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Acoustic resonances in cascade structures may cause structural damage and instability problems in aero-engines and other industrial plants; thus, developing corresponding prediction methods is important. However, works published in the open literature mostly focus on the special case of the stationary Parker modes and provide little knowledge into the rotating resonances in annular cascades, especially in the presence of non-zero background mean flows. This paper develops a three-dimensional semi-analytic model to study the acoustic resonances in an annular cascade in the presence of axial mean flow. The model applies an unsteady cascade response based on the three-dimensional lifting surface method to construct a matrix equation. Characteristic frequencies are solved in the complex domain by numerically searching for singular points. Both the oscillation frequency and the growth rate of the three-dimensional resonance modes are theoretically calculated for the first time under non-zero mean flow conditions. The results reveal an organised distribution with varying inter-blade phase angle and show obvious change with the background flow speed. It is found that the unsteady vortex shedding from the trailing edges of the cascade is a key factor influencing the dissipation rate of the resonance modes. In addition, the important effects of acoustic scattering by the cascade during resonances are examined, which qualitatively corroborate some previous experimental observations.
Centanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) in development for treatment of attention-deficit/hyperactivity disorder (ADHD). The effect of CTN on cardiac repolarization from a thorough QT (TQT) trial is reported.
Methods
In this double-blind, placebo (PBO)- and active-controlled, 3-period crossover TQT trial, healthy adults (18-65 years) were randomized to dosing sequences including CTN (800 mg supratherapeutic dose: 4 x 100 mg tablets in the morning and 5 hours later), CTN PBO (4 PBO tablets in the morning and 5 hours later), and active control moxifloxacin (400 mg + CTN PBO in the morning and CTN PBO 5 hours later). Morning doses were separated by 72 hours. Plasma was collected and data were extracted from continuously recorded ECGs for 24 hours following dosing. Effects on ECG parameters (QT interval with Fridericia correction factor [QTcF], PR and QRS intervals, and T- and U-wave morphology), and heart rate (HR) were assessed. The primary analysis was C-QTc, the relationship between drug concentration and PBO-corrected change from baseline in QTcF (ΔΔQTcF). Categorical analyses of ECG parameters were conducted for changes in QTcF, PR, and QRS intervals and in HR.
Results
Of 30 participants enrolled, 56.7% were male and 86.7% were White. Mean (SD) age was 37.6 (14.5) years; mean (SD) BMI was 26.4 (3.4) kg/m2. The slope (90% CI) of the C-QTc relationship for CTN was −0.001 (−0.003, 0.00002) msec/[ng/mL] and not significant. The predicted ΔΔQTcF (90% CI) at the geometric mean Cmax of CTN 800 mg was −2.72 (−6.92, 1.48) msec. A significant slope (90% CI) of the C-QTc relationship for moxifloxacin (0.004 [0.002, 0.006] msec/[ng/mL]) and a predicted ΔΔQTcF (90% CI) at the geometric mean Cmax of moxifloxacin 400 mg above 5 msec (11.75 [8.25, 15.24]) confirmed assay sensitivity. No ΔΔQTcF ≥10 msec was observed for CTN at any postdose time point; all upper limits of 90% CIs of ΔΔQTcF were <10 msec. The by-time-point analysis showed the maximum least squares mean difference in ΔQTcF (90% CI) between CTN and PBO was 1.64 (−1.40, 4.68) msec at 24 hours postdose. No CTN-treated participants had a QTcF increase of >30 msec; no relevant increases in PR or QRS interval or HR were observed. Four participants had >25% decrease in HR and <50 beats per minute. No abnormal U waves were observed; 1 participant had abnormal T-wave morphology. No serious TEAEs or deaths were reported. The most frequently reported TEAEs with CTN were nausea (24.1%), dizziness (24.1%), and decreased appetite (13.8%).
Conclusions
In this TQT trial, centanafadine, a potential first-in-class NDSRI in development for treatment of ADHD, had no clinically meaningful effect on cardiac repolarization and was generally safe and well tolerated.
Previous presentation: 2023 ACCP Annual Meeting, September 10–12, 2023, Bellevue, WA
Ridge B is one of the least studied areas in Antarctica but has been considered to be a potential location for the oldest ice on Earth. Among important parameters for calculating where very old ice may exist, geothermal heat flux (GHF) is critical but poorly understood. Here, GHF is determined by quantifying the transitions between dry and wet basal conditions using a radioglaciological method applied to airborne radio-echo sounding data. GHF is then constrained by a thermodynamic model matched to the transitions. The results show that GHF in Ridge B varies locally and ranges from 48.5 to 65.1 mW m−2, with an average value of 58.0 mW m−2, which is consistent with the current known GHF constrained by subglacial lakes and derived from Vostok ice core temperature measurements. Our work highlights the value of considering local GHF when locating the oldest ice in this potential region or other regions.
Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes.
Methods
Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions.
Results
Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13.
Conclusions
The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.
Sepiolite-based composites have great potential for application as flame-retardant and thermal-insulation material but their application and development are limited by poor mechanical properties. The objective of the present study was to combine polyvinyl alcohol (PVA) and 3-aminopropyltriethoxysilane (KH-550) with sepiolite (Sep) to improve its aerogel strength. A universal testing machine, thermogravimetry, and microcalorimetry were used to investigate the mechanical properties, thermal-stability, and flame-retardant properties, respectively, of aerogels. The results indicated that KH-550 can enhance effectively the mechanical properties and flame retardancy of aerogels. The compressive modulus of PVA/Sep vs KH-550/PVA/Sep aerogel was 209.28 vs. 474.43 kPa, the LOI index changed from 26.4 to 30.4%. The porosity of the aerogels was > 96% and the density was < 0.05 g/cm3. The thermal conductivity remained at between 0.0340 and 0.0390 W/(m·K), and the aerogel could recover to > 85% after a 50% compressive deformation. These data indicated that Sep-based aerogel would act as a flame retardant and a thermal insulating material with excellent mechanical properties.
Cardiac mass in children is rare and insidious onset, and primary cardiac mass is less than secondary mass. Among the malignant tumours in children with tumour thrombus in the venous system, about 98% of the cases are nephroblastoma. But it is still rare for the tumour thrombus to reach the level of the atrium or even enter the right ventricle. In this case, the child complained of chest tightness and palpitation and went to the doctor and found Wilms tumour complicated with intracardiac tumour thrombus.
One novel trend in reducing aero-engine noise is to utilize the silent flight mechanism of owls by applying perforations on fan stator vanes. Consequently, the establishment of relevant theoretical models is of particular interest. The current efforts made in this regard are just targeting the features based on two-dimensional models without including the three-dimensionality. In this paper, we present a three-dimensional solution for acoustic scattering by annular perforated cascades, and the dipole source corresponding to the unsteady pressure loading on the vanes is identified as the dominant sound source. By the singularity method, the acoustic response is obtained with the soft boundary condition applied on the vane surfaces. It is found that considerable noise reduction can be achieved for rotor–stator interaction with a modest uniform porosity, and accordingly two mechanisms are proposed to understand the effect of porosity on propagating sound. The first is that the perforations allowing a normal velocity across the vane reduce the unsteady loading induced by the incident disturbances. The second is that the three-dimensional interactions among the dipole sources at different positions are also dampened by the soft boundaries, thus the distribution of the unsteady pressure loading on the vanes will also change significantly compared to hard-vane cases. Non-uniform distributions of porosity are investigated further, indicating that perforations in the vane upstream area are more effective in reducing propagating noise. Our method is fully three-dimensional and capable of investigating non-uniform porosity, and thus is able to provide useful guidance for future soft vane designs.
This paper examines China's water governmentality in advancing the Lancang-Mekong Cooperation (LMC). It attends to how discourses, used as a political instrument, are framed, justified and contested in the reshaping of international hydrosocial territories. China's official and popular discourses present the LMC as promoting multilateral politics, economic benefits and social integration, while they obscure polarizing politics, external interventions and regional conflicts. Using strategies of positive publicity first, top-down communication and mutual empathy creation, these discourses aim to deflect attention away from controversies and geopolitics in the region to construct governable hydrosocial territories. However, in a transnational context where the Chinese state cannot unilaterally control geographical imaginaries, alternative discourses depict China as a “hydro-hegemon” that poses threats to downstream countries. The discursive dichotomy reflects multiple ontologies of water and power struggles in international river governance, bringing regional stability and sustainable development into question.
The purpose of the current study was to research the factors influencing thyroid volume (TVOL) in 6–12-year-old children and update the reference values. A cross-sectional study was carried out in iodine-sufficient areas of four provinces in China. Urine, edible salt and drinking water samples were collected from children. Children’s height, weight and TVOL were measured. Ridge regression was used to screen variables for solving the multicollinearity problem. Quantile regression was used to analyse the relationship between the quantiles of TVOL and other variables. In total, 5653 children aged 6–12 years were enrolled in this study, including 2838 boys and 2815 girls. There was no significant difference in TVOL between boys and girls (P > 0·05). Spearman correlation analysis showed that total TVOL was positively correlated with age, height, weight, body surface area (BSA) and BMI, and the correlation coefficients were 0·616, 0·663, 0·669, 0·685 and 0·479, respectively. Among them, the correlation between TVOL and BSA was the strongest. According to the ridge regression results, age and BSA influenced TVOL, and the ridge regression coefficients were 0·13 and 0·94, respectively. Quantile regression further showed that age and BSA had significant influences on the whole TVOL distribution (P < 0·001). Therefore, the TVOL of children aged 6–12 years in China was mainly influenced by age and BSA, and reference values for TVOL of different genders based on age and BSA were established.
Over-the-rotor liner exhibits the potential to further attenuate turbofan noise, but the physics involved remain to be explored. In this paper, a three-dimensional coupled singularity method is proposed to investigate the flow-acoustic coupling effects of axially overlapping annular rotor and finite-length liner in subsonic flow. The formulation adopts the orthogonal basis expansion of the generated disturbances in terms of the hard-walled duct modes. The sound scatterings at the rotor and the liner are then characterized, respectively, by the underdetermined dipole and monopole distributions. We derive a simultaneous solution to the coupled unsteady rotor and liner responses, which ensures that the resultant perturbed field satisfies both the impermeable boundary condition on the blade surfaces and the impedance boundary condition on the lined wall. The effect of a perforated porous-material liner on the wake–rotor interaction tones is investigated. The analysis reveals that for the sound field of varying mode and frequency characteristics, moving the inlet liner to the over-the-rotor location generally leads to limited loss or even an increase of upstream sound absorption, along with additional acoustic benefits in the aft duct. The flow-acoustic coupling between the axially overlapping rotor and liner is shown to alleviate significantly the unsteady blade loading and meanwhile intensify the fluid particle oscillation through the acoustically treated wall. Sound source reduction and sound dissipation enhancement are thus identified as the governing noise attenuation mechanisms. Finally, we extend the analysis to provide insights into the effectiveness of over-the-rotor acoustic treatment with shortened axial length.
Few studies have been conducted to investigate the association of kidney function decline with the trajectories of homocysteine (Hcy) over time, using repeated measurements. We aimed to investigate the association of kidney function with changes in plasma Hcy levels over time. Data were collected from the Rugao Longevity and Ageing Study. In detail, plasma Hcy and creatinine levels were measured in both waves (waves 2, 3 and 4) during the 3·5-year follow-up (n 1135). Wave 2 was regarded as the baseline survey. The estimated glomerular filtration rate (eGFR) was calculated based on creatinine. Subjects were categorised into four groups according to quartiles of eGFR at baseline. Linear mixed-effect models were used to investigate the association of eGFR with subsequent plasma Hcy levels. The mean eGFR at baseline was 90·84 (sd 11·42) ml/min per 1·73 m2. The mean plasma Hcy level was 14·09 (sd 6·82) at baseline and increased to 16·28 (sd 8·27) and 17·36 (sd 10·39) μmol/l during follow-ups. In the crude model, the interaction between time and eGFR at baseline was significant (β = −0·02, 95 % CI −0·02, −0·01, P = 0·002). After adjusting for confounding factors, a significant relationship remained (β = −0·02, 95 % CI −0·02, −0·01, P = 0·003), suggesting that kidney function decline at baseline was associated with a faster increase in Hcy levels. Kidney function decline is associated with a more pronounced increase in plasma Hcy levels. Further studies with longer follow-up periods and larger sample sizes are needed to validate our findings.
A 1178 J near diffraction limited 527 nm laser is realized in a complete closed-loop adaptive optics (AO) controlled off-axis multi-pass amplification laser system. Generated from a fiber laser and amplified by the pre-amplifier and the main amplifier, a 1053 nm laser beam with the energy of 1900 J is obtained and converted into a 527 nm laser beam by a KDP crystal with 62% conversion efficiency, 1178 J and beam quality of 7.93 times the diffraction limit (DL). By using a complete closed-loop AO configuration, the static and dynamic wavefront distortions of the laser system are measured and compensated. After correction, the diameter of the circle enclosing 80% energy is improved remarkably from 7.93DL to 1.29DL. The focal spot is highly concentrated and the 1178 J, 527 nm near diffraction limited laser is achieved.
The laser shock processing implemented by a laser-induced high-pressure plasma which propagates into the sample as a shockwave is innovatively applied as a post-processing technique on HfO2/SiO2 multilayer coatings for the first time. The pure mechanical post-processing has provided evidence of a considerable promotion effect of the laser-induced damage threshold, which increased by a factor of about 4.6 with appropriate processing parameters. The promotion mechanism is confirmed to be the comprehensive modification of the intrinsic defects and the mechanical properties, which made the applicability of this novel post-processing technique on various types of coatings possible. Based on experiments, an interaction equation for the plasma pressure is established, which clarifies the existence of the critical pressure and provides a theoretical basis for selecting optimal processing parameters. In addition to the further clarification of the underlying damage mechanism, the laser shock post-processing provides a promising technique to realize the comprehensive and effective improvement of the laser-induced damage resistance of coatings.
Echinococcus granulosus sensu lato has complex defence mechanisms that protect it from the anti-parasitic immune response for long periods. Echinococcus granulosus cyst fluid (EgCF) is involved in the immune escape. Nevertheless, whether and how EgCF modulates the inflammatory response in macrophages remains poorly understood. Here, real-time polymerase chain reaction and enzyme-linked immunosorbent assay revealed that EgCF could markedly attenuate the lipopolysaccharide (LPS)-induced production of pro-inflammatory factors including tumour necrosis factor-α, interleukin (IL)-12 and IL-6 but increase the expression of IL-10 at mRNA and protein levels in mouse peritoneal macrophages and RAW 264.7 cells. Mechanically, western blotting and immunofluorescence assay showed that EgCF abolished the activation of nuclear factor (NF)-κB p65, p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signalling pathways by LPS stimulation in mouse macrophages. EgCF's anti-inflammatory role was at least partly contributed by promoting proteasomal degradation of the critical adaptor TRAF6. Moreover, the EgCF-promoted anti-inflammatory response and TRAF6 proteasomal degradation were conserved in human THP-1 macrophages. These findings collectively reveal a novel mechanism by which EgCF suppresses inflammatory responses by inhibiting TRAF6 and the downstream activation of NF-κB and MAPK signalling in both human and mouse macrophages, providing new insights into the molecular mechanisms underlying the E. granulosus-induced immune evasion.
In the integrated navigation system using extended Kalman filter (EKF), the state error conventionally uses linear approximation to tackle the commonly nonlinear problem. However, this error definition can diverge the filter in some adverse situations due to significant distortion of the linear approximation. By contrast, the nonlinear state error defined in the Lie group satisfies the autonomous equation, which thus has distinctively better convergence property. This work proposes a novel strapdown inertial navigation system (SINS) nonlinear state error defined in the Lie group and derives the SINS equations of the Lie group EKF (LG-EKF) for the MIMU/GNSS/magnetometer integrated navigation system. The corresponding measurement equations are also derived. A land vehicle field test has been conducted to evaluate the performance of EKF, ST-EKF (state transformation extended Kalman filter) and LG-EKF, which verifies LG-EKF's superior estimation accuracy of the heading angle as well as the other two horizontal angles (pitch and roll). The LG-EKF proposed in this paper is unlimited in the choice of sensors, which means it can be applied with both high-end and low-end inertial sensors.
The mortality of coronavirus disease 2019 (COVID-19) differs between countries and regions. This study aimed to clarify the clinical characteristics of imported and second-generation cases in Shaanxi. This study included 134 COVID-19 cases in Shaanxi outside Wuhan. Clinical data were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. In total, 34.3% of the 134 patients were severe cases, 11.2% had complications. As of 7 March 2020, 91.8% patients were discharged and one patient (0.7%) died. Age, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, direct bilirubin, lactate dehydrogenase and hydroxybutyrate dehydrogenase showed difference between severe and no-severe cases (all P < 0.05). Baseline lymphocyte count was higher in survived patients than in non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The interleukin-6 (IL-6) level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest computed tomography images in 51.5% of the pneumonia cases. Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.
The vortex sound interaction in acoustic resonance induced by vortex shedding from a cylinder in a flow duct is numerically studied based on a nonlinear physical model, which consists of three meshless sub-models describing the vortex shedding, sound generation and propagation within the duct. In addition, the acoustic particle velocity near the separation point of the shear layer is solved and added onto the Kutta condition of the vortex shedding, which takes the acoustic feedback effect into consideration and makes the vortex sound interaction bi-directional. The predicted results of resonant frequency and amplitude are found to be in conformity with previous experiment data, especially, a continuous description of the onset–sustain–cease of lock-in phenomenon is well captured. The lock-in phenomenon is depicted as a vigorous competition between the vortex shedding frequency $(f_{s})$ and the inherent frequency of the acoustic $\unicode[STIX]{x1D6FD}$-mode $(f_{a})$. The mutual capturing behaviour of these two frequencies is dominated by $f_{a}$. Moreover, $f_{s}$ cannot always be locked onto $f_{a}$ within the whole lock-in region, which is in marked contrast to the previous understanding. In this aspect, two lock-in regions, the synchronous region and the $\unicode[STIX]{x1D6FD}$-mode dominant region, are defined according to the relevance of $f_{s}$ and $f_{a}$. The maximum resonant sound appears at the end of the synchronous region. The present model not only predicts the proper characteristics of frequency lock-in as observed in experiments, but also helps to provide a more detailed understanding of the underlying lock-in mechanism.
FM-to-AM (frequency modulation-to-amplitude modulation) conversion caused by nonuniform spectral transmission of broadband beam is harmful to high-power laser facility. Smoothing by spectral dispersion (SSD) beam is a special broadband beam for its monochromatic feature at the given time and space on the near field. The traditional method which uses the optical spectral transfer function as filters cannot accurately describe its AM characteristics. This paper presents the theoretical analysis of the etalon effect for SSD beam. With a low-order approximation, the analytic model of the temporal shape of SSD beam is obtained for the first time, which gives the detailed AM characteristics at local and integral aspects, such as the variation of ripples width and amplitude in general situation. We also analyze the FM-to-AM conversion on the focal plane; in the focusing process, the lens simply acts as an integrator to smooth the AM of SSD beam. Because AM control is necessary for the near field to avoid optics damage and for the far field to ensure an optimal interaction of laser–target, our investigations could provide some important phenomena and rules for pulse shape control.
Herein, in order to research the crystalline behaviors of cyclotetramethylenetetranitramine-aluminum (HM-Al) composites in solvents, the modified attachment energy model was applied to predict the morphologies of HMX in vacuum, dimethyl sulfoxide (DMSO), and ethanol. Then HMX-Al composites with Al coated and noncoated were prepared via solvent–nonsolvent method, and the morphologies were characterized. Results show that HMX interacts with DMSO and ethanol mainly via van der Waals force and electrostatic force. HMX grows into polyhedral crystals in two solvents. However, the shapes and the crystalline surface area distributions of the polyhedrons are different for two solvents. There are many aluminum particles embedded in HMX crystals of HMX-Al composite particles prepared via solvent–nonsolvent method, but Al particles cannot embed in HMX crystals in the existence of fluoropolymer. The crystal morphology predicted is consistent with the experimental results.
M3:2 high-speed steel (HSS) billets with or without Nb addition were prepared by spray deposition. The effects of Nb and post-thermal-mechanical processing (decomposition treatment and hot forging), as well as heat treatment, on the microstructure and properties of M3:2 HSS were investigated. The microstructure of the as-deposited M3:2 HSS consisted of equiaxed grains with a mean size of approximately 25 μm and discontinuous plate-like M2C and irregular MC carbides distributed along grain boundaries. 0.5% Nb addition can refine the M2C plates and spheroidize MC carbides. With 2% Nb addition, the refined grains with a mean size of approximately 12 μm and continuous net of M6C and a uniform distribution of NbC carbides were obtained. The decomposition of metastable M2C carbides can be accelerated with 0.5% Nb addition due to the refined size and lower thermodynamic stability of M2C plates. With the increased degree of decomposition of M2C carbide, the M6C and MC carbides became refined and more uniformly distributed after optimal thermal-mechanical processing and heat treatment, which leads to a significant increase in bend strength and toughness.