The propagation behavior of reaction wave for Ni/Al clad particle composites under shock loading.

Prior studies indicate that the reaction wave can propagate from the impact surface, but the possibility and the influencing factors of the reaction wave formation are still unclear. This work investigates the propagation behavior of the shock-induced reaction wave for Ni/Al clad particle composites with varying stoichiometry (from 0.5 to 0.75 of the Ni mole fraction) through molecular dynamics simulations. It is found that the solid-state reaction processes with or without wave propagation strongly depend on the conjunction of stoichiometry and shock intensity. Within the cases of wave propagation, the calculated propagation velocity (in the range of 135-170 m/s) increases linearly or exponentially with the Ni mole fraction. Furthermore, the thermodynamic criteria for the reaction wave formation, including Al melting at the collision surface and higher temperature gradient, are established by analysis of the shock-induced high-entropy layer. In addition, microstructural characterization reveals the intrinsic mechanisms of the propagation of the reaction wave and the formation of additional reaction wave, namely, the dissolution of Ni into Al and the coalescence of reaction zones. Apart from the propagation behavior, the initial stoichiometry influences the crystallization-dissolution of B2-NiAl during reaction processes, notably through an exponential growth relationship between maximum crystallinity and the Ni mole fraction. These findings may provide a physical basis for improving traditional reaction rate models to break through phenomenological understanding.

Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

N6-methyladenosine (m6A) sequencing reveals Heterodera glycines-induced dynamic methylation promoting soybean defense.

Unraveling the intricacies of soybean cyst nematode (Heterodera glycines) race 4 resistance and susceptibility in soybean breeding lines-11-452 (highly resistant) and Dongsheng1 (DS1, highly susceptible)-was the focal point of this study. Employing cutting-edge N6-methyladenosine (m6A)-seq and RNA-seq techniques, we delved into the impact of m6A modification on gene expression and plant defense responses. Through the evaluation of nematode development in both resistant and susceptible roots, a pivotal time point (3 days post inoculation) for m6A methylation sequencing was identified. Our sequencing data exhibited robust statistics, successful soybean genome mapping, and prevalent m6A peak distributions, primarily in 3'UTR (Untranslated region) and stop codon regions. Analysis of differentially expressed m6A peaks (DMPs) and expressed genes (DEGs) revealed distinctive patterns between resistant and susceptible genotypes. In the highly resistant line (11-452), key resistance and defense-associated genes displayed increased expression coupled with inhibited methylation, encompassing crucial players like R genes, receptor kinases, and transcription factors. Conversely, the highly susceptible DS1 line exhibited heightened expression correlated with decreased methylation in genes linked to susceptibility pathways, including Mildew Locus O (MLO)-like proteins and regulatory elements affecting defense mechanisms. Genome-wide assessments, GO/KEGG analyses, and DMP/DEG overlap emphasized the intricate interplay of m6A modifications, alternative splicing, microRNA and gene regulation in plant defense. Protein-protein interaction networks illuminated defense-pivotal genes, delineating divergent mechanisms in resistant and susceptible responses. This study sheds light on the dynamic correlation between methylation, splicing, and gene expression, providing profound insights into plant responses to nematode infection.

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience.

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a severe form of juvenile arthritis that is characterized by chronic joint inflammation and systemic symptoms such as fever, rash, and organ involvement. Anti-IL-6 receptor monoclonal antibody tocilizumab is an effective treatment. However, some patients still experience persisting or recurrent symptoms and the real-world effectiveness of canakinumab in Chinese patients with sJIA has never been reported. Therefore, this study aimed to assess the efficacy and safety of canakinumab in Chinese patients with sJIA using real-world data. METHODS: We conducted a retrospective study on children with active sJIA. Clinical features, laboratory data, corticosteroid dosage, and adverse events (AEs) were collected at baseline and at 4, 8, 12, and 24 weeks after initiating canakinumab treatment. RESULTS: Seven female and four male patients were included in the study. All patients had previously been treated with tocilizumab and were administered canakinumab for 12.4 ± 3.4 months. Notably, significant improvements were observed in both clinical signs and symptoms as well as laboratory indicators. Four children under corticosteroid treatment were able to successfully discontinue their corticosteroid therapy: one at week 4, two at week 12, and one at week 24. Notably, there was a significant reduction in the number of tender and swollen joints (P = 0.0059) as well as the systemic juvenile arthritis disease activity score (P < 0.0001). The most common AE was infection, but no patients experienced serious AEs. No cases of macrophage activation syndrome or death were reported during the follow-up period. CONCLUSIONS: Canakinumab was found to be potentially efficacious and safe in Chinese patients with sJIA. No new AEs were observed with canakinumab treatment.

Asiaticasics A-O, structurally intriguing coumarins from Toddalia asiatica with potential inflammatory inhibitory activity.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.

A hybrid deep learning approach to improve real-time effluent quality prediction in wastewater treatment plant.

Wastewater treatment plant (WWTP) operation is usually intricate due to large variations in influent characteristics and nonlinear sewage treatment processes. Effective modeling of WWTP effluent water quality can provide valuable decision-making support to facilitate their operations and management. In this study, we developed a novel hybrid deep learning model by combining the temporal convolutional network (TCN) model with the long short-term memory (LSTM) network model to improve the simulation of hourly total nitrogen (TN) concentration in WWTP effluent. The developed model was tested in a WWTP in Jiangsu Province, China, where the prediction results of the hybrid TCN-LSTM model were compared with those of single deep learning models (TCN and LSTM) and traditional machine learning model (feedforward neural network, FFNN). The hybrid TCN-LSTM model could achieve 33.1 % higher accuracy as compared to the single TCN or LSTM model, and its performance could improve by 63.6 % comparing to the traditional FFNN model. The developed hybrid model also exhibited a higher power prediction of WWTP effluent TN for the next multiple time steps within eight hours, as compared to the standalone TCN, LSTM, and FFNN models. Finally, employing model interpretation approach of Shapley additive explanation to identify the key parameters influencing the behavior of WWTP effluent water quality, it was found that removing variables that did not contribute to the model output could further improve modeling efficiency while optimizing monitoring and management strategies.

Involvement of Sep38ß in the Insecticidal Activity of Bacillus thuringiensis against Beet Armyworm, Spodoptera exigua (Lepidoptera).

The p38 mitogen-activated protein kinases (MAPKs) are associated with insect immunity, tissue repair, and the insecticidal activity of Bacillus thuringiensis (Bt). Here, a p38 MAPK family gene (Sep38ß) was identified from Spodoptera exigua. Among the developmental stages, the transcription level of Sep38ß was the highest in egg, followed by that in prepupa and pupa. Sep38ß expression peaked in Malpighian tubules and the hemolymph of fifth instar larvae. Knockdown of Sep38ß or injection of SB203580 (a p38 MAPK inhibitor) significantly downregulated the SeDUOX expression and reactive oxygen species (ROS) level in the midgut, accounting for deterioration of the midgut to scavenge pathogens and enhancement of Bt insecticidal activity. In conclusion, all the results demonstrate that Sep38ß regulates the immune-related ROS level in the insect midgut, which suppresses the insecticidal activity of Bt against S. exigua by 17-22%. Our study highlights that Sep38ß is essential for insect immunity and the insecticidal activity of Bt to S. exigua and is a potential target for pest control.

Atomic insights into shock-induced alloying reaction of premixed Ni/Al nanolaminates.

In material processing and handling processes, premixed interlayer often replace the ideal Ni/Al interface, which would become a new origin of alloying reaction. This work investigates shock-induced reaction mechanism and kinetics of premixed Ni/Al nanolaminates with molecular dynamics simulations and theoretical analysis. The reaction is found to be driven by the crystallization evolution in premixed interlayer and the diffusion of premixed atoms. Among them, multi-stage reaction patterns are strongly manifested by the crystallization evolution characteristics. Specifically, "crystallization-dissolution-secondary growth" and "crystallization-dissolution" of B2 phase respectively correspond to the solid-state and solid-liquid reaction cases, where crystallizations are fitted well by Johnson-Mehl-Avrami kinetics model. Interestingly, the different growth mechanisms of B2 grain are revealed, namely nuclei coalescence and atomic diffusion. Moreover, the analysis of microscopic diffusion theory indicates a certain non-random diffusion nature for solid-state reaction initiation, but near-purely random diffusion for solid-liquid reaction initiation. The diffused Al atoms possess a limited diffusion coefficient and enhanced diffusion correlation, resulting in extremely slow mixing rate in Ni layer. In addition, the influence law of Ni concentration in premixed interlayer on reactivity parameters can be quantitatively described by a quadratic function.

Modeling Indirect Greenhouse Gas Emissions Sources from Urban Wastewater Treatment Plants: Integrating Machine Learning Models to Compensate for Sparse Parameters with Abundant Observations.

Electricity consumption and sludge yield (SY) are important indirect greenhouse gas (GHG) emission sources in wastewater treatment plants (WWTPs). Predicting these byproducts is crucial for tailoring technology-related policy decisions. However, it challenges balancing mass balance models and mechanistic models that respectively have limited intervariable nexus representation and excessive requirements on operational parameters. Herein, we propose integrating two machine learning models, namely, gradient boosting tree (GBT) and deep learning (DL), to precisely pointwise model electricity consumption intensity (ECI) and SY for WWTPs in China. Results indicate that GBT and DL are capable of mining massive data to compensate for the lack of available parameters, providing a comprehensive modeling focusing on operation conditions and designed parameters, respectively. The proposed model reveals that lower ECI and SY were associated with higher treated wastewater volumes, more lenient effluent standards, and newer equipment. Moreover, ECI and SY showed different patterns when influent biochemical oxygen demand is above or below 100 mg/L in the anaerobic-anoxic-oxic process. Therefore, managing ECI and SY requires quantifying the coupling relationships between biochemical reactions instead of isolating each variable. Furthermore, the proposed models demonstrate potential economic-related inequalities resulting from synergizing water pollution and GHG emissions management.

The intricate role of annexin A2 in kidney: a comprehensive review.

Annexin A2 (Anxa2) is a calcium (Ca2+)-regulated phospholipid binding protein composed of a variable N-terminus and a conserved core domain. This protein has been widely found in many tissues and fluids, including tubule cells, glomerular epithelial cells, renal vessels, and urine. In acute kidney injury, the expression level of this protein is markedly elevated in response to acute stress. Moreover, Anxa2 is a novel biomarker and potential therapeutic target with prognostic value in chronic kidney disease. In addition, Anxa2 is associated not only with clear-cell renal cell carcinoma differentiation but also the formation of calcium-related nephrolithiasis. In this review, we discuss the characteristics and functions of Anxa2 and focus on recent reports on the role of Anxa2 in the kidney, which may be useful for future research.

Inverse design of chiral functional films by a robotic AI-guided system.

Artificial chiral materials and nanostructures with strong and tuneable chiroptical activities, including sign, magnitude, and wavelength distribution, are useful owing to their potential applications in chiral sensing, enantioselective catalysis, and chiroptical devices. Thus, the inverse design and customized manufacturing of these materials is highly desirable. Here, we use an artificial intelligence (AI) guided robotic chemist to accurately predict chiroptical activities from the experimental absorption spectra and structure/process parameters, and generate chiral films with targeted chiroptical activities across the full visible spectrum. The robotic AI-chemist carries out the entire process, including chiral film construction, characterization, and testing. A machine learned reverse design model using spectrum embedded descriptors is developed to predict optimal structure/process parameters for any targeted chiroptical property. A series of chiral films with a dissymmetry factor as high as 1.9 (gabs ~ 1.9) are identified out of more than 100 million possible structures, and their feasible application in circular polarization-selective color filters for multiplex laser display and switchable circularly polarized (CP) luminescence is demonstrated. Our findings not only provide chiral films with the highest reported chiroptical activity, but also have great fundamental value for the inverse design of chiroptical materials.

Deformation, damage, and reaction characteristics during the collision between Ni and Al nanoparticles.

The exothermic reaction during the collision between nanoparticles is of importance for the engineering applications of energetic powder materials. This work investigates collision-induced nanoparticle deformation, damage and reaction characteristics in a reactive Ni/Al system via molecular dynamics simulations. The morphological changes and reaction process are explored thoroughly for a wide range of impact velocities v and initial particle radius R. For lower impact velocities (1 km s-1 ≤ v ≤ 1.5 km s-1), the fully melted Al gradually clad the plastic deformed Ni nanoparticles to form an Al-shell/Ni-core structure, and the morphology ultimately develop into a nearly spherical shape possessing minimal surface energy. During this period, the self-sustaining reaction driven by the diffusion of Ni atoms into molten Al leads to slow melting of Ni nanoparticles, and the reaction and melting rates increase with the decrease of the particle radius. There exists one critical radius (R = 10 nm) beyond which the reaction is severely blocked due to the occurrence of fracture behavior at v = 1.5 km s-1. For intermediate velocities (2 km s-1 ≤ v < 3 km s-1), collision-induced debris clouds are observed, which satisfies the power-law distribution in the size of debris and results in an obvious reduction of the final reaction degree. Interestingly, we found that the reactive component in generated debris is lower for the larger-radius nanoparticle, which is also responsible for the lower final reaction degree and thermal kinetic energy. For higher velocities (v ≥ 3 km s-1), the occurrence of spallation damage reduces the contact area due to the formed micro-voids within Al and Ni nanoparticles and consequently the final reaction degree further.

Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis.

Background: Dysregulation of cell death and defective clearance of dying cells are closely related to the pathogenesis of lupus nephritis (LN). However, the contribution of a recently discovered form of programmed cell death (PCD) called ferroptosis to LN has not been explored in detail. The purpose of this study was to investigate the role of ferroptosis and its associated metabolic pathways in the pathogenesis of LN. Methods: The composite gene expression scores were calculated by averaging the z-scored transformed log2 expressed genes within each form of PCD and pathway. Immunohistochemistry and immunofluorescence assays were used to verify the bioinformatics results. Results: We determined that ferroptosis is prominently and specifically elevated in the glomerular compartment of LN patients compared to other forms of PCD and kidney disease. This finding was then verified by immunohistochemical staining of 4-HNE (a key indicator for ferroptosis) expression in our own cohort (P < 0.0001). Intercorrelation networks were observed between 4-HNE and blood urea nitrogen, SLE disease activity index, serum creatinine, and complement 4, and negatively correlated with glomerular filtration rate in our own LN cohort (P < 0.05). Furthermore, enhanced iron metabolism and reduced fatty acid synthesis may be the most important factors for ferroptosis within the glomerulus. Through analysis of a single cell sequencing dataset and verification of immunohistochemical and immunofluorescence staining, aberrantly activated lipid peroxidation in CD163+ macrophages and CD10+ PC+ (pyruvate carboxylase) epithelial cells indicated that they may be undergoing ferroptosis in the glomerular compartment. Conclusions: Two dysregulated genes, CD163 and PC, were identified and verified that were significantly associated with lipid peroxidation. Targeting ferroptosis in CD163+ macrophages and CD10+ PC+ epithelial cells may provide novel therapeutic approaches in LN.

Full-Length Transcriptome Analysis of Soybean Cyst Nematode (Heterodera glycines) Reveals an Association of Behaviors in Response to Attractive pH and Salt Solutions with Activation of Transmembrane Receptors, Ion Channels, and Ca2+ Transporters.

Soybean cyst nematode (Heterodera glycines Ichinohe), a devastating pathogen in soybean, was chosen as a model system to investigate nematode behavior and gene expression changes in response to acidic and basic pH and salt signals (pH 4.5, 5.25, 8.6, and 10 and NaCl) through full-length transcriptome sequencing of 18 samples. An average of 4.36 Gbp of clean reads per sample were generated, and 3972 novel genes and 29,529 novel transcripts were identified. Sequence structural variation during or after transcription may be associated with the nematode's behavioral response. The functional analysis of 1817/4962 differentially expressed genes/transcripts showed that signal transduction pathways, including transmembrane receptors, ion channels, and Ca2+ transporters, were activated, but pathways involved in nematode development (e.g., ribosome) and energy production (e.g., oxidative phosphorylation) were inhibited. A corresponding model was established. Our findings suggest that these receptors and ion channels might be potential targets for nematicides or drug discovery.

Diverse diterpenoids from Callicarpa rubella Lindl. as natural inhibitors of macrophage foam cell formation.

Ten undescribed diterpenoids namely rubellawus E-N of structural types pimarane (1, 3-4), nor-abietane (2), nor-pimarane (5-6), isopimarane (7-9), and nor-isopimarane (10), along with eleven known compounds, were isolated and identified from the aerial parts of Callicarpa rubella Lindl. The structures of the isolated compounds were confirmed by comprehensive spectroscopic analyses and quantum chemical computations. Pharmacologically, almost all the compounds exhibited a potential inhibitory effect on oxidized low-density lipoprotein-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment of atherosclerosis.

Bilateral central retinal artery occlusion as a presenting manifestation of systemic lupus erythematosus: a case-based review.

Central retinal artery occlusion (CRAO) is an ophthalmic emergency that typically results in permanent vision damage even despite vigorous treatment. In this article, we describe a case of acute vaso-occlusive retinopathy that presented as the primary manifestation of SLE in the absence of elevated levels of APLAs. After treatment with intravenous steroids, immunoglobulin, intrathecal injection of dexamethasone, plasma exchange, and intravenous cyclophosphamide, SLE was well controlled in the patient, but her vision was permanently lost in the left eye. We also go over a brief review of the currently available literature on retinal vaso-occlusive disease present in SLE. The pathology mechanism of CRAO is related to immune complex-mediated "vasculitis", which is typically associated with neuropsychiatric lupus. However, the literature review identified antiphospholipid antibody syndrome (APS) in only 6 of 19 patients, indicating that other mechanisms besides APS are associated with CRAO. Systemic immunosuppression and anticoagulants are required for the treatment of this severe vaso-occlusive retinopathy. Early recognition and aggressive intervention may prevent severe loss of vision.

Prognostic factors and clinical outcomes of breast cancer patients with disease progression during neoadjuvant systemic therapy.

BACKGROUND: Disease progression during neoadjuvant systemic therapy for breast cancer indicates poor prognosis, while predictors of the clinical outcomes of these patients remain unclear. By comparing the clinical outcomes of patients with different patterns of salvage treatment strategies, we try to evaluate the factors predicting distant failure and explore the favourable treatment for them. METHODS: Patients with disease progression during neoadjuvant systemic therapy for stage I-III breast cancer diagnosed between January 1, 2008 and July 31, 2021 in Fudan University Shanghai Cancer Center were enrolled. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions or the appearance of new breast or nodal lesions. Kaplan-Meier, univariate and multivariate Cox proportional hazard regressions were utilized to compare survival outcomes between different salvage treatment strategies. RESULTS: Among 3775 patients treated with NST, 60 (1.6%) patients encountered disease progression. A significant difference between the outcomes of patients receiving direct surgery and other salvage modalities was found (p = 0.007). Triple-negative breast cancer (p = 0.010) and not receiving direct surgery (p = 0.016) were independently associated with distant disease-free survival on multivariate analysis. CONCLUSIONS: Predictors of distant failure in patients with disease progression include triple-negative breast cancer and not receiving direct surgery. Direct surgery seems to be more favourable than other treatments for patients with disease progression. For inoperable patients, neoadjuvant radiation can increase their operability but not improve their prognosis.

Gypenoside biotransformation into ginsenoside F2 by endophytic Aspergillus niger from Gynostemma pentaphyllum.

Ginsenoside F2 is a protopanaxadiol saponin compound with various biological activities, including antioxidant, anti-inflammatory, and anticancer properties. Ginsenoside F2 can be found in ginseng, but in low quantities. Therefore, ginsenoside F2 production predominantly relies on the biotransformation of various ginsenosides, such as ginsenosides Rb1 and Rd. In this study, we reported the production of ginsenoside F2 by gypenoside biotransformation with Aspergillus niger JGL8, isolated from Gynostemma pentaphyllum. Ginsenoside F2 could be produced by two different biotransformation pathways, namely Gyp-V-Rd-F2 and Gyp-XVII-F2. The product exhibited antioxidant activity against free radicals (DPPH) with IC50 value of 29.54 µg/mL. Optimal biotransformation conditions were a pH of 5.0, temperature of 40 °C, and 2 mg/mL of substrate. Enzyme kinetic parameters revealed that the hydrolysis rate of Gyp-V, Rd, and Gyp-XVII was 0.625, 0.588, and 0.417 mM/h, respectively. In conclusion, we demonstrated that gypenoside is a substitutable substrate for ginsenoside F2 biotransformation.

Research on the Impact Mechanical Properties of Real-Time High-Temperature Granite and a Coupled Thermal-Mechanical Constitutive Model.

Studying the mechanical behavior of rocks under real-time high-temperature conditions is of great significance for the development of energy caverns, nuclear waste disposal projects, and tunneling engineering. In this study, a real-time high-temperature impact compression test was conducted on Sejila Mountain granite to explore the effects of temperature and external load on its mechanical properties. Based on the concepts of damage mechanics and statistics, a coupled thermal-mechanical (T-M) damage constitutive model was established, which considers the temperature effect and uses the double-shear unified strength as the yield criterion. The parameter expressions were clarified, and the accuracy and applicability of the model were verified by experimental data. The research results indicated that high temperatures had an obvious damaging and deteriorating effect on the strength of the granite, while an increase in impact velocity had an enhancing effect on the strength of the granite. The established constitutive model theoretical curve and test curve showed a high degree of agreement, indicating that the coupled T-M model can objectively represent the evolution process of damage in rocks and the physical meaning of its parameters is clear.

Atomistic study on reaction kinetics and reactivity of Ni/Al clad particles composites under shock loading.

In prior research on shock-induced reaction, the interfacial crystallization of intermetallics, which plays an important role in solid-state reaction kinetics, has not been explored in detail. This work comprehensively investigates the reaction kinetics and reactivity of Ni/Al clad particle composites under shock loading with molecular dynamics simulations. It is found that the reaction acceleration in a small particle system or the reaction propagation in a large particle system breaks down the heterogeneous nucleation and continuous growth of B2 phase at the Ni/Al interface. This makes the generation and dissolution of B2-NiAl show a staged pattern consistent with chemical evolution. Importantly, the crystallization processes are appropriately described by the well-established Johnson-Mehl-Avrami kinetics model. With the increase in Al particle size, the maximum crystallinity and growth rate of B2 phase decrease and the value of the fitted Avrami exponent decreases from 0.55 to 0.39, showing a good agreement with the solid-state reaction experiment. In addition, the calculations of reactivity reveal that the reaction initiation and propagation will be retarded, but the adiabatic reaction temperature can be elevated when Al particle size increases. An exponential decay relationship is found between the propagation velocity of the chemical front and the particle size. As expected, the shock simulations at non-ambient conditions indicate that elevating the initial temperature significantly enhances the reactivity of large particle systems and results in a power-law decrease in the ignition delay time and a linear-law increase in the propagation velocity.