both present pros and cons for biosensing applications and generally need different substrates and device geometries to be efficiently generated. This study investigates and characterizes ultra-high-frequency (UHF-) SAW resonator biosensors. It reveals the simultaneous presence of the two typical SAW modes, clearly separated in frequency, called slow and fast. The two modes are studied by numerical simulations and biosensing experiments with the glial-fibrillary-acidic-protein (GFAP) biomarker. The slow mode is generally more sensitive to changes in surface properties, such as temperature and mass changes, by a factor of about 1.4 with respect to the fast mode.

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

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 2004, first absolute gravity (AG) measurements were performed on the mountain tops of Mt. Zugspitze (2 sites) and Mt. Wank (1 site), and at the Wank foot (1 site). Wank (summit height 1780 m) and Zugspitze (2960 m) are about 20 km apart from each other and belong geologically to different parts of the Northern Limestone Alps. Bridging a time span of 15 years, the deduced gravity variations for Zugspitze are in the order of 0.30 μm/s² with a standard uncertainty of 0.04 μm/s². The Wank stations (foot and top) show no significant gravity variation. The vertical stability of Wank summit is also confirmed by results of continuous GNSS recordings. Because an Alpine mountain uplift of 1 or 2 mm/yr cannot explain the obtained gravity decline at Zugspitze, the dominating geophysical contributions are assumed to be due to the diminishing glaciers in the vicinity. The modelled gravity trend caused by glacier retreat between epochs 1999 and 2018 amounts to -0.012 μm/s²/yr at both Zugspitze AG sites. This explains more than half of the observed gravity decrease. Long-term variations on inter-annual and climate-relevant decadal scale will be investigated in the future using as a supplement superconducting gravimetry (installed in 2019) and GNSS equipment (since 2018).

There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.

We put forward a co-axial pump(optical)-probe(X-rays) experimental concept and show performance of the optical component. A Bessel beam generator with a central 100 micrometers-diameter hole (on the optical axis) was fabricated using femtosecond (fs) laser structuring inside a silica plate. This flat-axicon optical element produces a needle-like axial intensity distribution which can be used for the optical pump pulse. The fs-X-ray free electron laser (X-FEL) beam of sub-1 micrometer diameter can be introduced through the central hole along the optical axis onto a target as a probe. Different realisations of optical pump are discussed. Such optical elements facilitate alignment of ultra-short fs-pulses in space and time and can be used in light-matter interaction experiments at extreme energy densities on the surface and in the volume of targets. Full advantage of ultra-short 10 fs X-FEL probe pulses with fs-pump(optical) opens an unexplored temporal dimension of phase transitions and the fastest laser-induced rates of material heating and quenching. A wider field of applications of fs-laser-enabled structuring of materials and design of specific optical elements for astrophotonics is presented.

In this paper, spatial pulse position modulation (SPPM) is used as a case study to investigate the performance of the optical spatial modulation (SM) technique in outdoor atmospheric turbulence (AT). A closed-form expression for the upper bound on the asymptotic symbol error rate (SER) of SPPM in AT is derived and validated by closely-matching simulation results. The error performance is evaluated in weak to strong AT conditions. As the AT strength increases from the weak to strong, the channel fading coefficients become more dispersed and differentiable. Thus, a better error performance is observed under moderate-to-strong AT compared to weak AT. The performance in weak AT can be improved by applying unequal power allocation to make FSO links more distinguishable at the receiver. Receive diversity is considered to mitigate irradiance fluctuation and improve the robustness of the system to turbulence-induced channel fading. The diversity order is computed as half of the number of detectors. Performance comparisons, in terms of energy and spectral efficiencies, are drawn between the SPPM scheme and conventional MIMO schemes such as repetition coding and spatial multiplexing.

Barriers to inventing electronic devices involve challenges of iterating electronic designs due to long lead times for professional circuit board milling or high-costs of commercial milling machines. To overcome these barriers this study provides open source (OS) designs for a low-cost circuit milling machine. First, design modifications for mechanical and electrical sub-systems of the OS D3D Robotics prototyping system are provided. Next, Copper Carve, an OS custom graphical user interface, is developed to enable circuit board milling by implementing backlash and substrate distortion compensation. The performance of the OS D3D circuit mill is then quantified and validated for: positional accuracy, cut quality, feature accuracy and distortion compensation. Finally, the return on investment is calculated for inventors using it. The results show by properly compensating for motion inaccuracies with Copper Carve, the machine achieves a motion resolution of 10 microns, which is more than adequate for most circuit designs. The mill is at least five times less expensive than all commercial alternatives and the material costs of the D3D mill are repaid from fabricating 20-43 boards. The results show that the OS circuit mill is of high-enough quality to enable rapid invention and distributed manufacturing of complex products containing custom electronics.

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

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.

Quantum optimization is a significant area of quantum computing with anticipated near-term quantum advantages. Current quantum optimization algorithms, most of which are hybrid variational Hamiltonian-based algorithms, struggle on present quantum devices due to noise and decoherence. Existing techniques attempt to mitigate these issues through employing different Hamiltonian encodings or Hamiltonian clause pruning but often rely on optimistic assumptions rather than a deep analysis of the problem structure. We demonstrate how to formulate the problem Hamiltonian for the Quantum Approximate Optimization Algorithm to satisfy all the requirements that correctly describe the considered tactical aircraft deconfliction problem, achieving higher probabilities of measuring solutions compared to previous works. Our results indicate that constructing Hamiltonians from an unconventional, quantum-specific perspective with a high degree of entanglement results in linear number of entangleming gates instead of exponential and superior performance compared to standard formulations. Specifically, we achieve higher probabilities of measuring feasible solutions in 9 out of 9 instances compared to standard Hamiltonian formulations and surpass quadratic programming formulations known from quantum annealers in 7 out of 9 instances. These findings suggest that there is substantial potential for further research in quantum Hamiltonian design and that gate-based approaches may offer superior optimization performance over quantum annealers in the future.

Questions：SAP in mountainous cities of China serve as crucial carriers for species and wild food, constituting potential green infrastructure. These patches should be recognized as locally specific resources. This study investigates the transformation characteristics of the landscape patterns of SAP, along with their elements, across urban-rural gradients, providing foundational support for the planning of conservation and utilization strategies. Location: Yongchuan area of Chongqing in southwest China. Methods: The study investigated urban-rural gradient-based transformation of SAP. A four-direction transect space was selected and divided into uniform sample squares. Fragstats 4.3 calculated the landscape index of SAP, and Spearman correlation coefficients in SPSS were used to evaluate the influence of landform and artificial factors on agroforestry patch transformation. Results: 1) Patch area (PA), Plaque density (PD), and CLUMPY of SAP systematically transform, showing increased SAP areas and higher connectivity with greater distance from the city, resulting in reduced patch fragmentation. However, Edge density (ED) and Largest plaque index (LPI) exhibit irregular transformation patterns. 2) With increased distance from the city, woodland patch area and connectivity increase, leading to decreased fragmentation, dispersal, and lower fractal dimensions. Conversely, Cultivated land follows the opposite trend. garden land patch area, fractal dimension, fragmentation, and dispersal all increase, while connectivity decreases. 3) Landscape pattern transformations of SPA are significantly influenced by artificial factors. Woodland patches are influenced similarly by landform and artificial factors. In contrast, cultivated land and garden land patches are more significantly impacted by artificial factors. Conclusions: SAP exhibit differentiated conservation and utilization measures across urban-rural gradients. Small patches located far from urban centers may benefit from systematic conservation measures to prevent further fragmentation and erosion in peri-urban areas.

Small-scale facilities play a significant role in the landscape of nuclear physics research in Europe. They address a wide range of fundamental questions and are essential for teaching and training personnel in accelerator technology and science, providing them with diverse skill sets, complementary to large projects. The current status and perspectives of nuclear physics research at small-scale facilities in Europe will be given.

This paper aims to provide the smart grid research community with an open and accessible general mathematical framework to develop and implement optimal flexibility mechanisms in large-scale network applications. The motivation of this paper is twofold. On the one hand, flexibility mechanisms are currently a hot topic of research, which is aimed to mitigate variation and uncertainty of electricity demand and supply in decentralised grids with a high aggregated share of renewables. On the other hand, a large part of such related research is performed by heuristic methods, which are generally inefficient (such methods do not guarantee optimality) and difficult to extrapolate for different use cases. Alternatively, this paper presents an MPC-based (Model Predictive Control) framework explicitly including a generic flexibility mechanism which is easy to particularise to specific strategies such as Demand Response, Flexible Production and Energy Efficiency Services. The proposed framework is benchmarked with other non-optimal control configurations to better show the advantages it provides. The work of this paper is completed by the implementation of a generic use case which aims to further clarify the use of the framework and thus, to ease its adoption by other researchers in their specific flexibility mechanisms applications.

Crapemyrtle (Lagerstroemia indica L.: Lythraceae) is the most popular summer flowering tree in the U.S. Its total value sold has almost doubled since 1998. Consumers prize crapemyrtles for their beauty and pest resistance. However, current crapemyrtle production and use is being threatened by crapemyrtle bark scale (Acanthococcus lagerstroemiae (Kuwana, 1907)) (CMBS), which has been confirmed in 12 U.S. states after its first sighting in Texas in 2004. Our survey results indicate that producers anticipate a significant decrease in the value of crapemyrtle due to CMBS, in the magnitude of 29.93% and 33.79%, in our 2018 and 2019 surveys respectively. Our findings indicate industry demand for CMBS control. We used a non-parametric test to compare the producers’ responses to several questions regarding CMBS-control, among the different producer categories included in our sample. Incorporated businesses showed the most support, followed by part-nerships, and family/individual operations were the least supportive of science-based CMBS control research. Large businesses predicted a more serious decrease in crapemyrtles’ value as compared to smaller businesses. More businesses with high volume of crapemyrtle-related business considered the benefits of CMBS-control to be higher than its cost, as compared to other businesses. We also used a relative importance index to illustrate the ranking of different attrib-utes of crapemyrtles that producers consider while making decisions about growing/purchasing the plants. Flower color was found to be the most important attribute, followed by disease re-sistance. If the issue of CMBS gets out of control, the industry might need to find potential re-placements to crapemyrtle. The most popular landscape plants that can potentially replace crapemyrtle, in the opinion of producers we surveyed, are vitex (Texas lilac) and magnolia.

We consider the Dirac electron as a nonperturbative particle-like solution consistent with its own Kerr-Newman (KN) gravitational and electromagnetic field. We develop the earlier models of the KN electron regularized by Israel and López, and consider the non-perturbative electron model as a bag model formed by Higgs mechanism of symmetry breaking. The López regularization determines the unique shape of the electron in the form of a thin disk with a Compton radius reduced by 4π. In our model this disk is coupled with a closed circular string which is placed on the border of the disk and creates the caused by gravitation frame-dragging string tension produced by the vector potential of the Wilson loop. Using remarkable features of the Kerr-Schild coordinate system, which linearizes the Dirac equation, we obtain solutions of the Dirac equation consistent with the KN gravitational and electromagnetic field, and show that this solution takes the form of a massless relativistic string. Parallelism of this model with quantum representations in Heisenberg and Schrodinger pictures explains remarkable properties of the stringy electron model in the relativistic scattering processes.

Many models have been proposed to explain the intergalactic redshift using different observational data and different criteria for the goodness-of-fit of a model to the data. The purpose of this paper is to examine several suggested models using the same supernovae Ia data and gamma-ray burst (GRB) data with the same goodness-of-fit criterion and weigh them against the standard $\text{Λ}$ CDM model. We have used the redshift – distance modulus ( $z-\mu$ ) data for 580 supernovae Ia with $0.015\le z\le 1.414$ to determine the parameters for each model, and then use these model parameter to see how each model fits the sole SNe Ia data at $z=1.914$ and the GRB data up to $z=8.1$ . For the goodness-of-fit criterion, we have used the chi-square probability determined from the weighted least square sum through non-linear regression fit to the data relative to the values predicted by each model. We find that the standard ΛCDM model gives the highest chi-square probability in all cases albeit with a rather small margin over the next best model - the recently introduced nonadiabatic Einstein de Sitter model. We have made ( $z-\mu$ ) projections up to $z=1096$ for the best four models. The best two models differ in $\mu$ only by 0.328 at $z=1096$ , a tiny fraction of the measurement errors that are in the high redshift datasets.

The main foundations of the standard $\Lambda $CDM model of cosmology are that: 1) The redshifts of the galaxies are due to the expansion of the Universe plus peculiar motions; 2) The cosmic microwave background radiation and its anisotropies derive from the high energy primordial Universe when matter and radiation became decoupled; 3) The abundance pattern of the light elements is explained in terms of primordial nucleosynthesis; and 4) The formation and evolution of galaxies can be explained only in terms of gravitation within a inflation+dark matter+dark energy scenario. Numerous tests have been carried out on these ideas and, although the standard model works pretty well in fitting many observations, there are also many data that present apparent caveats to be understood with it. In this paper, I offer a review of these tests and problems, as well as some examples of alternative models.

In advanced world stroke is one of the disabling cause of death that can be managed with thrombolysis if presents early despite further risk of intracerebral haemorrhage. Secondary prevention is an important objective in ischaemic stroke where recurrence is very high with subsequent stroke. Carotid End Arterectomy impact a definitive and effective role for both symptomatic and asymptomatic carotid stenosis for secondary stroke prevention in selective cases. Thrombolysis is a potential primary management for certain group whereas carotid surgery employs secondary preventative measure in a specified ischaemic stroke group.

The sub-economic dynamics studies the relationship between people's economic impulses and market behavior. Using Bourbaki structuralism as a philosophical consideration and quantum chromodynamics as a conceptual and modeling method, sub-economic dynamics theory is constructed. In this theory, we discuss the deep structure of the free market and analyze the errors in Mises' anthropological arguments. Sub-economic dynamics is the psychological basis of market dynamics. Guided by the preface, this paper is divided into six sections: (1) The Free Market and Impulse Flavor Charge, including topics such as the fate of the free market, the food chain and psychology, and the flavor charge of economic impulses; (2) The Nature of Economic Impulses, including topics such as the flavor and generation of impulses and counter-impulses, and the bound state of impulses and fractional market charges; (3) Freud's Color Charge Space and Spin, including topics such as the Pauli exclusion rule and color charge, and Freud's personality theory; (4) Consciousness and Gluons; (5) Gauge Transformations and SU(3) Symmetry Group; and (6) General Discussion.

Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values < 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focus-es on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the glu-ten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and func-tional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and sin-gle arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, or GFD have no place in daily practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may have some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data sug-gest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.

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 objective of this study was to develop an ultrasonic-assisted procedure for the extraction of total phenolics from Citrus aurantium L. blossoms (CAB) and evaluate the free radical scavenging activity, anti-HMG-CoA reductase activity of total phenolics. In this work, a Box-Behnken design based on the single-factor experiments was used to explore the optimum extraction process. Under the optimum conditions (extraction solvent 70.31% ethanol, extraction temperature 61.94 °C, extraction time 51.73 min and liquid-to-solid ratio 35.63 mL/g), the extraction yield of total phenolics was 95.84 mg gallic acid equivalents (GAE)/g dry matter (DM), which was highly consistent with the theoretical value (96.12 mg GAE/g DM). The total phenolic extract showed excellent free radical scavenging properties against DPPH·, ABTS+·, ·OH and ·O2-, with the IC50 values of 197.007, 83.878, 218.643 and 158.885 μg/mL, respectively, and the extracts also showed good inhibition of HMG-CoA reductase activity, with the IC50 value of 117.165 μg/mL. Total phenolics from CAB could be a potential source of natural free radical scavenger and HMG-CoA reductase inhibitor.

Celiac disease (CD) is an immune-mediated gluten-induced enteropathy that affects predisposed individuals of all ages. Many patients with CD do not report gastrointestinal symptoms making it difficult to reach an early diagnosis. On the other hand, CD is related to a wide spectrum of extra-intestinal manifestations, being dermatitis herpetiformis (DH) the best characterized. These associated conditions may be the clue for reaching the diagnosis of CD. Over the last years, there have been multiple reports of the association between CD and several cutaneous manifestations that may improve with a gluten-free diet (GFD). The presence of some of these skin diseases, even in absence of gastrointestinal symptoms, should give rise to an appropriate screening for CD. The aim of this paper is to describe the different cutaneous manifestations that have been associated to CD and the possible mechanisms involved.

Background: Ice formation on power transmission lines presents significant risks, including structural damage and power outages. Traditional methods for detecting ice on these lines have limitations, particularly in challenging environmental conditions. This study aims to enhance ice detection accuracy by introducing a novel image segmentation and edge detection methodology using improved multi-scale Retinex and advanced morphological operations. Method: The proposed method integrates multi-stage image processing techniques, including image enhancement, grayscale conversion, thresholding, segmentation, object isolation, and edge detection. High-resolution binocular cameras were used to capture images of ice formations on transmission lines. The effectiveness of the method was assessed through a series of metrics, including accuracy, sensitivity, specificity, and precision, and compared with existing methodologies. Results: The proposed method demonstrated superior performance in both ice detection and thickness measurement. The method effectively identified and isolated ice formations under various conditions with an average accuracy of 98.35%, sensitivity of 91.63%, specificity of 99.42%, and precision of 96.03%. Additionally, the analysis of ice thickness measurements further highlighted the method’s accuracy, with a notably low root mean squared error (RMSE) of 1.20 mm and mean absolute error (MAE) of 1.10 mm, along with a strong R-squared value of 0.95. These statistical metrics show that the proposed method not only outperforms previous methods in consistency and alignment with manual measurements but also stands out as the most reliable option for tasks requiring precise measurements, offering significant advancements in accuracy and reliability over existing methodologies. Conclusions: The enhanced image segmentation and edge detection approach provides a more accurate and reliable method for monitoring ice formations on power transmission lines.

The present study aimed to evaluate the psychometric properties of the Greek version of the Jefferson Scale of Empathy—Student version (JSE-S) and its association with potential predictors among Greek-speaking undergraduate medical students. This study adopted a cross-sectional, comparative–descriptive research design. The study was conducted during October and November 2023. Cronbach’s α for the JSE-S was 0.846. Cronbach’s α values for the factors “perspective taking”, “compassionate care”, and “standing in the patient’s shoes” were 0.800, 0.715, and 0.748, respectively. The intraclass correlation coefficient for the JSE-S score in the test–retest study was 0.827 (95% CI = 0.647 to 0.915, p-value < 0.001), indicating a high level of reliability. The participants showed moderate empathy levels. Females scored higher than males on the Greek version of the JSE-S (108.8 vs. 102.8, p-value < 0.001). Moreover, students enrolled in the fourth academic year showed higher empathy mean scores than those enrolled in the first year (108.6 vs. 103.6, p-value = 0.012). Statistically significant empathy differences by specialty preferences or faith in God/supreme power were not found. The present study provided satisfactory evidence that the Greek JSE-S is a psychometrically sound measurement instrument. Empathy differences by gender were found in line with prior literature.

The study examines the behavior of the Mechanically Stabilized Earth (MSE) wall using available reinforcement materials in Danang, Vietnam. The MSE was reinforced by the self-fabricated galvanized steel grids using CB300V steel with 3 cm ribs. The backfill soil is a sandy clay soil from the local area with a low cohesion. A full-scale model with full instrumentation was installed to investigate the distribution of tensile forces along the reinforcement layers. The highest load that caused the wall to collapse due to internal instability (reinforcement rupture) was 302 kN/m2, which is 15 times the design load of 20 kN/m2. The failure surface within the reinforced soil had a parabolic sliding shape which is similar to the theoretical studies. At the failure load level, the maximum lateral displacement at the top of the wall facing was small (3.9 mm) which is significantly lower than the allowable displacements for the retaining wall. Furthermore, a numerical model using FLAC software was applied to simulate the performance of the MSE wall. The modeling results are in good agreement with the physical model. Thus, the self-fabricated galvanized steel grids could be confidentially used in combination with the local backfill soil for the MSE walls.

In the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for small-scale active pharmaceutical ingredient production. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well as continuous downstream processing, encompassing filtration, washing, and drying until the formation of free-flowing particles. We introduce a novel continuous nucleator designed based on solubility data and produced via 3D printing, enabling a fast and precise small-scale manufacturing of a nucleator meeting the requirements for nucleation and for the further growth processes. The nucleator was evaluated with regard to its suitability for continuous long-term operation across various coupled crystallizers. As a practical application example it is connected to a slug flow crystallizer to enable high-quality continuous crystallization. Additionally, the full integration of downstream processes using the continuous vacuum screw filter to achieve free-flowing product particles is realized. Even under non-optimized process conditions, with the help of in-situ generation of nuclei free-flowing product particles were successfully obtained. This is particularly useful during drug development when no material is available for seed addition and quickly obtain product for further characterization.

A numerical study for the effect of crest width, breaking parameter and trunk permeability on hydrodynamics and flow behavior in the vicinity of rubble-mound, permeable, zero-freeboard breakwaters (ZFBs) is presented. The modified two dimensional Navier-Stokes equations for two-phase flows in porous media with a Smagorinsky model for the subgrid scale stresses were solved numerically. An immersed-boundary/level-set method was used. The numerical model was validated for the cases of wave propagation over a submerged impermeable trapezoidal bar and over a low-crested permeable breakwater. Five cases of breakwaters were examined, and the main results are: (a) The size of the crest width, B, does not notably affect the wave reflection, vorticity and currents in the seaward region of ZFBs, while wave transmission, currents in the leeward side, and mean overtopping discharge, all decrease with increasing B. A non-monotonic behavior of the wave setup is also observed. (b) As the breaking parameter decreases, wave reflection, transmission, currents, mean overtopping discharge, and wave setup decrease. This observation is also verified by relevant empirical formulas. (c) As the ZFB trunk permeability decreases, an increase of the wave reflection, currents, wave setup, and a decrease of wave transmission and mean overtopping discharge is observed.

Computation of Common Middle Point seismic sections and their subsequent time migration and diffraction imaging provides very important knowledge about the internal structure of 3D heterogeneous geological media and are key elements for successive geological interpretation. Full-scale numerical simulation, that computes all single shot seismograms, provides a full understanding of how the features of the image reflect the properties of the subsurface prototype. Unfortunately, this kind of simulations of 3D seismic surveys for realistic geological media needs huge computer resources, especially for simulation of seismic waves’ propagation through multiscale media like cavernous fractured reservoirs. In order to significantly reduce the query of computer resources we propose to model these 3D seismic cubes directly rather than the shot-by-shot simulation with subsequent CMP stacking. To do that we modify the well known "exploding reflectors principle" for 3D heterogeneous multiscale media by use of the finite-difference technique on the base of grids locally refined in time and space. To be able to simulate realistic models and acquisition we develop scalable parallel software, which needs reasonable computational costs. Numerical results for simulation of Common Middle Points sections and their time migration are presented and discussed.

This paper introduces a model-free, "on-the-fly" learning control strategy for arrays of energy converters with adjustable generator damping. The devices are arranged so that they are affected simultaneously by the energy medium. Each device uses a different control strategy, of which at least one has to be the machine learning approach presented in this paper. During operation all energy converters record the absorbed power and control output; the machine learning device gets the data from the converter with the highest power absorption and so learns the best performing control strategy for each state. Consequently, the overall network has a better overall performance than each individual strategy. This concept is evaluated for wave energy converter (WEC) with numerical simulations and experiments with physical scale models in a wave tank. In the first of two numerical simulations, the learnable WEC works in an array with four WECs applying a constant damping factor. In the second simulation, two learnable WECs were learning with each other. It showed that in the first test the WEC was able to absorb as much as the best constant damping WEC, while in the second run it could absorb even slightly more. During the physical model test, the ANN showed its ability to select the better of two possible damping coefficients based on real world input data.

This paper develops Bayesian inference in reliability of a class of scale mixtures of log-normal failure time (SMLNFT) models with stochastic (or uncertain) constraint in their reliability measures. The class is comprehensive and includes existing failure time (FT) models (such as log-normal, log-Cauchy, and log-logistic FT models) as well as new models that are robust in terms of heavy-tailed FT observations. Since classical frequency approaches to reliability analysis based on the SMLNFT model with stochastic constraint are intractable, the Bayesian method is pursued utilizing a Markov chain Monte Carlo (MCMC) sampling based approach. This paper introduces a two-stage maximum entropy (MaxEnt) prior, which elicits a priori uncertain constraint and develops Bayesian hierarchical SMLNFT model by using the prior. The paper also proposes an MCMC method for Bayesian inference in the SMLNFT model reliability and calls attention to properties of the MaxEnt prior that are useful for method development. Finally, two data sets are used to illustrate how the proposed methodology works.

The increasing emergence of multidrug resistant (MDR) pathogens causes difficult-to-treat infections, with long-term hospitalizations and high incidence of death, thus representing a global public health problem. To manage MDR bacteria bugs, new antimicrobial strategies are necessary, and their introduction in practice is a daily challenge for scientists in the field. An extensively studied approach to treat MDR infections consists in inducing high levels of reactive oxygen species (ROS) by several methods. Although further clinical investigations are mandatory on the possible toxic effects of ROS to mammalian cells, clinical evaluations are extremely promising, and their topical use to treat infected wounds and ulcers, also in presence of biofilm, is already clinically approved. Biochar (BC) is a carbonaceous material obtained by pyrolysis of different vegetable and animal biomass feedstocks, at 200−1000 °C in limited presence of O2. Recently, it has been demonstrated that BC capability of removing organic and inorganic xenobiotics is mainly due to the presence of persistent free radicals (PFRs), which can activate oxygen, H2O2 or persulfate in the presence or not of transition metals by electron transfer thus generating ROS, which in turn degrade pollutants by advanced oxidation processes (AOPs). In this context, the antibacterial effects of BC containing PFRs have been demonstrated by some authors against Escherichia coli and Staphylococcus aureus, thus giving birth to our idea of the possible use of BC-derived PFRs as a novel method capable of inducing ROS generation for antimicrobial oxidative therapy. Here, the general aspects concerning ROS physiological and pathological production and regulation, and the mechanism by which they could exert antimicrobial effects have been reviewed. The methods currently adopted to induce ROS production for antimicrobial oxidative therapy have been discussed. Finally, for the first time, BC-related PFRs have been proposed as a new source of ROS for antimicrobial therapy via AOPs.

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

The work carried out first-principles calculations within the framework of density functional theory to study the structural stability of the CsSnI₃ compound and the influence of phase transitions on their electronic and optical properties. Using the GGA and SCAN functionals, the relaxed structures of the CsSnI₃ phases were obtained and their geometric characteristics were assessed. Using the Phonopy code based on VASP, calculations of phonon and thermodynamic properties were performed, and the temperatures of phase transitions of CsSnI₃ were determined. The temperature dependences of the thermodynamic parameters α-, β-, γ- and δ-phases of CsSnI₃ were analyzed. The trends in free energy, entropy, enthalpy, heat of formation energy and heat capacity were justified in terms of the pattern of changes in the total energy of the four phases of CsSnI₃ from VASP calculations. It is shown that at 0 K the non-perovskite structure of the CsSnI₃ compound (δ-CsSnI₃) is the most stable (followed by γ-CsSnI₃), and the tetragonal phase (β) is quite unstable, having the highest energy among the perovskite phases. It was revealed that at temperatures above 450 K the tetragonal phase becomes stable, and when the temperature drops, it transforms into the cubic phase (α-CsSnI₃). The phase transition between the β and γ phase of perovskite occurs in the range of 300-320 K, and at 320 K a black-yellow transformation of CsSnI₃ occurs in which the cubic phase (black perovskite) undergoes a phase transition to a non-perovskite conformation (yellow phase). The presence of temperature phase transitions between two orthorhombic phases of CsSnI₃ at 360 K was discovered, although direct transitions of the α⟷γ and γ⟷δ types have not yet been reported in any experiment, except for γ→δ transitions under the influence of moisture. Based on well-relaxed structures (from the SCAN calculations), the band gap widths for four CsSnI₃ phases were calculated and compared with experimental measurements. Electronic properties and Fermi level shifts as a result of phase transformations of CsSnI₃ were assessed using the HSE06 functional and machine learning prediction. The values of the complex dielectric constant and the refractive index of all phases of the CsSnI₃ were determined.

In the seasonally frozen regions, during the grouting of prestressed bridge ducts in low-temperature environments, incompletely cured grout materials undergo volumetric changes due to the freeze-thaw cycling, resulting in structural cracks along the prestressing ducts of the bridge, thereby diminishing the bridge's operational lifespan. To investigate the frost heaving characteristics of grout materials under freeze-thaw cycles and propose potential enhancements, this study was devised to conduct frost heaving stress tests on grout materials. Through this research, we gained insights into how various additives affect the frost heaving stress characteristics of grout materials under freeze-thaw cycles. Incorporating analyses of free water content, setting time, compressive strength, as well as macroscopic examinations such as XRD and SEM, this study delves into the mechanisms for enhancing frost heaving characteristics of grout materials. Furthermore, it proposes a research approach that utilizes multiple admixtures to improve the frost heaving properties of grout materials. Through frost heaving stress tests and other macroscopic experiments, the study investigates the influence of these combined admixtures on frost heaving stress in grout materials and elucidates the underlying improvement mechanisms. The results indicate that reducing the water-cement ratio, incorporating calcium formate, sulfoaluminate cement, air-entraining agents, and carbamide all have a positive impact on mitigating frost heaving stress in grout materials. However, the improvement mechanisms differ, and employing a single measure alone is insufficient to effectively reduce frost heaving stress while meeting performance criteria such as compressive strength, setting time, and flowability. Free water content emerges as a crucial indicator determining the magnitude of frost heaving stress in grout materials, with 11.5% of free water content representing the critical threshold for frost heaving in grout materials. Utilizing composite admixtures can simultaneously decrease free water content, lower the freezing point of free water, and alleviate frost heaving deformation, resulting in more efficient reduction of frost heaving stress. When the admixture content reaches 9.9%, frost heaving stress is eliminated, and the comprehensive performance parameters including compressive strength, setting time, and flowability meet the specified requirements.

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

Identifying or authenticating a computer user are necessary steps to keep systems secure on the network and to prevent fraudulent users from accessing accounts. Keystroke dynamics authentication can be used as an additional authentication method. Keystroke dynamics involves in-depth analysis of how you type on the keyboard, analysis of how long a key is pressed or the time between two consecutive keys. This field has seen a continuous growth in scientific research. In the last five years alone, about 10,000 scientific researches in this field have been published. One of the main problems facing researchers is the small number of public data sets that include how users type on the keyboard. This paper aims to provide researchers with a data set that includes how to type free text on the keyboard by 80 users. The data were collected in a single session via a web platform. The dataset contains 410,633 key-events collected in a total time interval of almost 24 hours. In similar research, most datasets are with texts written by users in English. The language in which the users wrote for this research is Romanian. This paper also provides an extensive analysis of the data set collected and presents relevant information for the analysis of the data set in future research.

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

Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1-2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance with it is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: a) periodic interviews by nutritionists; b) clinical follow-up; c) serological controls of specific antibodies; d) endoscopies with collection of duodenal biopsies; e) structured questionnaires; f) determination of gluten peptides derived from gluten in feces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within 2 years, while it is more delayed in adults, whose mucosa take longer to heal completely.

Meixner's historical remark in 1969 "... it can be shown that the concept of entropy in the absence of equilibrium is in fact not only questionable but that it cannot even be defined...." is investigated from today's insight. Several statements --such as the three laws of phenomenological thermodynamics, the embedding theorem and the adiabatical uniqueness-- are used to get rid of non-equilibrium entropy as a primitive concept. In this framework, Clausius inequality of open systems can be derived by use of the defining inequalities which establish the non-equilibrium quantities contact temperature and non-equilibrium molar entropy which allow to describe the interaction between the Schottky system and its controlling equilibrium environment.

Despite huge effort has been devoted to the design of the initiators and reaction conditions, it remains challenging to synthesize high molecular weight polypeptides with conventional solution phase synthesis. In this work, surface-initiated vapor deposition polymerization (SI-VDP) was utilized to graft synthetic polypeptides poly (γ-benzyl L-glutamate) (PBLG) from polystyrene (PS) resin beads by ring-opening polymerization of N-carboxyanhydrides (NCAs). It was demonstrated for the first time that high molecular weight bulk PBLG (> 500,000) could be readily obtained within one hour via solvent-free synthetic method which paves the way for the synthesis of copolypeptides with high molecular weight.

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters. A higher-order scheme is used to discretize geometry of the structure as well as the relevant physical quantities. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss-Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve computational efficiency, a Chebyshev approximation approach is applied to a fast calculation of the Green function that needs evaluation thousands of times. In addition, OpenMP parallel technique is used to the formation of influence coefficient matrix, which significantly reduces CPU time. Finally, computations are performed on wave exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates good performance of the present method.

Objective: To evaluate audiological outcomes, quality of life, and complications in patients implanted with Active middle ear implants (AMEI). The secondary objective is to investigate the required duration after implantation to reach satisfactory outcomes. Methods: This retrospective study included 31 patients implanted with Active middle ear implants (AMEI) with different methods of floating mass transducer attachment. Patients with incomplete medical records and those who did not respond to postoperative follow-up were excluded. Patients were assessed preoperatively, and at one, three, and six months postoperatively. The assessment included Pure Tone Average (PTA4), Speech Reception Threshold (SRT) and Speech Discrimination Score (SDS). The Speech Spatial and Qualities of Hearing scale (SSQ12) was also used to evaluate levels of satisfaction. Result: There are no significant differences found in PTA and SRT between the 3-, 6-, and 12-month visits. The speech reception threshold (SRT) showed a statistically significant improvement at 3, 6, and 12 months post-operative measures compared to pre-operative. Additionally, the SDS exhibited a significant increase only after 12 months, compared to the 3-month time point. However, satisfaction levels did not significantly differ between the 6-month and 12-month measurements following surgery. Conclusion: Vibrant Sound bridge improves subjective satisfaction scores and audiological test scores in patients with different types of hearing loss. AMEI has a low risk of medical or surgical complications, the ease of using a hearing implant, and the social benefits of good hearing and communication.

This study investigates the efficiency of a biogas-powered cooling system through the utilization of energy and exergy calculations. Biogas, which can be generated and stored in small-scale plants as needed, serves as a viable fuel source for absorption cooling systems. The present research focuses on the biogas consumption of a triple-effect absorption cooling system, specifically designed to supply a fixed cooling load of 100 kW under varying operational conditions. The study highlights the COP (Coefficient of Performance) and ECOP (Exergetic Coefficient of Performance) values of the system, along with the exergy destruction rates of its individual components, at the optimal temperatures of operation. Furthermore, to determine the necessary biogas consumption, the study explores the establishment of dedicated farms for various animal species, ensuring an adequate number of animals for biogas production. The findings reveal a COP of 1.78 and an ECOP of 35.4% at the optimized operating temperatures. The minimum mass flow rate of biogas is determined to be 0.0034 kg/s, facilitating the operation of the boiler with a methane content of 65%. The study concludes that a total of 290 head of cattle is required to generate the annual biogas consumption necessary for the cooling system. Also, number of the cattle is enough to establish 284 biogas plants in Bursa province in Türkiye.

Number of studies claim that tobacco control (TC) regulations are associated with reductions in smoking-related hospitalisation rates, however very few have estimated the impact of TC laws (TCL) at both countrywide and regional levels, and none of them - in relation to compliance with TC regulations. This study evaluates the effects of Russian TCL on hospital admission (HA) rates for pneumonia countrywide and in 10 Russian regions and the extent of these effects in connection with the compliance to TCL. Methods: HA rates for pneumonia during 2005–2019 were analysed to compare the periods before and after the adoption of TCL in 2013. An interrupted time series design and a Poisson regression model were used to estimate the immediate and long-term effects of TCL on pneumonia annual hospitalisation rates after the TCL adoption, compared with the pre-law period. The 10 Russian regions were compared using the TCL Implementation Scale (TCIS) developed on the basis of the results of Russian TC policy evaluation survey; Spearman’s rank correlation and linear regression models were employed. Results showed a 14.3% reduction in HA rates for pneumonia (RR 0.88; p=0.01) after the adoption of TCL in Russia with significant long-term effect after 2013 (RR 0.86; p=0.006). Regions with better enforcement of TCL exhibited greater reductions in pneumonia HA rates (rsp=−0.55; p=0.04); (=−4.21; p=0.02). Conclusions: TCL resulted in a sustained reduction in pneumonia hospitalisation rates, but these effects, varying by region, may depend on the scale of the TCL enforcement.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits in a population. To date, a total of 267 QTL for 29 quantitative traits have been reported in 13 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, scaffold sequences, or pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but were mainly based on simple sequence repeat (SSR) or single nucleotide polymorphism (SNP) markers. This article provides methods with software tools and database files to uniquely map SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules. Using these methods, 195 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters. Mapping of QTL from different studies to the same reference enables comparisons and facilitates genome-wide QTL analysis, candidate gene scanning, and breeding applications.

Nucleation is a fundamental and general process at the initial stage of first order phase transition. Although various models based on the classical nucleation theory (CNT) have been proposed to explain the energetics and kinetics of nucleation, detailed understanding on nanoscales are still required. Here we focus on homogeneous bubble nucleation, in which evaluation of the size dependence of bubble free energy is the key issue. We propose application of a formula in stochastic thermodynamics, the Jarzynski’s equality, for data analysis of molecular dynamics (MD) simulation to evaluate the free energy of bubble nucleation. As a test case, we performed a series of MD simulations with Lennard-Jones (LJ) fluid system. By applying an external spherical force field to equilibrated LJ liquid, we evaluated the free energy change during bubble growth as the Jarzynski’s ensemble average of required works. A fairly smooth free energy curve was obtained as a function of bubble radius in metastable liquid of mildly negative pressure conditions.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

We have considered a SEIR-SEI Vector-host mathematical model which captures malaria transmission dynamics, described and built on 7-dimensional nonlinear ordinary differential equations. We compute the basic reproduction number of the model; examine the positivity and boundedness of the model compartments in a region using well established methods viz: Cauchy’s differential theorem, Birkhoff & Rota’s theorem which verifies and reveals the well-posedness, and carrying capacity of the model respectively, the existence of the Disease-Free (DFE) and Endemic (EDE) equilibrium points were determined and examined. Using the Gaussian elimination method and the Routh-hurwitz criterion, we convey stability analyses at DFE and EDE points which indicates that the DFE (malaria-free) and the EDE (epidemic outbreak) point occurs when the basic reproduction number is less than unity (one) and greater than unity (one) respectively. We obtain a solution to the model using the Variational iteration method (VIM) (an unprecedented method) to each population compartments and verify the efficacy, reliability and validity of the proposed method by comparing the respective solutions via tables and combined plots with the computer in-built Runge-kutta-Felhberg of fourth-fifths order (RKF-45). We illustrate the combined plot profiles of each compartment in the model, showing the dynamic behavior of these compartments; then we speculate that VIM is efficient and capable to conduct analysis on Malaria models and other epidemiological models.

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

Free volume is an extremely important intrinsic defect in polymers. Structurally, the free volume is the randomly distributed holes in the polymer molecular chain segments. From the perspective of molecular movement, it is also the space needed for the movement of molecular segments. In proton exchange membrane fuel cells, the free volume is also the space needed for the directional conduction of protons. Irradiation grafting sulfonated polyvinylidene fluoride (PVDF) is one of the methods to produce proton exchange membrane with good proton channel rate. Using the LYS-1 program, based on the linear absorption coefficient and backscatter coefficient models, the percentage of annihilated positrons in PVDF in the two-layer model and the three-layer model was studied, and comparing the two fitting results it is determined that the model closest to the positron annihilation percentage required by the PALS experiment is the two-layer model, which allows the percentage of positrons that are annihilated in PVDF films with a thickness of 100 μm to reach 46% using the high energy positron source ⁴⁴Ti without using the positron moderator. Using positron annihilation lifetime spectrum (PALS) analysis methods, based on Eldrup's classical model of free volume, the influence of absorbed doses of α particles on the free volume and crystallinity of PVDF was investigated, respectively. Based on the two test results the model of cross-linking and degradation of polyvinylidene fluoride irradiated by α particles was determined. Afterwards, X-ray diffraction (XRD) methods was used to study the change of PVDF crystal area before and after irradiation. The XRD results are consistent with the results measured by PALS.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for survival of cancer patients. Therefore, extension and increasing quality of life of PC patients can be achieved by broadening the Cancer Screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need in standard, sensitive, robust, and commonly available screening and diagnosis tools for identification of early signs of cancer pathologies. In this respect, “Holy Grail” of cancer researchers and bioengineers for decades have been molecular sensing probes that would allow diagnosis, prognosis, and monitoring of cancer diseases by their interaction with cell-secreted and cellassociated PC biomarkers, e.g. PSA and PSMA correspondinly. At present, most PSA tests are performed at centralized laboratories using high throughput Total PSA immune analyzers which are suitable for dedicated laboratories and are not readily available for the broad health screening. Therefore, the current trend in detection of PC is developments of the portable biosensors for mobile laboratories and individual use. Phage display since its conception by George Smith in 1985 has emerged as a premier tool in molecular biology with widespread applications. This review describes how the paradigm of molecular evolution and phage display revolutionized the methods of early diagnosis and monitoring of PC.

With the rise of long-read sequencers and long-range technologies, delivering high-quality plant genome assemblies is no longer reserved to large consortia. Indeed, sequencing techniques but also computer algorithms have reached a point where the reconstruction of assemblies at the chromosome-scale is now feasible at the laboratory scale. Current technologies, and especially long-range technologies, are numerous and selecting the most promising one for the genome of interest is crucial to obtain optimal results. In this study, we resequenced the genome of the yellow sarson, Brassica rapa cv. Z1, using the Oxford Nanopore PromethION sequencer and assembled the sequenced data using current assemblers. To reconstruct complete chromosomes, we used and compared three long-range techniques, optical mapping, Omni-C and Pore-C sequencing libraries commercialized by Bionano Genomics, Dovetail Genomics and Oxford Nanopore Technologies respectively, or a combination of the three, in order to evaluate the capability of each technology.

This paper describes a proposed fractional filter-based multi-scale underwater and hazy image enhancement algorithm. The proposed system combines a modified global contrast operator with fractional order-based multi-scale filters used to generate several images, which are fused based on entropy and standard deviation. The multi-scale-global enhancement technique enables fully adaptive and controlled colour correction and contrast enhancement without over exposure of highlights when processing hazy and underwater images. This in addition to illumination/reflectance estimation coupled with global and local contrast enhancement. The proposed algorithm is also compared with the most recent available state-of-the-art multi-scale fusion de-hazing algorithm. Experimental comparisons indicate that the proposed approach yields better edge and contrast enhancement results without halo effect, colour degradation and is faster and more adaptive than all other algorithms from the literature.

Many tasks in a modern household are done by machines like e.g. a dishwasher or a vacuum cleaner and in the near future most household tasks can be done by smart service robots. This relieves the residents who in turn can enjoy their free time. This newly gained free time turns out to cause the so called spare time rebound effect due to more resource consumption [1,2]. We roughly quantify this rebound effect and propose a CO2 -budget model to reduce or even avoid it. In modern industry, automation and AI take over work from humans, leading to higher productivity of the company as a whole. This is the main reason for economic growth which leads to environmental problems due to higher consumption of natural resources. We show that, even though the effects of automation at home and in the industry are different (free time versus higher productivity) in the end they both lead to more resource consumption and environmental pollution. We discuss possible solutions to this problem such as carbon taxes, emissions trading systems and a carbon budget.

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

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90 loaded microspheres. This was a multicenter retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT) and 126 (36.3%) were classified as sarcopenic. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7) and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that sarcopenia (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p < 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p < 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment sarcopenia independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.

Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.

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.

The subject of this article is the dynamics of water in a soil pedostructure sample whose internal environment is subjected to a potential gradient created by the departure of water through surface evaporation. This work refers entirely to the results and conclusions of a fundamental theoretical study focused on the molecular thermodynamic equilibrium of the two aqueous phases of the soil pedostructure. The new concepts and descriptive variables of the hydro-thermodynamic equilibrium state of the soil medium, which have been established at the molecular level of the fluid phases of the pedostructure (water and air) in a previous article, are recalled here in the systemic paradigm of hydrostructural pedology. They allow access to the molecular description of water migration in the soil and go beyond the classical mono-scale description of soil water dynamics. We obtain a hydro-thermodynamic description of the soil's pedostructure at different hydro-functional scale levels including those relating to the water molecule and its atoms. The experimental results show a perfect agreement with the theory, validating at the same time the systemic approach which was the framework.

In this observational study, we compared continuous physiological signals during an active stand test in adults aged 50 years and over, characterized as frail by three different criteria, using data from The Irish Longitudinal Study on Ageing (TILDA). Four independent groups were identified: those characterized as frail only by one of the frailty tools used (the physical Frailty Phenotype (FP), the 32-item Frailty Index (FI), or the Clinical Frailty Scale (CFS) classification tree), and a fourth group where participants were not characterized as frail by any of these tools. Continuous non-invasive physiological signals were collected during an active stand test: systolic (sBP) and diastolic (dBP) blood pressure, as well as heart rate (HR), using digital artery photoplethysmography. Additionally, frontal lobe cerebral oxygenation (Oxy), deoxygenation (Deoxy), and tissue saturation index (TSI) were also non-invasively measured using near-infrared spectroscopy (NIRS). The signals were visualized across frailty groups and statistically compared using one-dimensional statistical parametric mapping (SPM). A total of 1,124 participants (mean age 63.5 years, 50.2% women) were included: 23 were characterized as frail only by FP, 97 by FI, 38 by CFS, and 966 by none of these criteria. SPM analyses revealed that only the group characterized as frail by FI had significantly different signals (p<0.05) compared to the non-frail group. Specifically, they exhibited a lesser increase in HR between 5-15 seconds post-stand and larger deficits in sBP and dBP between 15-40 seconds post-stand, and possibly a lower Delta TSI at 20 seconds post-stand. In this comparison, the FI proved more adept at capturing distinct physiological responses to standing, likely due to its direct inclusion of cardiovascular morbidities in its definition.

Individuals with low health literacy (HL) are known to have poorer health outcomes and to have higher mortality rates compared to individuals with higher HL: hence, the improvement of HL is a key outcome in modern healthcare systems. Healthcare providers are therefore asked to support patients’ literacy skills by encouraging the implementation of autonomy-supportive patient centered communication (PCC), which in turn requires the enhancement of patient engagement. Our main hypothesis is that the well-known relationship between autonomy-supportive PCC and HL is mediated by patient engagement which is known to play a role in HL promotion and that is related to PCC as well. The purpose of this study was to formulate a hypothetical structural equation model (SEM) linking PCC to patient engagement and HL. A cross-sectional survey design was employed involving 1007 Italian chronic patients. The hypothetical model was tested using SEM to verify the hypothesized mediation of patient engagement between PCC and HL. Results show that the theoretical model has a good fit indexes and that patient engagement fully mediates the relationship between PCC and HL. This finding suggests healthcare systems to implement a new paradigm where patients are supported to play an autonomous role in their own healthcare.

Compressive residual stresses in thin films can inhibit crack propagation under normal or sliding contact loading, with associated enhancement of the coating apparent toughness, load bearing capacity and wear resistance. This study investigates the influence of residual stress distributions on the thin film/substrate adhesion using a nanoindenter coupled with scanning electron microscope (SEM) investigations of indentation induced failure modes. Reactive and un-reactive magnetron sputtering with ion plating was used to coat a (100) silicon substrate with aluminum nitride (AlN) with and without an aluminum (Al) adhesion layer. The presence of an Al bond layer gives additional interfacial tensile stress because of the difference in thermal expansion coefficient. Additionally, a different magnitude of residual stresses in the AlN coating was achieved by changing the applied bias voltage onto the substrate. Wafer curvature method and incremental focused ion beam (FIB) milling, combined with high-resolution in situ scanning electron microscopy (SEM) imaging and full field strain analysis by digital image correlation (DIC), were used to measure the average and in-depth stress residual stress distribution in the produced coatings. The adhesion energy was then quantified by using a nanoindentation based model. Results demonstrate that the additional tensile residual stress in the aluminum adhesion layer decrease significantly the coating adhesion, even in presence of a higher compressive stress state in the AlN top-layer. Therefore, the coatings without Al-layer showed better adhesion because of a more homogeneous compressive residual stress in comparison with the coating having Al layer, even though both groups of coatings are produced under same bias voltage. Results are discussed, and some general suggestions are made on the correlation between coating/substrate property combination and the adhesion energy of multilayer stacks. The results suggested that Al bond-layer and inhomogeneous residual stresses affected the adhesion of AlN negatively to a substrate like silicon.