Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Interrupting the vicious cycle within neuron-microglia interactions may be a therapeutic goal in DE by limiting the inflammatory response.

In this study, the team employed full-scale crash tests to investigate the impact of post-densification technology on the safety performance of separated central median W-beam barriers under low compaction conditions. By precisely simulating the design and construction environment of the central median, the study comprehensively evaluated the barrier's containment, redirection, buffering, and anti-intrusion performances, as well as the deformation of both the barrier and vehicles under various collision scenarios. The results indicate that under low compaction soil conditions, the A-level separated central median barriers reinforced with post-densification technology effectively meet the specified protection requirements. By comparing the influence of soil strength variations on barrier performance under simulated rainfall conditions, it was confirmed that enhancing soil compaction significantly improves soil stability, effectively increases the overall strength and stability of the barriers, reduces deformation, and significantly enhances safety performance. This study not only validates the effectiveness of the reinforcement scheme but also provides new perspectives for the scientific research of safety barriers and offers crucial technical support for the optimal design of road safety protection facilities.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

We introduce a new class of Vertex Operator Algebras Y+ and their duals, which generalize the standard W-algebras WN of type sl(N). These algebras can be defined in terms of junctions of boundary conditions and interfaces in the GL-twisted N = 4 Super Yang Mills gauge theory. The aim of these technical calculations is to find the relation of these ortho-symplectic Y-algebras to truncations of even W\infinity.

In this paper, we study the well-posedness and asymptotics of a one-dimensional thermoelastic laminated beam system either with or without structural damping, where the heat conduction is given by Fourier's law effective in the rotation angle displacements. We show that the system is well-posed by using Lumer-Philips theorem, and prove that the system is exponentially stable if and only if the wave speeds are equal, by using the perturbed energy method and Gearhart-Herbst-Prüss-Huang theorem. Furthermore, we show that the system with structural damping is polynomially stable provided that the wave speeds are not equal, by using the second-order energy method.

This work presents the results regarding the synthesis of tungsten nanoparticles (W NPs) by magnetron sputtering combined with gas aggregation (MSGA) when H2 mixed with Ar is used as working gas, the amount of H2 being increased up to 82%. The results show that up to 40% H2 in discharge the synthesis rate increases over 60 times, rapidly decreasing for over 50% H2 in discharge. The W dust is still produced in H2 dominated discharge (82%), the deposition rate being small but not negligible (20 mg/hour). The obtained WNPs are isolated, with the diameter decreasing from 50 nm to 15 nm when the amount of H2 in discharge is smaller than 41%. Over this value, the particles tend to agglomerate, forming structures similar to film-like deposits. Also, the diameter of the deposited spots on substrates is dependent on the H2 content in discharge. This allows the efficient coating of substrates with dimensions up to 26 mm by translating them in front of the MSGA cluster source exit aperture. Supplementary, for 41% H2 in discharge, the influence of synthetic air leaks (0-5%) in discharge was investigated. The deposition rate decreases rapidly (ceasing for around 4% air in discharge) and the obtained nanoparticles tend to agglomerate (at 2% air content, the dust deposit has the aspect of a near continuous film). Chemical composition investigations show a pronounced tendency of oxidation, nitridation and oxynitride formation in the presence of air leaks.

The Ni-Co-Cr-W-Mo system is critical for the design of nickel-based super-alloys. This system stabilizes different topologically close packed (TCP) phases in many of the commercially super-alloys with high W and Mo contents. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermodynamic calculations are applied to investigate the thermodynamics of the precipitates in two different W content Ni-Co-Cr-W-Mo super-alloys. Computational thermodynamics verified experimental observation of the f u phase formation as a function of temperature and alloy chemistry, but the kinetics for the precipitation of M6C phase do not agree with the experimental findings. The major precipitates of alloy 1 at temperatures 700 and 750 °C during long time exposure are M23C6, γ′ phase, and MC, and alloy 2 are M23C6, γ′ phase, MC, M6C and u phase. The W addition is found to promote the precipitation of M6C and u phase during exposure. The M6C has higher W and lower Ni content than that of u phase, meanwhile, M6C is an unstable phase would transform into M12C after 5000 h exposure at 750 °C. A great quantity of needle-like u phases precipitated after exposure at 750 °C for 5000h, which have no effect on the impact property of alloy 2.

In this work, we consider a one-dimensional laminated beam in the case of non-equal wave speeds with only one infinite memory on the effective rotation angle. In this case, we establish the general decay result for the energy of solution without any kind of internal or boundary control. The main result is obtained by applying the method used in Guesmia et al. (Electron. J. Differential Equations 193: 1-45, 2012) and the second-order energy.

A time-sequential working, spatially multiplexed autostereoscopic 3D display design consisting of a fast switchable RGB-color filter array is presented. The wavelength-selective filter barrier emits the light from a display over a larger active area than common autostereoscopic barrier displays. An optical modelling of wavelength-selective barriers has been used for instance to calculate the light ray distribution properties of that arrangement. To find well working display designs, automated searches by simulation and computational evaluation has been proceeded. Wavelength-selective filter barrier arrangements exhibit characteristics different from common barrier displays with similar barrier pitch and ascent. In particular, these constructions show strong angular luminance dependency under barrier inclination specified by correspondent slant angle. In time-sequential implementation it is important to avoid that quick eye or eyelid movement lead to visible color artifacts. In the millisecond regime tunable liquid crystal Fabry-Pérot color filters for the colors red, green and blue are presented. They consist of a sub-micrometer thick nematic layer sandwiched between dielectric mirrors and ITO-electrodes. These cells shall switch narrow-banding light of red, green or blue. An array for a glasses-free 3D display has to be equipped with several thousand switchable filter elements having different color apertures. The newly introduced design is usable as a multi user display as well as a single user system with user adaptive control.

In an outstanding article published in 2008, Suzuki obtained a nice generalization of the Banach contraction principle from which derived a characterization of metric completeness. Although Suzuki’s theorem has been successfully generalized and extended in several directions and contexts, we here show by means of a simple example that the problem of achieving, in an obvious way, its full extension to the framework of w-distances does not have an emphatic response. Motivated by this fact we introduce the concept of presymmetric w-distance on metric spaces, we give some properties and examples of this new structure and show that it provides a reasonable setting to obtain a real and hardly forced w-distance generalization of Suzuki’s theorem. This is realized in our main result, which is a fixed point theorem that involves presymmetric w-distances and certain contractions of Suzuki-type. We also discuss the relationship between our main result and the well-known w-distance full generalization of the Banach contraction principle, due to Suzuki and Takahashi. Connected to this approach we prove another fixed point result that compare with our main result through some examples. Finally, we state a characterization of metric completeness by using our fixed point results.

In this paper, we study the global existence and exponential decay for a dynamic contact problem between a Timoshenko beam with second sound and two rigid obstacles, of which the heat flux is given by Cattaneo's law instead of the usual Fourier's law. The main difficulties arise from the irregular boundary terms, from the low regularity of the weak solution and from the weaker dissipative effects of heat conduction induced by Cattaneo's law. By considering related penalized problems, proving some a priori estimates and passing to the limit, we prove the global existence of the solutions. By considering the approximate framework, constructing some new functionals and applying the perturbed energy method, we obtain the exponential decay result for the approximate solution, and then prove the exponential decay rate to the original problem by utilizing the weak lower semicontinuity arguments.

AgW materials exhibit excellent properties and are widely used as contact materials in low- and medium-voltage switches. In this study, a pre-sintering and infiltration method was employed to pre-sinter W powder with Cu, Ni, and (Cu+Ni) addition in the low temperature range of 950–1050 °C. The low-temperature sintering behaviours of W skeletons with different additives were investigated. Subsequently, AgW70, AgW75, AgW80, and AgW85 materials were prepared through infiltration at 1050 °C. The microstructure morphology and physical properties of high-W contact materials were investigated using a metallographic microscope and scanning electron microscope. The mechanism of low-temperature sintering-infiltration of high-W contact materials was elucidated. The results indicated that pure W and 1% Cu-added W skeletons experience minimal linear shrinkage within the temperature range of 950–1050 °C. The linear shrinkage curves of W skeletons with different additives coincided under the conditions of 950–1000 °C/90 min. At 1050 °C, after sintering for 150 min, the particle boundaries in the W skeleton were fully spheroidised, with a dihedral angle of 120°. At 1050 °C and after 150 min of infiltration, cross-sectional micrographs of the AgW material revealed the presence of irregular Ni layers, where Ni spatially enveloped/encapsulated Ag. With an increase in the W content, the electrical conductivity and relative density of AgW(70–85) materials decreased, whereas the hardness of the materials increased.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

Cohesion in the refractory metals Cr, Mo, and W is phenomenologically described in this work via a n-body energy functional with a set of physically motivated parameters that were optimized to reproduce selected experimental properties characteristic of perfect and defective crystals. The functional contains four terms accounting for the hard-core repulsion, the Thomas-Fermi kinetic energy repulsion and for contributions to the binding energy of s and d valence electrons. Lattice dynamics, molecular statics, and molecular dynamics calculations show that this model describes satisfactorily thermodynamic properties of the studied metals whereas, unlike other empirical approaches from the literature, predictions of phonon dispersion relations and of surface and point defect energetics reveal in fair good agreement with experiments. These results suggest that the present model is well adapted to large-scale simulations and whenever total energy calculations of thermodynamic properties are unfeasible

A printed Vivaldi antenna that is optically transparent, ultra-wideband (UWB), and reconfigurable has been developed, fabricated, and tested at millimeter wave frequencies. It covers a broad frequency range of 20-30 GHz by using three PIN diodes. The diodes control the current flow to direct the beam of the antenna. The results of numerical simulations and measurements match at millimeter wave frequencies. The design of this antenna is unique as it allows for a reduction in size and ease of integration while also providing the ability to change the radiation pattern by up to 300 degrees, making it suitable for 5G and 6G communications. Additionally, this antenna can also be useful for RF applications that require dynamic switching of radiation patterns and cognitive radio.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Neutral beam injection (NBI) is used for thermonuclear plasma heating, non-inductive current drive, rotation, operation scenario control, and for plasma diagnostics in nuclear fusion devices. NBI is the main source of fast particles in plasma which transmit energy to thermal plasma during their slow-down. Steady-state tokamak operation is only possible when the sub-thermal particles energy is absorbed and effectively confined in plasma volume. While NBI purposes and applications vary through different fusion systems, the engineering tasks performed during research and development (R&D) stage of neutral beamline design have much in common. The NBI studies, especially addressing long pulse and high-power operation typically include a beam transmission analysis and power loads distribution at the structural components of the beamline. Thermo-structural analysis is applied next to heat removal circuits design. ‘Beam Transmission’ (BTR) code is a dedicated tool, developed by a physicist and used by NBI physicists and engineers. BTR was created and 1^st applied during R&D phase of the world’s largest tokamak ITER. BTR code is intended for public usage and routinely applied for detailed simulations of neutral beam propagation through complex beamlines. BTR is flexible and intuitive in input, user-friendly and fully interactive. Thanks to visualization and high performance BTR looks and feels like a real NB flight simulator. Despite BTR ‘mature’ age, the code is still in evolution. Support is available to all new BTR users.

In the present study, a multilayer high barrier thin blown film based on a polybutylene adipate terephthalate (PBAT) blend with polyhydroxyalkanoate (PHA), and composed of four layers, including a cellulose nanocrystals (CNC) barrier layer and an electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hot-tack layer, was characterized in terms of surface roughness, surface tension, migration, mechanical and peel performance, barrier properties and disintegration rate. The results showed a material with a smooth surface. The overall migration test showed that the material was suitable for its use as a food contact layer. The addition of the CNC interlayer had a significant effect on the mechanical properties of the system, drastically reducing the elongation at break and, thus, the flexibility of the material. However, the material retained its elastic modulus and tensile strength. The CNC coating had a negative impact on the peeling strength, weakening the inherently strong interlayer adhesivity of the electrospun PHBV fibers. The multilayer had a good barrier to water vapor, and especially to oxygen, with its permeance reduced by up to a 90 % when the CNC layer was present. Finally, the monolayer blend film disintegrated in a period of less than 55 days in a laboratory-scale composting experiment, while the multilayer system disintegrated in 60 days. Overall, the multilayer system formed a fully compostable structure with great potential for use in food packaging applications.

Density Functional Theory (DFT) full potential linearized augmented plane wave (FP-LAPW) method with the Modified Becke-Johnson (mBJ) approximation is used to perform spin polarised calculations of the transition metal perovskites MoScO₃ and WScO₃. Both depict half metallic behaviour with semiconducting and metallic in the minority and majority spins respectively. MoScO₃ and WScO₃ have indirect R− Γ band gaps in the minority spin channels of 3.61 and 3.82eV respectively. Moreover, they both show substantial magnetic moments of 2.99μ_B. In addition, we calculate the dielectric function, optical conductivity and the optical constants, namely, the refractive index, the reflectivity, the extinction and absorption coefficients.

We study the changes in quantum Fisher information (QFI) values for one quantum system consisting of a superposition of W and GHZ states. In a recent work [6], QFI values of this mentioned system studied. In this work, we extend this problem for the changes of QFI values in some noisy channels. We show the change in QFI depending on noise parameters. We report interesting results for different type of decoherence channels.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

Omicron SARS-CoV-2 variants have dominated the strains of COVID-19 circulating worldwide for the last two years. Although the mortality rate of the COVID-19 Omicron variants is only approximately half that of previous variants, vaccines effective against Omicron are needed. Demonstrating that a SARS-CoV-2 vaccine can protect against Omicron in an in vivo infection model, particularly in that of Syrian hamsters, is important for the preclinical characterization of SARS-CoV-2 vaccines. Here, we report on the evaluation of W-PreS-O for its ability to protect Syrian hamsters against infection by Omicron. W-PreS-O is a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron adsorbed to aluminum hydroxide. The Syrian hamsters were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo), and then they were infected with Omicron BA.1. Non-infected and non-vaccinated animals served as controls. Neutralizing antibody (nAB) titers, weight, lung symptoms (i.e., edema and pneumonia index), and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. W-PreS-O-vaccinated hamsters developed robust nABs against Omicron, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. Our data provide compelling evidence demonstrating that the W-PreS-O vaccine has protective effect against Omicron in a Syrian hamster in vivo infection model. W-PreS-O is therefore a highly promising candidate vaccine for Omicron infections, and it should be further evaluated in clinical studies.

This article provides exact analytical formulae for various kinds of rainbow step barrier options. These are highly flexible and sophisticated multi-asset barrier options based on the following principle : the option life is divided into several time intervals on which different barriers are monitored w.r.t. different underlying assets. From a mathematical point of view, new formulae are provided for the first passage time of a multidimensional geometric Brownian motion to a boundary defined as a step function. The article shows how to implement the obtained valuation formulae in a simple and very efficient manner. Numerical results highlight a strong sensitivity of rainbow step barrier options to the correlations between the underlying assets.

In this paper, we introduce a new generalization of the r-Stirling numbers of the second kind based on the q-numbers via an exponential generating function. We investigate their some properties and derive several relations among q-Bernoulli numbers and polynomials, and newly de…ned (q, r, w)-Stirling numbers of the second kind. We also obtain q-Bernstein polynomials as a linear combination of (q, r, w)-Stirling numbers of the second kind and q-Bernoulli polynomials in w.

In this paper, the mechanism of combined process of ion beam sputtering (IBS) and HF acid etching on the chemical structure defects of fused silica and its laser damage resistance perfor-mance were investigated. During the removal process of surface material, the sputtering effect causes lattice atoms to detach from their original positions, forming a large number of unsaturated structures on silica surface, which improves the chemical activity of Si and O atoms, accelerates the chemical reaction process between surface atoms and water molecules, increases the content of hydroxyl (OH-) groups in the shallow layer, and enhances the photothermal weak absorption intensity. However, the presence of OH- groups reduces the bonding strength of Si-O, destroys the spatial network structure of silica bulk, and reduces the mechanical strength of silica surface, resulting in a decrease in its laser damage resistance performance. The paper reveals for the first time the mechanism of IBS to change the structure characteristics of silica material, accelerate the surface hydroxylation process, and thereby reduces the laser damage resistance performance. This work provides technical guidance for effectively suppressing chemical structure defects on silica surface and improving laser damage resistance performance of optical components under high-flux laser irradiation.

In this study, we evaluated the antibacterial effect against Staphylococcus aureus and Salmonella Typhimurium in fried fish paste using floating electrode-dielectric barrier discharge (FE-DBD) plasma (1.1 kV, 43 kHz, N2 1.5 m/s, 1-60 min). In addition, quality evaluation (pH, VBN) of fried fish paste was conducted after FE-DBD plasma treatment. When FE-DBD plasma was treated for 1, 5, 10, 20, 30 and 60 min, S. aureus decreased by 0.16-1.13 log10 CFU/g, and S. Typhimurium decreased 0.25-1.13 log10 CFU/g. Both decreased > log10 CFU/g at 60 min. The D-value was 58.92 and R2 was 0.97 for S. aureus using first-order kinetics, and the D-value was 43.60 and R2 was 0.97 for S. Typhimurium using the Weibull model. There was no significant difference in pH after FE-DBD plasma treatment (p > 0.05). However, volatile basic nitrogen (VBN) significantly decreased as the treatment time increased (p < 0.05), and it was the lowest at 60 min to 3.46. Therefore, FE-DBD plasma treatment could be considered as a technology for preserving the quality of processed foods.

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin-6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are similar to those of other hyperinflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal-oral transmission. Increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options.

Tungsten and its alloys are considered as a key component in high temperature environment. Self-passivating W-Si-xY alloys with different Y contents made from the powders milled for different times were prepared by mechanical alloying (MA) and spark plasma sintering (SPS). Their microstructures and oxidation resistance were investigated. It is found that the oxidation resistance of the alloys with low Y contents (0Y and 2Y) made from 20 h-milled powders is worse than that of the alloys made from 4 h-milled powders. It is because the protective WO3/SiO2 composite layer is discontinuous. While the alloys with high Y contents (4Y and 6Y) made from 4 h and 20 h-milled powders show good oxidation resistance. Even, the thickness of the oxide layer of the alloys with 4Y and 6Y made from 20 h-milled powders after oxidation at 1000 ℃ for 2 h is 84.0 μm and 70.7 μm, less than that made from 4 h-milled powders. This is due to the size and distribution of W5Si3, Y2Si2O7 aggregates and W-Y-O melt. The synergistic effects of Y contents and milling time on the microstructures and oxidation resistance of the alloys are revealed.

In this study, the problem of overcoming the infinite energy barrier separating the bradyonic and tachyonic realms is investigated. Making use of the Majorana equation for particles with arbitrary spin and the Heisenberg uncertainty principle, it is proved that, under certain conditions of spatial confinement, quantum fluctuations allow particles with very small mass and velocity close to the speed of light to pass in the tachyonic realm, avoiding the problem of the infinite barrier (bradyon–tachyon tunnelling). This theoretical approach allows an avoidance of the difficulties encountered in quantum field theory when it is extended to particles with imaginary rest mass.

Quantum Fisher Information (QFI) is a very useful concept for analyzing situations that require phase sensitivity. It become a popular topic especially in Quantum Metrology domain. In this work, we study the changes in quantum Fisher information (QFI) values for one relative arbitrary phased quantum system consisting of a superposition of N Qubits W and GHZ states. In a recent work [7], QFI values of this mentioned system for N qubits were studied. In this work, we extend this problem for the changes of QFI values in some noisy channels for the studied system. We show the changes in QFI depending on noise parameters. We report interesting results for different type of decoherence channels. We show the general case results for this problem.

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI, ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and VH: CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum significantly up-regulated in the NSB group, respectively. Additionally, SOD (p < 0.05) and T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05) showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, serum anti-inflammatory cytokines, regulating intestinal barrier function and antioxidant capacity, SCFAs content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.

Background: Bacteria, among the earliest life forms on Earth, are integral to both human health and environmental ecosystems. They contribute to essential processes such as digestion, nutrient absorption, and immune defense, and play key roles in the biogeochemical cycles that sustain life. Objective: This paper explores the indispensable role of bacteria in human life and environmental health, emphasizing their contributions to digestion, nutrient absorption, immune protection, and ecosystem functioning. It also discusses advances in understanding the human microbiome and their implications for health and therapeutic interventions. Methods: The study reviews existing literature on the human microbiome, probiotics, and the role of bacteria in environmental nutrient cycling. It analyses experimental evidence and case studies, particularly focusing on the impact of fecal microbiota transplantation (FMT) as a therapeutic tool. Metagenomic analysis techniques are examined to highlight the diversity and functionality of gut bacteria. Results: Bacteria are found to be essential for breaking down food, providing vital nutrients, and protecting against pathogens. They play a critical role in maintaining a healthy immune system and are involved in the biogeochemical cycles necessary for ecosystem health. Metagenomic analysis reveals significant variations in bacterial populations associated with health and disease, emphasizing the importance of a balanced microbiota. FMT shows promise as an effective treatment for various diseases, including gastrointestinal, metabolic, and neurological disorders. Conclusions: Bacteria are crucial for human health and environmental stability. Maintaining a balanced microbiota is vital for overall well-being, and interventions such as probiotics and FMT can offer significant health benefits. Future research should focus on further understanding the complex interactions between bacteria and their hosts to develop targeted therapies for various health conditions.

In order to study the effects of irradiation on the physicochemical properties and digestion behavior of chickpea protein, chickpea protein concentrate (CPC) was treated with electron beam irradiation (EBI) at doses of 5, 10, 15 and 20 kGy, respectively. After irradiation, protein solubility first increased at 10 kGy and 15 kGy, and then decreased at higher dose of 20 kGy. This was supported by SDS-PAGE where the intensity of major protein bands first increased and then decreased. Increased does of EBI generally led to greater oxidative modification of proteins in CPC, indicated by reduced sulfhydryls and increased carbonyls. In addition, protein structure was modified by EBI shown by Fourier transform infrared spectroscopy analysis where α-helix generally decreased and β-sheet increased. Although the protein digestibility was not significantly affected by EBI, the peptidomic analysis of the digests revealed significant difference among CPC irradiated with varying doses. A total of 337 peptides were identified from CPC irradiated with 0 kGy, 10 kGy and 20 kGy, respectively, with 18 overlapping peptides and 60, 29 and 40 peptides specific to the groups of 0, 10 and 20 kGy respectively. Theoretical calculation showed that the distribution of peptide length, hydrophobicity, net charge, and C-terminal residues were affected by irradiation. The 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity showed a marginal decrease with increasing dose of irradiation. In conclusion, EBI led to oxidative modification and structural changes of the chickpea protein, which subsequently affected the physicochemical properties of peptides obtained from in-vitro digestion of CPC despite of similar digestibility.

Chromium (Cr) metal has garnered significant attention in alloy systems owing to its exceptional properties, such as high melting point, low density, and superior oxidation and corrosion resistance. However, its processing capabilities are hindered by the high Ductile-Brittle Transition Temperature (DBTT). Recently, powder bed fusion-laser beam for metals (PBF-LB/M) has emerged as a promising technique, offering the fabrication of net shapes and precise control over crystallographic texture. Nevertheless, research investigating the mechanism underlying crystallographic texture development in pure Cr via PBF-LB/M still needs to be conducted. This study explores the impact of scan speed on relative density and crystallographic texture. At the optimal scan speed, an increase in grain size attributed to epitaxial growth was observed, resulting in the formation of cubic texture. Consequently, a reduction in High Angle Grain Boundaries (HAGB) was achieved, suppressing defects such as cracks and enhancing relative density up to 98.1%. Furthermore, with increasing densification, Vickers hardness also exhibited a corresponding increase. These findings underscore the efficacy of PBF-LB/M for processing metals with high DBTT properties.

Greenhouse gas (GHG) emission-induced climate change, particularly occurring since the mid-20th century has been considerably affecting short-term weather conditions, such as increasing weather variability, and incidence of extreme weather-related events. Milk production is sensitive to such changes. In this study, we use spatial panel econometric models, Spatial Error Model (SEM) and Spatial Durbin Model (SDM), with a panel dataset at the state-level varying over seasons, to estimate the relationship between weather indicators and milk productivity, in an effort to reduce the bias of omitted climatic variables that can be time-varying and spatially correlated and cannot be directly captured by conventional panel data models. We find an inverse U-shaped effect of summer heat stress on milk production per cow (MPC), indicating that milk production reacts positively to a low-level increase in summer heat stress, and then MPC declines as heat stress continues increasing beyond a threshold value of 72. Additionally, fall precipitation exhibits an inverse U-shaped effect on MPC, showing that milk yield increases at a decreasing rate until fall precipitation rises to 14 inches and then over that threshold milk yield declines at an increasing rate. We also find that, relative to conventional panel data models, spatial panel econometric models could improve prediction performance by leading to smaller in-sample and out-sample root mean squared errors. Our study contributes to the literature by exploring the feasibility of promising spatial panel models and resulting in estimating weather influences on milk productivity with high model predicting performance.

Crystalline silver thin layers were obtained by high-energy pulsed laser ablation without heating of the deposition substrate. The fluid Plateau-Rayleigh (PRI), Rayleigh – Taylor (RTI) and Richtmyer – Meshkov (RMI) instabilities, as well as crown splash induced during pulsed laser deposition (PLD) in high energy regime, resulting in ring and pearl shaped structures, offer the benefit of increased sorption surface. These morphological structures obtained for the silver thin layers make them of interest for catalytic applications. The study presented with this work addresses both the fundamental and applied issues on the morphological structures obtained for the silver thin layer and their catalytic function in organic processes. In this sense, the catalytic action of the thin silver layer was highlighted by modifications of the Reactive Blue 21 dye (C.I.) in aqueous solution with sodium bicarbonate. Specific investigations and analyzes were carried out by electron microscopy and elemental analysis (SEM-EDX), atomic force microscopy (AFM) and profilometry, mass spectrometry, ablation plasma diagnosis, diffractograms (XRD), as well as IR spectroscopy (FTIR). In addition to the experimental investigation and analyzes, simulation of the ionization energy threshold was conducted in COMSOL for complementary evaluation on the involved processes and phenomena.

As screen sizes are becoming larger and larger, which are beyond human’s physical limitation for direct touching interaction, remote controls are inevitable. However, as techniques applied so far, inertial gyroscopes are susceptible to position inaccuracies, and gesture recognition is limited by cameras’ focus depth and viewing angle. Grating antenna light trapping technology will be an ideal candidate providing the ghost point problem for multipoint inputs can be solved. Therefore, we propose a differential amplitude modulation scheme for grating antenna based multi beam optical touch, which can recognize different incidence points. Where, the amplitude of the incident beams was coded with different pulse width at first. Then, after been trapped by the grating antenna and been transferred into currents by the lined detector arrays, the incident points of the individual beams were recognized and differentiated. The scheme was successfully verified on an 18-inch screen, where two-point optical touch with position accuracy error under 3mm and response time less than 7ms under modulation frequency of 10kHz on both incident beams are obtained. This work paves a practical way for remote multi-point touch, which can make digital mouse in consistent to the users pointing direction obeying natural three-point one ling aiming rule instantaneously.

Aneuploidy describes the gain or loss of entire chromosomes or chromosome arms. Already more than 100 years ago, aneuploidy was described to be featured in cancer and it is known today to be present in 68-90 % of cancers, depending on tumour entity. Aneuploidy is implicated to affect cancer growth, therapy response and frequently affects prognosis. Chromosomal instability (CIN) is recognized as the main cause of aneuploidy and is characterised as the fluent process of gaining or losing chromosomes. Chromosomally instable cells need to be kept in check, or cleared, to prohibit the sampling of aneuploid karyotypes able to drive tumorigenesis. Of note, even aneuploid cancer cells often show CIN, a feature that promotes therapy related drug-resistance. Here, we review how CIN can be prevented or limited to spread by the induction of cell death and the relevance of different p53 responses triggered in response to mitotic perturbations to prohibit the formation of cancer driving aneuploidies.

Imperfection sensitivity of large amplitude vibration of curved single-walled carbon nanotubes (SWCNTs) is considered in this study. The SWCNT is modeled as a Timoshenko nano-beam and its curved shape is included as an initial geometric imperfection term in the displacement field. Geometric nonlinearities of von Kármán type and nonlocal elasticity theory of Eringen are employed to derive governing equations of motion of nano-beam. Spatial discretization of governing equations and associated boundary conditions is performed using differential quadrature (DQ) method and the corresponding nonlinear eigenvalue problem is iteratively solved. Effects of value and location of the geometric imperfection, and the nonlocal small-scale parameter on the nonlinear frequency ratio and imperfection sensitivity of a curved SWCNT for various boundary conditions are investigated. The results show that the geometric imperfection plays a significant role in the nonlinear vibration characteristics of curved SWCNTs.

In the power plant industry, the turbine inlet temperature (TIT) plays a key role in the efficiency of the gas turbine and, therefore, the overall—in most cases combined—thermal power cycle efficiency. Gas turbine efficiency increases by increasing TIT. However, an increase of TIT would increase the turbine component temperature which can be critical (e.g., hot gas attack). Thermal barrier coatings (TBCs)—porous media coatings—can avoid this case and protect the surface of the turbine blade. This combination of TBC and film cooling produces a better cooling performance than conventional cooling processes. The effective thermal conductivity of this composite is highly important in design and other thermal/structural assessments. In this article, the effective thermal conductivity of a simplified model of TBC is evaluated. This work details a numerical study on the steady-state thermal response of two-phase porous media in two dimensions using personal finite element analysis (FEA) code. Specifically, the system response quantity (SRQ) under investigation is the dimensionless effective thermal conductivity of the domain. A thermally conductive matrix domain is modeled with a thermally conductive circular pore arranged in a uniform packing configuration. Both the pore size and the pore thermal conductivity are varied over a range of values to investigate the relative effects on the SRQ. In this investigation, an emphasis is placed on using code and solution verification techniques to evaluate the obtained results. The method of manufactured solutions (MMS) was used to perform code verification for the study, showing the FEA code to be second-order accurate. Solution verification was performed using the grid convergence index (GCI) approach with the global deviation uncertainty estimator on a series of five systematically refined meshes for each porosity and thermal conductivity model configuration. A comparison of the SRQs across all domain configurations is made, including uncertainty derived through the GCI analysis.

Parkinson’s Disease (PD) is a neurodegenerative and progressive disease that impacts the nerve cells in the brain and varies from person to person. The exact cause of PD is still unknown, and the diagnosis of PD does not include a specific objective test with certainty. Although deep learning has made great progress in medical neuroimaging analysis, these methods are very susceptible to biases present in neuroimaging datasets. An innovative decorrelated deep learning technique is introduced to mitigate class bias and scanner bias while simultaneously focusing on finding distinguishing characteristics in resting-state functional MRI (rs-fMRI) data, which assist in recognizing the PD with good accuracy. The decorrelation function reduces the non-linear correlation between features and bias in order to learn bias-invariant features. The Parkinson’s Progression Markers Initiative (PPMI) dataset, referred to as a single scanner imbalanced dataset in this study used to validate our method. The imbalanced dataset problem affects the performance of the deep learning framework by overfitting to the majority class. To resolve this problem, we propose a new Decorrelated Convolutional Neural Networks (DcCNN) framework by applying decorrelation-based optimization to Convolutional Neural Networks(CNN). An analysis of evaluation metrics comparisons shows that integrating the decorrelation function boosts the performance of PD recognition by removing class bias. Specifically, our DcCNN model performs significantly better than existing traditional approaches to tackle the imbalance problem. Finally, the same framework can be extended to create scanner invariant features without significantly impacting the performance of a model. The obtained dataset is a multi-scanner dataset which leads to scanner bias due to the differences in acquisition protocols and scanners. The multi-scanner dataset is a combination of two datasets, namely PPMI and FTLDNI - frontotemporal lobar degeneration neuroimaging initiative (NIFD) dataset. The results of t-distributed stochastic neighbor embedding (t-SNE) and scanner classification accuracy of our proposed Feature Extraction-DcCNN (FE-DcCNN) model validated the effective removal of scanner bias. Our method achieves an average accuracy of 77.80% on a multi-scanner dataset for differentiating PD from healthy control, which is superior to the DcCNN model trained on a single scanner imbalanced dataset.

Stream chemistry effectively integrates watershed ecosystem processes on both spatial and temporal scales. Streams of coastal areas integrate a more homogeneous, flat topography wherein there can be interactions between the stream and the body of water into which it drains, especially where tidal fluxes occur. The present study assessed water quality of Thompson Bayou, which comes to the campus of the University of West Florida in a wetland after flowing through 4 km of commercial and private property with associated impacts on water quality. Sampling was carried out for one year at eight discrete sites along Thompson Bayou from the UWF campus to the Escambia River. We used a portable field meter to measure temperature, pH, dissolved O2 (DO), and specific conductivity (SC). Except for temperature, all variables exhibited a spatial pattern of significant variation with distance, with consistent increases in DO and SC as the stream approached the river. These variables also exhibited a temporal pattern of significant seasonal variation, including—and especially—temperature. Data suggest that spatial and temporal patterns of water quality of Thompson Bayou are determined by (1) processing of water by the wetland, (2) interactions of the stream channel with upland forest stands, and (3) the tidal hydrology of the Escambia River.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

The dynamics of the topological charge of a vortex optical beam propagating in a turbulent air with accounting for the cubic nonlinearity is theoretically considered. On a number of examples, we show that the optical beam self-focusing manifests itself ambiguously depending on optical wave power. At near-critical values of beam power, self-focusing leads to enhanced spatial localization of optical vortices and substantial suppression of vortex walk-off relative to the beam axis caused by air turbulence. However, with increasing of optical intensity the modulation instability imposed by cubic nonlinearity becomes significant and contributes jointly with medium turbulence to faster divergence of vortex beams.

Lipid composition in the cellular membranes plays an important role in maintaining the struc-tural integrity of cells and in regulating cellular signaling that controls functions of both mem-brane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transport-ers, two integral membrane proteins, are known to contribute to lipid translocation across the li-pid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membrane in regulating cell signaling and how lipid transporters participate this process.

Beam dumps are indispensable components for particle accelerator facilities to absorb or dispose beam kinetic energy in a safe way. However, the design of beam dumps based on conventional technology, i.e. the energy deposition via beam-dense matter interaction, makes the beam dump facility complicated and large in size, partly due to nowadays’ high beam intensities and energies achieved. In addition, these high-power beams generate radioactive hazards, which need specific methods to deal with. On the other hand, the EuPRAXIA project can advance the laser-plasma accelerator significantly by achieving 1-5 GeV high quality electron beam in a compact layout. Nevertheless, the beam dump based on conventional technique will still produce radiation hazards and make the overall footprint less compact. Here, we propose to implement a plasma beam dump to absorb the kinetic energy from the EuPRAXIA beam. In doing so, the overall compactness of the EuPRAXIA layout will not be impacted, and the radioactivity generated by the facility can be mitigated. In this paper, results from particle-in-cell (PIC) simulations are presented for plasma beam dumps based on EuPRAXIA beam parameters.

To estimate the progressive collapse resistance capacity of a multi-column frame tube structure with the assembled truss beam composite floor (ATBCF), the pushdown analysis, and the nonlinear dynamic analysis as well, are conducted for such a structure by using the alternate load path (ALP) method. The bearing capacities of the remaining structures at three different work conditions, which are the side middle column failure, the edge middle column failure, and the corner column failure, are individually studied, and the collapse mechanism for the remaining structures is analyzed from the aspects of the internal force redistribution and the failure mode of the second defense line. Simultaneously, the influence of the column failure time on the dynamic response of the remaining structure and the dynamic amplification coefficient are discussed. The results show that the residual bearing capacity of the remaining structure with the bottom corner column failure is higher than that of the one with the side or edge middle column failure, while the latter has a stronger plastic deformation capacity. When the ALP method is adopted to operate the progressive collapse analysis, it is reasonable to take the column failure time as 0.1 times of the first-order vertical vibration period of the remaining structure, and it is suitable to set the dynamic amplification coefficient as of 2.0, which is the ratio of the maximum dynamic displacement to the static displacement of the remaining structure under the transient loading condition.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

This study introduces numerical advancements in an alternative design for the SPS Beam Dump Facility (BDF) at CERN. The design envisions a high-power operation target made of flowing liquid lead. The BDF is a proposed versatile facility at CERN, intended for both beam-dump-like and fixed-target experiments. The target behavior is assessed, assuming a proton beam with a momentum of 400 GeV/c, a pulse frequency of 1/7.2 Hz, and an average beam power of 355 kW. An evaluation is conducted using various Computational Fluid Dynamics (CFD) codes to analyze the behavior of liquid lead and to predict the thermal stress on the target vessel induced by the pulsed heat source generated by the charged particle beam. The comparison increases the reliability of the results, investigating the dependencies on the CFD modeling approach. The beam is modeled as a volumetric heat source with data coming from beam-lead interaction simulations provided by CERN and obtained with the Monte-Carlo code FLUKA. The velocity field and stress profiles are utilized to enhance the design of the lead loop and verify its viability and safety when operated with a liquid metal target.

This study aims to identify modern bureaucratic government phenomenon expressed in W.H. Auden’s poem “The Unknown Citizen” (UC). This phenomenon will be revealed through the use of figures of speech, symbols and imagery in the poem. This poem is chosen as the object of the study since phenomenon happened in the poem represents people’s life and government practice in the modern era. Government, in the poem, seems to be very dominant. Its bureaucratic apparatus is powerful. Through its sophisticated technology, the bureau of statistics is able to detect the citizen’s identity. But, ironically, it could have not identified UC’s name as he lived in the world. He, then, was honored by the state by being erected the marble monument. The poem is analyzed by applying phenomenological criticism. The analysis finds that the representation of modern government is expressed through symbols emphasized by dramatic irony and supported by the use of internal sensation imagery. UC is the allegory of the average person with his bravery he sacrifices for the country. The state ought to give him an honor. In this poem Auden, actually, wants to write a parody for establishing monuments in some countries to honor the struggles of their soldiers who died in the World War I. Those monuments are really tombs since the function of a monument is a state’s thanksgiving for their sacrifice.

In this work, we introduce the class of h-MN-convex functions by generalizing the concept of MN-convexity and combining it with h-convexity. Namely, let M : [0, 1] → [a, b] be a Mean function given by M (t) = M (t; a, b); where by M (t; a, b) we mean one of the following functions: A_t (a, b) := (1 − t) a + tb, G_t (a, b) = a^1−tb^t and H_t (a, b) := $\frac{ab}{ta+\left(1-t\right)b}=\frac{1}{A_t\left(\frac{1}{a},\frac{1}{b}\right)}$ with the property that M (0; a, b) = a and M (1; a, b) = b. Let I, J be two intervals subset of (0, ∞) such that (0, 1) ⊆ J and [a, b] ⊆ I. Consider a non-negative function h : J → (0, ∞), a function f : I → (0, ∞) is said to be h-MN-convex (concave) if the inequality f (M (t; x, y)) ≤ (≥) N (h(t); f (x), f (y)), holds for all x, y ∈ I and t ∈ [0, 1]. In this way, nine classes of h-MN-convex functions are established, and therefore some analytic properties for each class of functions are explored and investigated. Characterizations of each type are given. Various Jensen’s type inequalities and their converses are proved.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, using the Rosen and Israelit model of a nonsingular universe. In doing so we are in addition to obtaining a wavelength 10^30 times greater than Planck’s length so we can calculate DE, may be able to with the help of the Rosen and Israelit model have a first approximation as to the arrow of time, and a universe with massive gravity. We have left the particulars of the nonsingular starting point undefined but state that the Rosen and Israelit model postulates initial temperatures of 10^-180 Kelvin and also a value of about Planck temperature, at 10^-3 centimeters radii value which may satisfy initial conditions asked by t’Hooft for describing an arrow of time. A key assumption is that the DE is formed at 10^-3 cm, after an expansion of 10^30 times in radii, from the Planck length radius nonsingular starting point. The given starting point for DE in this set of assumptions is where there is a change in the cosmic acceleration, to a zero value, according to Rosen and Israel, with time t = 1.31 times 10^-42 seconds. Which may be where we may specify a potential magnitude, V, which has ties into inflaton physics. The particulars of the model from Rosen and Israelit allow a solution to be found, without discussion of where that nonsingular starting point came from, a point the author found in need of drastic remedies and fixes.

Starting with unitary quantum dynamics, we investigate how to add quantum measurements. Quantum measurements have four essential components: the furcation, the witness production, an alignment projection, and the actual choice decision. The first two components still lie in the domain of unitary quantum dynamics. The decoherence concept explains the third contribution. It can be based on the requirement that witnesses reaching the end of time on the wave function side and the conjugate one have to be identical. In this way, it also stays within the quantum dynamics domain. The surjection hypothesis explains the actual choice decision. It is based on a two boundary interpretation applied to the complete quantum universe. It offers a simple way to reduce these seemingly random projections to purely deterministic unitary quantum dynamics, eliminating the measurement problem.

Field studies were conducted in 2016, 2017, and 2020 in south-central and the Coastal Bend regions of Texas to determine the effects of various biostimulants and soil additives on corn growth and yield. In south-central Texas, the use of pop-up fertilizer (9-30-0 + Zn) either alone or in combination with either 2% N, bifenthrin, or bifenthrin + pyraclostrobin resulted in the greatest corn vigor but a yield response was only noted with pop-up fertilizer alone at 28062 or 46771 ml ha-1 in one year. In the Coastal Bend region, leaf tissue analysis showed that only Fe was affected with the use of any soil additive. Bacillus licheniformis + bacillus megaterium + bacillus pumilus increased Fe leaf tissue content by 20% over the untreated check. Radicoat seed coating at 438 ml ha-1 reduced corn plant stand by 10% and Pseudomonas brassicaceanum reduced corn height when compared with the untreated check; however, no differences in test weight or yield from the untreated check were noted with any soil additive. Little if any impacts of the use of biostimulants or soil amendments were seen in these studies.

Finishing coatings in the wood-based composites industry not only influence the final appearance of the product but also serve to protect against fungi, and molds, and reduce the release of harmful substances, particularly formaldehyde and volatile organic compounds (VOCs). Carbon-rich materials, such as those derived from birch bark extraction, specifically suberin acids, can fulfil this role. Previous research has demonstrated that adding suberin acid residues (SAR) at 20% and 50% by weight significantly enhances the gas barrier properties of surface finishing materials based on poly(lactide) (PLA) and polycaprolactone (PCL), particularly in terms of Total VOC (TVOC) and formaldehyde emissions. This study aims to explore whether these properties can be further improved through the incorporation of nano-zinc oxide (nano-ZnO). Previous research has shown that these nanoparticles possess strong resistance to biological factors and can positively affect the characteristics of nanofilms applied as surface protection. The study employed PLA and PCL finishing layers blended with SAR powder at 10% w/w and included 2% and 4% nano-zinc oxide nanoparticles. The resulting blends were milled to create a powder, which was subsequently pressed into 1 mm thick films. These films were then applied to raw particleboard surfaces. TVOC and formaldehyde emission tests were conducted. Additionally, the fungal resistance of the coated surfaces was assessed. The results showed that PLA/SAR and PCL/SAR composites with the addition of nano-zinc oxide nanoparticles exhibited significantly improved barrier properties, offering a promising avenue for developing biodegradable, formaldehyde-free coatings in the furniture industry with enhanced features. Furthermore, by utilizing SAR as a post-extraction residue, this project aligns perfectly with the concept of upcycling.

Delivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polar-ized pre-existing viewpoints and norms. In contrast, digital signs are an “in your face in your space” technology that has the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed: increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities.

Steel fibre reinforced concrete (SFRC) consists of short hooked steel fibres randomly distributed and oriented within the cementitious matrix. The contribution of fibre in bridging cracks to provide the stress transfer required relies upon the orientation of the fibre in the concrete. Bridging fibre aligned with a crack are less effective than those inclined to it. Therefore, understanding the pull-out behaviour of misaligned fibre is a key factor to quantify and optimize the design of SFRC in the structural applications. In the laboratory a single oriented fibre embedded in a solid cylinder of concrete is subjected to a pull-out test where the axis of a tensile force is aligned with the axis of the cylinder. Based upon the observed behaviour this paper presents a new analytical bounding approach to capture the pull-out response of misaligned hooked-end steel fibre embedded in a concrete matrix. The analysis is based upon a transversely isotropic condition assumed for the plasticity that occurs in the cold drawn fibre. The model accounts for the influence of fibre diameter and the combined strengths of the steel and concrete. The model predictions have also been compared with other experimental results published in the literature. The results showed that the model can predict pull-out loads reasonably for different fibre orientations between bounds of failure derived from the strengths of the two constituents. A critical orientation is observed at maximum strength. Therein, an understanding of the pull-out behaviour of misaligned, hooked-end fibres is necessary to optimize the strength of concrete from this method of reinforcement.

The daily path of the Sun across longitude yields night and day, but the Sun also travels across latitude on a belt 47° wide. The Sun meridian declination explains the annual budget of natural beam irradiance (NBI), which is the irradiance delivered to the Earth’s surface as a normal projec-tion from the Sun. Data for the sun meridian declination data were obtained from the geometric model. The distribution of NBI was weighed between the Tropics of Cancer and Capricorn. The variation patterns of the solar declination conform to the dynamics of pendular motion. The joint distributions of velocity or acceleration of meridian declination against declination fit circular graphs. The NBI budget fluctuates in inverse proportion to the velocity of declination, yielding 18 sun-paths per degree for latitudes above 20°, and 6 sun-paths per degree for latitudes under 20°. All sites of the planet, whose latitude coincide, whether within or between hemispheres, accumu-late an equivalent budget of NBI.

FLASH-RT represents a novel therapeutic radiation modality that holds remarkable potential for mitigating radiation therapy’s adverse side effects. This cutting-edge technology allows for the sparing of healthy tissue while precisely targeting cancerous cells by administering an ultra-high dose-rates of typically between 10 and 30 Gy in less than a few hundred milliseconds. FLASH-RT has demonstrated impressive results in small-animal models, prompting scientists to adapt and advance existing technologies to make it a viable treatment option for humans. However, producing the ultra-high-dose-rate radiation required for the therapy remains a significant challenge. Several radiation sources, such as very high energy electrons (VHEEs), low energy electrons, x-rays, and protons, have been studied for their ability to deliver the necessary dose. Among them, FLASH-x-ray has gained the most attention owing to its capacity to penetrate deeply seated tumours. Despite the complexity of the process, the potential advantages of FLASH-RT make it an exciting area of research. To achieve the FLASH effect, high-frequency, pulsed irradiated accelerator technology can be employed. Sparing healthy tissue, it may allow for more aggressive and effective cancer treatments, leading to a better quality of life for patients. Ongoing research and development will be necessary to refine and optimize this approach to radiation therapy.

The presence of the quantum Rayleigh scattering, or spontaneous emission, inside a dielectric medium such as a beam splitter or an interferometric filter, prevents a single-photon from propagating in a straight-line. Modelling a beam splitter by means of a unitary transformation is physically meaningless because of the loss of photons. Additional missing elements from the conventional theory are: 1) the quantum Rayleigh stimulated emission which can form groups of photons of the same frequencies, and 2) the unavoidable parametric amplification of single-photons in the original parametric crystal. An interference filter disturbs, through multiple internal reflections, the original stream of single-photons, thereby confirming the existence of groups of photons being spread out to lengthen the coherence time. The approach of modelling individual, single measurements with statistical ensemble probability amplitudes leads to the counterintuitive explanations of the experimental outcomes and should be replaced with pure states describing instantaneous measurements which are afterwards averaged.

Damage detection based on modal parameter changes becomes popular in the last decades. Nowadays are available robust and reliable mathematical relations to predict the natural frequency changes if damage parameters are known. Using these relations, it is possible to create databases containing a large variety of damage scenarios. Damage can be thus assessed by applying an inverse method. The problem is the complexity of the database, especially for structures with more cracks. In this paper, we propose two machine learning methods, namely the random forest (RF) and the artificial neural network (ANN) as search tools. The databases we developed contain damage scenarios for a prismatic cantilever beam with one crack and ideal and non-ideal boundary conditions. The crack assessment is made in two steps. First, a coarse damage location is found from the networks trained for scenarios comprising the whole beam. Afterward, the assessment is made involving a particular network trained for the segment of the beam on which the crack is previously found. Using the two machine learning methods, we succeed to estimate the crack location and severity with high accuracy for both simulation and laboratory experiments. Regarding the location of the crack, which is the main goal of the practitioners, the errors are less than 0.6%. Based on these achievements, we concluded that the damage assessment we propose, in conjunction with the machine learning methods, is robust and reliable.

As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxicants to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the blood stream resulting in rapid distribution in the body. Consequently, mucosal barriers present in nose, buccal and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where a) different cultivation conditions such as air-liquid interface or submerged cultures, b) varying barrier maturity and c) diverse media substitutes have been used. The current comparative nanotoxicological study therefore aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions and tissue type using standard Transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and Presto Blue assays of immature (e.g. 5 days) and mature (e.g. 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular responses to increasing nanoparticle exposures are highly cell type specific, where bronchial mucosal cell barriers models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures. Additionally, stronger toxicities are found using early mucosa barriers compared to later barrier models being maturated under air-liquid cultivation conditions.

The preparation of new materials based on starch for the development of biodegradable packaging is increasing, however, the poor properties of this biopolymer for this application causes an area of opportunities for the improvement of water vapour permeability (WVP), mechanical properties, thermal properties, hydrophilicity, water absorption, among others. Hence, starch has been combined with other polymers such as polyvinyl alcohol, which has shown an improvement in the mechanical properties of starch, also, the use of clays suggests that the properties of response to water can be improved. Therefore, in this work, the preparation and characterization of starch-PVA-nanoclay films prepared by solvent casting is reported. The results obtained suggest that the sonication of nanoclay is necessary to reach a good dispersion, which promotes a strong interaction among starch-PVA-nanoclay. In addition, the properties of WVP and mechanical properties of films improved with incorporation of nanoclay, the concentration of 0.5% w/v of nanoclay showed to be the best concentration due to concentrations of 1.0 and 1.5% w/v were poorer than 0.5% w/v. Accordingly, the successful incorporation of nanoclays into the matrix starch-PVA suggests that this material is a good candidate for use as packaging.

Based on the elasticity theory, this paper deals with the static analysis of a cracked double beam system in presence of a Winkler medium. The double-beam system is also supposed to be constrained at both ends by elastically flexible springs, with transverse and rotational stiffness. Using a variational formulation, the static governing equations are derived and solved by using analytical and numerical approaches. In the first approach, the closed-form solutions for the displacements functions are obtained based on the Euler-Bernoulli beam theory. In the second approach, the Cell-Discretization Method (CDM) is performed, according to which the two beams are reduced to a set of rigid bars linked together by means of elastic constraints, where the bending stiffness of the bars is concentrated. The resulting stiffness matrix is easily deduced, and the governing equations of the static problem can be immediately solved. A comparative analysis is performed in order to verify the accuracy and validity of the proposed method. This study focuses on the effect of various parameters including the crack depth and position, boundary conditions, elastic medium and slenderness. The validity of the proposed analysis is confirmed by comparing the present results with those obtained from the other approach. In particular, the results obtained by closed-form solution and Cell-discretization method (CDM) are compared by Finite element method (FEM). Accuracy of the results has been evaluated by making comparisons with the results in literature and reported in bibliography. It is demonstrated that the proposed algorithm provides a simple and powerful tool in dealing with the static analysis of a double-beam system. Finally, some concluding remarks are made.

Usually in quantum optics, the theory of large- and small-scale waveguide beam splitters is the same. In this paper it is shown that the theory of the nanoscale waveguide beamsplitter has a significant difference from a similar device, but of a larger scale. It is shown that the previously known theory of the waveguide beam splitter is a particular case of the theory presented here. The wave function at the output ports of the nanoscale beam splitter is analyzed. The results obtained are sensitive to the size of the beam splitter, the coupling parameter of the two waveguides, and the degree of nonmonochromaticity of the photons entering the first and second ports of the beam splitter. The results are important for quantum technologies using a nanosized beam splitter.

Optical modes bearing optical vortices are important light systems in which to encode information. Optical vortices are robust features of optical beams that do not dissipate upon propagation. Thus decoding the modal content of a beam is a vital component of the process. In this work we present a method to decode modal superpositions of light beams that contain optical vortices. We do so using shear interferometry, which presents a simple and effective means of determining the vortex content of a beam, and extract the parameters of the component vortex modes that constitute them. We find that optical modes in a beam are easily determined. Its modal content can be extracted when they are of comparable magnitude. The use of modes of well defined topological charge but not well defined radial-mode content, such as those produced by phase-only encoding, are much easier to diagnose than pure Laguerre-Gauss modes.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

We first of all define the arrow of time. Definition of the arrow of time will allow choosing different initial starting points. One of the issues we will also discuss is the interconnection be-tween the arrow of time, entropy and quantum information. Seth Lloyd in his 2001 work made a linkage between entropy, bits, and information via an axiomatic approach involving time in-tervals. Our take is a bit more general. We will discuss as well the t’Hooft’s statement as to in-itial conditions and times arrow, and how different cosmological models may influence initial conditions. Spoilers alert, if a nonsingular start to expansion existed, this would provide the most straightforward way to avoid a datum from classical relativity. That is, that in the actual equations of classical GR, there is no reason to have time asymmetry. Time asymmetry is built into initial conditions and we will detail several candidates. The first half of the paper brings up cosmology models and forming the arrow of time. The second is related to entropy itself and the problem of information. .

Heavy metal contamination of drinking water is a public health concern that requires the development of more efficient bioremediation techniques. Absorption technologies, including biosorption, provide opportunities for improvements to increase the diversity of metal ions removed and overall binding capacity. Microorganisms are a key component in wastewater treatment plants and they naturally bind metal ions through surface macromolecules but with limited capacity. The long-term goal of this work is to engineer capsule polymerases to synthesize molecules with novel functionalities. In previously published work, we showed that the Neisseria meningitidis serogroup W (NmW) galactose-sialic acid (Gal—NeuNAc) heteropolysaccharide binds lead effectively, thereby demonstrating the potential for using this capsular polysaccharide in environmental decontamination applications. In this study, computational analysis of the NmW capsule polymerase galactosyltransferase (GT) domain was used to gain insight into how the enzyme could be modified to enable the synthesis N-acetylgalactosamine-sialic acid (GalNAc—NeuNAc) heteropolysaccharide. Various computational approaches, including molecular modeling with I-TASSER and molecular dynamics simulations (MD) with NAMD, were utilized to identify key amino acid residues in the substrate binding pocket of the GT domain that may be key to conferring UDP-GalNAc specificity. Through these combined strategies and using BshA, a UDP-GlcNAc transferase, as a structural template, several NmW active site residues were identified as mutational targets to accommodate the proposed N-acetyl group in UDP-GalNAc. Thus, a rational approach for potentially conferring new properties to bacterial capsular polysaccharides is demonstrated.

The application of adaptive antennas in wireless communication systems is examined in this review of the literature, with particular attention to how well they can transmit and receive signals by dynamically adjusting radiation patterns. The review covers a range of artificial intelligence (AI) approaches that have been used to enhance adaptive antenna performance in beamforming, channel estimation, interference mitigation, and spectrum utilization. Although adaptive antennas have the potential to improve wireless communication systems, the paper also discusses their limitations, including computational complexity, interference sensitivity, and the significance of precise channel state information (CSI) estimates.

In this paper, we dive into the exciting world of wireless communication, focusing on how millimeter-wave technology and Multiple-Input Multiple-Output phased array antennas are shaping the future of 5G and the upcoming 6G technologies. We cover the latest advancements in millimeter-wave and beam-forming technologies, emphasizing their role in enhancing network security and efficiency in automotive vehicles through dual radar communication. Our discussion spans the benefits, applications, challenges, and solutions of these technologies individually from millimeter-wave to beam-forming technology and joint radar communications, alongside a look at their theoretical and practical implementations. We emphasize the integration of beam-forming technology in joint radar communications for future automotive vehicles and its impact on automotive systems, smart cities, and the Internet of Things (IoT). Looking ahead, we discuss the potential of these technologies to transform future tech landscapes, while also addressing the security implications of merging communication and radar capabilities. This paper aims to provide a clear view of the advancements and prospects of millimeter-wave, beam-forming, and dual radar communication technologies.

The authors present a stereotypical case presentation of x-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact Fibroblast Growth Factor 23 (FGF23) which lead to i) low serum phosphate levels, ii) increased fractional excretion of phosphorus, and iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in XLH patients is due to chronic hypophosphatemia. Additionally, XLH patients experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration’s (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

A novel technique using a W-band metasurface for the purpose of transmissive fine powder layer sensing is presented. The proposed technique may allow for the detection, identification, and characterization of inhomogeneous ultrafine powder layers which are effectively hundreds of times thinner than the incident wavelengths used to sense them. Such a technique may be useful during personnel screening processes (i.e., at an airport) and in industrial manufacturing environments where early detection and quantization of harmful airborne particulates can be a matter of security or safety. To our knowledge, the requisite science involved in such a novel W-band metasurface sensing technique has not been fully explored.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family has been recently associated with the development of autoimmune diseases, including SLE. IL-33 is an alarmin and a pleiotropic cytokine that affects various types of immune cells via binding to its receptor, ST2. In this study, we determine the impact of intraperitoneal IL-33 treatments in young lupus, NZB/W F1 mice. Mice were treated from the age of 6 to 11 weeks. We then assessed the proteinuria level, renal damage, survival rate, and anti-dsDNA antibodies. The induction of regulatory B (Breg) cells and changes in gene expression were also examined. In comparison to the control group, young NZB/W F1 mice administered with IL-33 had a better survival rate as well as reduced proteinuria level and lupus nephritis. IL-33 treatments significantly induced IgM anti-dsDNA antibody, IL-10 expressing Breg cells, and alternatively induced M2 macrophage gene signatures. These results imply that IL-33 exhibit regulatory roles during lupus onset via the expansion of protective IgM anti-dsDNA as well as regulatory cells such as Bregs and M2 macrophages.

The production of nanoparticles has recently surged due to their varied applications in biomedical, pharmaceutical, textile, and electronic sectors. However, this rapid increase in nanoparticle manufacturing has raised concerns about environmental pollution, particularly due to their potential adverse effects on human health. Among the various concerns, inhalation exposure to nanoparticles poses significant risks, especially affecting the respiratory system. Airway epithelial cells play a crucial role as the primary defense against inhaled particulate matter and pathogens. Studies have shown that nanoparticles can disrupt the airway epithelial barrier, triggering inflammatory responses, generating reactive oxygen species, and compromising cell viability. However, our understanding of how different types of nanoparticles specifically impact the airway epithelial barrier remains limited. To investigate nanoparticle-induced cellular responses and barrier dysfunction, both in vitro cell culture models and in vivo murine models are commonly utilized. In this review, we discuss the methodologies frequently employed to assess nanoparticle toxicity and barrier disruption. Furthermore, we analyze and compare the distinct effects of various nanoparticle types on the airway epithelial barrier. By elucidating the diverse responses elicited by different nanoparticles, we aim to provide insights that can guide future research endeavors in assessing and mitigating the potential risks associated with nanoparticle exposure.

We consider open non-twist Hamiltonian systems represented by an area-preserving two-dimensional map describing incompressible planar flows in the reference frame of a propagating wave, and possessing exits through which map orbits can escape. The corresponding escape basins have a fractal nature that can be revealed by the so-called basin entropy, a novel concept developed to quantify final-state uncertainty in dynamical systems. Since the map considered violates locally the twist condition, there is a shearless barrier that prevents global chaotic transport. In this paper we show that it is possible to determine the shearless barrier breakup by considering the variation of the escape basin entropy with a tunable parameter.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research on using shell nacre as cement with improved physico-chemical properties. To address this, the current study aimed to develop a chemical curable com-posite shell nacre cement (SNC) using shell nacre powder and an organically modified ceramic resin shell nacre containing ladder-structured siloxane methacrylate (SNLSM). Different amounts of shell nacre (24, 48, and 72 weight(wt)%) were added to the SNLSM resin matrix and the effect on the physicochemical properties of the cement was studied. The composite shell nacre cement SNC 72 containing 72 wt% shell nacre exhibited significantly higher mechanical properties (com-pressive strength >100 MPa, flexural strength > 35 MPa) and low linear polymerization shrinkage (0.4%) than other compositions. SNC 72 was radiopaque and the exotherm generated during the curing of the cement was minimal. Direct contact of cured SNC 72 with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the results of the study proved that the composite SNC 72 would be a promising candidate for bone defect management.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

In a bid to resolve lingering problems in cosmology, more focus is being tilted towards cosmological models in which physical constants of nature are not necessarily real constants, but varying with cosmic time. In this paper we have study cosmology in nonlinear electrodynamics with the Newton's gravitational constant $G$ not a constant but vary in form of power-law of the scale factor of the universe. The evolution of the scale factor $a (t)$ is studied in this model which depends on nonlinear electrodynamics fine tuning term of $\alpha$. Then we check the stability of the model using the speed of sound.

We show that if $f$ is a non-negative superquadratic function, then $A\mapsto\mathrm{Tr}f(A)$ is a superquadratic function on the matrix algebra. In particular, \begin{align*} \tr f\left( {\frac{{A + B}}{2}} \right) +\tr f\left(\left| {\frac{{A - B}}{2}}\right|\right) \leq \frac{{\tr {f\left( A \right)} + \tr {f\left( B \right)} }}{2} \end{align*} holds for all positive matrices $A,B$. In addition, we present a Klein's inequality for superquadratic functions as $$ \mathrm{Tr}[f(A)-f(B)-(A-B)f'(B)]\geq \mathrm{Tr}[f(|A-B|)] $$ for all positive matrices $A,B$. It gives in particular improvement of Klein's inequality for non-negative convex function. As a consequence, some variants of the Jensen trace inequality for superquadratic functions have been presented.

Cantilever beams are the most widely used form of strain-driven energy harvesting, which uses piezoelectric materials. Although researchers are constantly seeking improved power output from cantilever-beam-driven piezoelectric energy harvesters, a systematic and fundamental analysis of the effect of beam geometry on the power capacity of energy harvesters warrants further investigation. Most of the previous research accounts for beams that are fully coated with piezoelectric material. While a larger coating area increases energy output, it also escalates costs as piezoelectric materials are very expensive. Considering the high cost of piezoelectric materials when dealing with limited piezoelectric material, enhancing power output can be achieved by employing a larger base beam and coating a portion of it at the fixed end. As such, the aim of this work is to investigate a wide variety of cantilever beam shapes (e.g., trapezoidal, triangular, V-cut, concave, and convex) with partial piezoelectric material coating on the base beam to maximize the power output capacity of the harvester. To ascertain a comparable argument, the surface area, volume, and mass of all the considered beam shapes are kept consistent, as these parameters influence the power output of the harvester. The geometry of each shape is systematically varied to understand the effect of geometric configuration on the output power density. Finally, the power capacities of all types of beams are compared, and a design is proposed to obtain the maximum power output. It was found that when the surface area of both the beam and piezoelectric material is kept constant and piezoelectric material is located at the fixed end, a trapezoidal beam with a smaller base width and larger free end width is the most efficient in generating power as long as the structural integrity is maintained. The finding is completely opposite as was suggested by previous studies, which proposed that a trapezoidal beam with a smaller free end yields higher output. Instead, this study demonstrates that an inverted trapezoidal beam produced higher output, considering partial coating compared to the full beam coating used in previous studies. Additionally, a correlation is presented on how the beam resonance frequency shifts with variation in beam parameters.

The market for shark fin soup, a fashionable, high-end Chinese dish, has resulted in intensive shark fishing across all oceans. At the same time, 90% of teleost fish stocks are over-exploited, making sharks the most lucrative target: fisheries that have not previously hunted them are now. As top and middle predators, sharks have high ecological value and poor capacity to withstand fishing mortality, but though their numbers are plummeting, the secretive nature of the fin trade, along with the difficulties of obtaining relevant data, obscure their true status. In consumer countries, shark fin is a luxury item and rich consumers are willing to pay high prices. There is little interest in sustainability or legal trade. Thus market demand will continue to fuel the search for sharks and those accessible to fishing fleets are increasingly endangered. Current legal protections are not working, as is clearly seen in the case of the shortfin mako. Claims that sharks can withstand such targeted, industrial hunting and be sustainably fished under these circumstances are shown to be misguided. In the interests of averting a catastrophic collapse across the planet’s aquatic ecosystems, sharks must be given effective protection. We recommend that all sharks, chimaeras, manta rays, devil rays, and rhino rays be protected from international trade through an immediate CITES Appendix I listing. However, a binding international agreement for protection, not only of sharks, but of the loss of biodiversity in general, is what is most needed to allow marine and fresh water ecosystems to recover.

The emphasis in the automotive industry towards sustainable mobility has led to a significant interest in hybrid-electric propulsion systems with high energy density batteries. Addressing the needs of this strategy, the battery market is exploring new technologies to improve the safety and lifespan of electric vehicles. To this end, there is a focus on the all-solid-state battery (ASSB) technology for its cycle capabilities. Filling the current void in the literature pertaining to accurate ageing models for ASSBs, in this work, we present an enhanced version of the numerical ageing model, originally developed for liquid electrolyte based batteries, to forecast the development of the solid electrolyte interface layer that is the major cause of battery capacity fading. The model has been tested on prototype batteries and reveals an accuracy of 99%. The capacity fade in ASSBs has been investigated under different conditions, and the enhanced ageing model has been validated using experimental data from these batteries. The findings suggest that there is potential for solid-state batteries to be commercialized, although significant work is needed to match the manufacturing level of lithium-ion batteries with liquid electrolytes.

The blood-brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.

Rough volatility models are popularized by \cite{gatheral2018volatility}, where they have shown that the empirical volatility in the financial market is extremely consistent with rough volatility. Fractional Riccati equation as a part of computation for the characteristic function of rough Heston model is not known in explicit form as of now and therefore, we must rely on numerical methods to obtain a solution. In this paper, we give a short introduction to option pricing theory and an overview of the current advancements on the rough Heston model.

The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingdons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu,Fe,Mn). The consequent oxidative stress gives rise to protein plaques and neuronal cell death. An equilibrium exists between the functional requirement of the brain for Cu and Fe and their destructive potential with the production of reactive oxygen species. The importance of the brain barrier is highlighted in regulating the import of these metals. Upregulation of key transporters occurs in foetal and neonatal life when brain metal requirement is high and is down-regulated in adult life when need is minimal. By contrast a neonatal mode of CTR1 upregulation persists in feral N.Ronaldsay sheep. This has led to the premise that metal regulation may return to the default setting in ageing with implications for neurodegenerative disease.

In this study, Brillouin optical time-domain analysis (BOTDA) sensing technology was utilized for monitoring settlement in a similarity model of a highway subgrade. As contact winding cannot be used for an optical fiber that is buried directly in soil, uncoupling between. the fiber and the soil can occur. Thus, an optical-fiber-embedded beam (OFEB) was developed, and a method for measuring and calculating the beam deformation was proposed. A calibration test and a test on a similarity model of a subgrade were carried out to investigate the applicability and monitoring accuracy of the OFEB. It was concluded that the OFEB can accurately measure beam deflection, where the maximum relative error between measurements by the optical fiber and a displacement transducer was approximately 5%. The OFEB was embedded directly into a similarity model of a subgrade to monitor settlement. The deflection deformation of the OFEB was found to be close to the subgrade settlement over a certain settlement range with a relative error below 8.1%. Thus, the OFEB can be used to realize measure large-range distributed settlement in a subgrade. A numerical simulation was performed to identify appropriate beam dimensions and material design parameters, thereby extending the measurement range before decoupling of the OFEB and soil occurs. The enhancement of the measurement range and accuracy of the OFEB based on the preliminary experiments carried out in this study enables further investigation of settlement monitoring.

The conventional theory of neutron beams interacting with many-body systems treats the beam as a classical system, i.e. with its dynamical variables appearing in the quantum dynamics of the scattering process not as operators but only as c-numbers. Moreover, neutrons are described with plane waves, i.e. the concept of neutron's (finite) coherence length is here irrelevant. The same holds for electron, atom or X-ray scattering. This simplification results in the full decoupling of the probe particle's dynamics from the quantum dynamics of the scatterer---a well-known fact also reflected in the standard formalism of time-correlation functions (see textbooks). Making contact with modern quantum theoretical approaches (e.g., quantum entanglement, 'which-path detection' versus interference, von Neumann measurement, Week Values, etc.) new observable effects may be exposed and/or predicted, for instance, a momentum-transfer deficit and an intensity deficit in neutron scattering from protons of hydrogen-containing samples. 7

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.

We discuss the implementation of a suite of virtual diagnostics at the FACET-II facility currently under commissioning at SLAC National Accelerator Laboratory. The diagnostics will be used for prediction of the longitudinal phase space along the linac, spectral reconstruction of the bunch profile and non-destructive inference of transverse beam quality (emittance) using edge radiation at the injector dogleg and bunch compressor locations. These measurements will be folded in to adaptive feedbacks and ML-based reinforcement learning controls to improve the stability and optimize the performance of the machine for different experimental configurations. In this paper we describe each of these diagnostics with expected measurement results based on simulation data and discuss progress towards implementation in regular operations.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

During a survey in 2015 an impressive assemblage of organisms were found in a hypersaline pond of the Messolonghi saltworks. The salinity ranged between 50 and 180 ppt and the organisms recorded fell in the categories of Cyanobacteria (17 species), Chlorophytes (4 species), Diatoms (23 species), Dinoflagellates (1 species), Protozoa (40 species), Rotifers (8 species), Copepods (1 species), Artemia sp., one nematode and Alternaria sp. (Fungi). Fabrea salina was the most prominent protist in all samples and salinities. This ciliate has the potential to be a live-food candidate for marine fish larvae. Asteromonas gracilis proved a sturdy microalga performing excellently in a broad spectrum of culture salinities ies. Most of the specimens were identified only to the genus level and, based on their morphology, as there are no relevant records in Greece, there is a possibility for some of them to be either new species or strikingly different strains of certain species recorded elsewhere.

Mangroves offer vital ecological advantages including air and water filtration, coastal and estuarine habitat provision, sediment stabilization, and wave energy absorption. Their intricate root systems play a key role in safeguarding shorelines from tsunamis and erosive storms by dissipating wave energy. Moreover, mangroves shield against boat wakes and wind-waves, bolstering shoreline defense. Wave dissipation is a function of forest width, tree diameter, and forest density. Restoration efforts of juvenile mangroves in Florida’s Indian River Lagoon (IRL) aim to reduce wave energy in areas vulnerable to erosion. Physical model testing of wave dissipation through mangroves is limited due to the complexity in representing the mangrove structure, where prop roots are non-uniform in both diameter and location. Previous studies have quantified wave dissipating effects through use of scaled and parameterized mangrove structures. This study measures the dissipation effects of live mangroves in a wave flume, forced by conditions representative of the IRL. These measurements are used to validate a parameterized dowel model. Error between wave attenuation factors for the live mangrove and dowel system was on average 2.5%. Validation of the modularized dowel system allowed for further parameterized testing to understand forest structure effects, such as sediment stabilization and wave attenuation.

: Polymer single screw extrusion is a major industrial processing technique used to obtain plastics products. To assure high outputs, tight dimensional tolerances, and excellent product performance, extruder screws may show different design characteristics. Barrier screws, which contain a second flight in the compression zone, have become quite popular as they promote and stabilize polymer melting. Therefore, it is important to design efficiently extruder screws and decide whether a conventional screw will do the job efficiently, or a barrier-screw should be considered instead. This work uses multi-objective evolutionary algorithms to design conventional and barrier screws (Maillefer screws will be studied) with optimized geometry. Processing of two polymers, Low Density Polyethylene and Polypropylene, is analyzed. A methodology based on the use of Artificial Intelligence (AI) techniques, namely data mining, decision making and evolutionary algorithms, is presented and utilized to obtain results with practical significance, based on relevant performance measures (objectives) used in the optimization. For the various case studies selected, Maillefer screws were generally advantageous for processing LDPE, while for PP the use of both types of screws would be feasible.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Epidemiological studies indicate an increased risk of cancer from the consumption of very hot foods and beverages. The International Agency for Research on Cancer (IARC) has already recommended threshold values for the maximum drinking temperature of very hot beverages. The contact time and the contact temperature are decisive for the risk of injury when hot media come into contact with human skin. However, measuring the contact temperature is not easily possible in practice. In the present study, a numerical simulation based on the solution of the heat conduction equation was initially used to investigate whether and for what period of time a constant contact temperature is to be expected under oral conditions. For small circular 3-cm food samples (e.g., cooked potatoes) with 2.5 mm thickness in contact with the tongue, the simulation results in a constant contact temperature of 10 s before cooling. With a thickness of 0.5 mm, the contact temperature is only maintained 1 s. Hot beverages, which spread as a thin film and thereby increase their surface area, can therefore be consumed at higher temperatures than solid foods. Furthermore, a simple test technique with a "measuring spoon" was developed. A hot sample is placed on the tongue. Orientating measurements were used to determine which contact temperature was considered to be just comfortable for any period > 10 s and for which period of less than 10 s it was still just bearable. The contact temperature, which was still perceived as tolerable for periods > 10 s, was 46.5 °C. The time spans for the higher contact temperature 48 °C were between 2 and 4 s and for 49 °C between 1 and 2 s. The course of the contact temperatures determined in the experiment over time allows to calculate the corresponding threshold values of consumption temperatures for various foods. Consumption temperatures of about 56 °C for potatoes and 60 °C for cheese are still perceived as tolerable. In view of the fact that the contact temperature is obviously the determining factor for the risk of injury from burns in the oral cavity in addition to the contact time, it makes sense to reference threshold values to the contact temperature rather than to the surface or consumption temperature of a food product, which is current customary practice. If this contact temperature is defined as a threshold value, the surface or consumption temperature for any other food can be calculated.