近三年论文 · 68 篇 (点击展开摘要,时间倒序)
Acoustic radiation force exerted by progressive waves on subwavelength inhomogeneous scatterers
The acoustic radiation force exerted by plane progressive waves with wavenumber k on a scatterer of characteristic size a is calculated in the Born approximation using Westervelt's far-field integral [J. Acoust. Soc. Am. 29, 26-29 (1957), Eq. (2)]. In the subwavelength limit ka≪1 of the Born approximation, closed-form analytical expressions for the radiation force are obtained in terms of acoustic polarizabilities, which represent the response of the scatterer to dipole order. For subwavelength scatterers whose relative compressibility and density are even functions about their centroid, Gor'kov's O[(ka)4] force [Sov. Phys. Dokl. 6, 773-775 (1962), Eq. (10)] is recovered, whereas the radiation force on scatterers characterized by odd distributions is O[(ka)6]. Radiation forces on homogeneous and inhomogeneous spheres and cubes are considered as examples, for which the analytical expressions agree with solutions based on spherical wave expansions and Fourier transforms for ka≲0.8. The present work complements the volume integral obtained by Jerome and Hamilton [J. Acoust. Soc. Am. 150, 3417-3427 (2021), Eq. (16)] for the radiation force exerted by standing waves in the subwavelength limit of the Born approximation.
The effects of fitness self-testing with instant feedback on changes in health-related fitness among Chinese male college students
BACKGROUND: The decline in health-related physical fitness resulting from physical inactivity remains a critical global public health concern. Technology-supported fitness self-testing has the potential not only to improve students' testing experiences but also to enhance their health-related fitness. However, the effectiveness of such approaches has not yet been systematically examined, and their validity within university populations remains largely unestablished. METHOD: A quasi-experimental research design with a control group (n = 45) and an experimental group (n = 44), incorporating pre- and post-tests, was employed in this study. The experimental group completed monthly self-testing sessions accompanied by GAI-generated instant feedback over a 16-week period, whereas the control group participated in general physical education classes that included multiple physical activities. Health-related fitness (HRF) was assessed using BMI, the one-mile run, pull-ups, and sit and reach tests. VO₂max was included as a covariate to control for baseline differences in HRF between the two groups. Repeated-measures multivariate analysis of covariance (RM-MANCOVA) was conducted to examine the effects of the intervention on HRF outcomes. RESULTS: After controlling for baseline VO2max, RM-MANCOVA indicated significant time × group interaction for sit and reach (p < 0.001) and one-mile run (p < 0.05), with the intervention group demonstrating significant improvement in both tests. However, no significant differences were observed between groups for body mass index (BMI) and the pull-ups test. CONCLUSIONS: These findings suggested that HRF self-testing with instant GAI feedback was an effective intervention for improving certain HRF components, particularly flexibility and aerobic fitness. Further research is necessary to explore the long-term effects of self-testing and its application across diverse populations.
Upsample Anything: A Simple and Hard to Beat Baseline for Feature Upsampling
We present \textbf{Upsample Anything}, a lightweight test-time optimization (TTO) framework that restores low-resolution features to high-resolution, pixel-wise outputs without any training. Although Vision Foundation Models demonstrate strong generalization across diverse downstream tasks, their representations are typically downsampled by 14x/16x (e.g., ViT), which limits their direct use in pixel-level applications. Existing feature upsampling approaches depend on dataset-specific retraining or heavy implicit optimization, restricting scalability and generalization. Upsample Anything addresses these issues through a simple per-image optimization that learns an anisotropic Gaussian kernel combining spatial and range cues, effectively bridging Gaussian Splatting and Joint Bilateral Upsampling. The learned kernel acts as a universal, edge-aware operator that transfers seamlessly across architectures and modalities, enabling precise high-resolution reconstruction of features, depth, or probability maps. It runs in only $\approx0.419 \text{s}$ per 224x224 image and achieves state-of-the-art performance on semantic segmentation, depth estimation, and both depth and probability map upsampling. \textbf{Project page:} \href{https://seominseok0429.github.io/Upsample-Anything/}{https://seominseok0429.github.io/Upsample-Anything/}
Spherical wave expansion coefficients for radiation from a planar velocity source
A general theory for obtaining spherical wave function expansion coefficients for a sound beam transmitted by a planar velocity source is presented. By neglecting evanescent wave components and thus making the proposed method only approximate in the near field, it is shown that these coefficients can be obtained for any expansion point using just the normal velocity condition in the source plane. Additionally, simplifications are presented for axisymmetric sources. Results are compared with direct numerical evaluation of the Rayleigh integral for source conditions corresponding to a circular and rectangular piston. The present theory can be used in calculations of acoustic scattering and radiation force for spherical objects, or in spherical acoustical holography applications.
Time-domain computational approaches for modeling nonlinear sound fields with shocks
Numerical simulations of intense sound fields are employed in research involving therapeutic ultrasound, underwater acoustics, and air acoustics. Nonlinear evolution equations such as the Burgers and Khokhlov-Zabolotskaya-Kuznetsov equations generalized for biological tissue and relaxing media, and the one-way Westervelt equation, have been used for simulating strongly nonlinear sound fields with shocks. Marching schemes based on operator splitting enable modeling of different wave phenomena, e.g., nonlinearity, diffraction, attenuation, and dispersion, using the most effective algorithm for each effect. Simulation of strong nonlinear propagation effects leading to formation of steep shocks has been a challenging problem. Time-domain modeling has proven to be most effective because the number of operations over each propagation step is proportional to the number of grid points in the time window, whereas frequency-domain schemes require the number of harmonics squared. This talk will describe and compare specific features, accuracy, and effectiveness of various time-domain algorithms that have been developed over the years to simulate nonlinear effects in shock-wave propagation regimes. Algorithms based on the exact solution of the lossless Burgers equation with an interpolation procedure, an intrinsic coordinates algorithm, conventional conservative finite-difference schemes, and the Godunov-type shock-capturing method will be discussed. [Work partially supported by RSF No. 25-12-00157.]
Fast simulation of shock evolution in multirelaxing fluids using intrinsic coordinates
Discretization of thin shocks requires high computational cost for conventional time-domain algorithms that solve the augmented Burgers equation describing nonlinear propagation in a relaxing fluid. The Burgers equation can be expressed using intrinsic coordinates [Hammerton and Crighton, J. Fluid Mech. 252, 585–599 (1993)], in which waveforms remain single valued beyond the point at which waveform steepening renders them multivalued in physical coordinates. This coordinate transformation underlies a simulation approach in which shocks are inserted into the multivalued pressure waveform using the equal area rule from weak shock theory, yielding a single-valued waveform in physical coordinates without requiring fine discretization of the shock. A two-stage approach is developed by first solving the Burgers equation in intrinsic coordinates out to distances where shocks are no longer expected to be thin. Beyond that distance, the solution can be propagated in physical coordinates using a time-domain algorithm without restrictively small discretization. The two-stage approach significantly reduces computational cost compared to time-domain numerical solutions using exclusively physical coordinates and maintains high accuracy. This advantage is demonstrated with simulations of N waves propagating in air and shocks with exponential tails in seawater, each involving two relaxation mechanisms [Willis et al., JASA 157, 3824–3835 (2025)].
Radiation force exerted by progressive waves on a string in terms of polarizability
Polarizabilities represent the response of scatterers in the long-wavelength limit. The present work employs polarizabilities to calculate the radiation force exerted on a scatterer of length a and dimensionless mass density μ(x) by 1-D progressive waves on a string. The radiation force density equals 〈∂S/∂x〉according to momentum conservation at quadratic order, where the radiation stress S is obtained in the Born approximation in terms of the polarizabilities α 0 = ∫ a μ(x) dx and α 1 = 2k ∫ a μ(x) x dx, where k is the wavenumber. The radiation force equals 〈S(a/2)–S(–a/2)〉= k 4 ξ 0 2 τα 1 2/8, where ξ 0 is the incident wave amplitude and τ is the string’s tension. The force agrees with solutions based on Fourier transforms for ka « 1 [Morse and Ingard, Theoretical Acoustics (McGraw-Hill, 1968), Eq. (4.5.17)]. To the order of the present approximation, scatterers with μ(x) = μ(–x) do not experience radiation forces due to progressive waves on a string, while scatterers with μ(x) = –μ(–x) experience forces on the order of (ka)6. The results elucidate the approximations underlying the more involved calculation of radiation force exerted by progressive acoustic waves [Gokani et al., JASA 157 (2025); doi: 10.1121/10.0037572].
Accuracy of the slow scale approximation for predicting harmonic generation in plane shear wave propagation
Nonlinear shear wave propagation is typically modeled using the slow scale approximation, where it is assumed that nonlinear effects occur over the course of many wavelengths of propagation, i.e., that the nonlinear length z sh is larger than the wavelength λ. However, Catheline et al. [Phys. Rev. Lett. 91, 164301 (2003)] reported shock formation in an initially sinusoidal plane shear wave within one wavelength of propagation from the source in gelatin. Here, we investigate limits of the slow scale approximation for cubically nonlinear plane shear waves by comparing with the exact solution of the nonlinear wave equation. The dimensionless parameter Λ = λ/z sh quantifies the source amplitude limits before the slow scale approximation breaks down. As Λ (amplitude) increases, the slow scale approximation overpredicts phase speed, leading to an underestimation of shock formation distance and overestimation of waveform distortion and harmonic generation. For the case of Catheline et al., Λ = 1.07 and we find an 11% overprediction of the third harmonic amplitude at the shock formation distance. This analysis provides criteria on source amplitude for when the slow scale approximation may be invalid in the modeling of nonlinear shear wave propagation in soft tissues. [Work supported by the ARL:UT McKinney Fellowship in Acoustics.]
Measurement and analysis of second-harmonic generation in focused vortex beams
Acoustic vortex beams have been a topic of interest since the late 1990s, with applications including acoustic tweezers, underwater communication, and biomedical procedures [Guo et al. J. Appl. Phys. 132, 210701 (2022)]. Understanding nonlinearity in acoustic vortex beams can be important in various contexts. Presented here are measurements of the amplitude and phase of beam profiles at the source frequency and second harmonic. The vortex beams were generated by a focused circular piston source of radius 1.9 cm and focal length 15.2 cm operating in water at 2.25 MHz in conjunction with additively manufactured phase plates corresponding to orbital numbers of 1 and 2. Measurements confirmed the predicted vortex ring radius in the focal plane at the source frequency [Gokani et al., JASA Express Lett. 4, 124001 (2024)]. To isolate the effects of acoustic nonlinearity from nonlinearity of the source transducer, hydrophone measurements were made over a range of distances from the source, and beam profiles were compared with numerical solutions of the Westervelt equation. Acoustic holography was used to characterize the source transducer with and without the phase plate in order to examine nonideal aspects of the source. [CAG was supported by the ARL:UT McKinney Fellowship in Acoustics.]
Effects of affine source polarization on second-harmonic generation in focused shear wave beams in tissue-like media
Recent analyses of second-harmonic generation in a focused shear wave beam, both analytically [Kaufinger et al., Wave Motion 139, 103595 (2025)] and numerically [Kaufinger et al., JASA 157 (2025); doi: 10.1121/10.0037533], have been concerned primarily with radially polarized beams for comparison with corresponding measurements in tissue-mimicking gelatin phantoms [Cormack et al., IEEE TBME 71, 621 (2024)]. A radially polarized fundamental beam yields a second harmonic that also has radial polarization. However, other source polarizations may be considered. We consider the class of affine polarizations, for which the radiated beam polarization is described as a superposition of constant polarization, e.g., linear or elliptical, and first-order stretches and shears, e.g., radial, torsional, or pure shearing motion. An analytical and numerical assessment is conducted for second-harmonic generation in focused shear wave beams in tissue-like media with arbitrary affine source polarization. In general, it is found that the polarization of the second harmonic does not match that of the fundamental beam. Particular attention is devoted to the longitudinal component of the displacement field that may be used for elastography measurements in potential medical applications. [PGK is supported by the ARL:UT Chester M. McKinney Graduate Fellowship in Acoustics.]
Beyond I-Con: Exploring New Dimension of Distance Measures in Representation Learning
The Information Contrastive (I-Con) framework revealed that over 23 representation learning methods implicitly minimize KL divergence between data and learned distributions that encode similarities between data points. However, a KL-based loss may be misaligned with the true objective, and properties of KL divergence such as asymmetry and unboundedness may create optimization challenges. We present Beyond I-Con, a framework that enables systematic discovery of novel loss functions by exploring alternative statistical divergences. Key findings: (1) on unsupervised clustering of DINO-ViT embeddings, we achieve state-of-the-art results by modifying the PMI algorithm to use total variation (TV) distance; (2) supervised contrastive learning with Euclidean distance as the feature space metric is improved by replacing the standard loss function with Jenson-Shannon divergence (JSD); (3) on dimensionality reduction, we achieve superior qualitative results and better performance on downstream tasks than SNE by replacing KL with a bounded $f$-divergence. Our results highlight the importance of considering divergence choices in representation learning optimization.
Daratumumab-Based Quadruplet Therapy in Functional High-Risk RRMM (fRRMM) Patients Promotes CD8 T Cell Activation and Expansion in the Immune Microenvironment
An alternative approach to modeling radiation from baffled circular pistons (L)
The study of radiation from baffled circular pistons often begins with the Rayleigh integral. The present letter offers an alternative derivation of the Rayleigh integral by solving the Helmholtz equation for a baffled circular piston in an infinitely large cylindrical waveguide. While the Rayleigh integral is typically interpreted as a sum of simple sources, the present derivation shows that the Rayleigh integral can also be cast as a sum of Bessel beams. The alternative formulation is used to recover the axial pressure radiated by a baffled circular piston and solve the Helmholtz equation numerically for a vortex beam.
Head-on collision of longitudinal density pulses near phase transition: Insights from numerical simulations
Upon the head-on collision of two longitudinal pulses, the superposition principle breaks down when the system is driven close to a phase transition. This phenomenon has been demonstrated experimentally in lipid membranes and numerically in a van der Waals fluid model. To further investigate collision properties near a phase transition, this work numerically explores the dynamics of nonlinear pulse interactions across different regimes of the fluid model. We show that pulse annihilation does not result from the simplest (second-order) nonlinear approximation. Furthermore, even in the full nonlinear model, longitudinal pulses re-emerge but in a perpendicular direction. Additionally, we demonstrate that collision properties depend on both the stimulus amplitude and the distance between the two stimuli. Notably, an asymmetric collision site may arise when the two stimuli have different amplitudes.
Perturbation solution for second-harmonic generation in focused shear wave beams in soft solids
Use of intrinsic coordinates to simulate the evolution of shocks in multirelaxing fluids
Conventional time-domain algorithms that solve the augmented Burgers equation describing nonlinear propagation in a relaxing fluid have a high computational cost associated with discretizing thin shocks. The Burgers equation can be expressed using intrinsic coordinates [Hammerton and Crighton, J. Fluid Mech. 252, 585-599 (1993)], in which waveforms remain single valued beyond the point at which waveform steepening renders them multivalued in physical coordinates. Presented here is a fast simulation approach based on intrinsic coordinates with shocks inserted into the multivalued pressure waveform using the equal area rule from weak shock theory, yielding a single-valued waveform in physical coordinates without requiring fine discretization of the shock. A two-stage approach is developed by first solving the modified Burgers equation in intrinsic coordinates out to distances where shocks are no longer expected to be thin. Beyond that distance, the solution is propagated using a time-domain algorithm in physical coordinates without restrictively small discretization in time. The two-stage approach achieves high accuracy and significantly reduced computational cost when compared to time-domain numerical solutions using exclusively physical coordinates. Computational efficiency and accuracy are demonstrated with simulations of N waves propagating in air and shocks with exponential tails in seawater, each involving two relaxation mechanisms.
I-Con: A Unifying Framework for Representation Learning
As the field of representation learning grows, there has been a proliferation of different loss functions to solve different classes of problems. We introduce a single information-theoretic equation that generalizes a large collection of modern loss functions in machine learning. In particular, we introduce a framework that shows that several broad classes of machine learning methods are precisely minimizing an integrated KL divergence between two conditional distributions: the supervisory and learned representations. This viewpoint exposes a hidden information geometry underlying clustering, spectral methods, dimensionality reduction, contrastive learning, and supervised learning. This framework enables the development of new loss functions by combining successful techniques from across the literature. We not only present a wide array of proofs, connecting over 23 different approaches, but we also leverage these theoretical results to create state-of-the-art unsupervised image classifiers that achieve a +8% improvement over the prior state-of-the-art on unsupervised classification on ImageNet-1K. We also demonstrate that I-Con can be used to derive principled debiasing methods which improve contrastive representation learners.
The nonlinearity parameter <i>B</i>/<i>A</i>
The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.
Creative ways to study for an acoustics qualifying exam
Studying for a Ph.D. qualifying exam can be an imposing task for graduate students. Many students prepare for their qualifying exam by reading acoustics textbooks, reviewing class notes, and solving practice problems. The speakers synthesized these conventional modes of study into creative activities when preparing for their own qualifying exams: PGK recorded video derivations [https://www.youtube.com/@AcousticsDerivations.] and CAG assembled a website [https://chiragokani.github.io/class/quals/]. In this talk, the speakers share how these creative activities helped them review their fundamentals, deepen their understanding, synthesize new ideas, and acquire a more holistic view of acoustics. Since having passed their exams, the speakers continue to refer to the resources they created. First- and second-year students in the Graduate Program in Acoustics at the University of Texas at Austin have begun using these resources for their own study as well. The speakers highlight the value of creativity in the learning process and hope to inspire other students to find creative ways of studying for their own exams. [PGK and CAG are supported by the ARL:UT Chester M. McKinney Graduate Fellowship in Acoustics.]
Analytical solutions for acoustic vortex beam radiation from planar and spherically focused circular pistons
Acoustic vortex beams are quasiplanar waves with helical wavefronts characterized by the orbital number ℓ. Although Gaussian amplitude distributions result in closed-form analytical solutions for the entire paraxial field [Gokani et al., J. Acoust. Soc. Am. 155, 2707–2723 (2024)], acoustic vortex beams are usually radiated by sources with a uniform circular amplitude distribution. In this talk, analytical solutions for the field radiated by unfocused and focused uniform circular vortex sources of radius a are derived. Evaluation of the Fresnel diffraction integral in the far field of an unfocused source and in the focal plane of a focused source leads to a solution in terms of an infinite series of Bessel functions for ℓ&gt;−2. By calculating the first local maximum of this solution, it is found that the vortex ring radius is rℓ = ξ ℓ z/ ka in the far field of an unfocused source and rℓ = ξ ℓ d/ka in the focal plane of a focused source with focal distance d, where ξ ℓ = 1.23ℓ + 1.49 and k is the wavenumber. The solution given by the infinite series is reduced to closed forms for 0 ≤ ℓ ≤ 4, corresponding to orbital numbers commonly used in experiments. [CAG supported by the ARL:UT McKinney Fellowship in Acoustics.]
Focused shear wave beams for enhanced soft tissue elastography
The elastic response of soft tissues at audio frequencies is closely associated with disease-related changes in tissue microstructure and function. The propagation speed of shear waves in tissue, which is related to the shear modulus, is used to map tissue stiffness noninvasively, for example to assess breast lesion malignancy and liver disease severity. Conventional approaches for shear wave excitation are based on the acoustic radiation force or vibration of a small piston on the skin, both of which generate small-amplitude, diverging shear waves, and are limited in their ability for penetration to the required depths, especially in the assessment of liver stiffness because liver disease is often associated with obesity. Our group conceived and realized experimentally focused shear wave beams, generated by vibration of a concave piston source, which converge toward the measurement region, thereby maintaining high amplitude at the required depths. An overview is presented of recent progress in the application of focused shear wave elastography in the context of fatty liver disease assessment. Recent advances in the prediction of nonlinear effects in shear wave beam propagation will also be discussed. [P.G.K. was supported by the Chester M. McKinney Graduate Fellowship in Acoustics at ARL:UT.]
Radiation force on inhomogeneous subwavelength scatterers due to progressive waves
Gor’kov’s result for radiation force on a subwavelength homogeneous sphere in the direction of an incident progressive plane wave with time-averaged intensity〈I〉[Sov. Phys. Dokl. 6, 773–775 (1962)] is generalized to arbitrarily shaped inhomogeneous scatterers. Westervelt's surface integral in the far field [JASA 29, 26–29 (1957)] reduces by energy conservation to F ∥ =〈I/c 0〉∮ |Φ|2 (1 − e i •e r ) dΩ, where Φ is the scattered wave directivity, e i and e r are the incident and radial unit vectors, respectively, and dΩ is the differential solid angle. Since the scatterer size a is much smaller than the wavelength λ=2π/k, Φ can be calculated in terms of the acoustic polarizabilities α m = − ∫ f 1 dV, α d = ∫ 3f 2/(2+f 2) dV, and α c = k [3e i •e r ∫ r f 2/(2+f 2) dV − ∫ r f 1 dV], where f 1 and f 2 are Gor’kov’s contrast factors. For scatterers whose material properties are symmetric about the centroid r ≡ 0, α c vanishes, recovering Gor’kov’s O[(ka)4] force, while material asymmetry contributes at O[(ka)6]. The forces are verified by comparison to solutions based on partial wave expansions and Fourier transforms. [C.A.G. was supported by the ARL:UT McKinney Fellowship in Acoustics.]
Effect of homogenization on calculation of acoustic radiation force
Analytical methods for calculating acoustic radiation force are complicated by the presence of heterogeneity. For a multilayered sphere formed by biological substances having densities and compressibilities similar to those of the host fluid, the simplification provided by the Born approximation of the radiation force exerted by a 1-D standing wave was found by Jerome and Hamilton [JASA 150, 3417 (2021)] to be accurate via comparisons with the full solution by Wang et al. [J. Appl. Phys. 122, 094902 (2017)]. An alternative approximation based on replacing the layered sphere with a homogeneous effective medium, achieved by taking volume averages of the densities and compressibilities, was explored briefly by Gokani et al. [POMA 48, 045002 (2022)] in connection with particle sorting (acoustophoresis) in a microfluidic device that employs noncollinear plane waves. The present work explores the parameter range for which the simplification due to homogenization provides a reasonable approximation of the radiation force acting on layered spheres. Both 1-D standing waves and plane progressive waves are considered for the incident fields. Different densities and compressibilities of the layers are considered, as well as the ordering and thicknesses of the layers within the sphere. [CAC was supported by the ARL:UT McKinney Fellowship in Acoustics]
Second-harmonic generation in focused shear wave beams in tissue-like media with arbitrary amplitude shading at the source
Second-harmonic generation in a focused shear wave beam with Gaussian amplitude shading and radial polarization can be described analytically using a perturbation solution [Kaufinger et al., JASA 155, A350 (2024)]. Recently, focused radially polarized shear wave beams were generated in tissue-mimicking gelatin phantoms with an oscillating concave circular piston [Cormack et al., IEEE TBME 71, 621 (2024)]. To model second-harmonic generation in a focused shear wave beam with source conditions more relevant to the experiments, i.e., without Gaussian amplitude shading, the nonlinear evolution equation is solved numerically by successive approximations in k-space using a fourth-order Runge–Kutta stepping scheme. The linear solution is obtained first, which is then substituted into the quadratic terms to solve for the nonlinearly generated second harmonic. Emphasis is placed on how more realistic source conditions, including super-Gaussian amplitude shading or source conditions estimated from measurements, affect the generation of the second harmonic. Attention is also devoted to the longitudinal displacement field that is calculated locally from the transverse displacement field and the assumption of material incompressibility. [PGK is supported by the ARL:UT Chester M. McKinney Graduate Fellowship in Acoustics.]
Creative ways to study for an acoustics qualifying exam
Assessment of homogenizing material properties of scatterers to facilitate calculation of acoustic radiation force
Time-domain simulation tool with a graphical interface for modeling nonlinear waves with shocks in weakly absorptive media
Analytical solutions for acoustic vortex beam radiation from planar and spherically focused circular pistons
Analytical solutions for acoustic vortex beams radiated by sources with uniform circular amplitude distributions are derived in the paraxial approximation. Evaluation of the Fresnel diffraction integral in the far field of an unfocused source and in the focal plane of a focused source leads to solutions in terms of an infinite series of Bessel functions for orbital numbers ℓ>-2. These solutions are reduced to closed forms for 0≤ℓ≤4, which correspond to orbital numbers commonly used in experiments. A scaling law for the vortex ring radius is derived, and its relevance is characterized using ray theory.
Integrated Coding and Non-Coding Transcriptional Single-Cell Atlas of Multiple Myeloma: Unraveling the Effects of Myeloma Genotype on the Bone Marrow Microenvironment
Introduction: In recent years, multiple myeloma (MM) research has increasingly focused on unraveling the complex interactions between malignant plasma cells and their surrounding bone marrow microenvironment (BMME). To further elucidate these interactions, we developed a comprehensive single-cell atlas of the MM BMME, integrating both coding and noncoding (ncRNA) transcriptional profiles. By correlating these profiles with specific cytogenetic abnormalities in myeloma cells, we aim to uncover how ncRNAs regulate the phenotypic and functional states of myeloma cells and, consequently, shape the cellular landscape of the BMME. A detailed understanding of how the noncoding transcriptome affects the cellular components and immune landscape of the BMME is essential for advancing our knowledge of MM pathogenesis and identifying novel biomarkers and therapeutic targets. Methods: Our atlas was constructed using single-cell RNA sequencing data from 481 samples of CD138neg cells sorted from bone marrow aspirates of MM patients enrolled in the MMRF CoMMpass study. This dataset includes accompanying whole-genome sequencing and survival data, enabling correlative analysis between transcriptional profiles, cytogenetic abnormalities, and patient outcomes. To generate a combined coding and non-coding transcriptome, we developed an expanded human reference genome by systematically merging mRNA and ncRNA transcripts from the LncBook2.0 and GENECODEv42 reference genomes. The sequencing data was aligned to this expanded genome, followed by quality control processing, batch correction, clustering, and supervised analysis. Results: The resulting coding and non-coding atlas comprises over 1.9 million cells, spanning immune, plasma, and stromal compartments. Remarkably, ncRNAs constituted 46% of the associated genes, including 22,102 long ncRNAs (lncRNAs) and 3,112 small ncRNAs. Subclustering analysis of the major immune compartments (B lymphoid, myeloid, and NK and T lymphoid) yielded 70 subclusters, with ncRNAs representing 24-38% of the top 100 differentially expressed genes within each compartment. This underscores the significant role of ncRNAs in distinguishing immune subpopulations. Moreover, examining the association between specific cytogenetic abnormalities and the immune composition of the BMME, 30 subclusters were found to be differentially abundant (P &lt; 0.05) between cytogenetic abnormalities, supporting our hypothesis that myeloma cell genotypes significantly shape the immune microenvironment. For instance, patients with CCND1 amplification displayed an increase CD4+ central memory T cells with a decrease in CD8+ cytotoxic T cells. Similarly, patients with 1q21 gain exhibited an increase in TGFβ-stimulated monocytes, while a decrease in cytotoxic CD8+ T and CD56dim NK cells was observed in patients with 17p13 deletion. Next, examining which ncRNAs are associated with specific cytogenetic abnormalities, we identified 14 ncRNAs significantly differentially expressed across cytogenetic abnormalities. Increased expression of six of these ncRNAs were associated with poor overall survival both independently and in combination (P &lt; 0.05, HR = 3.7). Notably, three of these ncRNAs have documented roles in cancer progression but have not been previously studied in the context of MM. Subsequently stratifying patients based on their enrichment of these outcome-associated ncRNAs revealed even stronger associations with immune composition, including an increase in CD4+ regulatory T cells (P &lt; 0.05). This further supports our hypothesis that myeloma cell genotypes shape the BMME. Lastly, by constructing a gene regulatory network to predict the interactions between coding and noncoding RNAs, we illustrate the regulatory networks of ncRNAs modulating the phenotypes of myeloma and immune cell subpopulations. Conclusion: In summary, we present the first high-resolution transcriptomic atlas of the MM BMME, integrating both coding and noncoding RNAs. This study reveals distinct immune subpopulations associated with specific myeloma cell genotypes and highlights the central role of ncRNAs in modulating the phenotypic and functional states of both malignant and non-malignant cells in the MM BMME. Our findings emphasize the potential of ncRNAs as therapeutic targets and prognostic markers for MM, offering new avenues for research and clinical intervention.
Immune Profiling Reveals Distinct Features of Multiple Myeloma Subtypes Defined By Multi-Omics Network Analysis
Introduction: Multiple myeloma (MM) has a highly heterogeneous genomic landscape, challenging patient stratification and clinical management. By combining bulk tumor profiling with single-cell data of the tumor microenvironment (TME), we aimed to create a comprehensive multi-omics network model to dissect inter-tumor heterogeneity, which enabled us to characterize the immune cell landscape and correlate it with patient subgroups identified through multi-omics analysis of bulk tumor data, revealing significant features within each subgroup. Methods: We analyzed 185 samples collected at diagnosis from newly-diagnosed MM (NDMM) patients in MMRF CoMMpass, included in both our previous MM-PSN model (Bhalla et al, 2021) and the MMRF Immune Atlas (Pilcher et al, 2023). The CD138- fraction underwent 10X 3' single cell RNA seq (scRNA-seq), yielding 776,859 cells. Our dataset included 107,884 myeloid cells, 407,895 NK/T cells, 162,630 B/ erythroid cells, and 85,147 plasma cells. The analysis was performed using the R packages Seurat, CellphoneDB, pySCENIC, MOVICS and MOGONET. Results: We stratified 185 patients in the Immune Atlas cohort according to our multi-omics patient similarity network MM-PSN into the following groups: (i) hyperdiploidy (HD) and t(8;14) translocation of MYC (tMYC) (group 1, n = 105); (ii) translocations t(4;14) of MMSET (tMMSET) and t(14;16) of MAF (tMAF) (group 2, n = 46); and (iii) translocation t(11;14) of CCND1 (tCCND1) (group 3, n = 33). The overall cohort had a median progression-free survival (PFS) of 1082 days. The subgroups had the following median PFS: HD, 1094 days; tMMSET/tMAF, 634 days; and tCCND1, 1236 days. Group 1 had higher frequencies of hematopoietic stem cells (HSCs), plasmacytoid dendritic cells (pDCs) and B naïve cells (p&lt;0.05), compared to groups 2 and 3. This suggests HD and tMYC may be associated with TME changes, influencing cytokine and growth factor production, as indicated by IL4R (B naïve) and GZMB (pDC) enriched signatures. Moreover, patients with HD and gain(1q) had higher plasma and B cell frequencies and the lowest CD8 T cell frequency compared to all other HD patients (p&lt;0.001). Group 2, with tMMSET and tMAF, had higher frequencies of pro-B and large pre-B cells, and lower frequencies of CD4 and CD8 T naive cells (p&lt;0.05), suggesting an enrichment of immature B cells and depletion of naive T cells, indicating broader immune dysregulation. Notably, patients with both tMMSET and gain(1q), who had the most aggressive cases with the lowest PFS and OS in the original MM-PSN study, showed higher frequencies of plasma cells and proliferating immature B cells (Ki67+) (p&lt;0.001), as in HD with gain(1q). This supports and extends the MM-PSN findings associating gain(1q) with a more proliferative and aggressive myeloma clonotype. Finally, group 3 with tCCND1 had higher frequencies of CD4 naïve, CD8 naïve and CD56high NK cells, suggesting a larger pool of less differentiated T cells and potentially better T cell fitness. These findings align with the higher median PFS and better outcomes of tCCND1 in NDMM patients and may inform cellular therapies that leverage the improved T cell fitness in this subgroup. Conclusion: In this study, we enhanced our bulk tumor analysis of MMRF CoMMpass with TME profiling using scRNA data from the MMRF Immune Atlas. The analysis of patient subgroups revealed distinct tumor and immune landscapes. The presence of 1q gain correlated with a proliferative plasma cell compartment and was associated with lower survival rates and worse outcomes. These findings deepen our understanding of the TME's interaction with MM subtypes and provide a foundation for ongoing integrative analyses.
Single-Cell Analysis Reveals Depletion of Antigen-Presenting Cell (APC) and IFN-Stimulated CD4 T Cell Populations in High-Risk Newly Diagnosed Multiple Myeloma Patients
Introduction: In the past 15 years, survival in multiple myeloma (MM) has greatly improved due to new treatments, including immunomodulatory drugs (IMiDs) and T cell therapies (CAR-T and BiTEs). Recent studies suggest the MM microenvironment (TME) plays a key role in disease and treatment outcomes. Understanding the MM-TME in high-risk cases is crucial for better patient risk stratification and management. Methods: Bone marrow (BM) samples were collected at diagnosis from 72 NDMM patients, including 38 standard-risk (SR) and 34 high-risk (HR) patients. HR was defined by del(17p) and/or p53 mutations, biallelic del(1p32) or del(1p32) with gain(1q), t(4;14)/t(14;16)/t(14;20) with gain(1q) or del(1p), or B2M&gt; 5.5 mg/L with Creatinine &lt; 1.2mg/dL. We sequenced 567,340 BM cells using 10X 5' scRNA-seq, including 43,610 myeloid cells, 38,729 NK cells, 255,786 T cells, 35,626 B cells, and 90,688 myeloma cells. Tumor WES data from 40 patients (SR n = 22, HR n = 18) was integrated. Analysis was performed using R packages Seurat, InferCNV, and CellphoneDB. Results: The 72 patients were classified as high-risk (HR; n = 34) or standard-risk (SR; n = 38), according to the IMWG criteria above. Exploratory copy number alteration (CNA) analysis on tumor scRNA-seq paired with WES data available for the HR cohort (n = 18) detected MM subclones with segmental deletion of chr 17 (n = 4), gain of 1q (n = 8), and gain of chr 14 (n = 4), showing congruency between scRNA-seq and WES findings. ScRNA-seq identified 92 cell populations based on lineage markers as well as activation, exhaustion, senescence and proliferation markers. Overall, the SR group had a higher frequency of CD14+ S100+ monocytes, granulocyte-monocyte progenitors (GMP) and B memory cells (p &lt; 0.05) compared to the broad HR group, in alignment with previous findings (Pilcher et al, 2023). To further stratify our cohort, we subdivided HR patients into three subgroups: del(17p) and/or p53 mutation (group 1, n = 10); t(4;14), t(14;16), or (14;20) with del(1p32) or gain(1q) (group 2, n = 17); and B2M&gt; 5.5 mg/L with Creatinine &lt; 1.2 (group 3, n = 10). The analysis revealed higher frequencies of pre-B, B naive and B memory cells in SR compared to HR groups 1 and 3 (p &lt; 0.05). Various myeloid subpopulations, including CD14+ S100+ monocytes, GMP, plasmacytoid and classic dendritic cells, were more frequent in SR compared to HR group 1 (p &lt; 0.05), suggesting a depletion of antigen presentation cells (APCs) in the presence of p53 alterations in MM cells. In the NK/T cell compartment, we observed a lower frequency of IFN-stimulated CD4 central memory (CM) cells in HR group 2 (p = 0.02), while LEF1+ CD4 T helper cells were more frequent in HR group 3 (p = 0.03). Cell communication analysis revealed that LEF1+ CD4 T helper cells interact with TYROBP-expressing immunosuppressive myeloid cells (M2 Macrophages and CD14+ S100+ monocytes) via the CD44 receptor, indicating recruitment of these populations and migration to the MM-TME. These findings suggest that HR cytogenetics and clinical HR features correlate with a more immunosuppressive TME, characterized by more LEF1+ T helper cells and fewer IFN-stimulated CD4 CM cells. Conclusions: Single cell profiling of the MM TME identified immunosuppressive subpopulations and a depletion of APC and IFN-stimulated CD4 populations, crucial for immunosurveillance and anti-tumoral response, in HR patients, potentially contributing to therapy resistance and worse outcomes. Ongoing work aims to validate these findings and analyze the interplay between tumor cells and TME in HR patients.
Results Assessment Methods of Health-Related Fitness Test Batteries in School-Based Physical Education Programs: A Global Comparison
Purpose : This study aimed to compare the result assessment approaches used in the widely implemented health-related fitness batteries in school-based physical education programs. Method : Fitness test batteries implemented in the European Union (Assessing Levels of Physical Activity and Fitness), China (China’s National Physical Fitness Testing), the United States (Fitnessgram), and Russia (Ready for Labor and Defense [Gotov k Trudu i Oborone [GTO]]) were included in the study. The document analysis method was used to identify commonalities and differences of results assessment methods in the above test batteries. Results : It was found that the norm-referenced method has been used in Assessing Levels of Physical Activity and Fitness, China’s National Physical Fitness Testing, and GTO, and only Fitnessgram used the criterion-referenced method. Among the three norm-referenced evaluation methods, there were two variations: (a) total numerical points used in CNPFT, and (b) categories employed in Assessing Levels of Physical Activity and Fitness and GTO. Conclusions : Both norm-referenced and criterion-referenced evaluations were used in the current youth health-related fitness test batteries, suggesting that the current understanding of the purpose of school-based-fitness testing in schools has not reached a consensus.
Acoustical oceanography curriculum at The University of Texas at Austin
The acoustical oceanography (AO) curriculum at The University of Texas at Austin (UT) consists a number of courses and thesis research, which often includes field work. The core course is EE/ME 384N-5, Underwater Acoustics, which covers acoustic properties of the ocean, propagation, reflection, reverberation, scattering and target strength, ocean noise, array and signal processing and basic sonar design. The course is offered in alternate years and is cross-listed as both an electrical and mechanical engineering course. Prior to this, students usually take two semesters of physical acoustics: EE/ME 384N-1 and 2, Acoustics I and II, which covers plane waves in fluids, transient and steady-state reflection and transmission, lumped elements, refraction, ray acoustics, absorption and dispersion, spherical and cylindrical waves, radiation and scattering, multipole expansions, Green’s functions, waveguides, Fourier acoustics, and Kirchhoff theory of diffraction. Both are offered every year. Another course commonly taken by AO students is EE/ME 384N-3: Electromechanical Transducers, which covers basic modeling, analysis and design of acoustics and vibration transducers, including calibration. Recent student thesis topics have included marine acoustic ecology, the investigation of methane seeps, acoustic seagrass monitoring, and the assessment of glacial processes. Appropriate courses in UT’s natural and earth sciences departments supplement the acoustics courses.
P-236 Integrated Coding and Non-Coding Transcriptomic Atlas Reveals How Malignant Plasma Cells Shape the Bone Marrow Microenvironment in Multiple Myeloma
P-221 Plasma Cell Lineage and Driver Heterogeneity Associated With Multiple Myeloma Progression
Analytical solution for acoustic radiation force and torque on a spheroid near a rigid or free planar boundary
An analytical solution is developed for the acoustic radiation force and torque caused by an arbitrary sound field that is incident on a compressible spheroid of any size near a planar boundary that is either rigid or pressure release. The analysis is an extension of a recent solution for a compressible sphere near a planar boundary [Simon and Hamilton, J. Acoust. Soc. Am. 153, 627-642 (2023)]. Approximations that account for a boundary formed by a two-fluid interface may be incorporated as in the previous analysis for a sphere. The present solution is based on expansions of the total acoustic pressure field in spheroidal wave functions and the use of addition theorems. Verification of the solution is accomplished by comparison with a finite element model. Examples are presented for incident fields that are either plane or spherical waves. Effects resulting from the presence of the boundary are studied by comparing the full theory with a simplified model in which multiple scattering is neglected. Numerical implementation of the proposed solution is also discussed.
A Mixed Finite Element Approximation for Fluid Flows of Mixed Regimes in Porous Media
In this paper, we consider the complex flows when all three regimes pre-Darcy, Darcy and post-Darcy may be present in different portions of a same domain. We unify all three flow regimes under mathematics formulation. We describe the flow of a single-phase fluid in $${{\mathbb{R}}^{d}},\;d \geqslant 2$$ by a nonlinear degenerate system of density and momentum. A mixed finite element method is proposed for the approximation of the solution of the above system. The stabilit1y of the approximations are proved; the error estimates are derived for the numerical approximations for both continuous and discrete time procedures. The continuous dependence of numerical solutions on physical parameters are demonstrated. Experimental studies are presented regarding convergence rates and showing the dependence of the solution on the physical parameters.
Paraxial and ray approximations of acoustic vortex beams
A compact analytical solution obtained in the paraxial approximation is used to investigate focused and unfocused vortex beams radiated by a source with a Gaussian amplitude distribution. Comparisons with solutions of the Helmholtz equation are conducted to determine bounds on the parameter space in which the paraxial approximation is accurate. A linear relation is obtained for the dependence of the vortex ring radius on the topological charge, characterized by its orbital number, in the far field of an unfocused beam and in the focal plane of a focused beam. For a focused beam, it is shown that as the orbital number increases, the vortex ring not only increases in radius but also moves out of the focal plane in the direction of the source. For certain parameters, it is demonstrated that with increasing orbital number, the maximum amplitude in a focused beam becomes localized along a spheroidal surface enclosing a shadow zone in the prefocal region. This field structure is described analytically by ray theory developed in the present work, showing that the spheroidal surface in the prefocal region coincides with a simple expression for the coordinates of the caustic surface formed in a focused vortex beam.
Cryoprotectant agent characterization via acoustical and optical analyses
In the field of cryopreservation, there exists a class of substances known as cryoprotectant agents (CPAs), which display an ability to vitrify. These CPAs are used to prevent cellular damage during the preservation of human tissues. In a vitrified state, cells exist in a glass-like state, meaning there is no formation of mechanically damaging ice crystals during cryogenic freezing and thawing. Although a CPA’s ability to vitrify increases with concentration, its toxicity limits viable levels of use. This work seeks to find a correlation between acoustic properties of various CPAs and their concentrations via analyses of cavitation noise and cavitation jets, to accompany future studies on CPA toxicity. Four common CPAs, namely, dimethyl sulfoxide, ethylene glycol, propylene glycol, and formamide were investigated at various concentrations in aqueous mixtures and compared to pure water. The acoustic spectra of each CPA show an observable dependence on concentration levels and provide a potential way to probe the hydrogen bonding dynamics within the mixtures. [This is a SAWIAGOS project.]
Strong diffraction of nonlinear surface acoustic waves in crystals
Nonlinear distortion and shock formation in planar surface acoustic waves in anisotropic crystals have been modeled without [Hamilton et al., JASA (1999)] and with [Cormack et al., JASA 2022] piezoelectricity. Weak diffraction has been included in the paraxial approximation for nonlinear surface wave beams in isotropic solids [Shull et al., JASA (1995)]. Here, a procedure for including strong diffraction, i.e., without the paraxial approximation, in the model for nonlinear surface waves in crystals is presented, which incorporates the angular spectrum approach described by Kharusi and Farnell (JASA 1970). Anisotropy is defined by expressing the phase speed of a plane wave, and therefore, the magnitude of the corresponding wavenumber, as a function of the direction of propagation. Next, an explicit expression relating the two wavenumber components in the planar surface along which the wave propagates must be obtained as a function of direction, requiring iterative solution of a transcendental relation. The beam is then propagated incrementally away from the source, advancing the angular spectrum in k-space and including nonlinear interactions in the spatial domain to characterize the combined effects of diffraction and nonlinearity. Preliminary results are presented for converging nonlinear surface waves in crystals. [Work supported by IR&D at ARL:UT.]