3D track extraction from a fluorescent nuclear track detector via machine learning and an application to diagnostics of laser-driven ions.

We have developed an ion diagnostic method for laser-driven ion acceleration experiments that uses fluorescent nuclear track detectors (FNTDs). An FNTD records the particle tracks as color centers and does not require chemical etching, unlike CR-39 track detectors. The color centers are observed using a confocal laser microscope, and 3D particle tracks can be obtained by changing its focal position. The intensity of the color centers corresponds to the energy deposited by the ions. The nuclides of the ions can be determined from the intensity distribution of the color centers as a function of depth and the distance between the stopping point and the surface of the detector. To extract the intensity distribution, we must track the same ion tracks in the depth-layered microscopic images from the surface to the stopping point, even if they overlap with those of other ions. In addition, since an FNTD is sensitive not only to ions but also to electrons and photons, we must identify ion tracks among those from the latter particles. To analyze a statistical number of ion tracks, it is necessary to automate these processes. We have thus developed a method for automated ion detection and 3D tracking that relies on a support vector classifier and a kernelized correlation filter. This method was tested on a laser ion acceleration experiment performed using the J-KAREN-P laser. The method automatically detects ion tracks on FNTDs and tracks them in the depth direction. The training data are sampled from the Heavy-Ion Medical Accelerator in Chiba.

Latitudinal variation in thermal performance of the common coral Pocillopora spp.

Understanding how tropical corals respond to temperatures is important to evaluating their capacity to persist in a warmer future. We studied the common Pacific coral Pocillopora over 44° of latitude, and used populations at three islands with different thermal regimes to compare their responses to temperature using thermal performance curves (TPCs) for respiration and gross photosynthesis. Corals were sampled in the local autumn from Moorea, Guam and Okinawa, where mean±s.d. annual seawater temperature is 28.0±0.9°C, 28.9±0.7°C and 25.1±3.4°C, respectively. TPCs for respiration were similar among latitudes, the thermal optimum (Topt) was above the local maximum temperature at all three islands, and maximum respiration was lowest at Okinawa. TPCs for gross photosynthesis were wider, implying greater thermal eurytopy, with a higher Topt in Moorea versus Guam and Okinawa. Topt was above the maximum temperature in Moorea, but was similar to daily temperatures over 13% of the year in Okinawa and 53% of the year in Guam. There was greater annual variation in daily temperatures in Okinawa than Guam or Moorea, which translated to large variation in the supply of metabolic energy and photosynthetically fixed carbon at higher latitudes. Despite these trends, the differences in TPCs for Pocillopora spp. were not profoundly different across latitudes, reducing the likelihood that populations of these corals could better match their phenotypes to future more extreme temperatures through migration. Any such response would place a premium on high metabolic plasticity and tolerance of large seasonal variations in energy budgets.

Search for Antideuterons of Cosmic Origin Using the BESS-Polar II Magnetic-Rigidity Spectrometer.

We searched for antideuterons (d[over ¯]'s) in the 4.7×10^{9} cosmic-ray events observed during the BESS-Polar II flight at solar minimum in 2007-2008 but found no candidates. The resulting 95% C.L. upper limit on the d[over ¯] flux is 6.7×10^{-5} (m^{2} s sr GeV/n)^{-1} in an energy range from 0.163 to 1.100 GeV/n. The result has improved by more than a factor of 14 from the upper limit of BESS97, which had a potential comparable to that of BESS-Polar II in the search for cosmic-origin d[over ¯]'s and was conducted during the former solar minimum. The upper limit of d[over ¯] flux from BESS-Polar II is the first result achieving the sensitivity to constrain the latest theoretical predictions.

Automation of etch pit analyses on solid-state nuclear track detectors with machine learning for laser-driven ion acceleration.

Solid-state nuclear track detectors (SSNTDs) are often used as ion detectors in laser-driven ion acceleration experiments and are considered to be the most reliable ion diagnostics since they are sensitive only to ions and measure ions one by one. However, ion pit analyses require tremendous time and effort in chemical etching, microscope scanning, and ion pit identification by eyes. From a laser-driven ion acceleration experiment, there are typically millions of microscopic images, and it is practically impossible to analyze all of them by hand. This research aims to improve the efficiency and automation of SSNTD analyses for laser-driven ion acceleration. We use two sets of data obtained from calibration experiments with a conventional accelerator where ions with known nuclides and energies are generated and from actual laser experiments using SSNTDs. After chemical etching and scanning the SSNTDs with an optical microscope, we use machine learning to distinguish the ion etch pits from noises. From the results of the calibration experiment, we confirm highly accurate etch-pit detection with machine learning. We are also able to detect etch pits with machine learning from the laser-driven ion acceleration experiment, which is much noisier than calibration experiments. By using machine learning, we successfully identify ion etch pits ∼105 from more than 10 000 microscopic images with a precision of ≳95%. A million microscopic images can be examined with a recent entry-level computer within a day with high precision. Machine learning tremendously reduces the time consumption on ion etch pit analyses detected on SSNTDs.

Alcanivorax borkumensis biofilms enhance oil degradation by interfacial tubulation.

During the consumption of alkanes, Alcanivorax borkumensis will form a biofilm around an oil droplet, but the role this plays during degradation remains unclear. We identified a shift in biofilm morphology that depends on adaptation to oil consumption: Longer exposure leads to the appearance of dendritic biofilms optimized for oil consumption effected through tubulation of the interface. In situ microfluidic tracking enabled us to correlate tubulation to localized defects in the interfacial cell ordering. We demonstrate control over droplet deformation by using confinement to position defects, inducing dimpling in the droplets. We developed a model that elucidates biofilm morphology, linking tubulation to decreased interfacial tension and increased cell hydrophobicity.

Gastric functional monitoring by gastric electrical impedance tomography (gEIT) suit with dual-step fuzzy clustering.

Gastric Function has been successfully estimated by gastric electrical impedance tomography (gEIT) Suit with dual-step fuzzy clustering. The gEIT Suit which are made of elastic cloth with dual-planar electrodes and compact data acquisition (DAQ) system measures gastric impedance Z to visualize the gastric conductivity distribution σ. The dual-step fuzzy clustering extracts the clustered gastric conductivity distribution kσ, which accurately estimates the gastric function. The gEIT Suit with dual-step fuzzy clustering are applied to eight healthy persons during liquid meal consumption to estimate the gastric function under gastric accommodation phase of 200, 400 and 600 mL based on the gastric emptying phase. As the results, the gEIT Suit successfully estimate the gastric function. By the measured impedance Z, the subjects have a mean temporal impedance [Formula: see text]= - 9.27 [Ohm] and p-value of that [Formula: see text] p(Z) = 0.0013[-]as the t-test result. In the case of gastric conductivity distribution σ, the subjects have a value of spatial mean conductivity distribution ⟨σ⟩ = 0.23[-] and p-value of that ⟨σ⟩ p(σ) = 0.0140[-]. Lastly, in the case gastric volume V, subjects have a gastric volume V = 12.44 [%] and p-value p(V) = 0.0664[-].

Motor training promotes both synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex.

Layer V neurons in the primary motor cortex (M1) are important for motor skill learning. Since pretreatment of either CNQX or APV in rat M1 layer V impaired rotor rod learning, we analysed training-induced synaptic plasticity by whole-cell patch-clamp technique in acute brain slices. Rats trained for 1 day showed a decrease in small inhibitory postsynaptic current (mIPSC) frequency and an increase in the paired-pulse ratio of evoked IPSCs, suggesting a transient decrease in presynaptic GABA release in the early phase. Rats trained for 2 days showed an increase in miniature excitatory postsynaptic current (mEPSC) amplitudes/frequency and elevated AMPA/NMDA ratios, suggesting a long-term strengthening of AMPA receptor-mediated excitatory synapses. Importantly, rotor rod performance in trained rats was correlated with the mean mEPSC amplitude and the frequency obtained from that animal. In current-clamp analysis, 1-day-trained rats transiently decreased the current-induced firing rate, while 2-day-trained rats returned to pre-training levels, suggesting dynamic changes in intrinsic properties. Furthermore, western blot analysis of layer V detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in 1-day-trained rats, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in 2-day-trained rats. Finally, live-imaging analysis of Thy1-YFP transgenic mice showed that the training rapidly recruited a substantial number of spines for long-term plasticity in M1 layer V neurons. Taken together, these results indicate that motor training induces complex and diverse plasticity in M1 layer V pyramidal neurons. KEY POINTS: Here we examined motor training-induced synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex. The training reduced presynaptic GABA release in the early phase, but strengthened AMPA receptor-mediated excitatory synapses in the later phase: acquired motor performance after training correlated with the strength of excitatory synapses rather than inhibitory synapses. As to the intrinsic property, the training transiently decreased the firing rate in the early phase, but returned to pre-training levels in the later phase. Western blot analysis detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in the acute phase, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in the later phase. Live-imaging analysis of Thy1-YFP transgenic mice showed rapid and long-term spine plasticity in M1 layer V neurons, suggesting training-induced increases in self-entropy per spine.

Detection of current-sheet and bipolar ion flows in a self-generated antiparallel magnetic field of laser-produced plasmas for magnetic reconnection research.

Magnetic reconnection in laser-produced magnetized plasma is investigated by using optical diagnostics. The magnetic field is generated via the Biermann battery effect, and the inversely directed magnetic field lines interact with each other. It is shown by self-emission measurement that two colliding plasmas stagnate on a midplane, forming two planar dense regions, and that they interact later in time. Laser Thomson scattering spectra are distorted in the direction of the self-generated magnetic field, indicating asymmetric ion velocity distribution and plasma acceleration. In addition, the spectra perpendicular to the magnetic field show different peak intensity, suggesting an electron current formation. These results are interpreted as magnetic field dissipation, reconnection, and outflow acceleration. Two-directional laser Thomson scattering is, as discussed here, a powerful tool for the investigation of microphysics in the reconnection region.

A phase II study to explore biomarkers for the use of mFOLFOX6/XELOX plus bevacizumab as a first-line chemotherapy in patients with metastatic colorectal cancer (WJOG7612GTR).

BACKGROUND: The purpose of this prospective study was to assess the ability of plasma vascular endothelial growth factor-A short isoforms (pVEGF-Asi) to predict bevacizumab (BV) efficacy and to explore other circulating biomarkers in metastatic colorectal cancer (mCRC) patients treated with modified FOLFOX6/XELOX plus BV (mFOLFOX6/XELOX + BV). PATIENTS AND METHODS: Pre-treatment plasma samples were collected from 100 mCRC patients receiving first-line chemotherapy with mFOLFOX6/XELOX + BV. The plasma levels of 11 angiogenesis-associated molecules, including pVEGF-Asi and 22 cancer-associated gene mutations in circulating tumor DNA, were analyzed. For the primary endpoint, we assumed that the hazard ratio (HR) for progression-free survival (PFS) calculated using a Cox proportional hazards model was <1.15, comparing patients with a high versus those with a low pVEGF-Asi level divided according to the median pVEGF-Asi value. RESULTS: The median value of pVEGF-Asi was 37 (range 6.5-262) pg/ml. The HR for PFS between the high and low pVEGF-Asi patient groups was 1.3 [95% confidence interval (CI) 0.8-2.1; log rank, P = 0.25], which was larger than the predefined threshold of 1.15. The multivariate analysis demonstrated that PFS was significantly associated with plasma intercellular adhesion molecule-1 (pICAM-1) (≥190.0 versus <190.0 ng/ml; HR 2.1; 95% CI 1.3-3.5), RAS (mutant versus wild; HR 2.5; 95% CI 1.5-4.3), and FBXW7 (mutant versus wild; HR 2.8; 95% CI 1.2-6.8), whereas overall survival was significantly associated with pICAM-1 (HR 2.0; 95% CI 1.1-3.7) and RAS (HR 2.6; 95% CI 1.5-4.6). CONCLUSIONS: The addition of BV was unable to compensate for the poor PFS associated with a high pVEGF-Asi level, suggesting that pVEGF-Asi is unlikely to be a good predictive biomarker of the efficacy of mFOLFOX6/XELOX + BV therapy. The clinical significance of circulating ICAM-1, mutant RAS, and mutant FBXW7 levels should be studied further.

High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

Direct observations of pure electron outflow in magnetic reconnection.

Magnetic reconnection is a universal process in space, astrophysical, and laboratory plasmas. It alters magnetic field topology and results in energy release to the plasma. Here we report the experimental results of a pure electron outflow in magnetic reconnection, which is not accompanied with ion flows. By controlling an applied magnetic field in a laser produced plasma, we have constructed an experiment that magnetizes the electrons but not the ions. This allows us to isolate the electron dynamics from the ions. Collective Thomson scattering measurements reveal the electron Alfvénic outflow without ion outflow. The resultant plasmoid and whistler waves are observed with the magnetic induction probe measurements. We observe the unique features of electron-scale magnetic reconnection simultaneously in laser produced plasmas, including global structures, local plasma parameters, magnetic field, and waves.

High-power laser experiment forming a supercritical collisionless shock in a magnetized uniform plasma at rest.

We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.

Robustness of large-area suspended graphene under interaction with intense laser.

Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene.

Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP. PATIENTS AND METHODS: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1. RESULTS: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed. CONCLUSIONS: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.

Transfer of orbital angular momentum of light to plasmonic excitations in metamaterials.

The emergence of the vortex beam with orbital angular momentum (OAM) has provided intriguing possibilities to induce optical transitions beyond the framework of the electric dipole interaction. The uniqueness stems from the OAM transfer from light to material, as demonstrated in electronic transitions in atomic systems. In this study, we report on the OAM transfer to electrons in solid-state systems, which has been elusive to date. Using metamaterials (periodically textured metallic disks), we show that multipolar modes of the surface electromagnetic excitations (so-called spoof localized surface plasmons) are selectively induced by the terahertz vortex beam. Our results reveal selection rules governed by the conservation of the total angular momentum, which is confirmed by numerical simulations. The efficient transfer of light's OAM to elementary excitations in solid-state systems at room temperature opens up new possibilities of OAM manipulation.

Extracellular Vesicles of Stem Cells to Prevent BRONJ.

Extracellular vesicles (EVs), several tens to hundreds of nanometers in size, are vesicles secreted by cells for intercellular communication. EVs released from mesenchymal stem cells (MSC-EVs) have the potential to treat multiple diseases. This study aimed to determine the effects of MSC-EVs on bisphosphonate-related osteonecrosis of the jaw (BRONJ), whose pathogenesis and treatment are not yet established. To this end, zoledronic acid (ZOL) was administered to bone marrow cells and fibroblasts in vitro. In vivo, a BRONJ model was produced by administering ZOL to rats and extracting teeth. Each MSC-EV-treated and nontreated group was compared histologically and molecularly. In vitro, the nontreated group showed an increased number of ß-galactosidase-positive cells and expression of senescence-associated genes p21, pRB and senescence-related inflammatory cytokines. Conversely, MSC-EV administration decreased the number of senescent cells and expression levels of p21, pRB and inflammatory cytokines. In vivo, in the nontreated group, the socket was partially uncovered by the oral epithelium, leaving an exposed bone. Conversely, in the MSC-EV-treated group, the socket was healed. Besides, in the nontreated group, ß-galactosidase-positive cells existed in the socket and colocalized with the CD90 and periostin-positive cells. However, there were few ß-galactosidase-positive cells in the MSC-EV-treated group. Furthermore, gene expression of stem cell markers Bmi1 and Hmga2 and the vascular endothelial marker VEGF was significantly increased in the MSC-EV-treated group, compared with that in the nontreated group. These results indicate that MSC-EVs prevent ZOL-induced senescence in stem cells, osteoblasts, and fibroblasts and reduce inflammatory cytokines. Furthermore, administration of MSC-EVs prevented senescence of cells involved in wound healing and the spread of chronic inflammation around senescent cells, thereby promoting angiogenesis and bone regeneration and preventing BRONJ.