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Translational symmetry breaking is antagonistic to static fluidity but can be realized in superconductors, which host a quantum-mechanical coherent fluid formed by electron pairs. A peculiar example of such a state is the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state, induced by a time-reversal symmetry–breaking magnetic field applied to spin-singlet superconductors. This state is intrinsically accompanied by the superconducting spin smecticity, spin density–modulated fluidity with spontaneous translational-symmetry breaking. Detection of such spin smecticity provides unambiguous evidence for the FFLO state, but its observation has been challenging. Here, we report the characteristic “double-horn” nuclear magnetic resonance spectrum in the layered superconductor Sr 2 RuO 4 near its upper critical field, indicating the spatial sinusoidal modulation of spin density that is consistent with superconducting spin smecticity. Our work reveals that Sr 2 RuO 4 provides a versatile platform for studying FFLO physics.

We report the first experimental determination of the collision-energy dependence of the muon transfer rate from the ground state of muonic hydrogen to oxygen at near-thermal energies. A sharp increase by nearly an order of magnitude in the energy range 0 - 70 meV was found that is not observed in other gases. The results set a reliable reference for quantum-mechanical calculations of low-energy processes with exotic atoms, and provide firm ground for the measurement of the hyperfine splitting in muonic hydrogen and the determination of the Zemach radius of the proton by the FAMU collaboration., 30 pages, 10 figures

UTe2 is a recently discovered spin-triplet superconductor. One of the characteristic features of UTe2 is a magnetic field (H)-boosted superconductivity above 16 T when H is applied exactly parallel to the b axis. To date, this superconducting (SC) state has not been thoroughly investigated, and the SC properties as well as the spin state of this high-H SC (HHSC) phase are not well understood. In this study, we performed AC magnetic susceptibility and nuclear magnetic resonance (NMR) measurements and found that, up to 24.8 T, the HHSC state is intrinsic to UTe2 and quite sensitive to the H angle, and that its SC character is different from that in the low-H SC (LHSC) state. The dominant spin component of the spin-triplet pair is along the a axis in the LHSC state but is changed in the HHSC state along the b axis. Our results indicate that H-induced multiple SC states originate from the remaining spin degrees of freedom., 6 pages, 3 figures, 2 tables

During the AD 68/9 Civil Wars, Galba, Otho, Vitellius and then Vespasian fought for — and gained — control of the Roman Empire. Our textual sources suggest that this was a period of serious and sustained disruption. However, existing analyses of gold coinages produced in AD 68/9 show only a minor reduction in the purity of the gold coinage. Using X-ray fluorescence, we identify a number of heavily debased gold coins issued during the AD 68/9 Civil Wars, and many slightly debased coins issued in their immediate aftermath. We then confirm the interior composition of these coins totally non-destructively using muonic X-ray emission spectroscopy, thus eliminating hypothetical problems of ‘surface enrichment’ or compositional differences between ‘surface’ and ‘core’. Here we show that heavily debased Civil War gold coinages were indeed produced; that copper was used to debase Roman gold coins during this time, c. 185 years earlier than first shown; and that slightly debased gold coins were regularly issued in the years immediately after the Civil Wars. The metallurgical evidence from the gold coinage now allows us to show that the AD 68/9 Civil Wars caused significant and sustained disruption to the Roman economic system. More broadly, we have shown that muonic X-ray emission spectroscopy is a powerful tool for generating important archaeological conclusions from high-value cultural heritage objects that simply cannot be destructively analysed, but need to have their interior compositions sampled.

Parasitic plants that infect crops are devastating to agriculture throughout the world. These parasites develop a unique inducible organ called the haustorium that connects the vascular systems of the parasite and host to establish a flow of water and nutrients. Upon contact with the host, the haustorial epidermal cells at the interface with the host differentiate into specific cells called intrusive cells that grow endophytically toward the host vasculature. Following this, some of the intrusive cells re-differentiate to form a xylem bridge (XB) that connects the vasculatures of the parasite and host. Despite the prominent role of intrusive cells in host infection, the molecular mechanisms mediating parasitism in the intrusive cells remain poorly understood. In this study, we investigated differential gene expression in the intrusive cells of the facultative parasite Phtheirospermum japonicum in the family Orobanchaceae by RNA-sequencing of laser-microdissected haustoria. We then used promoter analyses to identify genes that are specifically induced in intrusive cells, and promoter fusions with genes encoding fluorescent proteins to develop intrusive cell-specific markers. Four of the identified intrusive cell-specific genes encode subtilisin-like serine proteases (SBTs), whose biological functions in parasitic plants are unknown. Expression of SBT inhibitors in intrusive cells inhibited both intrusive cell and XB development and reduced auxin response levels adjacent to the area of XB development. Therefore, we propose that subtilase activity plays an important role in haustorium development in P. japonicum.

Purpose In the CLEOPATRA study of patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer, the Japanese patient subgroup did not demonstrate the improved progression-free survival (PFS) of pertuzumab plus trastuzumab and docetaxel vs. placebo that was seen in the overall population. Therefore, COMACHI was conducted to confirm the efficacy and safety of this treatment regimen in this patient subgroup. Methods This was a phase IV study of pertuzumab plus trastuzumab and docetaxel in Japanese patients with histologically/cytologically confirmed inoperable or recurrent HER2-positive breast cancer. All patients received pertuzumab, trastuzumab, and docetaxel intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary endpoint was investigator-assessed PFS. Secondary endpoints were overall survival (OS), investigator-assessed objective response rate, and duration of response (DoR). Safety was also assessed. Results At final analysis, median investigator-assessed PFS was 22.8 months (95% CI 16.9–37.5). From first dose, OS rate at 1 year was 97.7%; and at 2 and 3 years were 88.5% and 79.1%, respectively. Of the 118 patients with measurable disease at baseline, response rate was 83.9% (95% CI 77.3–90.5) and median investigator-assessed DoR was 26.3 months (95% CI 17.1–not evaluable). Treatment was well tolerated, with no new safety signals detected. Conclusions Our results suggest similar efficacy and safety for pertuzumab plus trastuzumab and docetaxel in Japanese patients compared with the overall population of CLEOPATRA, providing further support for this combination therapy as standard of care for Japanese patients with inoperable or recurrent HER2-positive breast cancer.

The authors present the implementation of two amplifiers in a commercial flexible amorphous Indium Gallium Zinc Oxide (a-IGZO) thin-film transistor (TFT) technology: a Cherry Hooper (CH) amplifier and a 4-stage common source amplifier. The CH amplifier is designed as a pre-amplifier for wireless receivers. It is optimised for a high gain-bandwidth product (GBW). From a supply voltage of V DD = 8 V it provides 19.4 dB gain and has a − 3 dB -bandwidth of 5.3 MHz, while consuming 0.2 mW. It has a GBW of 49.35 MHz, which is more than a factor two better than previously reported a-IGZO TFT amplifiers. The 4-stage common source amplifier is designed as output buffer, has a very wide range of operating conditions and strong robustness against manufacturing tolerances. From a supply voltage of V DD = 8 V it provides 28.9 dB gain, has a − 3 dB -bandwidth of 1.2 MHz, and a GBW product of 33.43 MHz, while consuming 14.2 mW. Both circuits can operate from a supply voltage between 2.5 and 10 V.

Purpose The standard of care in the neoadjuvant setting for human epidermal growth factor receptor 2 (HER2)-positive breast cancer is dual HER2-targeted therapy. However, a need to minimize treatment-related toxicity and improve pathological complete response (pCR) rates, particularly in luminal HER2-positive disease, exists. Methods Neopeaks, a randomized, phase 2 study, compared docetaxel + carboplatin + trastuzumab + pertuzumab (TCbHP; 6 cycles; group A), TCbHP (4 cycles) followed by trastuzumab emtansine + pertuzumab (T-DM1+P; 4 cycles; group B), and T-DM1+P (4 cycles; group C) regimens in HER2‐positive primary breast cancer patients; concurrent hormone therapy with T-DM1+P was administered in case of estrogen receptor positivity (ER+). Based on tumor shrinkage, nonresponders in group C were switched to 5-fluorouracil + epirubicin + cyclophosphamide (FEC; 4 cycles). Primary endpoint was pCR (comprehensive pCR ypN0 [ypT0-TisypN0]). Results Of 236 patients enrolled, 204 were randomized to groups A (n = 51), B (n = 52), and C (n = 101). In group C, 80 (79%) patients continued T-DM1+P following favorable response, whereas 21 (21%) nonresponders switched to FEC. pCR rate was numerically higher with the TCbHP → T-DM1+P regimen (71%) versus the standard TCbHP (57%) and T-DM1+P (57%) regimens. The rate in group C was higher among responders continuing T-DM1+P (63%) versus nonresponders who switched to FEC (38%). pCR rates after initial 4 cycles of T-DM1+P (group C; 57%) and standard TCbHP regimen (57%) were equivalent. pCR rate in patients with ER+ was significantly higher in group B (69%) than groups A (43%) and C (51%), but was comparable in patients with ER− (67–76%). Compared with the T-DM1-based arm, the incidence of adverse events was higher in the taxane-based arms. Conclusion In the neoadjuvant setting, the pCR rate with the standard TCbHP → T-DM1+P regimen was numerically better than the TCbHP regimen alone and significantly better in patients with ER+. Personalization of the T-DM1+P regimen could serve as a reasonable approach to minimize toxicity while maintaining efficacy. Trial registration ID: UMIN-CTR: UMIN000014649.

Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are key signals and mediators of inflammatory bowel disease (IBD). Because these molecules are extremely short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, we have developed a miniaturized device that integrates genetically-engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, we genetically encoded bacteria to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (nanowatt power) integrated into the device convert the light from just 1 μL of bacterial culture into a wireless signal. We demonstrate biosensor monitoring in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3 ingestible form factor capable of supporting wireless communication. The wireless detection of short-lived, disease-associated molecules could support earlier diagnosis of disease than is currently possible, more accurate tracking of disease progression, and more timely communication between patient and their care team supporting remote personalized care.

The purpose of this study is to show land use considering green infrastructure (GI) in a Japanese depopulated rural district. First, we classified six zones of the target area, depending on inundation risk, living environment, and area of each land use, by cluster analysis. As a result, we showed three characteristics of land use. These are the central built-up area with high disaster risk and high land price, the east side area with low disaster risk, and the paddy field area with high disaster risk. Next, we estimated the probability of vacant houses by logistic regression analysis. Based on the results and the six classified zones, we showed the area with high probability of vacant houses and high disaster risk. This area was observed at the central built-up area. Considering future depopulation, such a housing area in the central built-up area needs to shrink.

A small-momentum-width muon beam, so-called ultra-slow muon beam, can be generated by laser ionization of muonium. To realize efficient ultra-slow muon generation, the Lyman-alpha and below 360 nm coherent light are required to resonantly excite the muonium from the ground state to 2p and sequentially ionizes excited muonium to the unbound state. At the J-PARC MLF Ultra-Slow Muon beamline, we have successfully generated Lyman-alpha coherent light exceeding 10 μJ using an all-solid-state laser and high-efficiency vacuum ultraviolet light generation technologies. In this paper, we will describe the intense Lyman-alpha light source.

Ultracold muonium (UCMu) is an important muonium (Mu) source for the generation of ultraslow muon beam for nanotechnological applications and understanding hydrogen dynamics in materials. In order to search for a new solid material for the generation of UCMu in vacuum, we have studied polycrystalline SiC using conventional muon spin rotation and relaxation method at low temperatures (5 K – 300 K). The high relaxation rates of Mu formed deep inside from the surface (full-stop case) and near the rear surface (half-stop case) were observed at low transverse field (TF 1.2 G). The relaxation rates of Mu at different temperatures in full-stop and half-stop cases were found to be the same within error-bars indicating the less possibility of emission of the UCMu from the surface of the SiC. We plan further study in KCl, porous silica, and chevron shaped electron rich microporuos materials.

Muonic atom X-ray Emission Spectroscopy (µ-XES) is a novel technique based on the detection of high-energy X-rays emitted after the interaction of a negative muon beam with matter. Thanks to the multi-elemental range, negligible self-absorption of the x-rays and the possibility of performing depth profile studies, the technique is a very powerful probe for the analysis of cultural heritage artefacts. By tuning the energy of the incident muon beam, indeed, it is possible to investigate the different layers that constitute a sample. In this work, we report preliminary results of the analysis on two fire-gilded surfaces, in which the data analysis is coupled with Monte Carlo-based simulation software. Here, to perform a depth profile characterization, the samples were analysed at different beam energies (or momentum). Each of the resulting x-ray spectra was then analysed and compared with the output of the simulations software and a remarkably good agreement was reached. The results of the work are promising and with this approach, it will be possible to enhance the capability offered by the technique, both in terms of data analysis and data interpretation.

The novel spin-triplet superconductor candidate UTe

Temperature fluctuations in saturated superfluid He II (at 1.9 K) were measured using small thermistors operated by a lock-in amplifier. The experiments were performed in a rectangular channel ( $$13\times 13\times 200~\hbox {mm}$$ ) with a heater set at the bottom. The temperature oscillated periodically, and a pulsive boiling sound appeared. The two become synchronized, and the oscillating frequencies strongly depend on the helium pressure and the heat flux. When the He pressure decreases, the oscillation frequency decreases. A simple model to predict the cyclic period is presented.

Mutant cardiac ryanodine receptor channels (RyR2) are “leaky,” and spontaneous Ca2+ release through these channels causes delayed afterdepolarizations that can deteriorate into ventricular fibrillation (VF). RYR2 is a causative gene of type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT). Some patients carrying RYR2 mutations in CPVT exhibit QT prolongation and are initially diagnosed with long QT syndrome. However, none have been reported to cause drug-induced VF in patients with RYR2 variants. We describe the first case of an elderly woman with drug-induced QT prolongation and VF who carried a novel RYR2variant but no other mutations related to long QT syndrome.

In situ femtosecond x-ray diffraction measurements and ab initio molecular dynamics simulations were performed to study the liquid structure of tantalum shock released from several hundred gigapascals (GPa) on the nanosecond timescale. The results show that the internal negative pressure applied to the liquid tantalum reached $\ensuremath{-}5.6\text{ }(0.8)\text{ }\text{ }\mathrm{GPa}$, suggesting the existence of a liquid-gas mixing state due to cavitation. This is the first direct evidence to prove the classical nucleation theory which predicts that liquids with high surface tension can support GPa regime tensile stress.

A negative muonium ion (${\mathrm{Mu}}^{\ensuremath{-}}$) source using an aluminum foil target (Al target) was developed as a low-energy muon source. ${\mathrm{Mu}}^{\ensuremath{-}}$ ions are produced by irradiating the Al target with a 3-MeV positive muon (${\ensuremath{\mu}}^{+}$) beam and observed using a microchannel plate. An experiment to produce ${\mathrm{Mu}}^{\ensuremath{-}}$ ions was conducted to evaluate the performance of this ${\mathrm{Mu}}^{\ensuremath{-}}$ ion source. The measured event rate of ${\mathrm{Mu}}^{\ensuremath{-}}$ ions was $(1.7\ifmmode\pm\else\textpm\fi{}0.3)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}\text{ }\text{ }{\mathrm{Mu}}^{\ensuremath{-}}/\mathrm{s}$ when the event rate of the incident ${\ensuremath{\mu}}^{+}$ beam was $1.3\ifmmode\times\else\texttimes\fi{}{10}^{6}/\mathrm{s}$. The experiment was conducted at the Muon Science Establishment, D-line in the Materials and Life Science Experimental Facility within the Japan Proton Accelerator Research Complex. The formation probability, defined as the ratio of the ${\mathrm{Mu}}^{\ensuremath{-}}$ ions to the incident muons on the Al target, was $(1.1\ifmmode\pm\else\textpm\fi{}0.2(\mathrm{stat}{)}_{+0.1}^{\ensuremath{-}0.0}(\mathrm{syst}))\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}6}$. This ${\mathrm{Mu}}^{\ensuremath{-}}$ ion source was first adopted in the commissioning of the muon accelerator at the D-line, and the event rate of the accelerated ${\mathrm{Mu}}^{\ensuremath{-}}$ ions was consistent with the expectation. This ${\mathrm{Mu}}^{\ensuremath{-}}$ ion source boosted the development of the muon accelerator, and the practicality of this low-energy muon source obtained using a relatively simple apparatus was demonstrated.

In this work, we present experimental results on the behavior of liquid water at megabar pressure. The experiment was performed using the HIPER (High-Intensity Plasma Experimental Research) laser facility, a uniaxial irradiation chamber of GEKKO XII (GXII) at the Institute of Laser Engineering (ILE), and the PHELIX at GSI (GSI Helmholtz Centre for Heavy Ion Research), a single-beam high-power laser facility, to launch a planar shock into solid multilayered water samples. Equation-of-state data of water (H2O) are obtained in the pressure range 0.50–4.6 Mbar by tuning the laser-drive parameters. The Hugoniot parameters (pressure, density, etc.) and the shock temperature were simultaneously determined by using VISAR and SOP as diagnostic tools and quartz as the standard material for impedance mismatch experiments. Finally, our experimental results are compared with hydrodynamic simulations tested with different equations of state, showing good compatibility with tabulated SESAME tables for water., The authors would like to acknowledge the support of the laser technical team at GEKKO XII (ILE) and PHELIX (GSI). This work received funding from the Euratom Research and Training Program 2014–2018 and 2019-2020 (Grant agreement no. 633053). The involved teams were operated within the framework of the Enabling Research Project ENR-IFE19.CEA-01, Study of Direct Drive and Shock Ignition for IFE: Theory, Simulations, Experiments, Diagnostics Development. JIHT RAS team members were supported by the Ministry of Science and Higher Education of the Russian Federation (State Assignment no. 075-00460-21-00).

Background The proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-I), evolocumab, reduced the risk of cardiovascular event in patients with peripheral artery disease in FOURIER trial. However, the effects of evolocumab on favorable limb outcomes in patients with critical limb ischemia (CLI) is still unclear. Purpose The aim of this study was to evaluate the impacts of evolocumab on favorable limb outcomes and lipid profile in patients with CLI. Methods This was a single center, prospective observational study. A total of 39 patients with CLI were enrolled between November 2016 to May 2019. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated group: E group (mean 69.4±11.7 years, n=14) and evolocumab non-treated group: Non-E group (mean 74.0±8.8 years, n=25). Baseline characteristics were assessed at admission. Lipid profile was evaluated at admission, 1, 3, 6, 12 and 18 months. The primary outcome was defined 18-month amputation-free survival (AFS). The secondary outcomes were defined 18-month overall survival (OS) and wound-free limb salvage. Mean follow-up period was 18±11 months. Results The patients in E group had greater reduction in levels of LDL cholesterol and non-HDL cholesterol than those in Non-E group over time. The reduction in MDA-LDL level was maintained at 1, 3, 6, 12 months, respectively. The 18-month AFS rate in the E-group was significantly higher than those in the Non-E group (log-rank p=0.02). The patients receiving evolocumab had a lower hazard regarding AFS (hazard ratio, 0.12; 95% confidence interval, 0.02–0.94; P=0.043) and a higher proportion of wound-free limb salvage at 12 months (E group [92%] vs Non-E group [57%], P=0.034) and 18 months (92% vs 52%, P=0.03). Otherwise, evolocumab administration was not associated with 18-month OS (log-rank p=0.053). Conclusions Evolocumab administration may be associated with the favorable outcome of 18-month AFS in the patients with CLI. Additionally, long-term administration of evolocumab over 12 months may improve wound-free limb salvage. Effects of evolocumab on limb outcomes Funding Acknowledgement Type of funding source: None