Prospects for discovering supersymmetric long-lived particles with MoEDAL.

We present a study on the possibility of searching for long-lived supersymmetric partners with the MoEDAL experiment at the LHC. MoEDAL is sensitive to highly ionising objects such as magnetic monopoles or massive (meta)stable electrically charged particles. We focus on prospects of directly detecting long-lived sleptons in a phenomenologically realistic model which involves an intermediate neutral long-lived particle in the decay chain. This scenario is not yet excluded by the current data from ATLAS or CMS, and is compatible with astrophysical constraints. Using Monte Carlo simulation, we compare the sensitivities of MoEDAL versus ATLAS in scenarios where MoEDAL could provide discovery reach complementary to ATLAS and CMS, thanks to looser selection criteria combined with the virtual absence of background. It is also interesting to point out that, in such scenarios, in which charged staus are the main long-lived candidates, the relevant mass range for MoEDAL is compatible with a potential role of Supersymmetry in providing an explanation for the anomalous events observed by the ANITA detector.

An ectomesenchymal chondromyxoid tumour on the lateral border of the tongue.

Ectomesenchymal chondromyxoid tumour (ECT) is an extremely rare intraoral mesenchymal tumour. Most of these tumours have been identified on the anterior aspect of the dorsal surface of the tongue. ECT is difficult to diagnose because of its rarity. We report a case of ECT arising on the lateral border of the tongue in a 67-year-old woman. The tumour, measuring 20 × 10 mm in size, was surgically removed. Histopathologically, the tumour was composed of small polygonal cells arranged in sheets, with a myxoid or hyalinized stroma. The tumour boundary was clear; however, the tumour showed a multinodular structure expanding along the tongue surface without obvious capsule. Careful examination revealed the tumour nodule to be spreading in a skip lesion-like fashion away from the main part of the tumour in the striated muscle layer. Although there was no evidence of recurrence at 18 months after the surgery, our observations suggest that surgery for ECT resection with a safety margin is more appropriate than enucleation.

Paternal height has an impact on birth weight of their offspring in a Japanese population: the Japan Environment and Children's Study.

This study examines the relationship between paternal height or body mass index (BMI) and birth weight of their offspring in a Japanese general population. The sample included 33,448 pregnant Japanese women and used fixed data, including maternal, paternal and infant characteristics, from the Japan Environment and Children's Study (JECS), an ongoing nationwide birth cohort study. Relationships between paternal height or BMI and infant birth weight [i.e., small for gestational age (SGA) and large for gestational age (LGA)] were examined using a multinomial logistic regression model. Since fetal programming may be a sex-specific process, male and female infants were analyzed separately. Multivariate analysis showed that the higher the paternal height, the higher the odds of LGA and the lower the odds of SGA in both male and female infants. The effects of paternal BMI on the odds of both SGA and LGA in male infants were similar to those of paternal height; however, paternal height had a stronger impact than BMI on the odds of male LGA. In addition, paternal BMI showed no association with the odds of SGA and only a weak association with the odds of LGA in female infants. This cohort study showed that paternal height was associated with birth weight of their offspring and had stronger effects than paternal BMI, suggesting that the impact of paternal height on infant birth weight could be explained by genetic factors. The sex-dependent effect of paternal BMI on infant birth weight may be due to epigenetic effects.

Cytohistology of morule in cribriform-morular variant of papillary thyroid carcinoma.

INTRODUCTION: Cribriform-morular variant (CMV) is a rare variant of papillary thyroid carcinoma. It frequently occurs in association with familial adenomatous polyposis (FAP), although some cases are sporadic. Herein, we report a case of CMV and analyse morule cytohistology. CASE REPORT: The patient was a 47-year-old woman with no familial history of FAP. A 3.0-cm unifocal mass was identified in the left thyroidal lobe. Fine-needle aspiration cytology revealed papillary clusters of atypical cells with nuclear grooves, which was suspected to be conventional papillary thyroid carcinoma. Histologically, the tumour comprised a papillary and cribriform growth of atypical cells with cytoplasmic accumulation and nuclear translocation of b-catenin. In addition, frequent morule formation was identified. DISCUSSION: In this case, we performed morule analysis through correlative light and electron microscopy (CLEM), and revealed its ultrastructure. Although CMV is a rare form of thyroid carcinoma, it should be considered along with its distinct clinicopathological characteristics.

Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Likelihood analysis of the pMSSM11 in light of LHC 13-TeV data.

We use MasterCode to perform a frequentist analysis of the constraints on a phenomenological MSSM model with 11 parameters, the pMSSM11, including constraints from ∼ 36 /fb of LHC data at 13 TeV and PICO, XENON1T and PandaX-II searches for dark matter scattering, as well as previous accelerator and astrophysical measurements, presenting fits both with and without the ( g - 2 ) µ constraint. The pMSSM11 is specified by the following parameters: 3 gaugino masses M 1 , 2 , 3 , a common mass for the first-and second-generation squarks m q ~ and a distinct third-generation squark mass m q ~ 3 , a common mass for the first-and second-generation sleptons m ℓ ~ and a distinct third-generation slepton mass m τ ~ , a common trilinear mixing parameter A, the Higgs mixing parameter µ , the pseudoscalar Higgs mass M A and tan ß . In the fit including ( g - 2 ) µ , a Bino-like χ ~ 1 0 is preferred, whereas a Higgsino-like χ ~ 1 0 is mildly favoured when the ( g - 2 ) µ constraint is dropped. We identify the mechanisms that operate in different regions of the pMSSM11 parameter space to bring the relic density of the lightest neutralino, χ ~ 1 0 , into the range indicated by cosmological data. In the fit including ( g - 2 ) µ , coannihilations with χ ~ 2 0 and the Wino-like χ ~ 1 ± or with nearly-degenerate first- and second-generation sleptons are active, whereas coannihilations with the χ ~ 2 0 and the Higgsino-like χ ~ 1 ± or with first- and second-generation squarks may be important when the ( g - 2 ) µ constraint is dropped. In the two cases, we present χ 2 functions in two-dimensional mass planes as well as their one-dimensional profile projections and best-fit spectra. Prospects remain for discovering strongly-interacting sparticles at the LHC, in both the scenarios with and without the ( g - 2 ) µ constraint, as well as for discovering electroweakly-interacting sparticles at a future linear e + e - collider such as the ILC or CLIC.

Likelihood analysis of the minimal AMSB model.

We perform a likelihood analysis of the minimal anomaly-mediated supersymmetry-breaking (mAMSB) model using constraints from cosmology and accelerator experiments. We find that either a wino-like or a Higgsino-like neutralino LSP, [Formula: see text], may provide the cold dark matter (DM), both with similar likelihoods. The upper limit on the DM density from Planck and other experiments enforces [Formula: see text] after the inclusion of Sommerfeld enhancement in its annihilations. If most of the cold DM density is provided by the [Formula: see text], the measured value of the Higgs mass favours a limited range of [Formula: see text] (and also for [Formula: see text] if [Formula: see text]) but the scalar mass [Formula: see text] is poorly constrained. In the wino-LSP case, [Formula: see text] is constrained to about [Formula: see text] and [Formula: see text] to [Formula: see text], whereas in the Higgsino-LSP case [Formula: see text] has just a lower limit [Formula: see text] ([Formula: see text]) and [Formula: see text] is constrained to [Formula: see text] in the [Formula: see text] ([Formula: see text]) scenario. In neither case can the anomalous magnetic moment of the muon, [Formula: see text], be improved significantly relative to its Standard Model (SM) value, nor do flavour measurements constrain the model significantly, and there are poor prospects for discovering supersymmetric particles at the LHC, though there are some prospects for direct DM detection. On the other hand, if the [Formula: see text] contributes only a fraction of the cold DM density, future LHC [Formula: see text]-based searches for gluinos, squarks and heavier chargino and neutralino states as well as disappearing track searches in the wino-like LSP region will be relevant, and interference effects enable [Formula: see text] to agree with the data better than in the SM in the case of wino-like DM with [Formula: see text].

Likelihood analysis of supersymmetric SU(5) GUTs.

We perform a likelihood analysis of the constraints from accelerator experiments and astrophysical observations on supersymmetric (SUSY) models with SU(5) boundary conditions on soft SUSY-breaking parameters at the GUT scale. The parameter space of the models studied has seven parameters: a universal gaugino mass [Formula: see text], distinct masses for the scalar partners of matter fermions in five- and ten-dimensional representations of SU(5), [Formula: see text] and [Formula: see text], and for the [Formula: see text] and [Formula: see text] Higgs representations [Formula: see text] and [Formula: see text], a universal trilinear soft SUSY-breaking parameter [Formula: see text], and the ratio of Higgs vevs [Formula: see text]. In addition to previous constraints from direct sparticle searches, low-energy and flavour observables, we incorporate constraints based on preliminary results from 13 TeV LHC searches for jets + [Formula: see text] events and long-lived particles, as well as the latest PandaX-II and LUX searches for direct Dark Matter detection. In addition to previously identified mechanisms for bringing the supersymmetric relic density into the range allowed by cosmology, we identify a novel [Formula: see text] coannihilation mechanism that appears in the supersymmetric SU(5) GUT model and discuss the role of [Formula: see text] coannihilation. We find complementarity between the prospects for direct Dark Matter detection and SUSY searches at the LHC.

Dissecting the structural basis for the intracellular delivery of OSW-1 by fluorescent probes.

The structural basis for the intracellular delivery of OSW-1 is investigated using fluorescent derivatives of OSW-1 and its closely related congeners. Despite the large differences in activity, all the fluorescent probes are found to translocate across the plasma membrane to the ER and Golgi apparatus. This observation suggests that the glycosylated cholestane moiety plays an important role in the cell internalization and intracellular localization property of OSW-1.

Synthesis of a fluorescent photoaffinity probe of OSW-1 by site-selective acylation of an inactive congener and biological evaluation.

A novel fluorescent photoaffinity probe of OSW-1 was prepared in two steps from a naturally occurring inactive congener by a sequential site-selective acylation strategy using Me2SnCl2. It displayed highly potent anticancer activity and a similar intracellular localization property to that of a fluorescently-tagged OSW-1, thereby demonstrating its potential utility in live cell studies.

Correction: Synthesis of a fluorescent photoaffinity probe of OSW-1 by site-selective acylation of an inactive congener and biological evaluation.

Correction for 'Synthesis of a fluorescent photoaffinity probe of OSW-1 by site-selective acylation of an inactive congener and biological evaluation' by K. Sakurai et al., Chem. Commun., 2017, DOI: .

Supersymmetric dark matter after LHC run 1.

Different mechanisms operate in various regions of the MSSM parameter space to bring the relic density of the lightest neutralino, [Formula: see text], assumed here to be the lightest SUSY particle (LSP) and thus the dark matter (DM) particle, into the range allowed by astrophysics and cosmology. These mechanisms include coannihilation with some nearly degenerate next-to-lightest supersymmetric particle such as the lighter stau [Formula: see text], stop [Formula: see text] or chargino [Formula: see text], resonant annihilation via direct-channel heavy Higgs bosons H / A, the light Higgs boson h or the Z boson, and enhanced annihilation via a larger Higgsino component of the LSP in the focus-point region. These mechanisms typically select lower-dimensional subspaces in MSSM scenarios such as the CMSSM, NUHM1, NUHM2, and pMSSM10. We analyze how future LHC and direct DM searches can complement each other in the exploration of the different DM mechanisms within these scenarios. We find that the [Formula: see text] coannihilation regions of the CMSSM, NUHM1, NUHM2 can largely be explored at the LHC via searches for [Formula: see text] events and long-lived charged particles, whereas their H / A funnel, focus-point and [Formula: see text] coannihilation regions can largely be explored by the LZ and Darwin DM direct detection experiments. We find that the dominant DM mechanism in our pMSSM10 analysis is [Formula: see text] coannihilation: parts of its parameter space can be explored by the LHC, and a larger portion by future direct DM searches.

The pMSSM10 after LHC run 1.

We present a frequentist analysis of the parameter space of the pMSSM10, in which the following ten soft SUSY-breaking parameters are specified independently at the mean scalar top mass scale [Formula: see text]: the gaugino masses [Formula: see text], the first-and second-generation squark masses [Formula: see text], the third-generation squark mass [Formula: see text], a common slepton mass [Formula: see text] and a common trilinear mixing parameter A, as well as the Higgs mixing parameter [Formula: see text], the pseudoscalar Higgs mass [Formula: see text] and [Formula: see text], the ratio of the two Higgs vacuum expectation values. We use the MultiNest sampling algorithm with [Formula: see text]1.2 [Formula: see text] points to sample the pMSSM10 parameter space. A dedicated study shows that the sensitivities to strongly interacting sparticle masses of ATLAS and CMS searches for jets, leptons [Formula: see text][Formula: see text] signals depend only weakly on many of the other pMSSM10 parameters. With the aid of the Atom and Scorpion codes, we also implement the LHC searches for electroweakly interacting sparticles and light stops, so as to confront the pMSSM10 parameter space with all relevant SUSY searches. In addition, our analysis includes Higgs mass and rate measurements using the HiggsSignals code, SUSY Higgs exclusion bounds, the measurements of [Formula: see text] by LHCb and CMS, other B-physics observables, electroweak precision observables, the cold dark matter density and the XENON100 and LUX searches for spin-independent dark matter scattering, assuming that the cold dark matter is mainly provided by the lightest neutralino [Formula: see text]. We show that the pMSSM10 is able to provide a supersymmetric interpretation of [Formula: see text], unlike the CMSSM, NUHM1 and NUHM2. As a result, we find (omitting Higgs rates) that the minimum [Formula: see text] with 18 degrees of freedom (d.o.f.) in the pMSSM10, corresponding to a [Formula: see text] probability of 30.8 %, to be compared with [Formula: see text] in the CMSSM (NUHM1) (NUHM2). We display the one-dimensional likelihood functions for sparticle masses, and we show that they may be significantly lighter in the pMSSM10 than in the other models, e.g., the gluino may be as light as [Formula: see text]1250 [Formula: see text] at the 68 % CL, and squarks, stops, electroweak gauginos and sleptons may be much lighter than in the CMSSM, NUHM1 and NUHM2. We discuss the discovery potential of future LHC runs, [Formula: see text] colliders and direct detection experiments.

Bone marrow-derived stromal cells are associated with gastric cancer progression.

BACKGROUND: The aim of this study was to clarify the role of bone marrow-derived stromal cells (BM-SCs) expressing CD271 in the development of gastric cancer. METHODS: The effect of human BM-SCs on the proliferation and motility of six gastric cancer cell lines, OCUM-2M, OCUM-2MD3, OCUM-12, KATO-III, NUGC-3, and MKN-74, was examined. CD271 expression levels in BM-SCs were analysed by flow cytometry. We also generated a gastric tumour model by orthotopic inoculation of OCUM-2MLN cells in mice that had received transplantation of bone marrow from the CAG-EGFP mice. The correlation between the clinicopathological features of 279 primary gastric carcinomas and CD271 expression in tumour stroma was examined by immunohistochemistry. RESULTS: Numerous BM-SCs infiltrated the gastric tumour microenvironment; CD271 expression was found in ∼25% of BM-SCs. Conditioned medium from BM-SCs significantly increased the proliferation of gastric cancer cell lines. Furthermore, conditioned medium from gastric cancer cells significantly increased the number of BM-SCs, whereas migration of OCUM-12 and NUGC-3 cells was significantly increased by conditioned medium from BM-SCs. CD271 expression in stromal cells was significantly associated with macroscopic type-4 cancers, diffuse-type tumours, and tumour invasion depth. The overall survival of patients (n=279) with CD271-positive stromal cells was significantly worse compared with that of patients with CD271-negative stromal cells. This is the first report of the significance of BM-SCs in gastric cancer progression. CONCLUSIONS: Bone marrow-derived stromal cells might have an important role in gastric cancer progression, and CD271-positive BM-SCs might be a useful prognostic factor for gastric cancer patients.

Permanent acceptance of mouse cardiac allografts with CD40 siRNA to induce regulatory myeloid cells by use of a novel polysaccharide siRNA delivery system.

The CD40/CD154 co-stimulatory pathway is crucial in alloimmune response. We developed a novel small interfering RNA (siRNA) delivery system with a poly-dA extension at the 5'-end of the siRNA sense strand that was stably incorporated into 1,3-ß-glucan (schizophyllan, SPG). This was captured and incorporated into dendritic cells (DCs) through its receptor, Dectin-1, specifically silencing CD40 genes (siCD40) to exert immunoregulatory activity. siCD40/SPG-treated CBA mice permanently accepted B10 fully mismatched cardiac allografts. Consistent with graft survival, the infiltration of CD4(+), CD8(+) T cells into the graft was lower, and that the numbers of CD40(low)CD11c(+) DCs cells and CD4(+)Foxp3(+)cells were increased in both the graft and in the recipient spleen. In addition, naive CBA recipients given an adoptive transfer of splenocytes from the primary recipients with siCD40/SPG accepted a heart graft from donor-type B10, but not third-party Balb/c mice. In conclusion, the treatment with siCD40/SPG targeting DCs could generate antigen-specific Tregs, resulting in the permanent acceptance of mouse cardiac allografts. These findings have important implications for clarifying the mechanism underlying the induction of tolerance in DCs, and also highlight the potential of immunomodulation and the feasibility of siRNA-based clinical therapy in the transplantation field.

Mutation in insulin receptor attenuates oxidative stress and apoptosis in pancreatic beta-cells induced by nutrition excess: reduced insulin signaling and ROS.

Type 2 diabetes results from the failure of beta-cells to adequately compensate for insulin resistance. Although the reduction of beta-cell mass is because of increased cell death and/or inadequate replication or neogenesis, the mechanism underlying beta-cell mass reduction is not fully understood. Here, we clarify the role of insulin signaling pathway in the beta-cell apoptosis using insulin resistant model mice. Wild-type mice and those carrying a mutation in the insulin receptor (mIR) were fed either regular chow or a high-fat diet for 6 weeks and subsequently investigated for beta-cell apoptosis, endoplasmic reticulum stress, and oxidative stress. Insulin tolerance tests revealed that mIR mice fed a high-fat diet (mIRHF) had higher insulin resistance. Beta-cell apoptosis was increased 2-fold in the wild-type mice fed a high-fat diet (wHF) compared with control mice, whereas beta-cell apoptosis in mIRHF mice did not increase compared with that in mIR mice. The expression of endoplasmic reticulum stress markers in isolated islets did not differ between the groups. Staining of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal in islets of wHF mice significantly increased, but the staining in mIRHF mice was not different from that in control group. Gene expression of the antioxidant enzyme MnSOD was significantly higher in mIRHF mice than those in the other 3 groups. A mutation in the insulin receptor attenuated the oxidative stress and apoptosis in beta-cells even though high caloric nutrient was loaded. Our results suggest that reduced insulin signaling protects beta-cells thorough decline of oxidative stress.

Removing arsenic from groundwater in Cambodia using high performance iron adsorbent.

In Cambodia, groundwater has been contaminated with arsenic, and purification of the water is an urgent issue. From 2010 to 2012, an international collaborative project between Japan and Cambodia for developing arsenic-removing technology from well water was conducted and supported by the foundation of New Energy and Industrial Technology Development Organization, Japan. Quality of well water was surveyed in Kandal, Prey Veng, and Kampong Cham Provinces, and a monitoring trial of the arsenic removal equipment using our patented amorphous iron (hydr)oxide adsorbent was performed. Of the 37 wells surveyed, arsenic concentration of 24 exceeded the Cambodian guideline value (50 µg L(-1)), and those of 27 exceeded the WHO guideline for drinking water (10 µg L(-1)). Levels of arsenic were extremely high in some wells (>1,000-6,000 µg L(-1)), suggesting that arsenic pollution of groundwater is serious in these areas. Based on the survey results, 16 arsenic removal equipments were installed in six schools, three temples, two health centers, four private houses, and one commune office. Over 10 months of monitoring, the average arsenic concentrations of the treated water were between 0 and 10 µg L(-1) at four locations, 10-50 µg L(-1) at eight locations, and >50 µg L(-1) at four locations. The arsenic removal rate ranged in 83.1-99.7%, with an average of 93.8%, indicating that the arsenic removal equipment greatly lower the risk of arsenic exposure to the residents. Results of the field trial showed that As concentration of the treated water could be reduced to <10 µg L(-1) by managing the As removal equipment properly, suggesting that the amorphous iron (hydr)oxide adsorbent has high adsorbing capacity for As not only in the laboratory environment but also in the field condition. This is one of the succeeding As removal techniques that could reduce As concentration of water below the WHO guideline value for As in situ.