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Electron systems with strong geometrical frustrations have flat bands, and their unusual band dispersions are expected to induce a wide variety of physical properties. However, for the emergence of such properties, the Fermi level must be pinned within the flat band. In this study, we performed first-principles calculations on pyrochlore oxide Pb$$_2$$ 2 Sb$$_2$$ 2 O$$_7$$ 7 and theoretically clarified that the self-doping mechanism induces pinning of the Fermi level in the flat band in this system. Therefore, a very high density of states is realized at the Fermi level, and the ferromagnetic state transforms into the ground state via a flat band mechanism, although the system does not contain any magnetic elements. This compound has the potential to serve as a new platform for projecting the properties of flat band systems in the real world.

In order to prepare microcapsules (MC) using polyvinylacetal diethyl-aminoacetate (AEA) gel, we have studied both the unique properties of AEA gel, in which cold-water solution forms a hard gel with exclusion of water at high temperature, and the microencapsulation technique for clarithromycin (CAM), which has an unpleasant taste (1, 2). In our previous paper (3), we described a new uniform-sized microencapsulation machine with a vibration nozzle with 536 holes 100µ in diameter designed for precise regulation of dissolution of CAM from MC.In order to evaluate the MC thus obtained, we prepared syrups (without water) by adding sweetening agents to MC, and conducted a dissolution test at various pHs using the method described in the Japanese Pharmacopoeia (12th edition), a test for bitter taste and a test to determine bioavailability (BA) in human subjects. At pHs below 4.0,100% of CAM in MC was dissolved from the syrup within 5min. However, there was little dissolution of CAM from syrup at pH6.8. The results of the test for bitter taste showed that the syrup preparations, which were administered to 12 male and female volunteers with 20ml water, masked bitter taste completely during the 60min period following administration of the syrup. The mean area under the serum concentration-time curve (AUCo-24) and the maximum serum concentration (Cmax) for administration of syrup preparations to 6 male volunteers were 5.66 ± 0.73µg·hr/ml and 0.66 ± 0.13µg/ml, respectively. Blood concentration was maintained at a level above the minimum inhibitory concentration for gram-positive bacteria for a period of about 14hr after administration, demonstrating the usefulness of the syrup preparation.

The anterior pituitary gland regulates growth, metabolism, and reproduction by secreting hormones. Folliculo-stellate (FS) cells are non-endocrine cells located among hormone-producing cells in the anterior pituitary glands. They form follicular lumens, which are sealed by tight junctions (TJs). Although FS cells are hypothesized to contribute to fine-tuning of endocrine cells, little is known about the exact roles of FS cells. Here, we investigated the molecular composition of TJs in FS cells. We demonstrated that occludin is a good marker for TJs in the pituitary gland and examined the structure of the lumens surrounded by FS cells. We also found that claudin-9 is a major component of TJs in the FS cells. In immunoelectron microscopy, claudin-9 was specifically localized at TJs of the FS cells. The expression of claudin-9 was gradually increased in the pituitary gland after birth, suggesting that claudin-9 is developmentally regulated and performs some specific functions on the paracellular barrier of follicles in the pituitary gland. Furthermore, we found that angulin-1, angulin-2, and tricellulin are localized at the tricellular contacts of the FS cells. Our findings provide a first comprehensive molecular profile of TJs in the FS cells, and may lead us towards unveiling the FS cell functions.

Aims This study aimed to investigate the effect of Bacillus subtilis var. natto on the susceptibility of the model host, Caenorhabditis elegans, to bacterial infection. Methods and results Caenorhabditis elegans worms were fed with a standard food consisting of Escherichia coli OP50 strain (control) or B. subtilis (natto) during their larval stage. The worms were then infected with pathogenic bacteria. We analyzed their survival time and RNA sequencing-based transcriptome. Upon infection with Staphylococcus aureus and Enterococcus faecalis, the survival time of B. subtilis (natto)-fed worms was longer than that of the control. Transcriptome analyses showed upregulation of genes associated with innate immunity and defense response to gram-positive bacteria in B. subtilis (natto)-fed worms. Conclusions Bacillus subtilis (natto) conferred an increased resistance of C. elegans to gram-positive bacteria. Our findings provided insights into the molecular mechanisms underlying B. subtilis (natto)-regulated host immunity and emphasized its probiotic properties for preventing and alleviating infections caused by gram-positive bacteria. Significance and impact of the study To the best of our knowledge, this is the first study to show that B. subtilis (natto) confers specific resistance against gram-positive bacteria.

Tight junctions (TJs) are composed of a claudin-based anastomosing network of TJ strands at which plasma membranes of adjacent epithelial cells are closely attached to regulate the paracellular permeability. Although the TJ proteins occludin and tricellulin have been known to be incorporated in the TJ strand network, their molecular functions remain unknown. Here, we established tricellulin/occludin-double knockout (dKO) MDCK II cells using a genome editing technique and evaluated the structure and barrier function of these cells. In freeze-fracture replica electron microscopy, the TJ strands of tricellulin/occludin-dKO cells had fewer branches and were less anastomosed compared with the controls. The paracellular permeability of ions and small tracers was increased in the dKO cells. A single KO of tricellulin or occludin had limited effects on the morphology and permeability of TJs. Mathematical simulation using a simplified TJ strand network model predicted that reduced cross-links in TJ strands lead to increased permeability of ions and small macromolecules. Furthermore, overexpression of occludin increased the complexity of TJ strand network and strengthened barrier function. Taken together, our data suggest that tricellulin and occludin mediate the formation and/or stabilization of TJ-strand branching points and contribute to the maintenance of epithelial barrier integrity.

TJs maintain the epithelial barrier by regulating paracellular permeability. Since TJs are under dynamically fluctuating intercellular tension, cells must continuously survey and repair any damage. However, the underlying mechanisms allowing cells to sense TJ damage and repair the barrier are not yet fully understood. Here, we showed that proteinases play an important role in the maintenance of the epithelial barrier. At TJ break sites, EpCAM–claudin-7 complexes on the basolateral membrane become accessible to apical membrane-anchored serine proteinases (MASPs) and the MASPs cleave EpCAM. Biochemical data and imaging analysis suggest that claudin-7 released from EpCAM contributes to the rapid repair of damaged TJs. Knockout (KO) of MASPs drastically reduced barrier function and live-imaging of TJ permeability showed that MASPs-KO cells exhibited increased size, duration, and frequency of leaks. Together, our results reveal a novel mechanism of TJ maintenance through the localized proteolysis of EpCAM at TJ leaks, and provide a better understanding of the dynamic regulation of epithelial permeability.

Background Insulin resistance in adipose tissue attenuates the suppression of lipolysis, leading to increased free fatty acid (FFA) release. The excess FFA may be involved in the development of type 2 diabetes. Purpose In this study, we investigated the association of adipose tissue insulin resistance and serum free fatty acid levels with the incidence of type 2 diabetes. Methods This is an observational study involving 6800 participants (3451 women, mean age 69.2 years) without diabetes who underwent 75-g oral glucose tolerance test (OGTT) at baseline. The participants were divided into the obesity and nonobesity groups on the basis of body mass index of ≥25 and Results Over a mean 5.3-year follow-up period, 485 participants developed type 2 diabetes. Multivariate logistic regression analyses showed that high adipo-IR was a significant predicator for incident type 2 diabetes in the obesity group, but not in nonobesity group. AUCFFA, HOMA-IR, and Matsuda index were significantly associated with incident type 2 diabetes in both the two groups (Table). Conclusion Serum FFA levels after glucose loading predict the incidence of type 2 diabetes. Adipose tissue insulin resistance was associated with the risk of type 2 diabetes in individuals with obesity, but not in individuals without obesity. Funding Acknowledgement Type of funding sources: None.

Background Diameter, intima–media thickness (IMT), and flow parameters, including resistance index (RI) and pulsatility index (PI), in the common carotid artery (CCA) are markers of arterial remodeling, atherosclerosis, and vascular resistance, respectively. These CCA parameters have usually been evaluated as markers of target organ damage. Little is known about whether these parameters predict a new onset of hypertension. Purpose In this study, we investigated the association of CCA parameters including IMT, diameter, RI, and PI with the incidence of hypertension. Methods This is an observational study involving 1249 participants (656 women, mean age 69.6 years) without hypertension, who underwent carotid artery ultrasonography at baseline. The participants were divided into elderly group (defined as age ≥70 years) and a middle-aged group. We defined obesity as BMI ≥25 kg/m2. CCA diameter was defined as the distance between the adventitia–media interface on the near wall and the media–adventitia interface on the far wall. IMT was defined as the distance between the lumen–intima and media–adventitia interfaces. RI was calculated as [peak systolic velocity (PSV)- end-diastolic velocity (EDV)]/PSV. PI was calculated as (PSV-EDV)/Vmean. Larger CCA diameter, increased IMT, high RI, and high PI were determined based on the optimal cutoff values from ROC curve analysis. Results Over a mean 5.1-year follow-up period, 524 participants developed hypertension. Multivariate logistic regression analyses showed that larger CCA diameter and increased IMT were significant predicators for incident hypertension in elderly group, but not in middle-aged group. High RI, and high PI were significant predicators for incident hypertension in both the two groups. CCA diameter, IMT, and RI predicted the incidence of hypertension only in nonobesity group, whereas PI predicted it in both obesity and nonobesity groups (Table). Conclusion CCA parameters assessed by ultrasonography are useful markers to estimate the risk of hypertension. In particular, PI is a better predictor for the incidence of hypertension. Funding Acknowledgement Type of funding sources: None.

Introduction Benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE) are common disorders in aging men and cause lower urinary tract symptoms. Hypertension induces atherosclerosis in the blood vessels of the lower urinary tract, subsequently following by the development of BPH and BPE. Clinical study demonstrated that anti-hypertensive drug angiotensin II type 1 receptor blocker (ARB) treatment improved storage and voiding scores in male patients with hypertension, whereas other antihypertensive drugs were not effective. ARB could improve prostatic hyperplasia independent of reducing blood pressure. Spontaneously hypertensive rats (SHRs) are widely used as genetically hypertensive model. SHRs also demonstrate decreased prostatic blood flow and develop glandular epithelial hyperplasia and morphological abnormalities in the ventral prostate. Objective We examined the effects of an ARB, losartan on glandular epithelial prostatic hyperplasia in SHRs. Methods Thirty-six-weeks old male SHRs were orally treated with losartan (3 or 10 mg/kg/day) or vehicle once daily for 18 weeks. Wistar Kyoto rats (WKYs) were treated with vehicle were used as controls (n = 8). After the oral treatment, effects of losartan were evaluated by measuring prostate weight, blood pressure, and prostatic blood flow. The tissue levels of malondialdehyde (oxidative stress marker; MDA), interleukin-6 (inflammatory cytokine; IL-6), and basic fibroblast growth factor (bFGF) levels in ventral prostate were measured by colorimetric assay and ELISA assay. Histological analysis for the ventral prostate was performed by hematoxylin and eosin (HE) staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The glandular epithelial area was determined by HE staining. TUNEL assay was performed to quantify the degree of apoptosis. The statistical differences were determined using one-way analysis of variance followed by the Tukey-Kramer test. Histological data were analyzed using the nonparametric Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni's correction for multiple comparison. Results Body weight did not significantly differ among the groups. The vehicle treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow compared to the vehicle treated WKYs. Treatment with losartan significantly decreased PBR and improved prostatic blood flow and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs. Conclusion Chronic losartan treatment could improve glandular epithelial prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might improve not only hypertension but also prostatic hyperplasia in humans. Disclosure Work supported by industry: no.

In this paper we introduce our method to explore new superconductors: bulk-combinatorial method. Using this method, we have succeeded in finding many new superconductors so far. We also show that the problems that arise when identifying new superconducting phases in this way are related to the famous mathematical puzzle, the so-called “1000 poisoned wine bottles”, under some assumptions.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Introduction Hydrogen sulfide (H2S) is the third endogenous gasotransmitter besides carbon monoxide and nitric oxide, and has a wide range of physiological functions such as neuromodulation, vasorelaxation and cytoprotection. Although in human prostate cancer cells, NaHS (a H2S donor) treatment was reported to inhibit proliferation and to elevate secretory function, physiological functions of H2S in the prostate tissue had not been investigated yet. Endogenous H2S is biosynthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). In addition, 3-mercaptopyruvate sulfurtransferase (MPST) synthesizes H2S from 3-mercaptopyruvate (3MP), which is produced from L-cysteine by cysteine aminotransferase (CAT) (CAT/MPST pathway). Recently, a new pathway for endogenous H2S biosynthesis is reported; D-cysteine is metabolized by D-amino acid oxidase (DAO) to 3MP, which is a substrate for MPST to synthesize H2S. Objective We investigated (1) tissue distribution of CBS, CSE, MPST, CAT and DAO, (2) endogenous H2S levels, and (3) effects of NaHS on contractility in the rat prostate. Methods Dorsolateral and ventral prostate (PR-D and PR-V), liver and cerebellum (L and C) were prepared from male Wistar rats (300-400 g) sacrificed with an overdose of sodium pentobarbital (80 mg/kg, ip). (1) Tissue distributions of 5 enzymes were investigated by real-time PCR, western blot and immunohistochemistry. L and C were used for positive controls. (2) H2S contents in the prostate tissues were measured by methylene blue method. (3) By using 1 x 5 mm strips of the prostate tissues, effects of NaHS (1 x 10-9 to 3 x 10-4 M) were evaluated on pre-contracted prostate strips by noradrenaline (10-5 M). Prostate strips were pretreated with propranolol (10-6 M) 30 min before the pre-contraction. Results (1) CBS, MPST and CAT were detected in the prostate. Expression levels of CBS in the PR-D were lower than those in the PR-V, and the levels of MPST in the PR-D were higher than those in the PR-V. In expression levels of CAT, there was no significant difference between two prostate tissues. On the other hand, CSE or DAO was not detected in these tissues. Immunoreactvities of these enzymes were mainly detected in the prostate glandular epithelium. (2) H2S was detected in the prostate tissues. (3) NaHS dose-dependently induced relaxation of pre-contracted PR-D and PR-V strips. There were no significant differences of the EC50 values or relaxation rate against the pre-contractions between two prostate tissues. Conclusion H2S synthesized by CBS- and CAT/MPST-mediated pathways has a role as an endogenous relaxation factor in the rat prostate. Therefore, endogenous H2S might open new avenues of therapeutic interventions for benign prostatic hyperplasia. Disclosure Work supported by industry: no.

Introduction The average age of paternity is rising in developed world. Hypertension is the most common chronic disease among adult males, affecting male fertility. Aging is an important risk factor for the development of atherosclerosis and hypertension. However, involvements of aging on hypertension related testicular injury are not fully clarified. Objective In this study, we investigated the involvements of aging on testes in spontaneously hypertensive rats (SHRs). Methods Male SHRs and Wistar Kyoto rats (WKYs; normotensive control) at the age of 36, 54 or 72 weeks (wk) were used (n=6, each age). At each age, body weight, testicular weight and blood pressure were measured. Serum testosterone and testicular tissue levels of malondialdehyde (MDA: a maker of lipid peroxide) were also measured by colorimetric assay and ELISA assay. Morphological changes in the testis were evaluated by hematoxylin and eosin staining. TUNEL staining was performed to quantify the apoptosis in testis. Results SHRs at 36, 54 o 72 wk showed a significant increase in mean blood pressure compared to WKYs at each age. SHRs at 54 or 72 but not 36 wk demonstrated a significant decrease in body weight and increase in testicular weight/body weight ratio compared to WKYs at each age. Testicular tissue levels of MDA in SHRs at all ages were significantly higher than those in WKYs at all ages. Serum testosterone in SHRs at 54 or 72 but not 36 wk was lower than that in WKYs at each age. SHRs at 54 or 72 but not 36 wk demonstrated obvious morphological changes such as thickening of blood vessel wall in testis, and seminiferous tubules with degeneration compared to the WKYs at each age. Number of TUNEL positive cells in testicular seminiferous tubules in SHRs at 36 wk was significantly greater than those in WKYs at 36 wk. While number of TUNEL positive cells in testicular seminiferous tubules in SHRs at 72 wk was significantly lower than those in WKYs at 72 wk. Conclusion Aged SHRs showed significant increases in oxidative damage and vacuolation in testes, and decrease in serum testosterone compared to age matched WKYs. Aging could exacerbate hypertension related testicular injury in rats. Disclosure Work supported by industry: no.

An isotropic tight-binding model with the nearest-neighbour hopping on a pyrochlore lattice gives a rich variety of physical properties due to the emergence of the flat-band. Moreover, by introducing spin-orbit coupling into this model, the topological properties of the system changes significantly. This model is well applicable to some pyrochlore oxides called s1/s2 pyrochlores. In this paper we apply this model to an s2 pyrochlore oxide Pb2Ta2O7 and found a characteristic quadratic touching of the quasi-flat band and dispersive band. Furthermore, when a ferromagnetic order appears due to this quasi-flat band, a pair of Weyl points appears in that direction.

Background As the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins at various positions along the nephron and in the outer and inner medulla. Proliferating stem cells expressing the nuclear transcription factor Pax2 give rise to renal epithelial cells. Pax2 expression ends once the epithelial cells differentiate into mature proximal and distal tubules, whereas expression of the related Pax8 protein continues. The collecting tubules and renal medulla are derived from Pax2-positive ureteric bud epithelia that continue to express Pax2 and Pax8 in adult kidneys. Despite the crucial role of Pax2 in renal development, functions for Pax2 or Pax8 in adult renal epithelia have not been established. Methods To examine the roles of Pax2 and Pax8 in the adult mouse kidney, we deleted either Pax2, Pax8, or both genes in adult mice and examined the resulting phenotypes and changes in gene expression patterns. We also explored the mechanism of Pax8-mediated activation of potential target genes in inner medullary collecting duct cells. Results Mice with induced deletions of both Pax2 and Pax8 exhibit severe polyuria that can be attributed to significant changes in the expression of solute carriers, such as the urea transporters encoded by Slc14a2, as well as aquaporins within the inner and outer medulla. Furthermore, Pax8 expression is induced by high-salt levels in collecting duct cells and activates the Slc14a2 gene by recruiting a histone methyltransferase complex to the promoter. Conclusions These data reveal novel functions for Pax proteins in adult renal epithelia that are essential for retaining water and concentrating urine.

High precision measurements of the ground state hyperfine structure (HFS) of muonium is a stringent tool for testing bound-state quantum electrodynamics (QED) theory, determining fundamental constants of the muon magnetic moment and mass, and searches for new physics. Muonium is the most suitable system to test QED because both theoretical and experimental values can be precisely determined. Previous measurements were performed decades ago at LAMPF with uncertainties mostly dominated by statistical errors. At the J-PARC Muon Science Facility (MUSE), the MuSEUM collaboration is planning complementary measurements of muonium HFS both at zero and high magnetic field. The new high-intensity muon beam that will soon be available at H-Line will provide an opportunity to improve the precision of these measurements by one order of magnitude. An overview of the different aspects of these new muonium HFS measurements, the current status of the preparation for high-field measurements, and the latest results at zero field are presented.

Background Renal interstitial fibrosis results from activation and proliferation of fibroblasts to myofibroblasts, secretion and accumulation of extracellular matrix, and displacement of normal renal tubules. In contrast to chronic renal disease, acute injury may be repaired, a process that includes a decrease in the number of myofibroblasts in the interstitium and degradation of the accumulated extracellular matrix, leaving little evidence of prior injury. Methods To investigate whether activated fibroblasts demonstrate changes in gene expression that correspond with regression after acute injury but are not observed in chronic models of fibrosis, we used microarrays to analyze gene expression patterns among fibroblast populations at different stages of injury or repair. We then mined the data for signaling pathways in fibroblasts corresponding to the acute proliferative, regression, and chronic phases of renal injury. Results We identified multiple gene clusters with changes that correlate with the three phases of renal injury, including changes in levels of receptors for the antifibrotic factor PGE2. In adult renal fibroblast cultures, PGE2 was able to upregulate many genes that are suppressed by the profibrotic cytokine TGF- β , whereas many PGE2-downregulated genes were activated by TGF- β . High levels of TGF- β suppressed expression of a subset of PG receptors in fibroblast cultures, making these cells resistant to any effects of PGE2. Conclusions Inherent gene expression changes in activated fibroblasts accompany the transition from AKI to repair and regeneration. In chronic models, however, activated fibroblasts are resistant to the antifibrotic effects of PGE2 due to suppression of a subset of PGE receptors.

The next generation of accelerators, from the compact to the large infrastructure dedicated to high energy physics, is highly demanding in terms of accelerating gradients. To upgrade performances of X band linacs at 11.424 GHz many resources are devoted to achieve high accelerating gradients and at the same time to obtain a high reliability. In the framework of a three-year funded project by the Vth Committee of the INFN to the Laboratori Nazionali di Frascati (LNF) and to the Laboratori Nazionali di Legnaro (LNL). Within a broad international collaboration the LNF has been involved in the design, manufacture and test of compact high power standing wave (SW) sections operating at high frequency while LNL is actively involved in the development of new materials and multilayers using PVD (Physical Vapor Deposition) methods. We will report about the status of the accelerating device and of the different ongoing R&D activities and characterization procedures such as tests of different materials and metallic coatings.

Producing hair cells of the inner ear is the major goal of ongoing research that combines advances in developmental and stem cell biology. The recent advent of an inner ear organoid protocol-resulting in three-dimensional stem cell-derived tissues resembling vestibular sensory epithelia-has sparked interest in applications such as regeneration, drug discovery, and disease modeling. In this study, we adapted this protocol for a novel mouse embryonic stem cell line with a fluorescent reporter for Pax2 expression. We used Pax2EGFP/+ organoid formation to model otic induction, the pivotal developmental event when preplacodal tissue adopts otic fate. We found upregulation of Pax2 and activation of ERK downstream of fibroblast growth factor signaling in organoid formation as in embryonic inner ear development. Pax2 expression was evident from the EGFP reporter beginning at the vesicle formation stage and persisting through generation of the sensory epithelium. The native ventralizing signal sonic hedgehog was largely absent from the cell aggregates as otic vesicles began to form, confirming the dorsal vestibular organoid fate. Nonetheless, cochlear- or vestibular-like neurons appeared to delaminate from the derived otic vesicles and formed synaptic contacts with hair cells in the organoids. Cell lines with transcriptional reporters such as Pax2EGFP/+ facilitate direct evaluation of morphological changes during organoid production, a major asset when establishing and validating the culture protocol.

Excitation-energy spectra of $^{11}\mathrm{C}$ nuclei near the ${\ensuremath{\eta}}^{\ensuremath{'}}$-meson production threshold have been measured by missing-mass spectroscopy using the $^{12}\mathrm{C}(p,d)$ reaction. A carbon target has been irradiated with a 2.5 GeV proton beam supplied by the synchrotron SIS-18 at GSI to produce ${\ensuremath{\eta}}^{\ensuremath{'}}$-meson bound states in $^{11}\mathrm{C}$ nuclei. Deuterons emitted at ${0}^{\ensuremath{\circ}}$ in the reaction have been momentum analyzed by the fragment separator (FRS), used as a high-resolution spectrometer. No distinct structure due to the formation of ${\ensuremath{\eta}}^{\ensuremath{'}}$-mesic states is observed although a high statistical sensitivity is achieved in the experimental spectra. Upper limits on the formation cross sections of ${\ensuremath{\eta}}^{\ensuremath{'}}$-mesic states are determined, and thereby a constraint imposed on the ${\ensuremath{\eta}}^{\ensuremath{'}}$-nucleus interaction is discussed.

Laser-induced melting in liquids (LIML) was applied to prepare spherical submicron-sized particles of gold (AuSMPs) from gold nanoparticles (AuNPs) stabilized using NaCl. Because undesirable byproducts, which might be generated when organic reagents such as citrate are used as the stabilizing reagent, are not generated from NaCl by laser irradiation, AuSMPs fabricated from AuNPs stabilized by NaCl will be low toxic. The AuSMPs were obtained by laser irradiation of the source AuNPs in NaCl solutions stabilized by NaCl at the proper concentration. Similar to the preparation of AuSMPs from AuNPs stabilized by citrate, the agglomeration of the source AuNPs, which is necessary to obtain AuSMPs, was controlled both by the NaCl concentration and by laser irradiation. However, the formation process and the laser-fluence dependence of the particle size of AuSMPs differed for various NaCl solutions and citrate solutions.

Epidemiological findings indicate that acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD), although the molecular mechanism remains unclear. Genetic fate mapping demonstrated that nephrons, functional units in the kidney, are repaired by surviving nephrons after AKI. However, the cell population that repairs damaged nephrons and their repair capacity limitations remain controversial. To answer these questions, we generated a new transgenic mouse strain in which mature proximal tubules, the segment predominantly damaged during AKI, could be genetically labelled at desired time points. Using this strain, massive proliferation of mature proximal tubules is observed during repair, with no dilution of the genetic label after the repair process, demonstrating that proximal tubules are repaired mainly by their own proliferation. Furthermore, acute tubular injury caused significant shortening of proximal tubules associated with interstitial fibrosis, suggesting that proximal tubules have a limited capacity to repair. Understanding the mechanism of this limitation might clarify the mechanism of the AKI-to-CKD continuum.

MuSEUM is an international collaboration aiming at a new precise measurement of the muonium hyperfine structure at J-PARC (Japan Proton Accelerator Research Complex). Utilizing its intense pulsed muon beam, we expect a ten-fold improvement for both measurements at high magnetic field and zero magnetic field. We have developed a sophisticated monitoring system, including a beam profile monitor to measure the 3D distribution of muonium atoms to suppress the systematic uncertainty.

The aim of the ASACUSA-CUSP experiment is to form a beam of antihydrogen atoms for in-flight precision spectroscopic measurements. This is performed by trapping and mixing antiprotons and positrons in a common nested-well potential, which is sitting in a double-cusp magnetic field with minimum-B field configuration. We have built a tracking detector, the ASACUSA Micromegas Tracker (AMT) [1], to monitor and resolve annihilations on-axis from annihilations on the trapping electrode walls of the experiment, which latter is a general signature of antihydrogen formation. Data taken during the summer of 2015 is presented in order to demonstrate the first performance of the AMT detector. In particular, data from on-axis trapping and slow extraction of antiprotons is used to illustrate the vertex reconstruction capability of the detector., JPS Conference Proceedings, 18, Proceedings of the 12th International Conference on Low Energy Antiproton Physics (LEAP2016), ISBN:978-4-89027-125-2

Background There are significant differences in the proportion of home death of cancer patients, 8.3% in Japan and 27.4% in the United Kingdom. However 63% of Japanese population hope home palliative care in their last 6 months. The palliative care unit (PCU) at the National Cancer Center Hospital East changed the administrative policy to amend patients unmet needs and strengthen the transition to palliative home care. Previous studies about the discharge from hospice indicated the factor of old age, female and poor performance status (PS). This study aimed to identify the factors tended to transfer to palliative home care in Japan. Methods We reviewed the medical records of 333 consecutive cancer patients admitted to our PCU during period from October 2010 until September 2011. Patients transferred to other hospitals were excluded in this study. We identified variables associated with the discharged group and the deceased at PCU group, using the univariate and multivariate analyses. Results There were 311 patients (Pts) during periods, 68 Pts (21.9%) discharged to palliative home care and 243 Pts (78.1%) deceased in our PCU. Characteristics of discharged group (68 Pts) were below: over 65 year-old (32%), female (53.0%), PS 4 (7.4%), a relatively good amount of oral intake in first hospital day (76.1%), morphine use over 120mg/day at admission (23.5%), living alone (9.7%), married (74.6%), primary caregiver was partner (67.7%). Univariate and multivariate analysis identified: admission from their own home (OR 4.41; 95%CI 2.08-9.75), a good PS of > 4 (OR 6.21; 95%CI 2.11-23.18), a heart rate Conclusion Our study indicated the factors tended to transfer to palliative home care from PCU in Japan, however this study had some limitations. A prospective study is required to validate these factors. Disclosure All authors have declared no conflicts of interest.

Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the η^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18 at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The momenta of deuterons emitted at 0° are precisely measured with the fragment separator (FRS) operated as a spectrometer. In contrast to theoretical predictions on the possible existence of deeply bound η^{'}-mesic states in carbon nuclei, no distinct structures are observed associated with the formation of bound states. The spectra are analyzed to set stringent constraints on the formation cross section and on the hitherto barely known η^{'}-nucleus interaction.

The aim of the ASACUSA-CUSP experiment at CERN is to produce a cold, polarised antihydrogen beam and perform a high precision measurement of the ground-state hyperfine transition frequency of the antihydrogen atom and compare it with that of the hydrogen atom using the same spectroscopic beam line. Towards this goal a significant step was successfully accomplished: synthesised antihydrogen atoms have been produced in a CUSP magnetic configuration and detected at the end of our spectrometer beam line in 2012 [1]. During a long shut down at CERN the ASACUSA-CUSP experiment had been renewed by introducing a new double-CUSP magnetic configuration and a new semi-cylindrical tracking detector (AMT) [2], and by improving the transport feature of low energy antiproton beams. The new tracking detector monitors the antihydrogen synthesis during the mixing cycle of antiprotons and positrons. In this work the latest results and improvements of the antihydrogen synthesis will be presented including highlights from the last beam time.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

We describe the development of neurological signs in four juvenile black-and-white ruffed lemurs (Varecia variegate), housed at a petting zoo in Japan. The clinical course was severe, with three lemurs dying within 1 day of the appearance of clinical signs. The other lemur was treated and survived. Pathological analyses demonstrated meningitis and the presence of gram-negative bacilli in the cerebrum, cerebellum, palatine tonsil and liver. Klebsiella pneumoniae was isolated from the brain of all of the dead lemurs. Multilocus sequence typing analysis showed that all the isolates were sequence type 86 (ST86). To our knowledge, this is the first determination of K. pneumoniae infection in ruffed lemurs of this genus. K. pneumoniae infection may represent a risk to lemurs and people who come into contact with infected animals.

Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the η^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18 at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The momenta of deuterons emitted at 0° are precisely measured with the fragment separator (FRS) operated as a spectrometer. In contrast to theoretical predictions on the possible existence of deeply bound η^{'}-mesic states in carbon nuclei, no distinct structures are observed associated with the formation of bound states. The spectra are analyzed to set stringent constraints on the formation cross section and on the hitherto barely known η^{'}-nucleus interaction.