Effective management of lung spindle cell carcinoma with ipilimumab, nivolumab, carboplatin, and paclitaxel, demonstrating efficacy in brain metastases treatment.

A 76-year-old woman with cT1bN2M1b stage IVA spindle cell carcinoma of the right lower lobe of the lung, no driver gene mutation, and programmed death ligand 1 < 1%, was started on ipilimumab+nivolumab+carboplatin+paclitaxel. After two courses, the patient initiated maintenance therapy with ipilimumab+nivolumab. New multiple brain metastases were observed during treatment but resolved with continued treatment. We report a unique case of spindle cell carcinoma treated with ipilimumab+nivolumab+carboplatin+paclitaxel that resulted in long-term response and resolution of new brain metastasis.

Reduction of the two-photon temporal distinguishability for measurement-device-independent quantum key distribution.

Measurement-device-independent quantum key distribution (MDI-QKD) has been proven to protect legitimate users from attacks against measurement devices. The MDI-QKD requires that the two photons arriving at the instrument be indistinguishable. Precise time control is required to eliminate the distinguishability due to differences in photon arrival times. In the conventional methods, the time difference between photons is measured at a measuring instrument (Charlie), and a control signal is transmitted to the users (Alice and Bob). However, this method requires a long feedback loop, and the control may become unstable for long-distance transmission. This article proposes a method in which the photon arrival time difference is detected and controlled at Charlie. The reference signal for the time control is generated by an optical frequency comb in synchronization with the quantum signal. Therefore, the quantum signal photons can also be synchronized by synchronizing the reference signal pulses. A proof-of-principle experiment confirmed that the time synchronization accuracy required for protocol execution could be obtained. This proposal simplifies the implementation of the MDI-QKD.

Oxidation-induced nanolite crystallization triggered the 2021 eruption of Fukutoku-Oka-no-Ba, Japan.

Nanometer-sized crystals (nanolites) play an important role in controlling eruptions by affecting the viscosity of magmas and inducing bubble nucleation. We present detailed microscopic and nanoscopic petrographic analyses of nanolite-bearing and nanolite-free pumice from the 2021 eruption of Fukutoku-Oka-no-Ba, Japan. The nanolite mineral assemblage includes biotite, which is absent from the phenocryst mineral assemblage, and magnetite and clinopyroxene, which are observed as phenocrysts. The boundary between the nanolite-bearing brown glass and nanolite-free colorless glass is either sharp or gradational, and the sharp boundaries also appear sharp under the transmitted electron microscope. X-ray absorption fine structure (XAFS) analysis of the volcanic glass revealed that the nanolite-free colorless glass records an oxygen fugacity of QFM + 0.98 (log units), whereas the nanolite-bearing brown glass records a higher apparent oxygen fugacity (~ QFM + 2). Thermodynamic modelling using MELTS indicates that higher oxygen fugacities increase the liquidus temperature and thus induced the crystallization of magnetite nanolites. The hydrous nanolite mineral assemblage and glass oxygen fugacity estimates suggest that an oxidizing fluid supplied by a hot mafic magma induced nanolite crystallization in the magma reservoir, before the magma fragmentation. The oxidation-induced nanolite crystallization then enhanced heterogeneous bubble nucleation, resulting in convection in the magma reservoir and triggering the eruption.

Deep learning generates custom-made logistic regression models for explaining how breast cancer subtypes are classified.

Differentiating the intrinsic subtypes of breast cancer is crucial for deciding the best treatment strategy. Deep learning can predict the subtypes from genetic information more accurately than conventional statistical methods, but to date, deep learning has not been directly utilized to examine which genes are associated with which subtypes. To clarify the mechanisms embedded in the intrinsic subtypes, we developed an explainable deep learning model called a point-wise linear (PWL) model that generates a custom-made logistic regression for each patient. Logistic regression, which is familiar to both physicians and medical informatics researchers, allows us to analyze the importance of the feature variables, and the PWL model harnesses these practical abilities of logistic regression. In this study, we show that analyzing breast cancer subtypes is clinically beneficial for patients and one of the best ways to validate the capability of the PWL model. First, we trained the PWL model with RNA-seq data to predict PAM50 intrinsic subtypes and applied it to the 41/50 genes of PAM50 through the subtype prediction task. Second, we developed a deep enrichment analysis method to reveal the relationships between the PAM50 subtypes and the copy numbers of breast cancer. Our findings showed that the PWL model utilized genes relevant to the cell cycle-related pathways. These preliminary successes in breast cancer subtype analysis demonstrate the potential of our analysis strategy to clarify the mechanisms underlying breast cancer and improve overall clinical outcomes.

Geological records of transient fluid drainage into the shallow mantle wedge.

Pore fluid pressure on subduction zone megathrusts is lowered by fluid drainage into the overlying plate, affecting subduction zone seismicity. However, the spatial and temporal scales of fluid flow through suprasubduction zones are poorly understood. We constrain the duration and velocity of fluid flow through a shallow mantle wedge based on the analyses of vein networks consisting of high-temperature serpentine in hydrated ultramafic rocks from the Oman ophiolite. On the basis of a diffusion model and the time-integrated fluid flux, we show that the channelized fluid flow was short-lived (2.1 × 10-1 to 1.1 × 101 years) and had a high fluid velocity (2.7 × 10-3 to 4.9 × 10-2 meters second-1), which is close to the propagation velocities of seismic events in present-day subduction zones. Our results suggest that the drainage of fluid into the overlying plate occurs as episodic pulses, which may influence the recurrence of megathrust earthquakes.

Super-resolution of X-ray CT images of rock samples by sparse representation: applications to the complex texture of serpentinite.

X-ray computed tomography (X-ray CT) has been widely used in the earth sciences, as it is non-destructive method for providing us the three-dimensional structures of rocks and sediments. Rock samples essentially possess various-scale structures, including millimeters to centimeter scales of layering and veins to micron-meter-scale mineral grains and porosities. As the limitations of the X-ray CT scanner, sample size and scanning time, it is not easy to extract information on multi-scale structures, even when hundreds meter scale core samples were obtained during drilling projects. As the first step to overcome such barriers on scale-resolution problems, we applied the super-resolution technique by sparse representation and dictionary-learning to X-ray CT images of rock core sample. By applications to serpentinized peridotite, which records the multi-stage water-rock interactions, we reveal that both grain-shapes, veins and background heterogeneities of high-resolution images can be reconstructed through super-resolution. We also show that the potential effectiveness of sparse super-resolution for feature extraction of complicated rock textures.

Machine-learning techniques for quantifying the protolith composition and mass transfer history of metabasalt.

The mass transfer history of rocks provides direct evidence for fluid-rock interaction within the lithosphere and is recorded by compositional changes, especially in trace elements. The general method adopted for mass transfer analysis is to compare the composition of the protolith/precursor with that of metamorphosed/altered rocks; however, in many cases the protolith cannot be sampled. With the aim of reconstructing the mass transfer history of metabasalt, this study developed protolith reconstruction models (PRMs) for metabasalt using machine-learning algorithms. We designed models to estimate basalt trace-element concentrations from the concentrations of a few (1-9) trace elements, trained with a compositional dataset for fresh basalts, including mid-ocean ridge, ocean-island, and volcanic arc basalts. The developed PRMs were able to estimate basalt trace-element compositions (e.g., Rb, Ba, U, K, Pb, Sr, and rare-earth elements) from only four input elements with a reproducibility of ~ 0.1 log10 units (i.e., ± 25%). As a representative example, we present PRMs where the input elements are Th, Nb, Zr, and Ti, which are typically immobile during metamorphism. Case studies demonstrate the applicability of PRMs to seafloor altered basalt and metabasalt. This method enables us to analyze quantitative mass transfer in regional metamorphic rocks or alteration zones where the protolith is heterogeneous or unknown.

Volatile-consuming reactions fracture rocks and self-accelerate fluid flow in the lithosphere.

Hydration and carbonation reactions within the Earth cause an increase in solid volume by up to several tens of vol%, which can induce stress and rock fracture. Observations of naturally hydrated and carbonated peridotite suggest that permeability and fluid flow are enhanced by reaction-induced fracturing. However, permeability enhancement during solid-volume-increasing reactions has not been achieved in the laboratory, and the mechanisms of reaction-accelerated fluid flow remain largely unknown. Here, we present experimental evidence of significant permeability enhancement by volume-increasing reactions under confining pressure. The hydromechanical behavior of hydration of sintered periclase [MgO + H2O → Mg(OH)2] depends mainly on the initial pore-fluid connectivity. Permeability increased by three orders of magnitude for low-connectivity samples, whereas it decreased by two orders of magnitude for high-connectivity samples. Permeability enhancement was caused by hierarchical fracturing of the reacting materials, whereas a decrease was associated with homogeneous pore clogging by the reaction products. These behaviors suggest that the fluid flow rate, relative to reaction rate, is the main control on hydromechanical evolution during volume-increasing reactions. We suggest that an extremely high reaction rate and low pore-fluid connectivity lead to local stress perturbations and are essential for reaction-induced fracturing and accelerated fluid flow during hydration/carbonation.

Spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers.

To realize simplified cost-efficient optical networks with routing flexibility and scaling potential, a spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers is proposed herein, which can route all spatial channels together as a unit. Numerical simulations and experiments were performed, and the results show that the signal paths for a 6-mode 19-core fiber can be simultaneously switched to the target output ports using the proposed method, and the mode-field patterns of the diffracted light can be maintained after joint switching. Further, the maximum port crosstalk can be reduced considerably from -11.6 to -25.1 dB by changing the position of the output port in the proposed method.

Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.

Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.

Condensation Behavior of Hierarchical Nano/Microstructured Surfaces Inspired by Euphorbia myrsinites.

In nature, many extant species exhibit functionalized surface structures during evolution. In particular, wettability affects the functionalization of the surface, and nano/microstructures have been found to enable functions, such as droplet jumping, thereby making self-cleaning, antifog, antibacterial, and antireflection surfaces. Important efforts are underway to understand the surface structure of plant leaves and establish rational design tools for the development of new engineering materials. In this study, we focused on the hierarchical nano/microstructure of the leaves of Euphorbia myrsinites (hereinafter, E. myrsinites), which has a hierarchical shape with microsized papillae, covered with nanosized protruding wax, and observed the condensation behavior on the leaf surface. Si is vertically etched via reactive ion etching (RIE) to artificially mimic the hierarchical nano/microstructures on the leaves of E. myrsinites. We made four types of artificial hierarchical structures, with micropillars having pillar diameters of 5.6 and 16 µm (pillar spacing of 20 and 40 µm, respectively) and heights of 6.5 and 19.5 µm, and nanopillars formed on the surface. The optical observation with a microscope revealed a very high density of condensed droplets on the artificial surface and a stable jumping behavior of droplets of 10 µm or more. Furthermore, in the samples with a micropillar diameter of 5.6 µm and a micropillar height of 19.5 µm, the droplets that had jumped and fallen thereupon bounced off, thereby preventing reattachment. As a result, no droplets of 35 µm or more could exist even after 10 min. In addition, it was clear that a small underlying droplet of less than 10 µm was generated at the bottom of the relatively large secondary droplet existing on the large micropillar of 16 µm, and a frequent coalescence of the droplets occurred. This study revealed the phenomenon of condensation on the surface of plants as well as made it possible to improve the heat exchange process by significantly promoting the heat transfer of condensation using artificial surfaces.

Formation of amorphous silica nanoparticles and its impact on permeability of fractured granite in superhot geothermal environments.

Superhot geothermal environments in granitic crusts of approximately 400-500 °C are a frontier of geothermal energy. In the development of such environments, there is a concern of a reduction of permeability of fractured granite due to the formation of fine particles of amorphous silica induced by the phase change from subcritical water to supercritical water or superheated steam. However, the formation of silica particles and a resultant reduction in permeability have not been demonstrated to date. Therefore, experiments were conducted on the formation of amorphous silica particles with various combinations of temperature (430-500 °C) and pressure (20-30 MPa), in which the phase change of Si-containing water from liquid to either supercritical fluid or vapor was induced. Amorphous silica nanoparticles occurred under all conditions with smaller particles for higher temperature. The permeability of fractured granite was also observed to decrease significantly within several hours during injection of the particles into rock at 450 °C and 30 MPa under a confining stress of 40 MPa, with slower permeability reduction at a smaller number of particles or in the presence of larger aperture fractures. The present study suggests that the nanoparticles are likely to form and destroy the permeability in superhot geothermal environments, against which countermeasures should be investigated.

Management of cesarean section in a patient with Fontan circulation: a case report of dramatic reduction of maternal oxygen consumption after delivery.

BACKGROUND: The anesthetic management of cesarean sections in Fontan-palliated parturients requires strict hemodynamic control. However, patient management with central venous oxygen saturation (ScvO2) and oxygen consumption (VO2) has never been reported. CASE PRESENTATION: A 30-year-old woman, who had received a total cavopulmonary connection for tricuspid atresia, was planned to undergo cesarean section at 38 weeks' gestation. During combined spinal-epidural anesthesia, ScvO2 in addition to arterial pressure-based cardiac output (APCO) and central venous pressure (CVP) was monitored, and the change of VO2 was evaluated. After delivery, her APCO was almost unchanged. However, her ScvO2 increased dramatically from 42.1 to 67.3% and her CVP increased from 9 to 11 mm Hg. The calculated mean maternal VO2 changed from 443 to 295 mL/min. CONCLUSIONS: In a cesarean section for a Fontan-palliated parturient, ScvO2 dramatically increased and maternal VO2 decreased by more than 25% after delivery.

Dropwise Condensation on a Hierarchical Nanopillar Structured Surface.

Nanopillar structure processing has been performed on condensation surfaces to control wettability and achieve a high heat transfer coefficient via dropwise condensation and jumping droplets. Modified dry etching was performed using gold (Au) nanoparticles generated by annealing Au as a mask. High-aspect-ratio nanopillar processing was also performed to produce uniform pillar surfaces and novel hierarchical pillar surfaces. A uniform nanopillar surface with pillars having diameters of 20-850 nm and a hierarchical pillar surface with thick pillars having diameters ranging from 100 to 860 nm and thin pillars with diameters ranging from 20 to 40 nm were mixed and fabricated. Condensation experiments were performed using the noncoated nanopillar surfaces, and the condensation behaviors on the silicon (Si) surfaces were observed from above using a microscope and from the side using a high-speed camera. On the uniform surface US-3 and the hierarchical surfaces HS-1 and HS-2, droplet jumps were observed frequently in the droplet size range of 20-50 µm. In contrast, as the droplet size increased to 50 µm or more, the number of jumps observed decreased as the droplet size increased. The frequency of droplet jumps on the hierarchical surfaces from the start of condensation to approximately 2 min was higher than that on the uniform surfaces, although the density of droplet formation on the hierarchical surfaces was not relatively large. On the basis of the observation of droplet behavior from the side surface, we identified that the primary jump was due to the coalescence of droplets adhering to the surface and that the subsequent jump was caused by the droplet coalescence when the jump droplets were reattached. The primary jump occurrence rate was high on all pillar surfaces.

State preparation robust to modulation signal degradation by use of a dual parallel modulator for high-speed BB84 quantum key distribution systems.

Security certification of quantum key distribution systems with a practical device is essential for their social deployment. Considering the transmitter, we investigate quantum state generation affected by degraded electrical signals from practical bandwidth-limited devices on high-speed phase-encoding BB84 quantum key distribution systems. The state preparation flaw caused by this degradation undesirably enhances the distinguishability between the two bases for the BB84 protocol and decreases the key generation rate. We propose the state preparation with a dual parallel modulator for increasing the robustness to signal degradation. To verify the effectiveness of the dual parallel modulator, we characterize the generated states using state tomography and estimate the key generation rate based on the Gottesman-Lo-Lütkenhaus-Preskill theory with fidelity derived from the estimated density matrices. Simulation results show that the key generation rate remains unaffected by modulation voltage shifts up to 20%.

Update of the GRIP web service.

G protein-coupled receptors (GPCRs) can form homodimers, heterodimers, or higher-order molecular complexes (oligomers). The reports on the change of functions through the oligomerization have been accumulated. Inhibition of GPCR oligomerization without affecting the protomer's overall structure would clarify the oligomer-specific functions although inhibition experiments are costly and require accurate information about the interface location. Unfortunately, the number of experimentally determined interfaces is limited. The precise prediction of the oligomerization interfaces is, therefore, useful for inhibition experiments to examine the oligomer-specific functions, which would accelerate investigations of the GPCR signaling. However, interface prediction for GPCR oligomerization is difficult because different GPCR subtypes belonging to the same subfamily often use different structural regions as their interfaces. We previously developed a high-performance method to predict the interfaces for GPCR oligomerization, by identifying the conserved surfaces with the sequence and structure information. Then, the structural characteristic of a GPCR structure is regarded to be a thick-tube like conformation that is approximately perpendicular to the membrane plane. Our method had successfully predicted all of the interfaces available on that day. We had launched a web server for our interface prediction of GPCRs (GRIP). We have improved the previous version of GRIP server and enhanced its usability. First, we discarded the approximation of the GPCR structure as the thick-tube-like conformation. This improvement increased the number of structures for the prediction. Second, the FUGUE-based template recommendation service was introduced to facilitate the choice of an appropriate structure for the prediction. The new prediction server is available at http://grip.b.dendai.ac.jp/∼grip/.

Wavefront superposition method for accurate and efficient mode conversion.

A wavefront superposition (WS) method is proposed for accurate and efficient mode conversion in mode-division multiplexing transmission. The WS method converts an input beam to the WS state, which is composed of the conversion target and radiation modes of a few-mode fiber. The appropriate weighting for the modal component of the WS state enables more efficient conversion than the conventional method in which the output beam consists only of the conversion target. Further, since the components of the radiation modes in the output are eliminated by the mode-filtering property of the few-mode fiber, no modal crosstalk occurs in the WS method. We examine the conversion performance of the WS method by a numerical simulation for the mode-multiplexing numbers 3, 6, 10, and 15. The WS method shows a 2.4 dB higher efficiency than the conventional method, while maintaining an extremely low modal crosstalk (less than -80 dB), even when the number of multiplexed modes is 15.

Silica nanoparticles produced by explosive flash vaporization during earthquakes.

Hydrothermal activity in the crust results in the precipitation of large volumes of silica and often involves the formation of ore deposits, the shaping of geothermal systems, and recurring earthquakes. Pore fluid pressures fluctuate between lithostatic and hydrostatic, depending on seismic activity, and some models suggest the possibility of flash vaporization, given that fluid pressures can drop to the level of vapour at fault jogs during seismic slip. The phase changes of water could create extremely high supersaturations of silica, but the mechanisms of quartz vein formation under such extreme conditions remain unclear. Here we describe flash experiments conducted with silica-saturated solutions under conditions ranging from subcritical to supercritical. We found that amorphous silica is produced instantaneously as spherical nano- to micron-scale particles via nucleation and aggregation during the evaporation of water droplets. The nanoparticles are transformed to microcrystalline quartz very rapidly by dissolution and precipitation in hydrothermal solutions, with this process requiring less than one day under supercritical conditions because of the huge surface areas involved. We suggest that such short-lived silica nanoparticles have significant impacts on the dynamic changes in mechanical behaviour and hydrology of hydrothermal systems in volcanic areas.

Proteolysis: a double-edged sword for the development of amyloidoses.

The yeast Saccharomyces cerevisiae has proven to be a useful model system to investigate the mechanism of prion generation and inheritance, to which studies in Sup35 made a great contribution. Recent studies demonstrated that 'protein misfolding and aggregation' (i.e. amyloidogenesis) is a common principle underlying the pathogenesis of neurodegenerative diseases including prion, amyotrophic lateral sclerosis (ALS), Perkinson's (PD), Alzheimer's (AD) diseases and polyglutamine (polyQ) diseases such as spinocerebellar ataxia (SCA) and Hantington's disease (HD). By these findings, the yeast has again been drawing increased attention as a useful system for studying neurodegenerative proteinopathies. So far, it has been reported that proteolytic cleavage of causative amyloidogenic proteins might affect the pathogenesis of the respective neurodegenerative diseases. Although those reports provide a clear phenomenological description, in the majority of cases, it has remained elusive if proteolysis is directly involved in the pathogenesis of the diseases. Recently, we have demonstrated in yeast that proteolysis suppresses prion generation. The yeast-based strategy might make a breakthrough to the unsolved issues.

Virtual phase conjugation based optical tomography for single-shot three-dimensional imaging.

We propose a virtual phase conjugation (VPC) based optical tomography (VPC-OT) for realizing single-shot optical tomographic imaging systems. Using a computer-based numerical beam propagation, the VPC combines pre-modulation and post-demodulation of the probe beam's wavefront, which provides an optical sectioning capability for resolving the depth coordinates. In VPC-OT, the physical optical microscope system and VPC are coupled using digital holography. Therefore, in contrast to conventional optical tomographic imaging (OTI) systems, this method does not require additional elements such as low-coherence light sources or confocal pinholes. It is challenging to obtain single-shot three-dimensional (3D) tomographic images using a conventional OTI system; however, this can be achieved using VPC-OT, which employs both digital holography and computer based numerical beam propagation. In addition, taking into account that VPC-OT is based on a complex amplitude detection using digital holography, this method allows us to simultaneously obtain quantitative phase contrast images. Using an objective lens with a numerical aperture (NA) of 0.8, we demonstrate a single-shot 3D imaging of frog blood cells with a depth resolution of 0.94 µm.