Tailoring extracellular vesicles (EVs) as targeted drug delivery systems to enhance the therapeutic efficacy showed superior advantage over liposomal therapies. Herein, we developed a novel nanotool for targeting B16.F10 murine melanoma, based on EVs stabilized with Polyethylene glycol (PEG) and loaded with doxorubicin (DOX). Nanosized EVs were efficiently enriched from melanoma cells cultured under metabolic stress by ultrafiltration coupled with size exclusion chromatography (UF-SEC) and characterized by size, morphology, and proteome. To reduce their clearance in vivo, EVs were PEGylated and passively loaded with DOX (PEG-EV-DOX). Our data suggested that the low PEG coverage of EVs might still favor EV surface protein interactions with target proteins from intratumor cells, ensuring their use as “Trojan horses” to deliver DOX to the tumor tissue. Moreover, our results showed a superior antitumor activity of PEG-EV-DOX in B16.F10 murine melanoma models in vitro and in vivo compared to that exerted by clinically applied liposomal DOX in the same tumor model. The PEG-EV-DOX administration in vivo reduced NF-κB activation and increased BAX expression, suggesting better prognosis of EV-based therapy than liposomal DOX treatment. Collectively, our results highlight the promising potential of EVs as optimal tools for systemic delivery of DOX to solid tumors.

The MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) Florian Goebel telescopes are a system of two Cherenkov telescopes located on the Canary island of La Palma (Spain), at the Roque de Los Muchachos Observatory, and operating in stereo mode since 2009. Their low energy threshold (reaching 15 GeV) allows the study of Active Galactic Nuclei (AGNs) in the very-high-energy gamma ray range with an impressive sensitivity up to the redshift limit of the existing IACT systems. MAGIC has collected many discoveries and comprehensive studies of different kinds of galaxies and their AGNs, also in a multi-wavelength context, expanding the knowledge of our Universe. Here we report the highlights which have been achieved by the MAGIC collaboration since the beginning of the operations.

This paper presents an exact solution to the Timoshenko beam theory (TBT) for first-order analysis, second-order analysis, and stability. The TBT covers cases associated with small deflections based on shear deformation considerations, whereas the Euler–Bernoulli beam theory (EBBT) neglects shear deformations. Thus, the Euler–Bernoulli beam is a special case of the Timoshenko beam. The moment-curvature relationship is one of the governing equations of the EBBT, and closed-form expressions of efforts and deformations are available in the literature. However, neither an equivalent to the moment-curvature relationship of EBBT nor closed-form expressions of efforts and deformations can be found in the TBT. In this paper, a moment-shear force-curvature relationship, the equivalent in TBT of the moment-curvature relationship of EBBT, was presented. Based on this relationship, first-order and second-order analyses were conducted, and closed-form expressions of efforts and deformations were derived for various load cases. Furthermore, beam stability was analyzed and buckling loads were calculated. Finally, first-order and second-order element stiffness matrices were determined.

This paper presents an approach to the Timoshenko beam theory (TBT) using the finite difference method (FDM). The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. The FDM is an approximate method for solving problems described with differential equations. It does not involve solving differential equations; equations are formulated with values at selected points of the structure. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. The model developed in this paper consisted of formulating differential equations with finite differences and introducing additional points at the beam’s ends and at positions of discontinuity (concentrated loads or moments, supports, hinges, springs, brutal change of stiffness, spring-mass system, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends. Moreover, grid points with variable spacing were considered, the grid being uniform within beam segments. First-order, second-order, and vibration analyses of structures were conducted with this model. Furthermore, tapered beams were analyzed (element stiffness matrix, second-order analysis, vibration analysis). Finally, a direct time integration method (DTIM) was presented; the FDM-based DTIM enabled the analysis of forced vibration of structures, with damping taken into account. The results obtained in this paper showed good agreement with those of other studies, and the accuracy was increased through a grid refinement. Especially in the first-order analysis of uniform beams, the results were exact for uniformly distributed and concentrated loads regardless of the grid.

This paper presents an approach to the elastic analysis of beams subjected to Saint-Venant torsion using Green’s theorem and the finite difference method (FDM). The Saint-Venant torsion of beams, also called free torsion or unrestrained torsion, is characterized by the absence of axial stresses due to torsion; only shear stresses are developed. A solution to this torsion problem consists of finding a stress function that satisfies the governing equation and the boundary conditions. The FDM is an approximate method for solving problems described with differential equations; it does not involve solving differential equations, equations are formulated with values at selected nodes of the structure. In this paper, the beam’s cross-section was discretized using a two-dimensional grid and additional nodes were introduced on the boundaries. The introduction of additional nodes allowed us to apply the governing equations at boundary nodes and satisfy the boundary conditions. Beams with solid sections as well as multiply connected cross-sections were analyzed using this model; shear stresses and localized stresses at reentrant corners, torsion constant, and warping displacements were determined. Furthermore, beams with thin-walled closed sections, single-cell or multiple-cell, were analyzed using the Prandtl stress function whereby a linear distribution of the shear stresses over the thickness was considered; closed-form solutions for shear stresses and torsion constant were derived. The results obtained in this study showed good agreement with the exact results for rectangular cross-sections, and the accuracy was increased through a grid refinement. For thin-walled closed sections, the shear stresses obtained at the centerline using the closed-form solutions were in agreement with the values using Bredt’s analysis but the maximal values in the cross-section, which did not necessarily occur at the position with the smallest thickness, were higher; in addition, the results using the closed-form solutions were in good agreement with those using FDM.

This paper presents an approach to the Euler-Bernoulli beam theory (EBBT) using the finite difference method (FDM). The EBBT covers the case of small deflections, and shear deformations are not considered. The FDM is an approximate method for solving problems described with differential equations. The FDM does not involve solving differential equations; equations are formulated with values at selected points of the structure. Generally, the finite difference approximations are derived based on fourth-order polynomial hypothesis (FOPH) and second-order polynomial hypothesis (SOPH) for the deflection curve; the FOPH is made for the fourth and third derivative of the deflection curve while the SOPH is made for its second and first derivative. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. In this paper, the FOPH was made for all of the derivatives of the deflection curve, and additional points were introduced at the beam’s ends and positions of discontinuity (concentrated loads or moments, supports, hinges, springs, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends and to satisfy the boundary and continuity conditions. Moreover, grid points with variable spacing were also considered, the grid being uniform within beam segments. First-order analysis, second-order analysis, and vibration analysis of structures were conducted with this model. Furthermore, tapered beams were analyzed (element stiffness matrix, second-order analysis). Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of structures, with damping taken into account. The results obtained in this paper showed good agreement with those of other studies, and the accuracy was increased through a grid refinement. Especially in the first-order analysis of uniform beams, the results were exact for uniformly distributed and concentrated loads regardless of the grid. Further research will be needed to investigate polynomial refinements (higher-order polynomials such as fifth-order, sixth-order…) of the deflection curve; the polynomial refinements aimed to increase the accuracy, whereby non-centered finite difference approximations at beam’s ends and positions of discontinuity would be used.

This paper aims to analyze arbitrarily loaded isotropic rectangular thin plates with two opposite edges supported (simply supported or clamped), from which one or both are clamped, and the other edges have arbitrary support conditions. Rectangular thin plates with two opposite edges simply supported are routinely analyzed using for the deflection the simple trigonometric series of Lévy or the double trigonometric series of Navier, while the loads are expanded in Fourier series. In this paper the flexibility method (or force method) of the linear beam theory was applied whereby the unknowns were the bending moments along the opposite edges; in this regard, the primary system was the plate simply supported along the above-mentioned opposite edges and subjected to the external loads, system solved using the Lévy solution, and the redundant system was the plate simply supported along the opposite edges and subjected to bending moments along those edges. In the redundant system, a modified Lévy solution was introduced to account for the edge moments. The compatibility equations (vanishing of the slopes at selected positions of the opposite edges) were set to determine the unknowns and so the efforts in the plate. The results obtained were in good agreement with the exact results.

This paper addresses the Hubble tension in cosmology by exploring dynamic dark energy models, specifically focusing on quintessence scalar fields. We develop a comprehensive theoretical framework for these models, examining various potential forms and their implications for the universe's evolution. We elaborate on the effects of dynamic dark energy on cosmological perturbations, analyzing its influence on the Cosmic Microwave Background (CMB) anisotropies and the formation of large-scale structures. By integrating the theoretical models with observational data, including Type Ia supernovae, CMB observations, and large-scale structure surveys, we investigate the potential of dynamic dark energy to resolve the discrepancies in measurements of the Hubble constant. Our findings suggest that dynamic dark energy models resolve the Hubble tension and have broader implications for our understanding of cosmic evolution and the universe's fate. This study aims to contribute to the ongoing discourse in cosmology, providing a new perspective on dark energy and its role in the expanding cosmos.

This paper presents an approach to the Kirchhoff-Love plate theory (KLPT) using the finite difference method (FDM). The KLPT covers the case of small deflections, and shear deformations are not considered. The FDM is an approximate method for solving problems described with differential equations. The FDM does not involve solving differential equations; equations are formulated with values at selected points of the structure. Generally in the case of KLPT, the finite difference approximations are derived based on the fourth-order polynomial hypothesis (FOPH) and second-order polynomial hypothesis (SOPH) for the deflection surface. The FOPH is made for the fourth and third derivative of the deflection surface while the SOPH is made for its second and first derivative; this leads to a 13-point stencil for the governing equation. In addition, the boundary conditions and not the governing equations are applied at the plate edges. In this paper, the FOPH was made for all of the derivatives of the deflection surface; this led to a 25-point stencil for the governing equation. Furthermore, additional nodes were introduced at plate edges and at positions of discontinuity (continuous supports/hinges, incorporated beams, stiffeners, brutal change of stiffness, etc.), the number of additional nodes corresponding to the number of boundary conditions at the node of interest. The introduction of additional nodes allowed us to apply the governing equations at the plate edges and to satisfy the boundary and continuity conditions. First-order analysis, second-order analysis, buckling analysis, and vibration analysis of plates were conducted with this model. Moreover, plates of varying thickness and plates with stiffeners were analyzed. Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of structures, with damping taken into account. In first-order, second-order, buckling, and vibration analyses of rectangular plates, the results obtained in this paper were in good agreement with those of well-established methods, and the accuracy was increased through a grid refinement.

This paper explores the interactions of dynamic dark energy with other components of the cosmos, such as dark matter and baryonic matter, and its wide-ranging implications in cosmology. By investigating the interplay between dynamic dark energy and the universe's large-scale structure, we aim to provide a deeper understanding of cosmic evolution and the behavior of dark energy in different cosmological epochs. We also examine the potential of dynamic dark energy to offer novel insights into long-standing cosmological puzzles and their impact on the formation and evolution of cosmic structures.

This paper is dedicated to examining dynamic dark energy models in the context of observational constraints and their implications for the universe's future. By integrating theoretical models with various observational data, we aim to provide a comprehensive view of how dynamic dark energy influences cosmic evolution and the universe's fate. This study tests these models against the latest observational evidence, including the Cosmic Microwave Background, supernovae, and large-scale structure surveys, to refine our understanding of the universe's accelerating expansion and the mysterious nature of dark energy.

In 1975, Fuller and Tabor have shown that roughness can destroy macroscopic adhesion. This means that in spite of the presence of adhesion at the microscopic scale, the macrosopic force of adhesion vanishes. The mechanism of vanishing macroscopic adhesion is very simple: during approach of elastic bodies, asperities are elastically deformed so strongly that after unloading they destroy the microscopic adhesive junctions. However, both in the moment of formation of microscopic adhesive junctions in the loading phase and their destruction during unloading, mechanical energy disappears. This means that the microscopic adhesion makes the contact dissipative even if there is no macroscopic force of adhesion. In particular, the force-distance dependency during indentation and pull-off do not coincide with each other showing some "adhesive hysteresis". When a ball rolls on such rough surface, there will be a final energy dissipation due to formation of a new contact at the frontline of the contact and its destruction at the rear part. Thus, microscopic adhesion will lead to appearance of rolling friction in an apparently non-adhesive contact. In the present paper, we calculate the approach and pull-off dependencies of force on distance, the dissipated energy in one loading-unloading cycle and estimate the force of rolling friction due to microscopic adhesion.

In the present study we introduce a deterministic mathematical model in order to study the interaction between the human immune system and a virus, like COVID 19. The mathematical analysis is based on the tools of dynamical systems theory, by modeling the interactions between the immune system and the virus, using a predator-prey method and following the ideas of G. Moza, from \cite{TGV}. It will be obtained some conclusions with medical relevance and the main three of them are the followings: 1) A deficiency of a single type of immunity in the early stages of virus proliferation, may lead to a large virus multiplication and the human body can loses the fight against this virus; 2) If the level of all components of the immunity system are at the normal threshold from the first moment of the infection and the immune system kill the virus at higher rate than the rate of virus reproduction, then the human body has the ability to stop the multiplication of the virus and liquidate it, that means the virus will be destroyed; 3) If the level of at least one type of immunity can be increased beyond the normal threshold, by medical interventions (like vaccination) in the early stages of virus infection, then the immune system has a better chance to win the fight with the virus.

In this study, we investigate Quantum Entanglement Asymmetry (QEA) as a potential explanation for the matter-antimatter imbalance observed in the universe. By integrating quantum mechanics with cosmological phenomena, the study proposes a model in which quantum entanglement among particle-antiparticle pairs in the early universe leads to an asymmetry favoring matter. Through theoretical development and numerical simulations, we explore how this model predicts unique patterns in Cosmic Microwave Background (CMB) anisotropies and the distribution of matter, setting a foundation for empirical verification. The study aims to enhance the understanding of cosmological asymmetries and highlight the significance of quantum entanglement in the universe's evolution.

In this paper it will be considered three deterministic models for the study of the interaction between the human immune system and a virus: the logistic model, the Gompertz model, and the generalized logistic model (or Richards model). A qualitative analysis of this models based on dynamical systems theory will be performed, by studying the local behavior of the equilibria and obtaining local dynamics properties from the linear stability point of view. Also, we will compare this models in order to understanding which is more appropriate to models the interaction between the human immune system and a virus. It will be obtained some natural medical interpretations which are available for all three models and can be useful to the medical community.

Symmetry concepts in parametrized dynamical systems may reduce the number of external parameters by a suitable normalization prescription. If, under the action of a symmetry group G, parameter space A becomes a (locally) trivial principal bundle, A ~ A/G x G, then the normalized dynamics only depends on the quotient A/G. In this way, the dynamics of fractional variables in homogeneous epidemic SI(R)S models, with standard incidence, absence of R-susceptibility and compartment independent birth and death rates, turns out to be isomorphic to (a marginally extended version of) Hethcote's classic endemic model, first presented in 1973. The paper studies a 10-parameter master model with constant and I -linear vaccination rates, vertical transmission and a vaccination rate for susceptible newborns. As recently shown by the author, all demographic parameters are redundant. After adjusting time scale, the remaining 5-parameter model admits a 3-dimensional abelian scaling symmetry. By normalization we end up with Hethcote's extended 2-parameter model. Thus, in view of symmetry concepts, reproving theorems on endemic bifurcation and stability in such models becomes needless.

A proposed low-temperature forging method aims to enhance stainless steel bearings by creating a martensitic subsurface layer, significantly boosting bearing fatigue life due to increased surface hardness. This technique induces beneficial residual stresses, particularly in axial bearings, streamlining their construction and improving machine elements. Challenges persist, especially with radial bearings, but simplicity in axial bearing forging promotes compact, resource-efficient facility construction. Future research will focus on applying this technique to axial bearing washers, potentially replicating success in other bearing components. Despite the energy ex-penditure for cooling during forging, the substantial increase in bearing fatigue life offsets this, enhancing overall longevity and reliability of critical machine components. Integration of this forging technique into bearing fabrication appears seamless, offering a promising trade-off be-tween energy use and enhanced performance.

This paper presents an approach to the analysis of beams with rectangular cross-sections subjected to Saint-Venant torsion using the Fourier analysis, body forces being not considered. The Saint-Venant torsion of beams, also called free torsion or unrestrained torsion, is characterized by the absence of axial stresses due to torsion; only shear stresses are developed. The solution to this torsion problem consists of finding the Prandtl stress function that satisfies the governing equation and the boundary conditions, the governing equation being such that the Laplacian of the stress function has a constant value within the cross-section. In this paper, Fourier sine series was utilized to describe the constant value of the above mentioned Laplacian, while double sine series or simple sine series was utilized to describe the Prandtl stress function. Closed-form solutions in form of infinite series were derived for shear stresses, torsional constant and warping function. Those solutions were identical to the exact solutions.

The object of this paper is the analysis of isotropic rectangular thin plates supported (simply supported or clamped) along two opposite edges whereby the other edges have arbitrary support conditions; the plates are subjected to external bending moments, concentrated or distributed, and perpendicular to the supported edges. The standard approach to this problem is to replace the bending moment with a couple of forces infinitely close and to use the known expressions of efforts and deformations for the plate subjected to concentrated forces; the results are then related to the first derivatives of those efforts and deformations with respect to the position of application of the load. In this study, the external bending moment was expanded into a Fourier series, leading to a distributed external bending moment, and the boundary conditions and continuity equations were applied. Various types of rectangular plates were analyzed, as well as plates of infinite length whose results were identical to those in the literature. In addition, results for cantilever plates of infinite length were presented.

This study presents an exact solution to the free vibration analysis of a uniform Timoshenko beam, with a harmonic vibration being assumed. The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. In this paper, a moment-shear force-circular frequency-curvature relationship was presented. The complete study was based on this relationship and closed-form expressions of efforts and deformations were derived. The free vibration response of single-span systems and spring-mass systems was analyzed; closed-form formulations of matrices expressing the boundary conditions were presented and the natural frequencies were determined by solving the eigenvalue problem. Systems with intermediate mass, spring, or spring-mass system were also analyzed. Furthermore, first-order dynamic stiffness matrices in local coordinates were derived. Finally, a second-order analysis of beams resting on an elastic Winkler foundation was conducted. The results obtained in this paper were in good agreement with those of other studies.

This paper presents an approach to the two-dimensional analysis of elastic isotropic deep beams using the finite difference method (FDM). Deep beams are subjected to in-plane loading and present a shear span to height ratio of less than 2.50; consequently, Euler-Bernoulli beam theory and Timoshenko beam theory do not apply. Deep beams analysis is generally conducted using numerical methods such as the finite element method and to a lesser extent the FDM; the strut-and-tie model and the stress field method are also widely utilized. Analytical approaches usually make use of the Airy stress function, where stresses are formulated in terms of the stress function; however, the exact solution of this function satisfying all of the boundary conditions can hardly be found, even for simple cases. In this paper, deep beams were analyzed using the FDM. The FDM is an approximate method for solving problems described with differential equations. The FDM does not involve solving differential equations; equations are formulated with values at selected nodes of the structure. Therefore, the deep beam was discretized with a two-dimensional grid, and additional nodes were introduced at the boundaries and at positions of discontinuity (openings, brutal change of material properties, non-uniform grid spacing), the number of additional nodes corresponding to the number of boundary conditions at the node of interest. The introduction of additional nodes allowed us to apply the governing equations at boundary nodes and satisfy the boundary and continuity conditions. An Airy stress function approach and a displacement potential function approach were considered in this study whereby strong formulations of equations (equilibrium, kinematic, and constitutive) were set. Stress and stability analyses were carried out with this model; furthermore, deep beams of varying stiffness, layered beams, and beams having openings were analyzed. For slender beams, the results obtained with the Airy stress function approach showed good agreement with those of the Euler-Bernoulli beam theory, and for deep beams, the shapes of stress distributions were in good agreement with a proper understanding of the behavior of structures. On the other hand, the displacement potential function approach delivered unsatisfactory results, probably due to the use of an inefficient equation solver; a more powerful tool will be needed in future research for this purpose.

The object of this paper is the bending analysis of isotropic rectangular Kirchhoff plates subjected to non-uniform heating (NUH) using the Fourier transform method. The bottom and top surfaces of the plate are assumed to have different changes in temperature, whereas the change in temperature of the mid-surface is zero. According to classical plate theory, the governing equation of the plate contains second derivatives of the NUH; these derivatives are zero by constant value of the NUH, which leads to its absence in the governing equation. This paper presented an approach by which Fourier sine transform was utilized to describe the NUH, while the double trigonometric series of Navier and the simple trigonometric series of Lévy were utilized to describe the deflection curve. Thus, the NUH appeared in the governing equation, which simplified the analysis. Rectangular plates simply supported along all edges were analyzed, bending moments, twisting moments, and deflections being determined. In addition, rectangular plates simply supported along two opposite edges were analyzed; the other edges having various support conditions (free, simply supported, and fixed).

This paper presents an approach to the vibration analysis of axially functionally graded non-prismatic Timoshenko beams (AFGNPTB) using the finite difference method (FDM). The characteristics (cross-sectional area, moment of inertia, elastic moduli, shear moduli, and mass density) of axially functionally graded beams vary along the longitudinal axis. The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. The FDM is an approximate method for solving problems described with differential equations. It does not involve solving differential equations; equations are formulated with values at selected points of the structure. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. In this paper, differential equations were formulated with finite differences, and additional points were introduced at the beam’s ends and at positions of discontinuity (supports, hinges, springs, concentrated mass, spring-mass system, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends and to satisfy the boundary and continuity conditions. Moreover, grid points with variable spacing were also considered, the grid being uniform within beam segments. Vibration analysis of AFGNPTB was conducted with this model, and natural frequencies were determined. Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of AFGNPTB, considering the damping. The results obtained in this study showed good agreement with those of other studies, and the accuracy was always increased through a grid refinement.

This paper presents an approach to the vibration analysis of axially functionally graded (AFG) non-prismatic Euler-Bernoulli beams using the finite difference method (FDM). The characteristics (cross-sectional area, moment of inertia, elastic moduli, and mass density) of AFG beams vary along the longitudinal axis. The FDM is an approximate method for solving problems described with differential equations. It does not involve solving differential equations; equations are formulated with values at selected points of the structure. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. In this paper, differential equations were formulated with finite differences, and additional points were introduced at the beam’s ends and at positions of discontinuity (supports, hinges, springs, concentrated mass, spring-mass system, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends and to satisfy the boundary and continuity conditions. Moreover, grid points with variable spacing were also considered, the grid being uniform within beam segments. Vibration analysis of AFG non-prismatic Euler-Bernoulli beams was conducted with this model, and natural frequencies were determined. Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of AFG non-prismatic Euler-Bernoulli beams, considering the damping. The results obtained in this paper showed good agreement with those of other studies, and the accuracy was always increased through a grid refinement.

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

A paradigm shift away from null hypothesis significance testing seems in progress. Based on simulations, we illustrate some of the underlying motivations. First, P-values vary strongly from study to study, hence dichotomous inference using significance thresholds is usually unjustified. Second, statistically significant results have overestimated effect sizes, a bias declining with increasing statistical power. Third, statistically non-significant results have underestimated effect sizes, and this bias gets stronger with higher statistical power. Fourth, the tested statistical hypotheses usually lack biological justification and are often uninformative. Despite these problems, a screen of 48 papers from the 2020 volume of the Journal of Evolutionary Biology exemplifies that significance testing is still used almost universally in evolutionary biology. All screened studies tested default null hypotheses of zero effect with the default significance threshold of p = 0.05, none presented a pre-specified alternative hypothesis, pre-study power calculation, and the probability of ‘false negatives’(beta error). The results sections of the papers presented 49 significance tests on average (median 23, range 0–390). Of 41 studies that contained verbal descriptions of a ‘statistically non-significant’ result, 26 (63%) falsely claimed the absence of an effect. We conclude that studies in ecology and evolutionary biology are mostly exploratory and descriptive. We should thus shift from claiming to ‘test’ specific hypotheses statistically to describing and discussing many hypotheses (possible true effect sizes) that are most compatible with our data, given our statistical model. We already have the means for doing so, because we routinely present compatibility (‘confidence’) intervals covering these hypotheses.

The rainfall study in the long term is essential for climatic change understanding and socioeconomic development. The main goal of this study is to explore the spatial and temporal variations of precipitation in different time scales (seasonal and annual) in Cameroon. The Mann–Kendall and Pettitt tests were applied to analyze the precipitation variability. On temporal plan, the different regions of Cameroon have recorded significant drops in annual rainfall that Pet-titt's test generally situates around the 1970s. The decreases observed for the northern part of Cameroon regions are between –5.4% (Adamawa) and –7.4% (Far North). Those of west-ern part regions oscillate between –7.5% (South-West) and –12.5% (West). The southern part of Cameroon regions recorded decreases varying between –4.3% (East) and –5.9% (Center). On spatial plan, the divisions of the northern, western and southern parts of Cameroon respectively recorded after the 1970s (a pivotal period in the evolution of precipitation on temporal plan), a precipitation decrease towards the South, the South-West and the West. This study's findings could be helpful for planning and managing water resources in Cameroon.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

The Standard Model (SM) of particle physics successfully describes electromagnetic, weak, and strong forces but omits gravity. We introduce the Kinematrix Field Theory (KFT), integrating gravity into this fundamental force framework through a novel particle, the kinematon. This gauge boson, existing in both massless and massive forms, advances the SM's scope to address enigmas like dark matter and neutrino masses. We detail the mathematical structure of the KFT and establish Feynman rules for kinematon interactions with fermions and gauge bosons. The KFT, synergizing with the Higgs mechanism and general relativity, aspires to a unified quantum theory of gravity. We explore the kinematon's phenomenological implications and potential experimental signatures, forecasting significant advancements in fundamental physics and setting a course for future explorations in the SM.

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

In this paper, we will consider an autonomous two-dimensional ODE Kolmogorov type 1 system with three parameters, which is a particular system of the general predator–prey systems with 2 a Holling type II. By reformulating this system as a set of two second order differential equations, we 3 will investigate the nonlinear dynamics of the system from the Jacobi stability point of view, using 4 the Kosambi-Cartan-Chern (KCC) geometric theory. We will determine the nonlinear connection, the 5 Berwald connection and the five KCC-invariants which express the intrinsic geometric properties 6 of the system, including the deviation curvature tensor. Furthermore, we will obtain necessary and 7 sufficient conditions on the parameters of the system in order to have the Jacobi stability near the 8 equilibrium points and we will point out these on a few examples.

According the JKR theory of adhesive contact, changes of the contact configuration after formation of the adhesive neck and before detaching are completely reversible. This means, that after formation of the initial contact, the force-distance dependencies should coincide, independently on the direction of the process (indentation or pull-off). In the majority of real systems, this invariance is not observed. The reasons for this may be either plastic deformation in the contacting bodies or surface roughness. One further mechanism of irreversibility (and corresponding energy dissipation) may be chemical heterogeneity of the contact interface leading to the spatial dependence of the specific work of adhesion. In the present paper, this "chemical" mechanism is analyzed on a simple example of an axisymmetric contact (with axisymmetric heterogeneity). It is shown that in the asymptotic case of a "microscopic heterogeneity", the system follows, during both indentation and pull-off, JKR curves, however, corresponding to different specific surface energies. After the turning point of the movement, the contact area first does not change and the transition from one JKR curve to the other occurs via a linear dependency of the force on indentation depth. The macroscopic behavior is not sensitive to the absolute and relative widths of the regions with different surface energy but depends mainly on the values of the specific surface energy.

The application of dry lubrication in rolling contacts is challenging due to wear. In previous studies graphene platelets applied as dry lubricants on the surfaces of angular contact ball bearings demonstrated superior properties. These specific bearings, experiencing both rolling and spinning motion, create more severe conditions for dry lubricants. The applied graphene platelets have a thickness of few graphene layers in the nm range and a diameter in the µm range. Such platelets can be produced by mechanical exfoliation from graphite. To delve deeper into the lubrication effects, investigations were carried out using a milli tribometer. In the tests, a fixed steel ball is sliding against an oscillating counterpart under defined load. During the measurements, the applied load and tangential forces on the ball are recorded to calculate the friction. In our case, a steel ball with a diameter of 6 mm was used against graphene-based films on flat bearing surfaces (axial bearing washer). Comparative investigations included nano graphite particles and fullerene as dry lubricants, in addition to graphene platelets of various staple thicknesses. To increase the adhesion of the films to the surfaces, a pre-rolling process was implemented. Afterwards, the friction on the compressed films was measured. The results indicate that the pre-rolling process effectively reduces the friction of the system. After testing, the surfaces underwent analysis using laser scanning microscopy to assess the formed films, wear, and material transfer. It has been demonstrated that the pre-rolling process leads to the formation of a very thin compacted film with surface protective properties. On the ball as counterpart, the graphene platelets generate a transfer film on the contacting surface.

This review focuses on the synthesis and biological activity of flavones and their related flavonoidic compounds: flavonols and aurones. Among the biological activities of flavones and aurones, the anticancer, antioxidant and antimicrobial properties are highlighted and detailed in this review. The most applied method for the synthesis of flavones and aurones is based on the oxidative cyclisation of o-hydroxychalcones. Depending on the reaction conditions and the structure of the precursor, in some cases several cyclization products result simultaneously: flavones, flavanones, flavonols and aurones. Based on the literature data and the results obtained in our research group, our aim is to highlight the most promising methods for the synthesis of flavones, as well as the synthetic routes for the other structurally related cyclization products, hydroxyflavones and aurones, considering that in practice it is difficult to predict which is the main or exclusive cyclisation product of o-hydroxychalcones under certain reaction conditions.

Objective: The aim of this in vitro study was to evaluate the accuracy of resin-based fixed dental restorations, namely veneers, single crowns, and four-unit fixed partial dental prosthesis (FPDs) using two different 3D printers and polymer-based materials. Materials and Methods: A standard maxillary polyurethane jaw model containing prepared teeth was scanned using an intraoral scanner. The generated STL data were used to design the restorations virtually using CAD software. Two 3D printers were utilized for the provisional digital light processing and stereolithography for the castable resin patterns. Each printer produced 10 specimens of each type of restoration, for a total of 80 restorations. The 3d-printed restorations were then 3D scanned using the same intraoral scanner and evaluated for external and internal dimensional accuracy in terms of trueness and precision. A one-way ANOVA and Two-sample T-Test were implemented to compute the precision (variability between groups) and trueness (with the designed CAD model). A level of statistical significance of p-Value

Atherosclerotic cardiovascular disease, a leading cause of morbidity and mortality worldwide, is a chronic inflammatory disease, linked to a state oxidative stress, with several well-identified culprits, of which low-density-lipoprotein cholesterol (LDL-C) and lipoprotein(a). No specific treatment is currently available to lower lipoprotein(a). It is, therefore, of paramount importance to identify nutritional factors that could lower lipoprotein(a). Growing evidence shows that although reducing saturated fatty acid (SFA) intake decreases LDL-C, it could increase lipoprotein(a). Optimal dietary recommendations may therefore differ depending on an in-dividual’s baseline lipoprotein(a) and LDL-C levels. Assessing the diet-induced true LDL-C response and net balance of these two atherogenic entities is difficult because LDL-C measurement is confounded by lipoprotein(a) cholesterol content. We have estimated, for the first time, the net atherogenic result of diet-induced variations of both LDL-C and lipoprotein(a), thanks to our new concept of LDLapoB risk equivalent=apoB+lp(a)x5 (in nmol/L). This is illustrated, via the rare case of a physician with very high lipoprotein(a) and hypobetalipoproteinemia. She experiences twice a considerable lipoprotein(a) increase (+32%, + 28mg/dL, + 67nmol/L) and higher LDLapoB risk equivalent (138mg/dL versus 123mg/dL) on a mediterranean diet, low in SFA. A reasonable SFA intake, despite causing marginal LDL-C increase, may be advisable in patients with high lipoprotein(a) who need personalized dietary recommendations.

Objectives: Treatment of aortic pathologies involving the distal ascending aorta, aortic arch, and descending aorta remains a complex and challenging procedure. Appropriate management is important to achieve satisfactory outcome. Surgical management aims to reduce the time of circulatory arrest. The optimal level of hypothermia is still a matter of debate. The present meta-analysis shows the influence of different temperature levels on mortality and morbidity following aortic arch surgery. Methods: We performed a meta-analysis of published data between January 2000 and March 2020 based on a literature research. 120 studies were included with a total of 32 323 patients divided into three different groups of systemic hypothermia (temperature group 1: ≥ 25 °C, temperature group 2: 25-20°C, temperature group 3: ≤ 20°C) were used for statistical analysis. Results: Early mortality was lowest in temperature group 1 compared to group 2 (OR = 1.42; 95% CI, 1.09-1.85; p=0.01) and group 3 (OR = 1.74; 95% CI, 1.20–2.52; p=0.003). Perioperative stroke appeared to be less frequently in temperature group 1 versus group 2 (OR = 1.48; 95% CI, 1.20-1.82; p=0.0002) and group 3 (OR = 1.61; 95% CI, 1.19 - 2.18; p=0.002). Similar results are obtained concerning new renal insufficiency (group 1 versus group 2: OR = 1.20; 95% CI, 0.91-1.57, p=0.19; group 1 versus 3: OR = 0.94; 95% CI, 0.67 - 1.32, p=0.73) and re-exploration for bleeding (group 1 versus group 2: OR = 1.10; 95% CI, 0.80-1.53, p=0.55; group 1 versus group 3: OR = 1.92; 95% CI, 1.26 - 2.94, p=0,0025). Conclusions: We observed that moderate level of hypothermia during circulatory arrest reduced the incidence of early mortality. Most dreaded neurologic complications occurred less frequently in TG 1. In contrast there was no difference with regards with new onset of renal failure which is commonly accepted as a reliable marker of the quality of visceral organ protection.

A hybrid material, consisting of commercially available nitrocellulose (NC) membrane non-covalently modified with amino-polyethylene glycol functionalized reduced graphene oxide (NH2-PEG-rGO) nanoparticles, was successfully synthesized for oligonucleotide extraction. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the modification of the NC membrane, revealing characteristic peaks of both compounds NC and NH2-PEG-rGO. Scanning Electron Microscopy (SEM) exhibited morphological changes in the NC/NH2-PEG-rGO hybrid membrane, marked by the introduction of NH2-PEG-rGO particles, resulting in a distinctly smothered surface compared to the porous surface of the NC control membrane. Wettability assays revealed hydrophobic behavior for the NC/NH2-PEG-rGO hybrid membrane, with a water contact angle exceeding 90°, contrasting with the hydrophilic behavior characterized by a 16.7° contact angle in the NC membrane. The performance of the NC/NH2-PEG-rGO hybrid membrane was evaluated for the extraction of ssDNA with fewer than 50 nucleotides from solutions containing various ionic species (MnCl2, MgCl2, and MnCl2/MgCl2). The NC/NH2-PEG-rGO hybrid membrane exhibited optimal performance when incubated in MgCl2, presenting the highest fluorescence emission at 525 relative fluorescence units (r.f.u.). This corresponds to the extraction of approximately 610 pg (≈13%) of the total oligo-DNA, underscoring the efficacy of the pristine material, which extracts 286 pg (≈6%) of oligo-DNA in complex solutions.

Globally, increasing rates of obesity are one of the most important health issues. The association between breakfast skipping and body weight is contradictory between cross-sectional and interventional studies. The systematic review and meta-analyses aim to summarize this association based on observational longitudinal studies. We included prospective studies on breakfast skipping and overweight/obesity or weight change in adults. Literature was searched until September 2020 in PubMed and Web of Science. Summary RRs with a 95% CI were estimated in pairwise meta-analyses by applying a random-effects model. In total, 9 studies were included in the systematic review and 6 of them were included in the meta-analyses. The meta-analysis indicated an 13% increased RR for overweight/obesity when breakfast was skipped on ≥ 3 days per week compared to ≤ 2 days per week (95% CI: 1.06, 1.21, n=3 studies). The meta-analysis on weight change displays a 21% increased RR for weight gain for breakfast skippers compared to breakfast eaters (95% CI: 1.05, 1.40, n=2 studies). The meta-analysis on BMI change displayed no difference between breakfast skipping and eating (RR=1.02, 95% CI: 0.99, 1.05, n=2 studies). This study provides low meta-evidence for an increased risk for overweight/obesity and weight gain for breakfast skipping.

This article analyzes the perspectives of professional training of the public administration staff, from the viewpoint of the sustainability criteria, starting from the experiences of the online courses run in the last two years. In order to understand the nature, type and magnitude of the changes caused by the Covid-19 pandemic in the field of professional training for public administration, we performed a survey among public institution employees, by applying a questionnaire. The instrument included qualitative elements, to allow the framing of statistical results. The article is grounded on the hypothesis that the professional training activities in the last two years were organized preponderantly online and it aims to analyze the sustainability of the new teaching systems/methods. The limitations of the study are given by the fact that each administrative system has structure particularities and its own legal framework regarding the professional training of public administration staff, what makes that the model proposed cannot be applied in all countries. The study provides a model of online professional training for public administration staff, sustainable, based on the experience accumulated in the last two years.

The order Mononegavirales harbors numerous viruses of significant relevance for human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the mononegavirales interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals.

Li-ion battery packs are the heart of modern electric vehicles. Due to their perishable nature, it is crucial to supervise them closely. In addition to on-board supervision over safety and range, insights into the battery’s degradation are also becoming increasingly important, not only for the vehicle manufacturers but also for vehicle users. The concept of digital twins has already emerged on the field of automotive technology, and can also help to digitalize the vehicle’s battery. In this work, we set up a data pipeline and digital battery twin to track the battery state, including state of charge (SOC), state of health (Capacity) (SOHc ) and state of health (Resistance) (SOHr ). To achieve this goal, we reverse-engineer the diagnostics interface of a 2014 e-Golf to query for Unified Diagnostic Services (UDS) messages containing both battery pack and cell-individual data. An on-board diagnosis (OBD) logger records the data with edge-processing capability. Pushing this data into the cloud twin system using IoT-technology, we can fit battery models to the data and infer cell individual internal resistance from them. We find that the resistances of the cells differ by a magnitude of two. Furthermore, we propose an architecture for the battery twin in which the twin fleet shares resources like models by encapsulating them in Docker containers run on a cloud stack. By using web technology, we present the analyzed results on a web interface.

Authentication systems based on biometrics characteristics and data represents one of the most important trend in the evolution of our world. In the near future, biometrics systems will be everywhere in the society, such as government, education, smart cities, banks etc. Due to its uniqueness characteristic, biometrics systems will become also vulnerable, privacy being one of the most important challenge. The classic cryptographic primitives are not sufficient to assure a strong level of secureness for privacy. The following work paper represents an effort to present the main cryptographic techniques and algorithms that can give us the possibility to raise a certain level of secureness for privacy. We will show their own challenges (strengths and weaknesses). We will demonstrate how we can use the most common and well-known techniques and algorithms in order to get a maximum efficiency and a high level in assuring the integrity of the biometrics data.

This analysis focuses on identifying the most efficient and cost-effective method of supplying power to a remote site, exploring photovoltaics (PV) and small wind turbines as primary power sources, and evaluating battery banks and hydrogen storage fuel cell systems as potential storage options. The hydrogen storage system converts surplus renewable power into hydrogen through an elec-trolyzer, storing it for later use in a fuel cell when renewable sources produce less power, enabling efficient energy storage during peak production periods. A sensitivity analysis of wind speed and hydrogen subsystem cost was conducted to evaluate the hydrogen storage system's performance. The optimal system graph suggests that the hydrogen subsystem must significantly decrease in cost to rival the battery bank, and in most cases, both the hydrogen system and battery bank were recommended together, offering reliable and efficient power for the remote site. While the battery bank is presently the more feasible option for powering the remote site, continuous monitoring and evaluation of both systems, considering site location, energy needs, and available resources, are essential to determine the most suitable power supply approach as technology advances and costs evolve over time.

The Hertzian contact theory, as well as most of the other classical theories of normal and tangential contact, provides displacements and the distribution of normal and tangential stress components directly in the contact surface. However, other components of the full stress tensor in the material may essentially influence the material behaviour in contact. Of particular interest are principal stresses and the equivalent von Mises stress, as well as the gradient of the hydrostatic pressure. For many engineering and biomechanical problems, it would be important to find these stress characteristics at least in the contact plane. In the present paper, we show that the complete stress state in the contact plane can be easily found for axially symmetric contacts under very general assumptions. We provide simple explicit equations for all stress components and the normal component of the gradient of hydrostatic pressure in the form of one-dimensional integrals.

Microalgae are abundant components of biosphere rich in low molecular weight carbohy-drate-containing natural products (glycoconjugates). Glycoconjugates take a part in processes of photosynthesis, provide producers with important biological properties, influence other organ-isms and known by biological activities. Some of them, for example glycosylated toxins and ar-senicals, are detrimental and can be transferring via food chains into higher organisms including humans. So far, the studies on a series of particular groups of microalgal glycoconjugates were not comprehensively discussed in special reviews. In this review, a special focus was made on the isolation, structure determination, properties and approaches to the search for new bioactive metabolites. Analysis of literature data concerning structures, functions and biological activities of ribosylated arsenicals, galactosylated and sulfoquinovosylated lipids, phosphoglycolipids, gly-coside derivatives of toxins, and other groups of glycoconjugates was carried out and discussed. The discovery of a great variety of new carbohydrate-containing metabolites, important biological roles some of them, participation in regulation of microalgal blooms via viral infections as well as the detection of potent immunomodulatory activity, shown by these type metabolites could be attributed to the most interesting recent achievements. Structures, properties and biological roles of glycoconjugates from microalgae attract a great attention growing year to year.

We examine the nonequilibrium production of topological defects -- braids -- in semiflexible filament bundles under cycles of compression and tension. During these cycles, the period of compression facilitates the thermally activated pair production of braid/anti-braid pairs, which then may separate when the bundle is under tension. As result, appropriately tuned alternating periods of compression and extension should lead to the proliferation of braid defects in a bundle so that linear density of these pairs far exceeds that expected in thermal equilibrium. Secondly, we examine the slow extension of braided bundles under tension, showing that their end-to-end length creeps nonmonotonically under a fixed force due to braid deformation and the motion of the braid pair along the bundle. We conclude with a few speculations regarding experiments on semiflexible filament bundles and their networks.

In this study, a new approach for estimating volume variations of lakes and reservoirs using water levels from satellite altimetry and surface areas from optical imagery is presented. Both input data sets, namely water level time series and surface area time series, are provided by DGFI-TUM‘s Database of Hydrological Time Series of Inland Waters (DAHITI). The approach is divided into three parts. In the first part, a hypsometry model based on the new modified Strahler approach is computed by combining water levels and surface areas. The hypsometry model describes the dependency between water levels and surface areas of lakes and reservoirs. In the second part, a bathymetry between minimum and maximum surface area is computed. For this purpose, DAHITI land-water masks are stacked using water levels derived from the hypsometry model. Finally, water levels and surface areas are intersected with the bathymetry to estimate a time series of volume variations in relation to the minimum observed surface area. The results are validated with volume time series derived from in-situ water levels in combination with bathymetric surveys. In this study, 28 lakes and reservoirs located in Texas are investigated. The absolute volumes of the investigated lakes and reservoirs vary between 0.099 km³ and 6.448 km³. The correlation coefficients of the resulting volume variation time series with validation data vary between 0.80 and 0.99. Overall, the relative errors with respect to volume variations vary between 2.8% and 14.9% with an average of 8.3% for all 28 investigated lakes and reservoirs. When comparing the resulting RMSE with absolute volumes, the absolute errors vary between 1.5% and 6.4% with an average of 3.1%. This study shows that volume variations can be calculated with a high accuracy which depends essentially on the quality of the used water levels and surface areas. In addition, this study provides a hypsometry model, high-resolution bathymetry and water level time series derived from surface areas based on the hypsometry model. All data sets are publicly available on the Database of Hydrological Time Series of Inland Waters (DAHITI, https://dahiti.dgfi.tum.de).

Fused deposition modeling (FDM) is a rather new technology in the production of personalized dosage forms. Melting and printing of polymer–active pharmaceutical ingredient (API) – mixtures can be used to produce oral dosage forms with different dosage as well as release behavior. This process is utilized to increase the bioavailability of pharmaceutically relevant active ingredients that are poorly soluble in physiological medium by transforming them into solid amorphous dispersions (ASD). Release from such ASDs is expected to be faster and higher compared to the raw materials and thus enhance bioavailability. Printing directly from powder while forming ASDs was realized. Different techniques to change release patterns as well as a non-destructive way for determination of API distribution were shown. By measuring the melt viscosities of mixtures printed a rheological model for the printer used is proposed.

In order to counter the impending shortage of skilled professionals in the aging societies of our time in many western countries such as Germany, solutions for business and society are urgently needed. Here, artificial intelligence (AI) can play an important role in mitigating the problem with the help of diverse applications. At the same time, it is important to consider both the needs of the respective employee1 and the company to ensure that the use of AI has a positive impact on the organization and finds social acceptance. In this article, we describe the newly developed OSQE model (Optimize, Secure, Qualify, Expand), which for the first time outlines an AI cycle against the shortage of skilled professionals in a holistic approach that focuses equally on people and companies. This can serve organizations as a guide for strategy development, decision-making for and implementation of AI-supported measures in an entire cycle of an employee's affiliation with a company. The model takes three driving forces into account: companies, professionals, and AI applications. In the model, the measures to be implemented are prioritized with ascending numbering based on what would be most urgent for a company to implement. All measures relate to areas of action that place people at the center and can be assigned to the classic cycle of belonging of an employee in the company. In this regard, the opportunities that AI offers to professionals and companies are highlighted.

The paper deals with the problems of direct kinematics related to a 2T6R robot, the direct kinematics of the plane mechanism of the robot. The direct kinematics of this proposed new robot help to study the movement, including the dynamic one, to determine the forces in the mechanism and to model the possible trajectories of the final effector point, thus determining the robot's working space and some of its multiple possible uses. Two totally different methods were used to verify the calculation relations, the results obtained by both methods being practically identical. The first method used is an original trigonometric method, and the second is an original geometrically analytical method.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Addressing the increasing nursing demand in the face of a limited nursing workforce, understanding job satisfaction and retention becomes critical. Our cross-sectional study, conducted among 2,572 nurses in Bavaria, Germany, uncovers a dichotomy where nurses have strong empathy for their profession yet yearn for significant improvements. The top areas identified for enhancement include (i) ensuring sufficient time for patient care, (ii) providing a reliable service organization with minimal unplanned shift changes, and (iii) streamlining nursing documentation. Moreover, the largest disparity between expectations and job satisfaction was measured in patient care time. Multivariable regression analysis further investigates factors influencing intentions to stay in the profession, including (i) demographic aspects (age, living conditions), (ii) working area, (iii) working hours, (iv) career choice satisfaction, (v) career opportunities, (vi) payment, (vii) working and rest times, and (viii) satisfaction derived from aiding individuals in challenging life situations. The findings uncover a need to change nursing conditions, and measures for younger nurses and elderly care nursing. Although there are limitations, and a potential bias due to convenience sampling, our study provides key insights into nursing conditions. Future research should broaden its scope to investigate nurse job satisfaction and retention, emphasizing potential relief tools such as digitization.

The transport sector in Germany causes one-quarter of energy-related greenhouse gas emissions. One potential solution to reduce these emissions is the use of battery electric vehicles. Although a number of life cycle assessments have been conducted for these vehicles, the influence of a transport system wide transition has not been researched sufficiently. Therefore, we developed a method which combines life cycle assessment with an agent-based transport simulation and synthetic electric, diesel and gasoline powered vehicle models. We use the transport simulation to obtain the number of vehicles, their lifetime mileage and road-specific consumption. Subsequently we analyze the product systems’ vehicle production, use phase and End-of-Life. The results are scaled depending on the covered distance, the vehicle weight and the consumption for the whole life cycle. The results indicate that the sole transition of drive trains is insufficient to significantly lower the greenhouse gas emissions. However, sensitivity analyses demonstrate that there is a considerable potential to reduce greenhouse gas emissions with higher shares of renewable energies, a different vehicle distribution and a higher lifetime mileage. The method facilitates the assessment of the ecological impacts of the complete car based transportation in urban agglomerations and is able to analyze different transport sectors.

Oral mucositis (OM) is inflammation of the mouth caused by damage to the mucous membranes that line the mouth and throat. It is a side effect of cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy, chemotherapy, and/or immunotherapy with immune checkpoint inhibitors. The etiology and pathogenic mechanisms of OM is complex and multifaceted, involving cytotoxicity (cell death), inflammation, infection, change in microbiome, and immune-mediated cytotoxicity. We summarize the literature about attempts to use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) to elucidate the biological pathways associated with the development or the severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and local environment (microbiomics).

The paper proposes a universal algorithm for parallelizing calculations that arise when using highly-optimized minimization functions available in many computing packages. The main idea of the proposed algorithm is based on the fact that although the “inner workings” of the minimization function used may not be known to the user, it inevitably uses in its work auxiliary functions that implement the calculation of the minimized functional and its gradient, which are usually implemented by the user, which means that in most cases they can be parallelized relatively easily. The paper discusses in detail both the parallelization algorithm and its software implementation using MPI parallel programming technology. Examples of the software implementation of the proposed algorithm are demonstrated using the Python programming language, but can be easily rewritten using the C/C++/Fortran programming languages.

Powerful emitters of the ultraviolet C (UVC) light in the wavelength range of 230-280nm are necessary for the development of effective and safe optical disinfection technologies, high-sensitive optical spectroscopy and non-line-of-sight optical communication. This review considers such UVC-emitters with electron-beam pumping of heterostructures with quantum wells in the (Al,Ga)N material system. The important advantages of these emitters include the absence of the critical problem of p-type doping and the possibility of achieving record (up to several tens of watts for peak values) output optical power values in the UVC range. The review consistently considers about a decade of world experience in the implementation of various UV emitters with various types of thermionic, field-emission, and plasma-cathode electron guns (sources) used to excite various designs of active (light-emitting) regions in heterostructures with quantum wells AlxGa1-xN/AlyGa1-yN (x = 0 − 0.5, y = 0.6 − 1) fabricated either by metal-organic chemical vapor deposition or by plasma-activated molecular beam epitaxy. Special attention is paid to the production of heterostructures with multiple quantum wells/two-dimensional(2D) quantum disks GaN/AlN with a monolayer (1ML ~ 0.25nm) thickness, which ensures a high internal quantum efficiency of radiative recombination in the UVC range, low elastic stresses in heterostructures, and a high output UVC-optical powers.

Many engineered approaches have been proposed over the years for solving the hard problem of performing indoor localisation using smartphone sensors. However, specialising these solutions for difficult edge cases remains challenging. Here we propose an end-to-end hybrid multimodal deep neural network localisation system, MM-Loc, relying on zero hand-engineered features, learning them automatically from data instead. This is achieved by using modality-specific neural networks to extract preliminary features from each sensing modality, which are then combined by cross-modality neural structures. We show that our choice of modality-specific neural architectures is capable of estimating the location with good accuracy independently. But for better accuracy, a multimodal neural network fusing the features of early modality-specific representations is a better proposition. Our proposed MM-Loc solution is tested on cross-modality samples characterised by different sampling rates and data representation (inertial sensors, magnetic and WiFi signals), outperforming traditional approaches for location estimation. MM-Loc elegantly trains directly from data unlike conventional indoor positioning systems, which rely on human intuition.

The quest for surgical advancements regarding the enhancement of the submental and cervicofacial regions has witnessed a remarkable upsurge in recent years. Informed patients are actively seeking sophisticated plastic surgery techniques to achieve comprehensive rejuvenation in these specific areas. Our clinical practice encounters an annual influx of approximately 400 patients, with 20% of them aged over 60, seeking facial rejuvenation encompassing the details of lower third of the face and neck. Common concerns expressed by these patients include sagging of the jawline, the emergence of deep perioral wrinkles, and the formation of "marionette lines" within the lower third of the face. Furthermore, the manifestation of age-related signs, including neck laxity, submental adipose accumulation, "witch's chin" deformity, and weakened platysma musculature, is frequently encountered within this intricate anatomical domain. This review aims to summarize the recent technical improvements, historical evolution, indications, postoperative care and challenges for facial rejuvenation of the lower third of the face and neck. Lastly, the application of minimally invasive procedures as part of a comprehensive approach to an aging face will also be discussed.

Solar photovoltaic (PV) technology is a cornerstone of the global effort to transition towards cleaner and more sustainable energy systems. This paper explores the pivotal role of PV technology in re-ducing greenhouse gas emissions and combatting the pressing issue of climate change. At the heart of its efficacy lies the efficiency of PV materials, which dictates the extent to which sunlight is transformed into electricity. Over the last decade, substantial advancements in PV efficiency have propelled the widespread adoption of solar PV technology on a global scale. The efficiency of PV materials is a critical factor, determining how effectively sunlight is transformed into electricity. Enhanced efficiency, achieved through a decade of progress, has driven the global expansion of solar PV. Multi-junction photovoltaic materials have now exceeded 40% efficiency in lab tests. China leads the world in solar PV installations, boasting over 253 GW of installed capacity by the end of 2021. Other prominent countries in this sector are the United States, Japan, Germany, and India. Supportive policies like feed-in tariffs, net metering, tax incentives, and cost reductions in PV modules have made solar PV increasingly competitive against fossil fuel-based power generation. Solar PV technology holds immense potential for creating a cleaner, reliable, scalable, and cost-effective electricity system. To expedite its deployment and foster a more sustainable energy future, continued investment in research and development, along with supportive policies and market mechanisms, is essential. This paper underscores the pivotal role of solar PV technology in the global energy transition and advocates for a concerted effort to unlock its full potential in achieving a more sustainable and resilient energy future.

Although previous studies have focused on the adverse effects of the COVID-19 pandemic on various professional groups (particularly in the health and nursing care sector), this study aims to close a research gap by assessing perspectives of students and young professionals in epidemiology and public health in Germany in terms of shifts in workload, work content, and related challenges caused by the pandemic. We conducted a cross-sectional survey between mid-February and mid-March 2022. Quantitative data were analyzed via standardized mean differences. Qualitative data based on answers to open-ended questions were analyzed via a qualitative content analysis. Overall, 172 individuals participated in this survey. Results indicate that students felt burdened the most by lack of exchange with other students and lecturers. Study participants employed in public health experienced changes in their employment, because they had changes in their work content- and administration-wise, which was accompanied with a high burden due to the workload. Multiple demands that can have an impact on both acquired skills and mental health during the professional qualification phase were mentioned by the participants. Therefore, more in-depth analyses are needed for investigating the impact the pandemic will have on the (future) public health workforce in the long run.

Vertical Indoor Farming (VIF) with hydroponics offers a promising perspective for sustainable food production. Intelligent control of VIF system components plays a key role in reducing operating costs and increasing crop yields. Modern machine vision (MV) systems use Deep Learning (DL) in combination with camera systems for various tasks in agriculture, such as disease and nutrient deficiency detection, and flower and fruit identification and classification for pollination and harvesting. This study presents the applicability of MV technology with DL modelling to detect the growth stages of chilli plants using YOLOv8 networks. The influence of different bird’s eye and side view datasets and different YOLOv8 architectures was analysed. To generate the image data for training and testing the YOLO models, chilli plants were grown in a hydroponic environment and imaged throughout their life cycle using four camera systems. The growth stages were divided into growing, flowering and fruiting classes. All trained YOLOv8 models showed reliable identification of growth stages with high accuracy. The results indicate that models trained with data from both views show better generalisation. YOLO’s middle architecture achieved the best performance.

The term immersive technology refers to various types of technologies and perspectives that are constantly changing and developing. It can be used for different purposes and domains such as: education, healthcare, entertainment, arts, and engineering. This research paper aims to examine which training method is more effective between the traditional approach, using PowerPoint and the immersive technology approach, through mixed reality using a HoloLens 2 device. The experiment involves comparing two groups of students who received different training methods: the first group saw a PowerPoint slide with an image of the human muscular system, while the second group saw a 3D hologram of the human body that showed the same muscle groups as in PowerPoint. The researchers wanted to test whether mixed reality devices could enhance students' cognitive functions and to investigate if the IQ of the participants had any influence in the effectiveness of the teaching method. The main finding of this study is that the instructions given with mixed reality technology, via the Microsoft HoloLens 2 device, are more appropriate for participants who have an IQ score below 100 points. For the other participants, with an IQ score above 100 points, the PowerPoint support was more suitable.

Amid to the COVID-19 pandemic, digital health literacy (DHL) has become a significant public health concern. This research aims to assess information seeking behavior, as well as the ability to find relevant information and deal with DHL among university students in Pakistan. An online-based cross-sectional survey, using a web-based interviewing technique, was conducted to collect data on DHL. Simple bivariate and multivariate linear regression was performed to assess the association of key characteristics with DHL. The results show a high DHL related to COVID-19 in 54.3% of students. Most of the Pakistani students demonstrated ~50% DHL in all dimensions, except of reliability. Multivariate findings showed that gender, sense of coherence and importance of information were found to be significantly associated with DHL. However, a negative association was observed with students’ satisfaction with information. This led to the conclusion that critical operational and navigations skills are essential to achieve COVID-19 DHL and cope with stress, particularly to promote both personal and community health. Focused interventions and strategies should be designed to enhance DHL amongst university students to combat the pandemic.

(1) Background: The mediolateral patella displacement is of interest for diagnostics and clinically relevant research questions. Apart from manual testing, no standardized method is currently available. Proper quantification of patella mobility is necessary to understand pathologies at the patellofemoral joint better; (2) Methods: Patella mobility was assessed in 25 healthy individuals using a Patellostabilometer, a new prototype instrument for quantification of the mediolateral patella displacement. The participants underwent measurements of the mediolateral displacement three times using the Patellostabilometer. A maximal force of 10N was applied for patella movement. Additionally, leg length, circumference of the knee, upper- and lower leg was measured. (3) Results: Lateral patella displacement of 18.27±3.76 mm (range 15.85-20.64mm, interquartile range (IQR) of 4.79) was measured. The medial patella displacement showed 24.47±6.59mm (range 19.29-29.76mm, IQR of 10.47). The test-retest measurement error was 2.32±1.76mm (IQR of 2.38mm), with five outliers. There was greater test-retest variability between the measurements of the medial displacement comparing to the lateral one (4) Conclusions: The test-retest variability reached 7% of the patella displacement. Other parameters provided no significant correlations. Based on the natural patellofemoral mobility a precise and clinically relevant quantification of patella mobility is allowed.

Spatial planning holds a key role in preventing or mitigating the impacts of climate change on both cities and rural areas, taking a forward-thinking and holistic approach to urban and regional development. As such, spatial planning deals with challenges occurring at different scales and across sectors. The international literature points out the need for horizontal and vertical cooperation to tackle climate change impacts. While there is abundant knowledge regarding the challenges related to climate change at different spatial levels, procedural integration into planning frameworks and practice is currently under-researched. This paper presents a novel theoretical framework that integrates various steps towards a holistic, integrative and adaptive climate proofing process. An iterative process was used for conceptual development, based on literature review followed by external feedback meetings and two workshops with the core team of planning experts responsible for exchange across federal states. By specifically addressing the challenges relating to cross-regional and cross-sectoral planning, this novel framework attempts to (i) facilitate a hierarchy of measures, (ii) maximise co-benefits for various adaptation purposes and climate change mitigation and (iii) foster the long-term institutionalisation of integrative processes across sectors, planning areas and policy levels.

Even though the current classic aerospace propulsion methods are greatly improved, some of the most modern methods have already been introduced, among which the propulsion with electric motors. Energy can be obtained from hydrogen burners, honeycomb burners to protect the burning of hydrogen that burns 10 times faster than conventional oil fuels or alcohols. Hydrogen storage is also done in honeycomb cell reservoirs. Getting solar photovoltaic power even during flight is not yet profitable or efficient, but it can be proposed in the future for lighter and/or spacecraft. A great desire is to dismantle water in hydrogen and oxygen directly on the aircraft, so the stored fuel is actually water and the one actually used is the hydrogen removed from the water. In this case, there is no need for hydrogen storage. And other modern methods of propulsion and energy acquisition are briefly presented in the paper.

Long-chain branched metallocene-catalyzed high-density polyethylenes (LCB-mHDPE) were solution blended to obtain blends with varying degrees of branching. A high molecular LCB-mHDPE was mixed with low molecular LCB-mHDPE are varying concentrations, whose rheological behavior is similar but whose molar mass and molar mass distribution is significantly different. Those blends were characterized rheologically to study the effects of concentration, molar mass distribution, and long-chain branching level of the low molecular LCB-mHDPE. Owing to the ultra-long relaxation times of the high molecular LCB-mHDPE, the blends started behaving clearly more long-chain branched than the base materials. The thermorheological complexity showed an apparent increase in the activation energies Ea determined from G’, G”, and especially δ. Ea(δ), which for LCB-mHDPE is a peak function, turned out to produce even more pronounced peaks than observed for regular LCB-mPE and also LCB-mPE with broader molar mass distribution. Thus, it is possible to estimate the molar mass distribution from the details of the thermorheological complexity.

Sulphuric acid is a widely used raw material in the chemical industry. Its corrosive effect on materials varies considerably, depending on impurities, temperature and water content. Accordingly, good corrosion resistance under all conditions is very difficult to achieve. This is especially an issue for micro process apparatus with very thin walls. Furthermore, such devices are often joint by diffusion bonding what may alter materials properties due to high temperatures and long dwell times. In fact, for each new material, the diffusion bonding parameters must be optimized and the impact on mechanical as well as corrosion properties must be investigated. In this paper, two high molybdenum alloys, namely Hastelloy B3 and BC-1, were evaluated. Diffusion bonding tests were performed using ten layers of sheet material in between round stock. Corrosion tests were performed in 70 % sulphuric acid at 100°C for 1000 h. Tensile tests on both alloys were carried out for different material conditions, to determine the change in mechanical strength and elongation at fracture values. In general, independent of the condition of the materials, the fracture behavior of both alloys was found to be ductile and the specimens show the typical dimple structure, in the case of diffusion bonded samples, interrupted by weak spots or rather non-bonded areas. These areas are obviously causing the onset of material failure and thus, a degradation of mechanical properties. Tensile samples, that were aged in 70% sulphuric acid at 100°C for 1000 hours showed local corrosion attacks at the grain boundaries at the circumferential surfaces and especially at the joining planes – for Hastelloy B3 much more pronounced than for Hastelloy BC-1. Accordingly, a further decrease of both, the stress- and elongation at fracture values is observed. However, the typical material parameters like 0.2 % yield strength used for dimensioning components are found to be sufficient high, even when operating the materials under such harsh conditions. When concluding the results, at least Hastelloy BC-1 reveals both sufficient good mechanical properties and an excellent corrosion resistance, regardless of the heat treatment, and could be considered for manufacturing micro-process engineering apparatuses operated in a sulphuric acid environment. This is a significant advance compared to the results obtained within a AiF project, previously carried out on four different materials to investigate the corrosion resistance in sulphuric acid.

The performance of choice-reaction tasks during athletic movement has been demonstrated to evoke unfavorable lower limb biomechanics. However, the mechanism of this observation is unknown. We conducted a systematic review examining the association between 1) the biomechanical and functional safety of unplanned sports-related movements (e.g. jumps/runs with spontaneously indicated landing leg/cutting direction) and 2) markers of perceptual-cognitive function (PGF). A literature search in three databases (Pubmed, ScienceDirect, Google Scholar) identified five relevant articles. Study quality, rated by means of a modified Downs & Black checklist, was moderate to high (average: 13.5/16 points). Four of five papers, in at least one parameter, found either an association of lower PGF and reduced task safety or significantly reduced task safety in low vs. high PGF performers. Yet, as a) the outcomes, populations and statistical methods of the included trials were highly heterogeneous and b) only two out of five studies had an adequate control condition (pre-planned movement task), evidence was classified as conflicting. In sum, PGF may represent a factor increasing injury risk during unplanned sports-related movements but future research strengthening the evidence of this association is warranted.

Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The prevalence of this disease is associated with various factors, including age, heredity, and race. Recent research in prostate cancer genetics has identified several genetic variants that may be associated with an increased risk of developing the disease. However, despite the significance of these findings, genetic markers for prostate cancer are not currently utilized in clinical practice as reliable indicators of the disease. In addition to genetics, epigenetic alterations also play a crucial role in prostate cancer development. Aberrant DNA methylation, changes in chromatin structure, and microRNA (miRNA) expression are major epigenetic events that influence oncogenesis. Existing markers for prostate cancer, such as prostate-specific antigen (PSA), have limitations in terms of sensitivity and specificity. The cost of testing, follow-up procedures, and treatment for false-positive results and overdiagnosis contributes to the overall healthcare expenditure. Improving the effectiveness of prostate cancer diagnosis and prognosis requires either narrowing the risk group by identifying new genetic factors or enhancing the sensitivity and specificity of existing markers. Immunological biomarkers (both circulating and intra-tumoral), including markers of immune response and immune dysfunction, represent a potentially useful area of research for enhancing the diagnosis and prognosis of prostate cancer. Our review emphasizes the need for developing novel immunological biomarkers to improve the diagnosis, prognosis, and management of prostate cancer. We highlight the most recent achievements in the identification of biomarkers provided by circulating monocytes and tumor-associated macrophages (TAMs). We highlight that monocytes-derived and TAMs-derived biomarkers can enable to establish the missing links between genetic predisposition, hormonal metabolism and immune responses in prostate cancer.

This study examines the impact of the impregnation of fireclay-based conventional (CC) and medium cement castables (MCC) with liquid sodium silicate glass under vacuum conditions. The goal is to assess how this treatment affects physical, mechanical properties, and durability (alkali and thermal shock resistance) of these castables used in biomass combustion boilers, where they are exposed to temperatures up to 1100°C. The research work employs standard test methods to evaluate physical and mechanical properties. Additionally, advanced techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and specific tests for alkali resistance and thermal shock resistance are used. The research findings suggest that impregnation with sodium silicate glass under vacuum significantly enhances the alkali resistance of both CC and MCC castables. This improvement is primarily due to the reduction in porosity and the increase in density. SEM images reveal that impregnated samples are coated with a glassy layer and the pores are partially filled with sodium silicate. Tests for alkali resistance demonstrate the formation of a protective glassy layer (with a thickness of 0.9-1.5 mm) on the castables surfaces, thereby reducing further penetration of alkali into deeper layers of the samples. However, it is important to mention that impregnated refractory castables have reduced resistance to thermal shock cycles.

Longer operating time in radical prostatectomy may escalate the risk of perioperative complications. Various factors like cancer extent, procedure’s level of difficulty, habitus and previous surgeries may lengthen robotic assisted radical prostatectomy (RARP) and therefor compromise outcomes. Objective: this study investigates the influence of operating time on outcomes after RARP in real life settings in a monocentric single surgeon study. Methods: 500 consecutive patients who underwent RARP between April 2019 and August 2022 were included. Patients were divided in three groups. Short (n=157; 31.4%) under or equal to 120 minutes, average (n=255; 51%) between 121 and 180 minutes, long (n=88; 17,6%) above 180 minutes console-time. Demographic, baseline and perioperative data were analyzed and compared between groups. Univariate logistic regression was completed to investigate the association between console-time and outcomes and to predict factors which may prolong surgery. Results: hospital stay and catheter days were significantly longer in group 3 with medians 6 and 7 days (p<0.001 and <0.001, respectively). Those findings were confirmed in univariate analysis, p=0.012 for Catheter days and p<0.001 for Hospital stay. Moreover, major complications were higher in patients with longer procedures p=0.008. Prostate volume was the only predictor for prolonged console time (p=0.005). Conclusion: RARP is a safe procedure and most patients will be discharged uneventfully. Yet longer console-time is associated with longer hospital stay, catheter days and major complications. Caution has to be taken in large prostate to avoid longer procedures, which may prevent postoperative advert events.

Intussusceptive pillars, regarded as a hallmark of intussusceptive angiogenesis, have been described in developing vasculature of many organs and organisms. The aim of this study was to resolve the question about pillar formation and their further maturation employing zebrafish caudal vein plexus (CVP). The CVP development was monitored by in vivo confocal microscopy in high spatio-temporal resolution using the transgenic zebrafish model Fli1a:eGPF//Gata1:dsRed. We tracked back the formation of pillars (diameter ≤4µm) and intercapillary meshes (diameter >4µm) and analysed their morphology and behaviour. Transluminal pillars in the CVP arose by a combination of sprouting, lumen expansion, and/or by creation of intraluminal folds, and those mechanisms were not associated directly with blood flow. The follow-up of pillars indicated that one third of them disappeared between 28-48 hours post fertilisation (hpf) and of the remaining ones only 1/17 changed their cross-section area by >50%. The majority of the bigger meshes (39/62) increased their cross-section area by >50%. Plexus simplification and establishment of hierarchy was dominated by the dynamics of intercapillary meshes, which formed mainly by sprouting angiogenesis. These meshes were observed to grow, reshape, and merge with each other. Our observations suggested an alternative view on intussusceptive angiogenesis in the CVP.

Pure orbital blowout fractures occur within the confines of the internal orbital wall. Restoration of orbital form and volume is paramount to prevent functional and esthetic impairment. The anatomical peculiarity of the orbit has encouraged surgeons to develop implants with customized features to restore its architecture. This has resulted in worldwide clinical demand for patient-specific implants (PSIs) designed to fit precisely in the patient's unique anatomy. Fused filament fabrication (FFF) three-dimensional (3D) printing technology has enabled the fabrication of implant-grade polymers such as Polyetheretherketone (PEEK), paving the way for a more sophisticated generation of biomaterials. This study evaluates the FFF 3D printed PEEK orbital mesh customized implants with a metric considering the relevant design, biomechanical, and morphological parameters. The performance of the implants is studied as a function of varying thicknesses and porous design constructs through a finite element (FE) based computational model and a decision matrix based statistical approach. The maximum stress values achieved in our results predict the high durability of the implants, and the maximum deformation values were under one-tenth of a millimeter (mm) domain in all the implant profile configurations. The circular patterned implant (0.9 mm) had the best performance score. The study demonstrates that compounding multi-design computational analysis with 3D printing can be beneficial for the optimal restoration of the orbital floor.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

The gravel road pavement has a lower construction cost but poorer performance than the asphalt surface. It also emits dust and deforms under the impact of vehicle loads and ambient air factors. The resulting ripples and ruts are constantly deepening, increasing vehicle vibrations and fuel consumption, reducing safe driving speed and comfort. In this article, existing pavement quality evaluation indexes are analysed, and a methodology for their adaptation for roads with gravel pavement is proposed. This article reports the measured wave depth and length of the gravel pavement profile by the straightedge method of a 160 m long road section in three road exploitation stages. The measured pavement elevation was processed according to ISO 8608, and vehicle frequency response has been investigated using simulations in MATLAB/Simulink. The applied International Roughness Index (IRI) analysis showed that a speed of 30-45 km/h instead of 80 km/h provides the objective results of IRI calculation on the flexible pavement due to a decreasing velocity of vehicle's unsprung mass on a more deteriorated road pavement state. The influence of the corrugation phenomenon of gravel pavement has been explored, identifying specific driving safety and comfort cases. Finally, an increase in the Dynamic Load Coefficient (DLC) at a low speed of 30 km/h on the most deteriorated pavement and a high speed of 90 km/h on the middle-quality pavement demonstrates the demand for timely gravel pavement maintenance and the complicated prediction of a safe driving speed for drivers.

Water and water habitats are essential to life and to the wellness of the communities that rely on them, as the Danube river is subject to human impact and vice versa, periodic surveys are required to determine the status of its pollution levels. In this work we used known microbiological indicators as well as physico-chemical ones to assess the ecotoxicological status of the Danube river from eleven locations partially forming the “Romanian–Bulgarian Danube Sector”. Most of the microbial communities found, and their densities, could be explained by point and diffuse sources scattered along the sector such as discharged household and farm wastewater, as well as nearby agricultural areas where fertilizers have been used and then leaked in the water stream during rainfalls. However, microbial data on non-point sources that lead to diffuse pollution of surface waters could be linked to such parameters and furthermore shown a slight correlation with the current status of fish communities.

This paper presents a device for measuring and maintaining the constant water level in a tank. The device uses a capacity sensor to measure the water level. The sensor has a DC voltage output proportional to the water level in the tank. This voltage can be used in other automation too. The water level, in percentages, is displayed on a vu meter with 8 LEDs. The circuit for maintaining the constant level consists in a comparator with hysteresis. The level of the water is adjustable, using a reference voltage from a potentiometer (marked in percentages). The level of the water is compared with the prescribed level and the difference between them commands the start/stop of the water pump which supplies the tank through a relay. The device is powered by 220 V and is isolated from the environment.

The PII protein is an evolutionary highly conserved regulatory protein from bacteria to higher plants. In bacteria it modulates the activity of several enzymes, transporters and regulatory factors by interacting with them and thereby regulating important metabolic hubs like carbon/nitrogen homeostasis. More than two decades ago the PII protein was characterized for the first time in plants, but its physiological role is still not sufficiently resolved. To gain more insights into the function of this protein, we investigated the interaction behaviour of AtPII with candidate proteins by BiFC and FRET/FLIM in planta and with GFP/RFP traps in vitro. In the course of these studies we found that AtPII interacts in chloroplasts with itself as well as with known interactors like NAGK in dot-like aggregates, which we named PII foci. In these novel protein aggregates AtPII interacts also with yet unknown partners, which are known to be involved in plastidic protein degradation. Further studies revealed that the C-terminal part of AtPII is crucial for the formation of PII foci. Altogether, the presented results indicate a novel mode of interaction for PII proteins with other proteins in plants, which may be a new starting point for the elucidation of physiological functions of PII proteins in plants.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.

The paper concludes that the choice of charging strategy depends on the specific requirements and limitations of the off-grid solar PV system, and that a careful analysis of the factors that affect performance is necessary to identify the most appropriate approach. Also provides valuable insights for designing and optimizing off-grid solar PV systems, which can help to improve the efficiency, reliability, and cost-effectiveness of these systems.

The hydrochemical composition of the Upper Jurassic groundwaters in the South German Mo-lasse Basin (SGMB) indicates a heterogeneous and varying hydrogeochemical evolution, which contradicts previous flow model concepts. For this study, the data of 88 Tertiary, Cretaceous and Upper Jurassic groundwater samples were investigated for hydrochemical elements, 2H/18O-H2O isotopes, 87Sr/86Sr ratios as well as δ11B values. In addition, the geochemical composition, 87Sr/86Sr and δ11B values were analysed from depth-oriented Upper Jurassic rock samples to delineate water-rock interactions in the aquifer systems. Slightly elevated 87Sr/86Sr ratios of the carbonates compared to the typical signatures of marine Upper Jurassic carbonates indicate a synsedimentary radiogenic influence due to the erosion of the adjacent Bohemian Massif. However, these values cannot explain the significant higher Sr-isotope fingerprint of the groundwaters in the central SGMB. Different water types occur in the Upper Jurassic aquifer, primarily distinguished by the dominant cations, calcium or sodium with subclasses of the major anions. The calcium-dominated groundwaters occur mainly at the western and northern margins of the SGMB. The sodi-um-dominated ion exchange groundwaters instead dominate in the central and eastern SGMB. With increasing strontium content, the 87Sr/86Sr ratios of the Upper Jurassic groundwater samples either indicate a strontium uptake by carbonate of the host rocks, or a prevailing radiogenic sig-nature. This implies a basic interaction with terrestrial or marine Tertiary sediments. The results illustrate a downward transformational fluid flow systematic via the thick Tertiary sediment cover into the Upper Jurassic carbonate formation in the SGMB, highlighting a new understanding on the evolution of the Upper Jurassic groundwaters and a basin-wide recharge mechanism.

Global anaesthesia workforce limitations contribute to emigration of skilled anaesthesiologists from lower- to higher-income countries, jeopardizing workforce balance and patient outcomes in Pakistan. This study aims to explore challenges experienced by anaesthesiologists in Punjab, Pakistan’s most populous province, and necessary changes to encourage their retention. We conducted a qualitative study to examine perspectives of anaesthesiologists who chose to serve in Pakistan. We drew data from semi-structured interviews conducted with 25 purposively-sampled consultant anaesthesiologists. We analysed data thematically and distinguished the practice hurdles faced by anaesthesiologists in public and private hospitals of Punjab. The main reasons to work abroad could be broadly categorized under two inductive themes, i.e. practice hurdles in public and private sector. Both had distinct issues which compromised the number and quality of anaesthesia workforce in the country. The key outcomes were workplace security, promotion/incentive issues and gender inequalities in the government sector. The private sector had improper salaries and facilities, anaesthesiologist’s dependency on surgeons for getting work and lack of out-of-theatre practice which minimise the scope and earnings of anaesthesiologist within the country. There is a need to overcome surgeon dependency and hospital manipulation by fixing salary percentages for each surgical case and encouraging direct patient-anaesthesiologist relationships.

Full Matrix Capture is a multi-channel data acquisition method which enables flexible, high resolution imaging using ultrasound arrays. However, the measurement time and data volume are increased considerably. Both of these costs can be circumvented via compressed sensing, which exploits prior knowledge of the underlying model and its sparsity to reduce the amount of data needed to produce a high resolution image. In order to design compression matrices that are physically realizable without sophisticated hardware constraints, structured subsampling patterns are designed and evaluated in this work. The design is based on the analysis of the Cramér-Rao Bound of a single scatterer in a homogeneous, isotropic medium. A numerical comparison of the point spread functions obtained with different compression matrices and the Fast Iterative Shrinkage/Thresholding Algorithm shows that the best performance is achieved when each transmit event can use a different subset of receiving elements and each receiving element uses a different section of the echo signal spectrum. Such a design has the advantage of outperforming other structured patterns to the extent that suboptimal selection matrices provide a good performance and can be efficiently computed with greedy approaches.

The influence of aluminosilicate pozzolanic waste, specifically spent fluid catalytic cracking catalyst (FCCW) and metakaolin waste (MK) from expanded glass industry, on the properties of hardened Portland cement paste were analysed. The study involved replacing part of cement with FCCW and MK and observing their impact on hydration, microstructure, density and compressive strength of hardened cement paste. Various analysis methods were employed, including X-ray diffraction (XRD), thermogravimetric analysis (TG), and scanning electron microscopy (SEM), to understand the changes in the structure of hardened cement paste during hydration. The findings revealed that FCCW tends to accelerate cement hydration process due to its high surface area and pozzolanic activity. Notably, the formation of portlandite crystals was observed on FCCW particle surfaces in a specific direction. These crystals appeared smaller and developed in different directions in compositions containing a composite binder with mixture of FCCW and MK in a ratio 1:1. This could be influenced by pozzolanic reactions activated by fine particles of MK and the formation of calcium silicate hydrates (CSH) and calcium alumino silicate hydrates (CASH) in the presence of portlandite. XRD and TG results indicated that the specimens containing a composite binder exhibited the least amount of portlandite. The compressive strength of these specimens increased compared to control specimens, although the amount of cement was 9% lower.

This paper summarizes over a decade of collaborative eco-archaeological research along the central coast of California involving researchers from the University of California, Berkeley, tribal citizens from the Amah Mutsun Tribal Band, and California Department of Parks and Recreation archaeologists. Our research employs remote sensing methods to document and assess cultural resources threatened by coastal erosion and geophysical methods to identify archaeological deposits, minimize impacts on sensitive cultural resources, and provide tribal and state collaborators with a suite of data to consider before proceeding with any form of invasive archaeological excavation. Our case study of recent eco-archaeological research developed to define the historical biogeography of threatened and endangered anadromous salmonids demonstrates how remote sensing technologies help identify dense archaeological deposits, remove barriers, and create bridges through equitable and inclusive research practices between archaeologists and the Amah Mutsun Tribal Band. These experiences have resulted in the incorporation of remote sensing techniques as a central approach of the Amah Mutsun Tribal Band when conducting archaeology in their traditional territories.

Introduction: Alzheimer's disease (AD) is the first cause of dementia worldwide without any current curative treatment. Facing an increasing prevalence and its associated costs, AD represents a public health challenge. Usual diagnostic methods still rely on extended interviews and paper tests provided by an exterior examiner. We aim to create a novel, quick cognitive-screening tool on a numerical tablet. Methods: This program, built and edited with Unity®, runs on Android® for the Samsung Galaxy Tab S7 FE®. Composed of seven tasks inspired by the Mini-Mental Status Examination and the Montréal Cognitive Assessment, it browses several cognitive functions. The architectural design of this tablet application is distinguished by its multifaceted capabilities, encompassing not only seamless offline functionality but also a mechanism to ensure the singularity of data amalgamated from diverse sites. Additionally, a paramount emphasis is placed on safeguarding the confidentiality of patient information in the healthcare domain. Furthermore, the application empowers individual site managers to access and peruse specific datasets, enhancing their operational efficacy and decision-making processes. We performed a preliminary usability assessment among healthy subjects. Results: 24 healthy patients were included with a final F-SUS score of "excellent". Participants perceived the tool as simple to use and achieved the test in a mean time of 142 seconds. No technical errors occurred. Conclusion: These preliminary results suggest that our new assessment on a numerical tablet allows a short cognitive screening.

The current trends in environment protection and sustainable development demand the investigations in the field of searching new perspective sources for any production. Oat husks seems to be a perspective resource. Cellulose isolated from oat wastes can be used for the production of different materials such as hydro and aerogels, bacterial, nanocrystal and nanofibrillated cellulose, cellulose based composites and ethers. All these materials can be spent in different industries: production of pharmaceuticals, medicine (including targeted delivery of drugs, sponges etc.), agriculture (controlled delivery of pesticides or fertilizers), electronics, production of films, membranes, plastics, coatings, paints, biodegradable packages. In this review, we will demonstrate prospects for using oat husks to obtain cellulose and for obtaining materials based on the main oat husk polysaccharide. This review will evaluate the main achievements in this area. The analysis will allow a reader to form an analytical opinion about the prospects for using oat husks as a source for obtaining valuable products.

Consideration of the individual bone characteristics of the wrist plays a key role in well-functioning biomedical devices and successful surgical procedures. Although geometric differences and individual bone sizes have been analyzed in the literature, detailed morphologic descriptions and correlations covering the entire wrist reported in a clinical context are lacking. This study aimed to perform a comprehensive and automatic analysis of wrist morphology using the freely available “Open Source Carpal Database” (OSCD). We quantified the dimensions of each of the individual carpal bones and their combination. These dimensions were extracted in n=117 datasets of the wrist of the OSCD in anatomical directions and analyzed using descriptive statics and correlation analysis to investigate morphological characteristics under gender-specific aspects. We found that there exist statistical differences between genders, and we concluded that gender specificity is an important variable affecting the utilization of biomedical device designs and clinical treatment.

Purpose: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids. Methods: We included 39 BSCR patients followed for ≥1 year. Patients were classified into 2 groups according to their initial treatment: methylprednisolone followed by prednisone (n=28) and prednisone alone (n=11). We analyzed the progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. Results: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day. Conclusion: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p

Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. PREDATORR study (2014) shows that in Romania, 34,6% of adults aged 20-79 y/o are overweight, 31,4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania's population in the abnormal weight group. Our study aims to investigate the current staus of genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes: leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY) and fat-mass and obesity-associated (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene's AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40-49, with an approximately sevenfold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, not statistically significant. The FTO rs9939609 gene's AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 1e-04), LEP and GHRL gene (p = 0.0047), GHRL and FTO gene (p=0.03). The outcomes of this study, to our knowledge, one of the very few on the Romanian population, aimed to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks.

The upper limb force-velocity relationship (FVR) is a crucial aspect of athletic performance, par-ticularly in para sports where upper limb movements play a leading role in activities such as wheelchair propulsion. Athletes’ mechanical capacities can be evaluated on the field or in lab conditions. However, no studies have indicated a relationship between ergometers and field FVR or performances. Understanding para-athletes’ upper limb FVR can provide important insights for developing effective training programs and improving athletic performance in wheelchair bas-ketball players. Twenty-three wheelchair basketball players (12 women and 11 men) from French national teams performed a battery of three tests consisting of a 20 m sprint (SP) with Inertial measurement units (IMU) on wheels, a horizontal upper limb push-offs on a frictionless sled with two Kistler force plates (HBP), and a crank ergometer sprints test (CES) derived from arm er-gometer sprints using Brachumera, Lode. For the SP test, the FVR was computed with an estimation of force from the acceleration, the rolling resistance, and an estimation of the air resistance. Correlations between each variable measured were computed via Pearson correlations in R, as-suming strong relationships for r=0.7-1.0, moderate when r=0.40-0.69, and weak relationship when r<0.1-0.39. Significant differences were assumed when p<0.05. Strong correlations were found between the results of three tests conducted. The correlation coefficient between maximal theo-retical force (F0) data ranged from 0.85 to 0.88 and that between maximal theoretical power (P0) data ranged from 0.87 to 0.94. However, for maximal theoretical velocity (V0) data, the correlations between the three tests were less important. The performance variables showed a strong corre-lation with power measured on the HBP test without load. There is a significant relationship between HBP, CES, and SP variables. There is a correlation between performances on the three tests in our population, especially for the power. However, the V0 value of HBP was not representative of any performances. This work can show multiple protocols to assess para-athletes’ performances and show that upper limb symmetry depends on the gesture of the task and personal sports’ wheelchairs.

The present study reports on the fabrication and performance of ammonia sensors based on single-walled carbon nanotubes (SWCNTs) coated with gold nanoparticles (AuNPs). The sensors were subjected to controlled concentrations of ammonia at two temperatures, namely 25 oC and 140 oC, and their response was monitored through successive cycles of ammonia exposure and nitrogen purging. The results demonstrate that the sputtering-based deposition of AuNPs on SWCNTs led to the best sensor performance, characterized by a rapid increase in resistance values upon exposure to ammonia, and efficient recovery at 140 oC. By contrast, the sensor with chemically impregnated AuNPs exhibited a slower response time. Furthermore, a novel device was developed that combined MoS2-AuNPs (sputtering)-SWCNTs, and it showed improved sensor performance compared to the devices with only AuNPs. Overall, the study provides valuable insights into the fabrication and optimization of SWCNT-based ammonia sensors for various applications, especially for detecting and quantifying small amounts of ammonia (concentrations below 1 ppm).

Affinity chromatography on procainamide-Sepharose has been an important step in the purification of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) since its introduction in 1978. The procainamide affinity gel has limitations. In the present report a new affinity gel called Hupresin^® was evaluated for its ability to purify truncated, partly-deglycosylated human butyrylcholinesterase (rHuBChE) expressed in a stably transfected CHO cell line. We present a detailed example of the purification of rHuBChE secreted into 3940 mL of serum-free culture medium. The starting material contained 13,163 units of BChE activity (20.9 mg). rHuBChE was purified to homogeneity in a single step by passage over 82 mL of Hupresin^® and elution with 0.1 M tetramethylammonium bromide in 20 mM TrisCl pH 7.5. The fraction with the highest specific activity of 630 units/mg contained 11 mg of BChE. Hupresin^® is superior to procainamide-Sepharose for purification of BChE, but is not suitable for purifying native AChE because Hupresin^® binds AChE so tightly that AChE is desorbed with denaturing solvents such as 50% acetonitrile or 1% trifluoroacetic acid. Procainamide-Sepharose will continue to be useful for purification of AChE.

Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together. Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

Browsing of wild ungulates can have profound effects on the structure and composition of forests. In the Swiss National Park, the density of wild ungulates including red deer (Cervus elaphus), ibex (Capra ibex), and chamois (Rupicapra rupicapra) is exceptionally high due to strict protection and the absence of large predators. We examined count data of larch (Larix decidua), cembra pine (Pinus cembra), spruce (Picea abies), upright mountain pine (Pinus mugo subsp. uncinata), and mountain ash (Sorbus aucuparia) of four sampling years between 1991 and 2021 and modelled how different topographic and location factors affected the probability of browsing on saplings of larch, cembra pine, and spruce. Despite the high density of wild ungulates, the numbers of saplings and young trees increased over the past 30 years. The probability of browsing on saplings was highest for larch at a height of 10 – 40 cm and increased with increasing elevation. In our study area, open grasslands are mainly located above the tree line, which might explain the positive correlation between elevation and the probability of browsing. Other factors like exposition and slope, available food resources and disturbance by humans did not have clear effects on the probability of browsing.

Background: Machine learning can analyze vast amounts of data and make predictions for events in the future. Our group created machine learning models for vital sign predictions. To transport the information of these predictions without numbers and numerical values and make them easily usable for human caregivers, we aimed to integrate them into the Philips Visual-Patient-avatar, an avatar-based visualization of patient monitoring. Methods: We conducted a computer-based simulation study with 70 participants in three European university hospitals. We validated the vital sign prediction visualizations by testing their identification by anesthesiologists and intensivists. Each prediction visualization consisted of a condition (e.g., blood pressure low) and an urgency (a visual indication of the timespan in which the condition is expected to occur). To obtain qualitative user feedback, we also conducted standardised interviews and derived statements that participants later rated in an online survey. Results: The mixed logistic regression model showed 77.9% (95%CI 73.2-82.0%) correct identification of prediction visualizations (i.e. condition and urgency both correctly identified) and 93.8% (95%CI 93.7-93.8%) for conditions only (i.e. without considering urgencies). Forty-nine of 70 participants completed the online survey. The online survey participants agreed that the prediction visualizations were fun to use (32/49, 65.3%), and that they could imagine working with them in the future (30/49, 61.2%). They also agreed that identifying the urgencies was difficult (32/49, 65.3%). Conclusions: This study found that care providers correctly identified >90% of the conditions (i.e. without considering urgencies). The accuracy of identification decreased when considering urgencies in addition to conditions. Therefore, in future development of the technology, we will focus on either only displaying conditions (without urgencies) or improve the visualizations of urgency to enhance usability for human users.