Nonlinear Increase Research Articles

Trends in Exclusive Non-Cigarette Tobacco Smoking in England: A Population Survey 2013-2023.

The UK Government intends to implement a "smokefree generation" policy prohibiting the sale of all tobacco products to people born after 2008. National surveys provide comprehensive data on cigarette smoking, but little is known about patterns of non-cigarette tobacco smoking across key population groups. Using data from a nationally representative cross-sectional survey of adults in England, collected monthly between September 2013 and September 2023 (n = 196721), we estimated time trends in exclusive non-cigarette tobacco (eg, cigar/pipe/shisha) smoking prevalence, overall and by age, gender, occupational social grade, region, ethnicity, and vaping status. Interviews were conducted face-to-face until March 2020 and via telephone thereafter. From September 2013 to September 2023, there was a non-linear increase in exclusive non-cigarette tobacco smoking prevalence (from 0.36% to 1.68%; prevalence ratio = 4.72 [95% CI = 3.43-6.48]). Prevalence was relatively stable up to February 2020 (at an average of 0.46%), then increased sharply at the start of the COVID-19 pandemic (at the same time as survey methods changed), to 0.90% (0.82%-0.99%) in March 2020. This was followed by a steadier rise, peaking at 1.97% in May 2022, before falling slightly to 1.68% by September 2023. In 2022/2023, 1 in 10 smokers (10.8% [9.64%-12.0%]) exclusively used non-cigarette tobacco. The rise in prevalence was observed across all subgroups but was most pronounced among younger adults (eg, reaching 3.21% of 18-year-olds vs. 1.09% of 65-year-olds). Prevalence was consistently higher among men and current vapers. Although exclusive use of non-cigarette combustible tobacco remains rare among adults in England, it has increased in recent years, particularly among younger ages. As of September 2023, there were approximately 772800 adult exclusive non-cigarette tobacco smokers in England; around five times more than a decade earlier. The proportion of adults in England who do not use cigarettes at all but smoke other combustible tobacco products has increased substantially in recent years, with a particularly pronounced rise among young people. The inclusion of non-cigarette combustible tobacco products under the proposed "smokefree generation" policy is therefore likely to be important for achieving the greatest reduction in youth uptake of tobacco smoking, as it would ensure young people who are unable to legally buy cigarettes do not buy other combustible tobacco products that are similarly harmful to health.

Nonlinear waveform steepening in time reversal focusing of airborne, one-dimensional sound waves, and the absence of Mach stems

Time reversal (TR) is a process that can be used to generate high amplitude focusing of sound. Previous research has shown that TR in reverberant environments can generate peak levels that exceed 200 dB with airborne, audible sound [Patchett and Anderson, J. Acoust. Soc. Am. 151(6), (2022)], and 134 dB with airborne ultrasound [Wallace and Anderson, J. Acoust. Soc. Am. 150(2), (2021)]. Particularly, in the focusing of audible sound, these high amplitude focused waveforms exhibit multiple nonlinear properties including waveform steepening and a nonlinear increase in compressions due to the generation of free space Mach stems. This study attempts to remove the Mach stems by generating the focus in a 1D system, since Mach stems require higher dimensional spaces to form. The system of pipes used ensures a planar 1D reverberant environment. Results show that waveform steepening remains as expected but that the nonlinear increase in compression amplitudes disappears without the ability for Mach stems to form. This provides further confirmation that Mach stems are the cause of the nonlinear increase in compression amplitudes observed with high amplitude TR.

An analytical investigation on nonlinear vibrations and stability of Timoshenko pipes conveying two-phase flow

The primary objective of this study is to conduct a comprehensive investigation on the nonlinear free vibration and stability analysis of the multilayer graphene reinforced pipe conveying liquid–gas two–phase flow based on the Timoshenko beam model. The Halpin–Tsai micromechanics model is employed which provides a means to evaluate and analyze the mechanical behavior and performance of the multilayer FG reinforced pipe. According to Von–Kármán strain relations and applying the Hamilton's principle, the governing equations of motion are derived. The Galerkin technique is operated to convert the partial differential equation (PDE) to the ordinary differential equation (ODE). The homotopy analysis method is employed to solve the fourth order nonlinear differential equation. Closed–form expressions for the nth nonlinear frequency and time history as well as the critical flow velocity based on the Timoshenko theory are achieved. The results demonstrate that neglecting the effects of rotary inertia and shear deformation may cause some errors by the increment of the initial amplitude. Furthermore, the critical flow velocity, depends not only on the mechanical and geometrical properties of the pipe but also on the initial mode shape excitation. The results indicate that by the increment of flow velocity, liquid density and slenderness ratio, the nonlinear frequency decreases, on the other hand, by the increment of the initial amplitude, the nonlinear frequency increases.

Investigations into penetration depth profiles of hydrogenic species in beryllium plasma-facing components via molecular dynamics simulations

During the operation of nuclear fusion reactors, plasma-facing components lining the reactor vessel are continually bombarded by plasma species. The penetration and subsequent trapping of these bombarding plasma ions has implications for component damage as well as in-vessel inventory. Accurately predicting the expected ion penetration depth profiles at a range of plasma ion and surface temperatures typical of fusion reactor operating conditions will inform the scrape-off layer design to limit particle radiation damage and tritium trapping in order to prolong the lifetime of the plasma-facing components and satisfy the DT fuel cycle requirements. By defining a statistical distribution for ion penetration depth and describing the evolution of its parameters across the fusion parameter space of interest, the expected ion deposition depth profiles can be calculated for any subset of ion and surface temperature ranges as needed. Molecular dynamics simulations were used to study the bombardment of beryllium lattices with surface temperatures of up to 1100 K by 5 eV–150 eV deuterium and tritium ions, and the resulting ion penetration depths were investigated. The distributions of two penetration depth quantities, considered from the perspectives of lattice damage and hydrogen retention are defined and their distribution parameter dependence on surface and ion temperature is identified. The expected positive correlation between penetration depth and ion temperature is observed, where the non-linear relationship between these quantities indicates the expected form of the velocity dependence of nuclear stopping power at low bombardment energies. Isotope effects on the distributions are also investigated, with results suggesting that heavier ions have comparably lower mobility within the sample and will generally accumulate closer to the surface. A short study on ion deposition rates is also performed; a non-linear increase of deposition rate with increasing bombarding ion energy has been observed, and evidence of a weak positive surface temperature correlation has been noted.

Kinetics of N- to M-Polar Switching in Ferroelectric Al1-xScxN Capacitors.

Ferroelectric wurtzite-type aluminum scandium nitride (Al1-xScxN) presents unique properties that can enhance the performance of non-volatile memory technologies. The realization of the full potential of Al1-xScxN requires a comprehensive understanding of the mechanism of polarization reversal and domain structure dynamics involved in the ferroelectric switching process. In this work, transient current integration measurements performed by a pulse switching method are combined with domain imaging by piezoresponse force microscopy (PFM) to investigate the kinetics of domain nucleation and wall motion during polarization reversal in Al0.85Sc0.15N capacitors. In the studied electric field range (from 4.4 to 5.6MVcm-1), ferroelectric switching proceeds via domain nucleation and wall movement. The currently available phenomenological models are shown to not fully capture all the details of the complex dynamics of polarization reversal in Al0.85Sc0.15N. PFM reveals a non-linear increase of both domain nucleation rate and lateral wall velocity during the switching process, as well as the dependency of the domain pattern on the polarization reversal direction. A continuously faster N- to M-polar switching upon cycling is reported and ascribed to an increasing number of M-polar nucleation sites and density of domain walls.

Static and dynamic responses to hyperoxia of normal placenta across gestation with T2*-weighted MRI sequences.

T2*-weighted magnetic resonance imaging (MRI) sequences have been identified as non-invasive tools with which to study placental oxygenation in vivo. This study aimed to use these to investigate both static and dynamic responses to hyperoxia of the normal placenta across gestation. We conducted a single-center prospective study including 52 uncomplicated pregnancies. Two T2*-weighted sequences (T2* relaxometry) were performed, one before and one after maternal hyperoxia. The distribution of placental T2* values was modeled by fitting a gamma probability density function (T2* ), describing the structure of the histogram using the mean T2* value, the shape parameter (α) and the rate (β). A dynamic acquisition (blood-oxygen-level-dependent (BOLD) MRI) was also performed before and during maternal oxygen supply, until placental oxygen saturation had been achieved. The signal change over time was modeled using a sigmoid function, to determine the intensity of enhancement (ΔBOLD (% with respect to baseline)), a temporal variation coefficient (λ (min-1), controlling the slope of the curve) and the maximum steepness (Vmax (% of placental enhancement/min)). The histogram analysis of the T2* values in normoxia showed a whole-placenta variation, with a decreasing linear trend in the mean T2* value (Pearson's correlation coefficient (R) = -0.83 (95% CI, -0.9 to -0.71), P < 0.001), along with an increasingly peaked and narrower distribution of T2* values with advancing gestation. After maternal hyperoxia, the mean T2* ratios (mean T2*hyperoxia/mean T2*baseline) were positively correlated with gestational age, while the other histogram parameters remained stable, suggesting a translation of the histogram towards higher values with a similar appearance after maternal hyperoxia. ΔBOLD showed a non-linear increase across gestation. Conversely, λ showed an inverted trend across gestation, with a weaker correlation (R = -0.33 (95% CI, -0.58 to -0.02), P = 0.04, R2 = 0.1). As a combination of ΔBOLD and λ, the changes in Vmax throughout gestation were influenced mainly by the changes in ΔBOLD and showed a positive non-linear correlation with gestational age. Our results suggest that the decrease in the T2* placental signal as gestation progresses does not reflect placental dysfunction. The BOLD dynamic signal change is representative of a free-diffusion model of oxygenation and highlights the increasing differences in oxygen saturation between mother and fetus as gestation progresses (ΔBOLD) and in the placental permeability to oxygen (λ). © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

565 – Safety and pharmacokinetic profiles of a humanized monoclonal antibody TQH2722 targeting interleukin 4 receptor alpha (IL-4Rα) in health adult subjects

Abstract Introduction/Background TQH2722 is a humanized monoclonal antibody targeting interleukin 4 receptor alpha (IL4Rα) which leads to the dual-blockade of interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, inhibiting the T-helper cell type 2 immune pathway. Th2 inflammation is implicated in the pathobiology of diseases such as asthma and atopic dermatitis. We describe the safety and pharmacokinetic results from a first-in-human study in healthy subjects. Objectives To evaluate the safety, tolerability, pharmacokinetic characteristics, and immunogenicity of TQH2722 injection in healthy adult subjects. Methods This randomized, double-blind, placebo-controlled, ascending-dose phase I study (NCT05409326) was conducted in China. Each adult subject received a single subcutaneous (sc.) TQH2722 dose or placebo in single ascending-dose (SAD) cohorts, and 4 doses of TQH2722 or placebo administrated Q2W in multiple ascending-dose (MAD) cohorts. Pharmacokinetic samples were collected prior to first dose administration through 56 days after initial dosing in SAD cohorts. In the MAD cohorts, samples were collected before every administration until 56 days after last dosing. Results As of 28 September 2023, all subjects had completed the study, with the database locked while remaining unblinded. Sixty-six (66) healthy subjects were enrolled in this study. The SAD cohorts consisted of single doses of TQH2722 of 50 mg (n-4), 150 mg (n=10 active, 2 placebo), 300, 600, and 1200 mg cohorts, each receiving TQH2722 (n=8) or placebo (n=2). Ten subjects were enrolled in each of the 150 and 600 mg MAD cohorts receiving TQH2722 (n=8) or placebo (n=2). No dose-limiting toxicities or SAEs were observed and only 3 subjects experienced a grade 3 AE including 1 subject of increased triglycerides, 1 subject with increased creatine kinase and 1 subject with decreased blood potassium). All other AEs were of grade 1 or 2. The incidence and severity of AEs were not dose dependent. No SAEs or AEs led to treatment discontinuation. The pharmacokinetics of TQH2722 were indicative of an anti-receptor mAb in that TQH2722 exhibited nonlinear target-mediated clearance. Maximum serum concentration was reached after 2.78-6.75 days with the half-life of a single sc. administration of TQH2722 increasing by dose level, ranging between 4 and 18 days. Conclusions TQH2722 was safe and well tolerated in healthy volunteers. Injection site reactions and laboratory abnormalities were the most reported AEs, with grade 1-2 as the major severity. Most AEs resolved on their own. Single dosing showed non-linear increases of the drug exposure as the dosage increased. These data support further clinical development of TQH2722 as a therapeutic treatment for patients with Atopic Dermatitis and other related diseases mediated by Th2 inflammation.

Femtosecond laser-treated copper sintering surface to enhance pool boiling heat transfer

Surface properties have a crucial effect on advancing boiling heat transfer (BHT). This study proposes a porous microgroove-structured surface fabricated via copper powder sintering and femtosecond laser processing to enhance pool boiling heat transfer. Copper powder sintering creates a porous layer, and the application of a femtosecond laser subsequently induces the formation of a microgroove structure atop the porous layer. Eight porous microgroove-structured surfaces were fabricated under different laser surface energy densities. Laser surface energy density was controlled by laser power and scanning speed. Pool boiling experiments were conducted for each sample, including smooth, porous, microgroove, and porous microgroove structures. Interestingly, a distinctive displacement was identified within the heat flux curve of porous microgroove-structured surfaces. The wall superheat decreased with increasing heat flux, causing the graph to shift to the left. To elucidate this phenomenon bubble visualization on the boiling surfaces was performed for each sample. It was observed that a porous microgroove-structured surface could effectively activate several bubble nucleation sites. Additionally, secondary pool boiling on the porous microgroove-structured surface was observed leading to the unique “hook back” shift in the boiling curve and the nonlinear increase of HTC. A pool boiling enhancement mechanism was proposed based on experimental data and bubble visualization. This study offers a pathway for advancing heat dissipation efficiency and understanding of surface engineering strategies.

Nonlinear Boost of Optical Angular Momentum Selectivity by Hybrid Nanolaser Circuits.

Selective control of light is essential for optical science and technology, with numerous applications. However, optical selectivity in the angular momentum of light has been quite limited, remaining constant by increasing the incident light power on previous passive optical devices. Here, we demonstrate a nonlinear boost of optical selectivity in both the spin and orbital angular momentum of light through near-field selective excitation of single-mode nanolasers. Our designed hybrid nanolaser circuits consist of plasmonic metasurfaces and individually placed perovskite nanowires, enabling subwavelength focusing of angular-momentum-distinctive plasmonic fields and further selective excitation of nanolasers in nanowires. The optically selected nanolaser with a nonlinear increase of light emission greatly enhances the baseline optical selectivity offered by the metasurface from about 0.4 up to near unity. Our demonstrated hybrid nanophotonic platform may find important applications in all-optical logic gates and nanowire networks, ultrafast optical switches, nanophotonic detectors, and on-chip optical and quantum information processing.

How motivation and enjoyment spread their wings during English Foreign Language learning: A pseudo-longitudinal investigation into Moroccan learners

The current study uses a pseudo-longitudinal design to investigate the trajectory of three lower-order dimensions of Foreign Language Enjoyment (FLE): FLE Teacher, FLE Personal and FLE Social (Botes et al., 2021) as well as 11 items/scales reflecting attitudes and motivation in the mini- Attitudes/Motivation Test Battery (Tennant & Gardner, 2004) of 85 Beginner, 322 Intermediate and 95 Advanced Moroccan English Foreign Language learners. Data were collected through an online questionnaire. One-way ANOVAs revealed a significant but non-linear increase for the values of three FLE dimensions across skill levels. Further one-way ANOVAs showed that the values of seven positively oriented motivation scales increased significantly and that the two anxiety scales decreased significantly across skill levels (very small effect sizes). Scheffé post-hoc tests confirmed that the strongest increase happened between Beginner and Intermediate levels for the FLE dimensions before levelling off at an Advanced level. This non-linear pattern was less clear-cut for the motivation scales. Correlation analyses revealed stronger relationships between the FLE dimensions and motivation scales at higher skill levels. We argue that FLE and motivation gradually reinforce each other at high skill levels. Some pedagogical implications are formulated.

The Fluid–Solid Interaction in the Nonlinear Pressure–Flux Relationship of Bordered Pits in Oriental Arborvitae (Platycladus orientalis)

The nonlinear pressure–flux relationship in the xylem of a conifer is attributed to the fluid–solid interaction within the bordered pits. However, the fluid–solid interactions between the torus–margo structure and the water flow within the pit lack comprehensive understanding. Herein, a fluid–solid interaction model was developed including the deformation of the torus–margo and the flow of water transportation. Nine pit samples were reconstructed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) pictures. Fluid–solid coupling models for pits in the stems of oriental arborvitae (Platycladus orientalis) were developed. The deflection of the torus was roughly proportional to the pressure difference between adjacent tracheids, while the pit resistance exhibited a considerable nonlinear increase. From 250 to 1750 Pa, the pit resistance increased from 4.1466 × 1016 Pa·s/m3 to 8.8344 × 1016 Pa·s/m3. The pit resistance decreased, and the pit’s ability to regulate water flow enhanced when the pit diameter increased. Both the pit resistance and the pit’s ability to regulate water decreased when the pit depth increased. The decrease in Young’s modulus for the margo promoted the nonlinear pressure–flux relationship in bordered pits. The findings provide theoretical evidence for the nonlinear relationship between pressure and flux in bordered pits, as well as for the prevention of gas bubble transit through a bordered pit during tracheid cavitation. The passive hydraulic regulation of bordered pits could increase flow resistance and reduce the water flow rate in the xylem, inhibiting tree transpiration.

Bragg scattering of nonlinear surface waves by sinusoidal sandbars

Based on the multiple-scale expansion technique, a new set of extended nonlinear Schrödinger (ENLS) equations up to the third order is derived to account for the additional high-order bottom and dispersion effects as well as the nonlinear wave interaction on wave transformation over periodic sandbars of sinusoidal geometry. By employing the small-amplitude wave assumption, a closed-form analytical solution for Bragg scattering is obtained from the linearised ENLS equations, which demonstrates that a downshift of wave frequency of the maximum reflection is mainly due to the inclusion of the high-order bottom effect. The factors that affect the downshift of the resonant frequency are identified and a theoretical expression in parabolic form is derived to quantify the downshift magnitude. The fully ENLS equations are further analysed to reveal the additional wave nonlinear effects on Bragg scattering characteristics. Under the condition of infinitesimal sandbar amplitude, the ENLS equations render a theoretical expression of the critical value of $kh$ when the nonlinear wave self-modulation effect and the nonlinear wave cross-modulation effect are equal, whereas the former effect is responsible for wavenumber upshifting and the latter downshifting. When $kh$ is larger than the critical value, the increase of wave nonlinearity will enhance the downshift magnitude of the Bragg resonance, and vice versa. For finite amplitude of the bottom sandbar, the ENLS equations are solved numerically to examine the influence of both wave nonlinearity and sandbar amplitude on the characteristics of Bragg resonance. The results reveal that as the increase of sandbar amplitude, the critical $kh$ increases monotonically.

Nonlinear increase in seawater 87Sr ∕ 86Sr in the Oligocene to early Miocene and implications for climate-sensitive weathering

Abstract. The 87Sr / 86Sr of marine carbonates provides a key constraint on the balance of continental weathering and hydrothermal Sr fluxes to the ocean, and the mid-Oligocene to mid-Miocene period features the most rapid rates of increase in the 87Sr / 86Sr of the Cenozoic. Because previous records of the 87Sr / 86Sr increase with time were based on biostratigraphically defined age models in diverse locations, it was difficult to unambiguously distinguish million-year-scale variations in the rate of 87Sr / 86Sr change from variations in sedimentation rate. In this study, we produce the first 87Sr / 86Sr results from an Oligocene to early Miocene site with a precise age-model-derived orbital tuning of high-resolution benthic δ18O at Equatorial Pacific Ocean Drilling Program (ODP) Site 1218. Our new dataset resolves transient decreases in 87Sr / 86Sr, as well as periods of relative stasis. These changes can be directly compared with the high-resolution benthic δ18O at the same site. We find that slowing of the rate of 87Sr / 86Sr increase coincides with the onset of Antarctic ice expansion at the beginning of the mid-Oligocene glacial interval, and a rapid steeping in the 87Sr / 86Sr increase coincides with the benthic δ18O evidence for rapid ice retreat. This pattern may reflect either northward shifts in the Intertropical Convergence Zone precipitation to areas of nonradiogenic bedrock and/or lowered weathering fluxes from highly radiogenic glacial flours on Antarctica. We additionally generate the first 87Sr / 86Sr data from ODP Site 1168 on the Tasman Rise and Integrated Ocean Drilling Program (IODP) Site 1406 of the Newfoundland Margin during the Oligocene to early Miocene to improve the precision of age correlation of these Northern Hemisphere and Southern Hemisphere midlatitude sites and to better estimate the duration of early Miocene hiatus and condensed sedimentation.

3D mesoscale study on the effect of ITZ and aggregate properties on the fracture behaviors of concrete based on discrete element method

The discrete element method (DEM) was utilized to study the effect of the interface transition zone (ITZ) and coarse aggregate properties on the compressive fracture behaviors of concrete at a micromechanical level, in which the ITZ was represented by the contact bond and the coarse aggregate was crushable. The linear parallel bonded model was introduced to represent the constitutive model of concrete, and the meso-scale parameters were determined by laboratory mechanical tests. And then, a series of numerical tests were conducted under compressive loading, and the research objects contain ITZ strength, and aggregate properties (i.e., strength, content, size, and shape). The simulation results show that as the ITZ strength increases, the compressive strength shows a nonlinear increase trend. Moreover, as the aggregate strength and content increase, both compressive strength and strain to damage consequently increase, the aggregate shape is independent of the compressive strength. The increase in the aggregate size can reduce the total surface area of the aggregate, leading to a small compressive strength. The compressive strength appears to increase first and then decrease in trend as aggregate surface roughness increases. In addition, the increase in aggregate strength and content induces the failure pattern changes from local microcrack propagation to global failure. Overall, this work comprehensively evaluates the effect of ITZ and coarse aggregate properties on the damage of concrete at a micromechanical level.

The Training and Development Process for a Multiple-Grand-Slam Finalist in Tennis.

To investigate the training and development process of a multiple-Grand-Slam finalist. A mixed-methods case-study design was used to capture the quantitative and qualitative aspects related to the training and successful development process. We used a 3-step data-collection process and pragmatic analyses of (1)training history based on logs, plans, and questionnaires; (2)in-depth semistructured interviews with the player's head coach/father, physical coach, and team administrator/mother; and (3)systematic quality assurance through negotiation among researchers and all key informants, including the player. The player's exceptional performance level was achieved by a progressive, nonlinear increase in annual training load during childhood and early youth, stabilizing at 800 sessions and 1250 to 1300hours per year at the age of 19. The annual tennis-specific training plateaued at ∼750hours from the age of 15, and 60 to 80 matches were played in most of the analyzed years. Point-play accounted for approximately 50% of the total amount of specific tennis training, clearly ahead of ground strokes (∼30%), serve/return (∼15%), and smash/volley (∼5%). Physical-conditioning hours increased 5-fold from 12 to 19years, before stabilizing at ∼500hours at senior age. Key success factors included the athlete's multidimensional sports talent, discipline, and inner drive; a highly dedicated father and tennis-enthusiastic family; and strong support from a complementary and interdisciplinary performance team. This study provides novel information regarding the training and development process for a world-leading tennis player, providing a point of departure for the development of future talents.

Resolving decades of debate: the surprising role of high-temperature covalency in the structure of liquid gallium.

Liquid metals (LMs) have the potential to revolutionise many important technologies, ranging from battery components to catalytic reactions. Low melting temperature gallium (Ga) is particularly promising as a solvent in many LM alloys, due to the low energy cost of maintaining its liquid state. However, despite 30+ years of study on the nature of Ga's liquid structure, it remains enigmatic with significant disagreement among the many published reports. In this work, we reconcile many of the conflicts through analysis of extensive ab initio molecular dynamics simulations of bulk Ga liquid at different temperatures. Contrary to previous assumptions, covalency becomes more important in the liquid at higher temperatures, meaning that covalency is not a significant feature of the liquid near the phase transition temperature. This explains the experimental observation of a decrease of resistivity of the metal upon melting, and its subsequent anomalously nonlinear increase with temperature. This revised understanding of structuring in the liquid has implications for the way these alloys are tailored for specific applications in the rapidly developing field of LMs.

Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies.

Semorinemab is a monoclonal antibody that targets the N-terminal domain of the tau protein that is in clinical development for the treatment of Alzheimer's disease. To perform model-based evaluations of the observed pharmacokinetics in serum and the total plasma tau target-engagement dynamics from clinical studies evaluating semorinemab. The observed semorinemab pharmacokinetics and plasma tau target engagement from phase 1 and 2 clinical studies were modeled using a non-linear mixed effect target-mediated drug disposition model. The model was simulated to understand target engagement at clinical dose levels. The clinical studies testing semorinemab were evaluated in healthy volunteers, subjects with prodromal-to-mild Alzheimer's disease, and subjects with mild-to-moderate Alzheimer's disease. The data included a total of 8430 semorinemab serum concentrations and 4772 total tau protein plasma concentrations from 463 subjects treated with a range of single and multiple doses of semorinemab. Serum concentrations of semorinemab and the total plasma tau concentrations were measured after administration of a range of doses of semorinemab to subjects with Alzheimer's disease. A sensitivity analysis was performed wherein key target-mediated drug disposition model parameters were estimated separately between healthy volunteers, subjects with prodromal-to-mild Alzheimer's disease, and subjects with mild-to-moderate Alzheimer's disease. Serum concentrations of semorinemab were consistent across studies and showed a dose-proportional increase across the evaluated dose range. The pharmacokinetic profile was comparable between healthy volunteers and subjects with Alzheimer's disease. Total plasma tau concentrations increased in a dose-dependent non-linear manner upon semorinemab administration. The target-mediated drug disposition model adequately described the serum pharmacokinetics and protein dynamics with an estimated antibody-ligand binding strength, Kss, of 42.7 nM. The estimated values of clearance and central volume of distribution were 0.109 L/day/70 kg and 2.95 L/70 kg, respectively, and were consistent with typical values for IgG mAbs. In the sensitivity analysis, Kss (32 nM) and baseline tau protein (0.30 µM) were estimated to be lower for healthy volunteers compared to subjects with Alzheimer's disease but were comparable between subjects with Alzheimer's disease of different severities (Kss: 52-57 nM, baseline tau: 0.44-0.47 µM). The models suggested that peripheral target engagement was over 90% at the clinical doses in each of the diagnostic subgroups. Our target-mediated drug disposition model adequately described the serum pharmacokinetics and the peripheral non-linear increase with dose of the total tau. The model confirmed that these dose-response relationships were consistent across populations of healthy volunteers and subjects with different severities of Alzheimer's disease.

Research on parameterized modeling and mechanical characteristics of shearer cables.

Shearer cables, subjected to large deformations and exposed to harsh working conditions during frequent back-and-forth movements, pose difficulties in achieving comprehensive mechanical performance and extended fatigue life. This study addresses parametric modeling challenges related to determining tangency within and between layers, recursively generating spiral curves from the (n-1)-th level to the n-th level, and constructing irregular surfaces for insulation and sheath. Investigating tensile and bending properties, the research explores the impact of varying pitch diameter ratios at different stranding levels, stranding directions, and monofilaments on mechanical performance across scales. The results reveal a nonlinear increase in stress in power and control conductors with growing pitch diameter ratios. The optimal combination is determined as a pitch diameter ratio of 6 for cabling, 5 for the control conductor, and 14 for the power conductor. The predicted fatigue life of the improved cable by Ncode aligns with bending test results, demonstrating functionality up to 15.12e4 cycles. Stress distribution in parallel stranding is lower and more even, tending to scatter. Conversely, counter stranding experiences relatively higher stress, ensuring a more stable structure. While maintaining a constant effective conductor cross-sectional area, finer monofilaments result in higher cross-sectional filling ratios, enhancing tensile and bending performance.

Non-negligible photostriction that accompanies the photoinduced phase transition process in VO&lt;sub&gt;2&lt;/sub&gt;

&lt;p&gt;VO&lt;sub&gt;2&lt;/sub&gt; experiences a transition from an insulating monoclinic phase to a metallic rutile phase near room temperature, which can be triggered by photoexcitation. This unique phenomenon highlights the significant potential of VO&lt;sub&gt;2&lt;/sub&gt; in optoelectronic applications. However, the photoinduced shape deformation, also known as photostriction, which occurs during this phase transition has been largely overlooked. Here, we present findings on the photostriction of VO&lt;sub&gt;2&lt;/sub&gt; ceramics and investigate the impact of photoinduced phase transition on its photostriction behavior. Large photostriction exceeding 0.1% is achievable in VO&lt;sub&gt;2&lt;/sub&gt; ceramics when illuminated by both 405 and 655 nm monochromatic laser. In contrast to the majority of inorganic photostrictive materials, VO&lt;sub&gt;2&lt;/sub&gt; demonstrates a nonlinear increase in photostriction as light intensity increases. Upon surpassing the threshold light intensity, the photo-triggered M-to-R phase transition leads to an anomalous increase, approximately 40%, in photostriction. Furthermore, the photoexcited structural evolution and the variation in photostrictive response to different light wavelengths are also depicted by ab initio molecular dynamics simulations. This study not only demonstrates VO&lt;sub&gt;2&lt;/sub&gt; as an excellent inorganic material for photo-actuating applications, but also validates the effectiveness of utilizing photoinduced phase transition to explore high-performance inorganic photostrictive materials.&lt;/p&gt;

The effect of the various porous layers on thermomechanical buckling of FGM sandwich plates

This study focuses on the thermal buckling behavior of sandwich porous plates made up of metal-ceramic functionally graded material (FGM) components using a new sinusoidal high order shear theory. The sandwich plate consists of a core plate made of either pure metal or pure ceramic, with face layers composed of a functional gradient of metal and ceramic constituents. This study examined the porosity and four porosity distribution functions in plates with FGM face layers and nonlinear temperature increase and material grading index of the face layers on the thermal buckling loads of sandwich plates.