Tilting pad journal bearings (TPJBs) have high vibration stability and are widely used in high-speed turbomachinery. In recent years, direct-lubricated TPJBs have been used to reduce bearing losses and bearing metal temperatures at high shaft speeds. However, it is known that direct-lubricated TPJBs can change their vibration characteristics and generate sub-synchronous vibrations (SSV) when the oil supply flow rate is insufficient, due to starved lubrication. Modeling of the dynamic behavior of TPJBs under starved lubrication that has been reported so far has been limited to calculation of stiffness and damping coefficients that linearize the oil film reaction force and stability analysis using them, and to the author's knowledge, there are no examples of numerical evaluation of SSV of TPJBs under starved lubrication using nonlinear transient analysis. In this study, we propose a nonlinear transient analysis model of TPJBs considering starved lubrication and numerically investigate the effects of each design parameter on the nonlinear transient behavior of TPJBs. A rigid Jeffcott rotor model supported by five-pad TPJBs was considered, and its unbalance response was analyzed. A parameter study was then conducted on the effects of pad arrangement which is Load on pad (LOP) and Load between pad (LBP), shaft speed, oil supply flow rate, and specific load. It was confirmed that broadband SSV occurs for both LOP and LBP under conditions of high shaft speed and low oil supply flow rate. It was also confirmed that under low specific load conditions, the SSV of LOP and LBP are similar, but under high specific load conditions, the vibration level of the SSV of LBP is smaller than that of LOP. These trends qualitatively match the experiment results of Decamillo et al. (2008), demonstrating the validity of this analysis model.

MRI-guided needle insertion is considered as a radiation-free, minimally invasive treatment. However, constraints such as the confined space within the gantry and strong magnetic field environment necessitate the use of robotic technology to assist the operator. Many existing MRI-compatible robots face challenges of increased size and complexity owing to the need for multiple degree-of-freedom (DOF). Therefore, we developed a compact 5-DOF manipulator system using a spherical gear-based pneumatic motor. This motor generates pitch and yaw DOF within a single module, thereby enabling a simple joint structure without a rotational center offset. This paper details the manipulator's mechanical design and evaluates its puncture accuracy using phantoms, as well as its compatibility within a 1.5-T MRI environment. The experimental results showed no reduction in the image SNR owing to robotic actuation, achieving an average error of 4.5 mm with this prototype. This accuracy is sufficient for accessing clinically significant lesions, thereby demonstrating the effectiveness of the proposed method. Furthermore, the system was confirmed to operate normally even under remote actuation conditions via a 6.5-m-long pneumatic transmission line. These results demonstrate the fundamental utility of the proposed non-magnetic pneumatic drive mechanism, suggesting the potential for future application in MRI-guided punctures.

We investigate magnetic field amplification driven by the nonresonant hybrid (NRH, or Bell) instability and its impact on cosmic-ray (CR) acceleration at the reverse shocks of ultrafast outflows (UFOs) from active galactic nuclei. Previous kinetic studies by particle-in-cell simulations have demonstrated that when the maximum CR energy is near the injection scale, the NRH instability efficiently amplifies the magnetic field up to the saturation level. However, the efficiency of the NRH instability decreases as the maximum energy increases, since the CR current is carried by escaping CRs near the maximum energy. We employ a one-dimensional MHD-CR framework solving telegraph-type diffusion-convection equations to trace the coupled evolution of CRs, magnetic fields, and shock dynamics under realistic parameters. We find a distinct transition with magnetic field strength. For weak background fields (B0 less than or similar to 10-4 G), the NRH instability efficiently amplifies upstream turbulence, driving a self-regulated state where Emax becomes independent of the initial strength of the magnetic turbulence. In contrast, for stronger background fields (B0 greater than or similar to 10-3 G), the escaping CR current is too weak to drive the NRH instability, and magnetic turbulence further decays through parametric instabilities, potentially reducing the acceleration efficiency. We give a physical interpretation for the transition and discuss conditions for PeV to EeV acceleration at UFO reverse shocks.

The TeV γ-ray source HESS J1023-575 (HESSJ 1023 hereafter) is one of the brightest H.E.S.S. sources near the young massive cluster Westerlund 2. HESS J1023 shows a remarkable positional alignment with the Jet and Arc CO clouds on its eastern and western sides over 170 pc length. We have carried out sub-pc scale observations of the CO clouds with ALMA and have discovered that the clouds consist of numerous thin filamentary features of ∼0.5 pc width and 10–20 pc length at distance of 7.5 kpc, which are well aligned with the Jet-Arc axis. Based on the magneto-hydrodynamical model of microquasar jets launched from the center of the γ-ray source HESS J1023-575, we present an interpretation that the thin filamentary clouds are the footprints of the microquasar jets on the HI gas. The model also explains the dissimilar Jet vs. Arc clouds in terms of HI density difference on each side. By using the density of the CO and HI gas and the γ-ray luminosity, we have calculated the cosmic ray proton energy W_ p to be 7×10^48 erg under the hadronic scheme, which is ten times larger than those derived in the TeV γ-ray SNRs RX J1713.7-3946 and RX J0852.0-4622. It is likely that HESS J1023 has been active over 1-10 Myr, which is significantly longer than the duration of cosmic ray acceleration of the SNRs. HESS J1023 is therefore an outstanding source of cosmic rays equivalent to at least 1000 SNRs, and is possibly the most powerful CR accelerator in the Galactic disk. A high energy compact source in HESS J1023, which is likely a Myr-old black hole or neutron star, remains veiled due to heavy extinction.

Abstract Human cytochrome P450 2C9 (CYP2C9) is a hepatic microsomal enzyme involved in the oxidative metabolism of clinically important drugs, but the structural organization of its oligomeric assemblies outside crystallographic packing environments remains poorly understood. Here, we report the cryo-EM structure of human CYP2C9 determined under aqueous, membrane-free conditions at 3.31 Å resolution. The structure reveals a C2-symmetric hexameric assembly organized as a dimer of trimers. Individual protomers retain the conserved P450 fold and heme-binding architecture observed in previously reported crystal structures, indicating that assembly formation does not substantially perturb the catalytic core. The hexamer is stabilized by defined intra-trimer interfaces involving the N-terminal region and residues around Trp212 and Phe482, together with inter-trimer interfaces involving Leu71 and the 220–227 loop. These interfaces are distinct from the crystal packing contacts observed in CYP2C9 crystal structures, demonstrating that the assembly is not a simple recapitulation of crystallographic packing. Notably, the inter-trimer interface is located near the FG-loop-containing surface previously implicated in membrane association. This suggests that the observed hexamer may represent a membrane-free association of two trimers through membrane-related surfaces, whereas the trimeric arrangement itself may be compatible with membrane-associated organization. The structure therefore provides a framework for investigating how trimer formation, membrane interaction and local conformational changes in the FG-loop region may influence CYP2C9 function.

Supernova remnants (SNRs) are widely considered to be the primary accelerators of Galactic cosmic rays. In recent years, detailed observations have significantly progressed for young SNRs interacting with molecular clouds, a prime example being RX J1713.7-3946. When molecular clouds are clumpy, their impact can affect not only radiation properties but also shock wave propagation. Therefore, a quantitative understanding linking observational quantities with the ambient medium structure is highly required. In this study, we perform three-dimensional hydrodynamic simulations to model a molecular cloud with an inhomogeneous density structure driven by supersonic turbulence and subsequent SNR formation. To investigate various pre-supernova environments, we systematically vary the medium clumpiness by replacing gas below a threshold number density with a low-density hot gas, quantifying the relationship between the forward shock velocity and the volume filling factor of the high-density clumps. As a result, we find that at an elapsed time of 1000 yr-a typical age for a young SNR-the forward shock can evolve consistently with the fast shock velocity measured in RX J1713.7-3946, provided that the clump volume filling factor is approximately 10

Glycogen phosphorylase (GP) plays a central role in glycogen metabolism. While the structure and regulation of mammalian GPs have been extensively studied, the corresponding mechanisms in gut bacterial GPs remain poorly understood. Here, we investigate GPs from Escherichia coli (EcGP), Segatella copri (ScGP), and Dorea longicatena (DlGP), which represent three phylogenetic clades of GPs, using enzymatic assays, cryo-electron microscopy (cryo-EM), and X-ray crystallography. We find that ScGP forms a unique pentamer that undergoes adenosine monophosphate (AMP)-dependent assembly into a dimer-of-pentamer, which inhibits activity by restricting substrate access to the catalytic site. EcGP exists in equilibrium among monomers, dimers, and tetramers, with AMP promoting tetramer dissociation and enhancing catalytic efficiency. In contrast, DlGP remains predominantly monomeric and is unresponsive to AMP. These findings uncover structural and regulatory diversity among gut bacterial GPs. Notably, the oligomeric states of GPs modulate substrate accessibility and enzyme activation, suggesting a distinct mode of allosteric regulation beyond the canonical T-to-R transition model. Because bacterial GPs contribute to the generation of glucose, their regulation may influence the composition of gut-derived metabolites that affect host glucose homeostasis and insulin sensitivity. Our study provides mechanistic insight into the structural and functional diversity of gut bacterial GPs and lays a foundation for future exploration of microbiome-mediated metabolic interactions.

Fluid-film journal bearings are widely used as essential components in rotating machinery due to their high damping properties. In recent years, operating journal bearings under starved lubrication has been considered as a strategy to reduce bearing losses from the perspective of energy efficiency. However, precisely evaluating dynamic behavior is essential to achieve a balance between energy efficiency and reliability. In this study, the nonlinear vibration characteristics of a flexible rotor system supported by a circular journal bearing were investigated under starved lubrication. First, the Elrod-Adams model was used to analyze the dynamic characteristics when the rate at which oil was supplied was reduced. This model is based on the conservation of mass, and can represent ruptures and reformation regions of the oil film under starved conditions. We adopted the shooting method to investigate the onset speed of instability (OSI) induced by the journal bearing accurately. This approach is an analytical technique used to determine periodic solutions and evaluate their stability. The results confirm the previously reported tendency of the OSI to increase with reduced oil supply, and additionally show that the strength of the stability decreased. This implies that the OSI of a given system may be inversely lowered by destabilizing forces originating from other turbomachinery elements such as impellers or turbines.

Abstract Journal bearings are widely used in rotating machinery due to their strong damping properties. Recently, the idea of operating journal bearings under starved lubrication conditions to reduce energy loss has attracted attention. However, this condition introduces complex nonlinear behaviors that can affect the stability of the system. In this study, periodic vibration of a flexible rotor system supported by a circular journal bearing under starved conditions was analyzed using the harmonic balance method in an alternating frequency-time domain (HB-AFT). The stability of the obtained solutions was evaluated under flooded and starved lubrication conditions. The results showed that although starvation did sometimes destabilize the system under the experimental parameters, the results of a parameter study indicated that specific design choices such as larger clearances or optimized oil supply angles can expand the stable operating region.

Abstract Background: In cancers with substantial unmet medical need (UMN), the limited availability of reliable and tumor-selective surface biomarkers continues to hinder therapeutic development. This challenge is particularly evident in triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC), where currently available targets often show insufficient specificity or restricted applicability across patient subgroups. Methods: We established the Inverse Biomarker Exploration Technology (IBMET), a systematic framework designed to detect pathological structural alterations on tumor cells. IBMET utilizes a large alpaca-derived VHH antibody repertoire as highly sensitive structural probes. Alpacas were immunized with multiple tumor cell lines, and the resulting VHH library was analyzed using phage display and next-generation sequencing. Candidate antibodies were selected based on statistical enrichment and evaluated by IHC/IF across an extensive panel of tumor and normal tissues. Antigen identification was performed by cross-linking immunoprecipitation, SDS-PAGE, and LC-MS/MS. Clinical relevance was examined using a breast cancer biopsy cohort (n = 106). Results: IBMET identified several structural biomarker candidates relevant to TNBC and PDAC. The lead antibody, VHH89, selectively recognized a previously uncharacterized low-molecular-weight isoform of ALCAM (approximately 70 kDa; designated ALCAM70). VHH89 showed lesion-selective staining in tumor tissues with minimal reactivity in normal organs, indicating a high degree of tumor specificity. In clinical breast cancer specimens, VHH89 demonstrated positivity in more than 20% of TNBC cases. In addition, subsets of pancreatic cancer and cholangiocarcinoma specimens also showed VHH89 positivity, suggesting that this isoform may represent a structurally altered antigen present across multiple tumor types. Conclusion: IBMET offers a reproducible and scalable approach for identifying structurally defined biomarkers that may not be detectable using genomic or transcriptomic analyses alone. By systematically excluding antibodies that react with normal tissues and enriching for tumor-associated conformational epitopes, IBMET broadens the spectrum of actionable targets for aggressive cancers. These findings support the potential integration of IBMET-derived antibodies into the development of next-generation antibody-drug conjugates, radioligand therapies, and companion diagnostics. To facilitate broader validation, COGNANO will make eight PDAC-selective VHH antibodies available for research use at AACR 2026. Citation Format: Akihiro Imura, Ryota Maeda, Hiroyuki Yamazaki, Tsuyoshi Inoue, Sadako Aakashi-Tanaka, Hiroko Tsukada. Ultra-sensitive structural biomarker discovery for TNBC and pancreatic cancer using a deep VHH repertoire (IBMET): A translational platform for tissue-agnostic target identification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6414.

In rotating machinery, quasi-periodic vibrations can arise from the coexistence of synchronous and asynchronous components; therefore, accurate and computationally efficient prediction at the design stage is crucial. The Variable Coefficient Harmonic Balance Method (VCHBM) can efficiently compute quasi-periodic solutions. However, the solution of the resulting nonlinear algebraic equations strongly depends on the initial guess. In particular, estimating an unknown quasi-periodic frequency requires highly accurate results from direct numerical integration, which constitutes a practical bottleneck. In this study, to improve the initial-guess search in the VCHBM, we introduce the Levenberg–Marquardt method to update the Fourier coefficients. We further formulate the update of the unknown quasi-periodic frequency as a fixed-point iteration based on residual-norm minimization and accelerate its convergence using Anderson acceleration. Applications to an internally damped Jeffcott rotor and a turbocharger model supported by semi-floating ring bearings show that the proposed method converges stably from a wider range of initial estimates than the conventional Newton–Raphson method and accurately reproduces quasi-periodic steady-state solutions consistent with direct numerical integration (Runge–Kutta). In addition, we demonstrate that this method can trace solution branches, including unstable solutions and bifurcation points, which are difficult to capture via numerical integration.

Abstract Some terrestrial tardigrades can endure severe oxidative stress in part through their gene-expanded repertoire of antioxidant proteins. However, among these antioxidant proteins, Rv PrxL, a peroxiredoxin (Prx)-like protein from Ramazzottius varieornatus strain YOKOZUNA-1, is unusual in that the catalytic cysteine is replaced by glutamate, apparently incapacitating canonical peroxidase function. In this study, we investigated the structure and function of this atypical Prx. Biochemical assays demonstrated that Rv PrxL completely lacks canonical peroxidase and chaperone activities. Cryo-EM analysis revealed a unique 20-mer structure of Rv PrxL. We also observed that the tardigrade-specific N-terminal region of Rv PrxL helps retain the high-order oligomeric assembly even in the presence of highly concentrated hydrogen peroxide. The N-terminal region also promotes nuclear localization of Rv PrxL and mediates binding to nucleic acids including nuclear RNAs. Furthermore, combining a standard cryo-EM method and a new approach in which cell L ysates are Ap plied D irectly o n cryo-EM G rids (LApDoG), we visualized two distinct nucleic acid–binding modes of Rv PrxL, termed “on-ring” and “in-ring”, which likely reflect distinct physiological roles or modes of action. Collectively, these findings show that Rv PrxL has been neofunctionalized to interact with nucleic acids in the nucleus, highlighting unexpected functional diversification of antioxidant proteins in tardigrades.

Stars are thought to form predominantly within filamentary molecular clouds. Recent studies have suggested that active star formation, including the formation of stellar clusters and massive stars, occurs within so-called "hub" structures, where multiple filaments converge. Understanding the formation and evolution of such hub-filament systems is therefore essential for unveiling the physical processes responsible for cluster and massive star formation, although the full picture remains incomplete. To address this, we have focused on filament-filament collisions as a potential formation mechanism of the hubs. In this study, we investigate the fundamental evolutionary processes of oblique collisions between two magnetized filaments using three-dimensional ideal magnetohydrodynamical simulations. As a model of initial filaments, we consider two identical finite-length magnetized filaments, varying the collision angle between their long axes, the collision velocity, which is set perpendicular to the long axes, and the initial line mass. We find that as the collision angle decreases from orthogonal to parallel, the compressed cloud becomes more prone to gravitational collapse. In addition, the instability of the post-collision compressed cloud can be explained by its energy balance. Specifically, if the absolute value of the gravitational energy exceeds the sum of the kinetic, thermal, and magnetic energies immediately after the collision, the cloud undergoes gravitational collapse. Conversely, if the gravitational energy is smaller, the cloud expands. In addition, we estimate the upper limit of the collision velocity that enables hub-filament formation and identify the collision conditions favorable for massive star formation.

Background: Psychological stress can exacerbate the development of allergies; however, the underlying mechanisms remain poorly understood. IgE-mediated cutaneous allergic inflammation (IgE-CAI) is a basophil-dependent skin allergy with eosinophil infiltration at inflammatory sites. Its resolution involves anti-inflammatory programmed death ligand 2 (PD L2)-positive macrophages. Objective: This study sought to elucidate the cellular and molecular mechanisms by which psychological stress exacerbates IgE-CAI. Methods: Neural tissue involved in stress-induced IgE-CAI exacerbation was identified by performing denervation and brain destruction experiments in mice. Immune cell transplantation, RNA sequencing, flow cytometry, and ELISA were used to identify and characterize immune cells with stress- altered functioning, followed by identification of key factors involved in IgE-CAI exacerbation. Results: Stress-induced exacerbation of IgE-CAI was found to be sympathetic and b2-adrenergic receptor (Adrb2)-dependent. Adoptive transfer experiments revealed that stress diminished the anti-inflammatory functions of PD-L2-positive macrophages through Adrb2, exacerbating the inflammation. RNA sequencing analysis indicated that PD-L2-positive macrophages in stressed mice exhibit reduced expression of efferocytosis-related genes, including Gas6 and MerTK. Consequently, the efferocytic capacity of these macrophages decreased, resulting in increased numbers of dead cells in the lesions. The exacerbation and upregulation of Ccl24 expression in IgE-CAI skin lesions were countered by a Caspase-1 inhibitor. Conclusions: Psychological stress diminishes the efferocytotic capacity of PD-L2-positive macrophages, causing an accumulation of dead cells. This, in turn, heightens eosinophil infiltration through Caspase-1-dependent production of CCL24, exacerbating IgE-CAI. (J Allergy Clin Immunol 2025;155:865-79.)

In vertical rotating shaft-bearing systems, synchronous vibration undergoes destabilization and stabilization owing to the self-excited vibration. Recently, these phenomena have been clarified numerically, experimentally, and analytically based on a newly proposed analytical method. In this method, a two-step linearization of the nonlinear journal bearing (JB) force and generalized eigenvalue analysis are proposed to directly determine the stability of the synchronous orbit. However, this method cannot be used directly for inclined-rotor systems with a large gravitational effect. Moreover, stability changes caused by gravity variations in inclined-rotor systems have not been fully investigated. This study extended the analytical method to one with weighted average dynamic coefficients to efficiently predict the stability changes of synchronous whirling vibrations in inclined rotor systems. The extended analytical method clearly clarifies gravity-induced stability changes in comparison with the numerical (shooting) method. Our analytical method enhances the ability of rotor dynamics software to calculate the stability thresholds of inclined rotor systems with gravity variations.

In this paper, a modified HB-AFT method applying quaternion-based geometrically exact beam (GEB) systems is proposed, considering both rotational inertia and gyroscopic terms to ensure calculation accuracy. The partial derivatives of the inertial, internal, external, and constraint forces with respect to the quaternion-based state variable are derived. It is difficult to transform the equations of motion of GEB systems into the M, C, K forms, which are typically necessary for the traditional HB-AFT method. This study uses a method to expand the residual of the equations of motion of the entire GEB system and demonstrates that it smoothly performs dynamic analysis of cantilever beam structures. The accuracy of the proposed method is verified through comparison with direct simulation and the commercial software SIMPACK. The frequency responses indicate that the rotational inertia and gyroscopic terms have a considerable effect under specific conditions, such as a high frequency of external loads, and large rotational inertia. Furthermore, for cantilever beam structures, this study indicates that rotational inertia plays a major role in dynamic characteristics compared with gyroscopic effect, and the computational efficiency of HB-AFT is 8.4-13.8 times higher than that of direct simulation.