Scale Separation of Shear-Induced Criticality in Glasses.

In a sheared steady state, glasses reach a nonequilibrium criticality called yielding criticality. We report that the qualitative nature of this nonequilibrium critical phenomenon depends on the details of the system and that responses and fluctuations are governed by different critical correlation lengths in specific situations. This scale separation of critical lengths arises when the screening of elastic propagation of mechanical signals is not negligible. We also discuss the determinant of the impact of screening effects from the viewpoint of the microscopic dissipation mechanism.

[Safety Analysis Using Event Tree Analysis for Multi-Ion Therapy].

At the National Institutes for Quantum Science and Technology (QST), a multi-ion therapy using helium, carbon, oxygen, and neon ions has been studied for charged particle therapy with more optimal biological effects. To make multi-ion therapy clinically feasible, a new treatment system was developed to realize the changes of the ion species in each irradiation using the Heavy Ion Medial Accelerator in Chiba (HIMAC). Since radiation therapy is safety-critical, it is necessary to construct a safety system that includes multiple safety barriers in the new treatment system for multi-ion therapy and to perform a safety analysis for the prevention of serious accidents. In this study, we conducted a safety analysis using event tree analysis (ETA) for newly introduced processes in the treatment planning, accelerator, and irradiation system of the multi-ion therapy. ETA is an optimal method to verify multiple safety barriers that are essential for medical safety and to shorten the time for safety analysis by focusing only on the new processes. Through ETA, we clarified the types of malfunctions and human errors that may lead to serious accidents in the new system for multi-ion therapy, and verified whether safety barriers such as interlock systems and human check procedures are sufficient to prevent such malfunctions and human errors. As a result, 6 initial events which may lead to serious accidents were listed in the treatment planning process, 16 initial events were listed in the accelerator system, and 13 initial events were listed in the irradiation system. Among these 35 initial events, 5 cautionary initial events were identified that could lead to serious final events and they had a probability of occurrence higher than 10-4. Meanwhile, the others were all initial events that do not lead to serious accidents, or the initial events that can lead to serious accidents but were considered to have sufficient safety barriers. The safety analysis using ETA successfully identified the system malfunctions and the human errors that can lead to serious accidents, and the multiple safety barriers against them were systematically analyzed. It became clear that the multiple safety barriers were not sufficient for some initial events. We plan to improve the safety barriers for the five cautionary initial events before the start of the clinical trial. Based on these findings, we achieved our objective to conduct a safety analysis for a new treatment system for multi-ion therapy. The safety analysis procedure using ETA proposed by this study will be effective when new systems for radiotherapy are established at QST and other facilities in the future as well.

End-to-end dosimetry audit for three-dimensional image-guided brachytherapy for cervical cancer.

BACKGROUND: End-to-end dosimetry audit for brachytherapy is challenging due to the steep dose gradient. However, it is an efficient method to detect unintended errors in actual clinical practice. PURPOSE: We aimed to develop an on-site end-to-end test phantom for three-dimensional image-guided brachytherapy (IGBT) for cervical cancer. METHODS: The test phantom we developed consisted of a water tank with an applicator/detector holder. The holder was designed to accommodate the applicator and insert an ionization chamber (PinPoint; PTW, Freiburg, Germany) to measure the dose at point A. Imaging and reconstruction were performed in the same way as performed for a patient. The feasibility of our test phantom was assessed in two different hospitals using tandem and ovoid (made of either metal or carbon) applicators that the hospitals provided. RESULTS: The measured and calculated doses at point A were compared for each applicator. We observed that the values obtained using metal applicators were consistently lower, on an average by -2.3%, than the calculated values, while those obtained using carbon applicators were comparable to the calculated values. This difference can be attributed to the attenuation of the dose by the metal applicators, resulting in a lower dose at point A. The majority of treatment planning system, including the one used in this study, do not account for the material of applicator. CONCLUSIONS: An end-to-end test phantom for IGBT was developed, tested, and applied in a dosimetry audit in hospitals and showed favorable results for evaluating the point A dose.

Dose-averaged LET optimized carbon-ion radiotherapy for head and neck cancers.

This feasibility study confirmed the initial safety and efficacy of a novel carbon-ion radiotherapy (CIRT) using linear energy transfer (LET) painting for head and neck cancer. This study is the first step toward establishing CIRT with LET painting in clinical practice and making it a standard practice in the future.

Instantaneous normal modes of glass-forming liquids during the athermal relaxation process of the steepest descent algorithm.

Understanding glass formation by quenching remains a challenge in soft condensed matter physics. Recent numerical studies on steepest descent dynamics, which is one of the simplest models of quenching, revealed that quenched liquids undergo slow relaxation with a power law towards mechanical equilibrium and that the late stage of this process is governed by local rearrangements of particles. These advances motivate the detailed study of instantaneous normal modes during the relaxation process because the glassy dynamics is considered to be governed by stationary points of the potential energy landscape. Here, we performed a normal mode analysis of configurations during the steepest descent dynamics and found that the dynamics is driven by almost flat directions of the potential energy landscape at long times. These directions correspond to localized modes and we characterized them in terms of their statistics and structure using methods developed in the study of local minima of the potential energy landscape.

Novel in silico screening system for plant defense activators using deep learning-based prediction of reactive oxygen species accumulation.

BACKGROUND: Plant defense activators offer advantages over pesticides by avoiding the emergence of drug-resistant pathogens. However, only a limited number of compounds have been reported. Reactive oxygen species (ROS) act as not only antimicrobial agents but also signaling molecules that trigger immune responses. They also affect various cellular processes, highlighting the potential ROS modulators as plant defense activators. Establishing a high-throughput screening system for ROS modulators holds great promise for identifying lead chemical compounds with novel modes of action (MoAs). RESULTS: We established a novel in silico screening system for plant defense activators using deep learning-based predictions of ROS accumulation combined with the chemical properties of the compounds as explanatory variables. Our screening strategy comprised four phases: (1) development of a ROS inference system based on a deep neural network that combines ROS production data in plant cells and multidimensional chemical features of chemical compounds; (2) in silico extensive-scale screening of seven million commercially available compounds using the ROS inference model; (3) secondary screening by visualization of the chemical space of compounds using the generative topographic mapping; and (4) confirmation and validation of the identified compounds as potential ROS modulators within plant cells. We further characterized the effects of selected chemical compounds on plant cells using molecular biology methods, including pathogenic signal-triggered enzymatic ROS induction and programmed cell death as immune responses. Our results indicate that deep learning-based screening systems can rapidly and effectively identify potential immune signal-inducible ROS modulators with distinct chemical characteristics compared with the actual ROS measurement system in plant cells. CONCLUSIONS: We developed a model system capable of inferring a diverse range of ROS activity control agents that activate immune responses through the assimilation of chemical features of candidate pesticide compounds. By employing this system in the prescreening phase of actual ROS measurement in plant cells, we anticipate enhanced efficiency and reduced pesticide discovery costs. The in-silico screening methods for identifying plant ROS modulators hold the potential to facilitate the development of diverse plant defense activators with novel MoAs.

Interlaboratory comparison of electron paramagnetic resonance tooth enamel dosimetry with investigations of the dose responses of the standard samples.

A total of seven Japanese laboratories participated in an intercomparison study to estimate the dose given to tooth enamel samples, using the electron spin resonance method. Each of four of the participating laboratories prepared a set of tooth enamel samples, using the electron spin resonance method. Four of the participating laboratories each prepared a set of tooth enamel samples, consisting of seven standard aliquots irradiated from 100 to 2000 mGy and three samples with an 'unknown' dose between 140 and 960 mGy, were intended to eliminate bias from sample preparation. Although not all seven laboratories measured all four sets of samples, the major finding was that systematic biases in estimating doses may be caused by differences in laboratory measurements rather than by the enamel extracting procedures. When doses were averaged by measurements made by multiple laboratories, the averaged values were close to the actual values. Scattering in the intercepts in the standard dose response would be a serious problem in actual dosimetry where no background sample is available.

Microrheology near jamming.

The jamming transition is a nonequilibrium critical phenomenon, which governs characteristic mechanical properties of jammed soft materials, such as pastes, emulsions, and granular matters. Both experiments and theory of jammed soft materials have revealed that the complex modulus measured by conventional macrorheology exhibits a characteristic frequency dependence. Microrheology is a new type of method to obtain the complex modulus, which transforms the microscopic motion of probes to the complex modulus through the generalized Stokes relation (GSR). Although microrheology has been applied to jammed soft materials, its theoretical understanding is limited. In particular, the validity of the GSR near the jamming transition is far from obvious since there is a diverging length scale lc, which characterizes the heterogeneous response of jammed particles. Here, we study the microrheology of jammed particles by theory and numerical simulation. First, we develop a linear response formalism to calculate the response function of the probe particle, which is transformed to the complex modulus via the GSR. Then, we apply our formalism to a numerical model of jammed particles and find that the storage and loss modulus follow characteristic scaling laws near the jamming transition. Importantly, the observed scaling law coincides with that in macrorheology, which indicates that the GSR holds even near the jamming transition. We rationalize this equivalence by asymptotic analysis of the obtained formalism and numerical analysis on the displacement field of jammed particles under a local perturbation.

Shear-induced criticality in glasses shares qualitative similarities with the Gardner phase.

Although glass phases are ubiquitously found in various soft matter systems, we are still far from a complete understanding of them. The concept of marginal stability predicted by infinite-dimensional mean-field theories is drawing attention as a candidate for a universal and distinguishing unique feature of glasses. While among theoretical predictions, the non-Debye scaling has indeed been observed universally over various classes of glasses, the Gardner phase is found only in a limited portion of them. In this work, we numerically demonstrate that plastic events observed in two-dimensional Lennard-Jones glasses under quasistatic shear exhibit statistical properties that are qualitatively consistent with the picture of an infinitely hierarchical energy landscape associated with the Gardner phase.

Non-phononic density of states of two-dimensional glasses revealed by random pinning.

The vibrational density of states of glasses is considerably different from that of crystals. In particular, there exist spatially localized vibrational modes in glasses. The density of states of these non-phononic modes has been observed to follow g(ω) ∝ ω4, where ω is the frequency. However, in two-dimensional systems, the abundance of phonons makes it difficult to accurately determine this non-phononic density of states because they are strongly coupled to non-phononic modes and yield strong system-size and preparation-protocol dependencies. In this article, we utilize the random pinning method to suppress phonons and disentangle their coupling with non-phononic modes and successfully calculate their density of states as g(ω) ∝ ω4. We also study their localization properties and confirm that low-frequency non-phononic modes in pinned systems are truly localized without far-field contributions. We finally discuss the excess density of states over the Debye value that results from the hybridization of phonons and non-phononic modes.

Johari-Goldstein ß relaxation in glassy dynamics originates from two-scale energy landscape.

Supercooled liquids undergo complicated structural relaxation processes, which have been a long-standing problem in both experimental and theoretical aspects of condensed matter physics. In particular, past experiments widely observed for many types of molecular liquids that relaxation dynamics separated into two distinct processes at low temperatures. One of the possible interpretations is that this separation originates from the two-scale hierarchical topography of the potential energy landscape; however, it has never been verified. Molecular dynamics simulations are a promising approach to tackle this issue, but we must overcome laborious difficulties. First, we must handle a model of molecular liquids that is computationally demanding compared to simple spherical models, which have been intensively studied but show only a slower process: α relaxation. Second, we must reach a sufficiently low-temperature regime where the two processes become well-separated. Here, we handle an asymmetric dimer system that exhibits a faster process: Johari-Goldstein ß relaxation. Then, we employ the parallel tempering method to access the low-temperature regime. These laborious efforts enable us to investigate the potential energy landscape in detail and unveil the first direct evidence of the topographic hierarchy that induces the ß relaxation. We also successfully characterize the microscopic motions of particles during each relaxation process. Finally, we study the correlation between low-frequency modes and two relaxation processes. Our results establish a fundamental and comprehensive understanding of experimentally observed relaxation dynamics in supercooled liquids.

[A Survey of Dosimetry in the Magnetic Field of MR-Linacs].

In recent years, MR-Linac, a radiotherapy linear accelerator (linac) equipped with magnetic resonance (MR) imaging, has been deployed in clinical facilities across Japan. Because of the magnetic field of MR-Linac, which can affect the dose distributions and dose response of ionization chambers, conventional reference dosimetry for absorbed dose to water using an ionization chamber becomes impractical. Consequently, the magnetic field effect should be considered in the reference dosimetry for MR-Linac. Although numerous studies have delved into this matter and several magnetic field correction methods have been proposed to extend the conventional formalism, a practical protocol for reference dosimetry for MR-Linac remains elusive.The purpose of this review are as follows: (i) to summarize and evaluate literature and existing datasets as well as identify any gaps that highlight areas for the future research on this topic; (ii) to elucidate dosimetric challenges associated with ionization chamber dosimetry in magnetic fields; and (iii) to propose a formalism for reference dosimetry for MR-Linac based on available literature and datasets. This review focuses on studies based on commercially available MR-Linacs and datasets, specifically tailored for reference-class cylindrical ion chambers.

Low-frequency vibrational states in ideal glasses with random pinning.

Glasses exhibit spatially localized vibrations in the low-frequency regime. These localized modes emerge below the boson peak frequency ω_{BP}, and their vibrational densities of state follow g(ω)∝ω^{4} (ω is frequency). Here, we attempt to address how the localized vibrations behave through the ideal glass transition. To do this, we employ a random pinning method, which enables us to study the thermodynamic glass transition. We find that the localized vibrations survive even in equilibrium glass states. Remarkably, the localized vibrations still maintain the properties of appearance below ω_{BP} and g(ω)∝ω^{4}. Our results provide important insight into the material properties of ideal glasses.

Microdosimetric investigation for multi-ion therapy by means of silicon on insulator (SOI) microdosimeter.

Objective.Ion radiotherapy with protons or carbon ions is one of the most advanced clinical methods for cancer treatment. To further improve the local tumor control, ion radiotherapy using multiple ion species has been investigated. Due to complexity of dose distributions delivered by multi-ion therapy in a tumor, a validation strategy for the planned treatment efficacy must be established that can be potentially used in the quality assurance (QA) protocol for the multi-ion treatment plans. In previous work, we demonstrated that the microdosimetric approach using the silicon on insulator (SOI) microdosimeter is practical for validating cell surviving fraction (SF) of MIA PaCa-2 cells in the independent fields of helium, carbon, oxygen, and neon ion beams.Approach.This paper extends the previous study, and we demonstrate a microdosimetry based approach as a pilot study to build the QA protocol in the multi-ion therapy predicting the cell SF along the spread-out Bragg peak obtained by combined irradiations of He+O and C+Ne ions. Across the study, the SOI microdosimeter system MicroPlus was used for measurement of the lineal energy in individual ion fields followed by deriving the lineal energy of combined ion fields delivered by a pencil beam scanning system at HIMAC.Main results.The predicted cell SF based on derived lineal energy and dose in the combined fields was in good agreement with the planned cell SF by our in-house treatment planning system.Significance.The presented results indicated the potential benefit of the SOI microdosimeter system MicroPlus as the QA system in the multi-ion radiotherapy.

Multi-Institutional Study of End-to-End Dose Delivery Quality Assurance Testing for Image-Guided Brachytherapy Using a Gel Dosimeter.

PURPOSE: To quantify dose delivery errors for high-dose-rate image-guided brachytherapy (HDR-IGBT) using an independent end-to-end dose delivery quality assurance test at multiple institutions. The novelty of our study is that this is the first multi-institutional end-to-end dose delivery study in the world. MATERIALS AND METHODS: The postal audit used a polymer gel dosimeter in a cylindrical acrylic container for the afterloading system. Image acquisition using computed tomography, treatment planning, and irradiation were performed at each institution. Dose distribution comparison between the plan and gel measurement was performed. The percentage of pixels satisfying the absolute-dose gamma criterion was reviewed. RESULTS: Thirty-five institutions participated in this study. The dose uncertainty was 3.6% ± 2.3% (mean ± 1.96σ). The geometric uncertainty with a coverage factor of k = 2 was 3.5 mm. The tolerance level was set to the gamma passing rate of 95% with the agreement criterion of 5% (global)/3 mm, which was determined from the uncertainty estimation. The percentage of pixels satisfying the gamma criterion was 90.4% ± 32.2% (mean ± 1.96σ). Sixty-six percent (23/35) of the institutions passed the verification. Of the institutions that failed the verification, 75% (9/12) had incorrect inputs of the offset between the catheter tip and indexer length in treatment planning and 17% (2/12) had incorrect catheter reconstruction in treatment planning. CONCLUSIONS: The methodology should be useful for comprehensively checking the accuracy of HDR-IGBT dose delivery and credentialing clinical studies. The results of our study highlight the high risk of large source positional errors while delivering dose for HDR-IGBT in clinical practices.

Phonon transport properties of particulate physical gels.

Particulate physical gels are sparse, low-density amorphous materials in which clusters of glasses are connected to form a heterogeneous network structure. This structure is characterized by two length scales, ξs and ξG: ξs measures the length of heterogeneities in the network structure and ξG is the size of glassy clusters. Accordingly, the vibrational states (eigenmodes) of such a material also exhibit a multiscale nature with two characteristic frequencies, ω* and ωG, which are associated with ξs and ξG, respectively: (i) phonon-like vibrations in the homogeneous medium at ω<ω*, (ii) phonon-like vibrations in the heterogeneous medium at ω*<ω<ωG, and (iii) disordered vibrations in the glassy clusters at ω > ωG. Here, we demonstrate that the multiscale characteristics seen in the static structures and vibrational states also extend to the phonon transport properties. Phonon transport exhibits two distinct crossovers at frequencies ω* and ωG (or at wavenumbers of ∼ξs -1 and ∼ξG -1). In particular, both transverse and longitudinal phonons cross over between Rayleigh scattering at ω<ω* and diffusive damping at ω>ω*. Remarkably, the Ioffe-Regel limit is located at the very low frequency of ω*. Thus, phonon transport is localized above ω*, even where phonon-like vibrational states persist. This markedly strong scattering behavior is caused by the sparse, porous structure of the gel.

Structural, mechanical, and vibrational properties of particulate physical gels.

Our lives are surrounded by a rich assortment of disordered materials. In particular, glasses are well known as dense, amorphous materials, whereas gels exist in low-density, disordered states. Recent progress has provided a significant step forward in understanding the material properties of glasses, such as mechanical, vibrational, and transport properties. In contrast, our understanding of particulate physical gels is still highly limited. Here, using molecular dynamics simulations, we study a simple model of particulate physical gels, the Lennard-Jones (LJ) gels, and provide a comprehensive understanding of their structural, mechanical, and vibrational properties, all of which are markedly different from those of LJ glasses. First, the LJ gels show sparse, heterogeneous structures, and the length scale ξs of the structures grows as the density is lowered. Second, the LJ gels are extremely soft, with both shear G and bulk K moduli being orders of magnitude smaller than those of LJ glasses. Third, many low-frequency vibrational modes are excited, which form a characteristic plateau with the onset frequency ω* in the vibrational density of states. Structural, mechanical, and vibrational properties, characterized by ξs, G, K, and ω*, respectively, show power-law scaling behaviors with the density, which establishes a close relationship between them. Throughout this work, we also reveal that LJ gels are multiscale, solid-state materials: (i) homogeneous elastic bodies at long lengths, (ii) heterogeneous elastic bodies with fractal structures at intermediate lengths, and (iii) amorphous structural bodies at short lengths.

Instantaneous Normal Modes Reveal Structural Signatures for the Herschel-Bulkley Rheology in Sheared Glasses.

The Herschel-Bulkley law, a universal constitutive relation, has been empirically known to be applicable to a vast range of soft materials, including sheared glasses. Although the Herschel-Bulkley law has attracted public attention, its structural origin has remained an open question. In this Letter, by means of atomistic simulation of binary Lennard-Jones glasses, we report that the instantaneous normal modes with negative eigenvalues, or so-called imaginary modes, serve as the structural signatures for the Herschel-Bulkley rheology in sheared glasses.

Unified view of avalanche criticality in sheared glasses.

Plastic events in sheared glasses are considered an example of so-called avalanches, whose sizes obey a power-law probability distribution with the avalanche critical exponent τ. Although the so-called mean-field depinning (MFD) theory predicts a universal value of this exponent, τ_{MFD}=1.5, such a simplification is now known to connote qualitative disagreement with realistic systems. Numerically and experimentally, different values of τ have been reported depending on the literature. Moreover, in the elastic regime, it has been noted that the critical exponent can be different from that in the steady state, and even criticality itself is a matter of debate. Because these confusingly varying results have been reported under different setups, our knowledge of avalanche criticality in sheared glasses is greatly limited. To gain a unified understanding, in this work, we conduct a comprehensive numerical investigation of avalanches in Lennard-Jones glasses under athermal quasistatic shear. In particular, by excluding the ambiguity and arbitrariness that has crept into the conventional measurement schemes, we achieve high-precision measurement and demonstrate that the exponent τ in the steady state follows the prediction of MFD theory, τ_{MFD}=1.5. Our results also suggest that there are two qualitatively different avalanche events. This binariness leads to the nonuniversal behavior of the avalanche size distribution and is likely to be the cause of the varying values of τ reported thus far. To investigate the dependence of criticality and universality on applied shear, we further study the statistics of avalanches in the elastic regime and the ensemble of the first avalanche event in different samples, which provide information about the unperturbed system. We show that while the unperturbed system is indeed off-critical, criticality gradually develops as shear is applied. The degree of criticality is encoded in the fractal dimension of the avalanches, which starts from zero in the off-critical unperturbed state and saturates in the steady state. Moreover, the critical exponent τ is consistent with the prediction of the MFD τ_{MFD} universally, regardless of the amount of applied shear, once the system becomes critical.

Dose response of a radiophotoluminescent glass dosimeter for TomoTherapy, CyberKnife, and flattening-filter-free linear accelerator output measurements in dosimetry audit.

PURPOSE: We experimentally determined the radiophotoluminescent glass dosimeter (RPLD) dose responses for TomoTherapy, CyberKnife, and flattening-filter-free (FFF) linear accelerator (linac) outputs for dosimetry audits in Japan. METHODS: A custom-made solid phantom with a narrow central-axis spacing of three RPLD elements was used for output measurement to minimise the dose-gradient effect of the non-flattening filter beams. For RPLD dose estimation, we used the ISO 22127 formalism. Additional unit-specific correction factors were introduced and determined via the measured data. For TomoTherapy (7 units) and CyberKnife (4 units), the doses were measured under machine-specific reference fields. For FFF linac (5 units), in addition to the reference condition, we obtained the field-size effects for the range from 5×5 cm to 25×25 cm. RESULTS: The correction factors were estimated as 1.008 and 0.999 for TomoTherapy and CyberKnife, respectively. For FFF linac, they ranged from 1.011 to 0.988 for 6 MV and from 1.011 to 0.997 for 10 MV as a function of the side length of the square field from 5 to 25 cm. The estimated uncertainties of the absorbed dose to water measured by RPLD for the units were 1.32%, 1.35%, and 1.30% for TomoTherapy, CyberKnife, and FFF linac, respectively. A summary of the dosimetry audits of these treatment units using the obtained correction factors is also presented. The average percentage differences between the measured and hospital-stated doses were <1% under all conditions. CONCLUSION: RPLD can be successfully used as a dosimetry audit tool for modern treatment units.