Large Enhancement of Thermoelectric Efficiency Due to a Pressure-Induced Lifshitz Transition in SnSe.

The Lifshitz transition, a change in Fermi surface topology, is likely to greatly influence exotic correlated phenomena in solids, such as high-temperature superconductivity and complex magnetism. However, since the observation of Fermi surfaces is generally difficult in the strongly correlated systems, a direct link between the Lifshitz transition and quantum phenomena has been elusive so far. Here, we report a marked impact of the pressure-induced Lifshitz transition on thermoelectric performance for SnSe, a promising thermoelectric material without a strong electron correlation. By applying pressure up to 1.6 GPa, we have observed a large enhancement of the thermoelectric power factor by more than 100% over a wide temperature range (10-300 K). Furthermore, the high carrier mobility enables the detection of quantum oscillations of resistivity, revealing the emergence of new Fermi pockets at ∼0.86 GPa. The observed thermoelectric properties linked to the multivalley band structure are quantitatively reproduced by first-principles calculations, providing novel insight into designing the SnSe-related materials for potential valleytronic as well as thermoelectric applications.

Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy.

BACKGROUND: Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified. METHODS: The cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo [n = 43] and HDM 300 IR [n = 46]) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace™ Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV. RESULTS: HDM-reactive IL-5+ IL-13+ CD27- CD161+ CD4+ cells and ST2+ CD45RO+ CD4+ cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+ CD45RO+ CD4+ cells were significantly lower in active-responders. CONCLUSION: Allergen-reactive ST2+ CD45RO+ CD4+ cells or those combined with IL-5+ IL-13+ CD27- CD161+ CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.

Genetic analyses of GII.17 norovirus strains in diarrheal disease outbreaks from December 2014 to March 2015 in Japan reveal a novel polymerase sequence and amino acid substitutions in the capsid region.

A novel GII.P17-GII.17 variant norovirus emerged as a major cause of norovirus outbreaks from December 2014 to March 2015 in Japan. Named Hu/GII/JP/2014/GII.P17-GII.17, this variant has a newly identified GII.P17 type RNA-dependent RNA polymerase, while the capsid sequence displays amino acid substitutions around histo-blood group antigen (HBGA) binding sites. Several variants caused by mutations in the capsid region have previously been observed in the GII.4 genotype. Monitoring the GII.17 variant's geographical spread and evolution is important.

Risk factors for hepatocellular carcinoma in hepatitis C patients with normal alanine aminotransferase treated with pegylated interferon and ribavirin.

Pegylated interferon (Peg-IFN) plus ribavirin combination therapy is effective in patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase levels (NALT). However, it remains unclear whether the risk of hepatocellular carcinoma (HCC) incidence is actually reduced in virological responders. In this study, HCC incidence was examined for 809 patients with NALT (ALT ≤ 40 IU/mL) treated with Peg-IFN alpha-2b and ribavirin for a mean observation period of 36.2 ± 16.5 months. The risk factors for HCC incidence were analysed by Kaplan-Meier method and Cox proportional hazards model. On multivariate analysis among NALT patients, the risk of HCC incidence was significantly reduced in patients with sustained virological response (SVR) or relapse compared with those showing nonresponse (NR) (SVR vs NR, hazard ratio (HR): 0.16, P = 0.009, relapse vs NR, HR: 0.11, P = 0.037). Other risk factors were older age (≥65 years vs <60 years, HR: 6.0, P = 0.032, 60-64 vs <60 years, HR: 3.2, P = 0.212) and male gender (HR: 3.9, P = 0.031). Among 176 patients with PNALT (ALT ≤ 30 IU/mL), only one patient developed HCC and no significant risk factors associated with HCC development were found. In conclusion, antiviral therapy for NALT patients with HCV infection can lower the HCC incidence in responders, particularly for aged and male patients. The indication of antiviral therapy for PNALT (ALT ≤ 30 IU/mL) patients should be carefully determined.

Novel method of screening the oxidation and reduction abilities of photocatalytic materials.

Two analytical methods for the evaluation of photocatalytic oxidation and reduction abilities were developed using a photocatalytic microreactor; one is product analysis and the other is reaction rate analysis. Two simple organic conversion reactions were selected for the oxidation and reduction. Since the reactions were one-to-one conversions from the reactant species to the product species, the product analysis was simply performed using gas chromatography, and the reactions were monitored in situ in the photocatalytic microreactor using the UV absorption spectra. The partial oxidation and reduction abilities for each functional group can be judged from the yield and selectivity, and the corresponding reaction rate, while the total oxidation ability can be judged from the conversion. We demonstrated the application of these methods for several kinds of visible light photocatalysts.

Photoexcited carrier dynamics of double-layered CdS/CdSe quantum dot sensitized solar cells measured by heterodyne transient grating and transient absorption methods.

The charge dynamics in the double-layered quantum dot sensitized solar cell (QDSSC) was studied to clarify the reason why the cell performance was much improved by a double-layer coating, by using the heterodyne transient grating (HD-TG) and transient absorption methods, based on a previous study for a conventional QDSSC (N. Maeda et al., Phys. Chem. Chem. Phys., 2013, 15, 11006.) In the double-layered QDSSC, the layer order of CdS and CdSe affected the cell performance. When CdS is in between TiO2 and CdSe, the conversion efficiency was enhanced by 70%, while it was lowered by 50% in the opposite order. From the information on charge dynamics, it was found that electrons were efficiently injected to TiO2 by appropriate band alignment of CdS and CdSe, while only a part of the electrons were transferred to the TiO2 when the layer order was opposite. Furthermore, the reverse electron transfer does not matter for the conversion efficiency, because the process increased even for the appropriate layer order.

Molecular dynamics in azobenzene liquid crystal polymer films measured by time-resolved techniques.

Photo-induced molecular motion in a liquid crystal polymer film including azobenzene was studied by the heterodyne transient grating method. The film was confined in a liquid crystal cell, where it is a photomobile film under free-standing conditions. By observation of the refractive index change induced by a laser pulse, contraction of the film was observed on the order of several hundreds of nanoseconds, and the subsequent reorientation and molecular rotation dynamics were observed from a few microseconds to a hundred milliseconds. Finally, the cis isomer of azobenzene was thermally returned back to the trans isomer in about ten seconds because the film could not be bent in the liquid crystal cell. Since the contraction, reorientation and molecular rotation took place before the cis to trans back-transformation, these processes correspond to the preliminary molecular motion preceding the macroscopic bending of the film.

Genome-wide association study of degenerative bony changes of the temporomandibular joint.

OBJECTIVES: To identify susceptibility genes underlying degenerative bony changes of the temporomandibular joint (TMJ). MATERIALS AND METHODS: Bony changes of the TMJ condylar head were diagnosed by examination of panoramic radiographs and/or magnetic resonance images and/or computed tomography images. We conducted a genome-wide association study (GWAS) of 146 cases with TMJ degeneration and 374 controls from East Asian populations using an Illumina HumanOmniExpress BeadChip. After rigorous quality-control filtering, approximately 550,000 single nucleotide polymorphisms (SNPs) were used for tests of associations with disease status. RESULTS: Forty-one SNPs at 22 independent loci showed association signals at P < 1 × 10(-4). The SNP rs878962, which maps on an intron of TSPAN9 on chromosome 12, showed the strongest association (combined OR = 1.89, 95% confidence interval = 1.43-2.50, P = 8.1 × 10(-6)). According to in silico predictions of the 41 SNPs, two intronic SNPs of APOL3 (rs80575) and MRC2 (rs2460300) may fall within regulatory elements and affect DNA-protein interactions. We could not replicate SNPs located on genes that have been reported to be associated with temporomandibular disorder or temporomandibular osteoarthritis in previous studies at P < 1 × 10(-4). CONCLUSIONS: Our GWAS identified 22 independent loci showing suggestive association signals with degenerative bony changes of the TMJ. These loci provide good candidates for future follow-up studies.

Non-targeted analyses of animal plasma: betaine and choline represent the nutritional and metabolic status.

Simple liquid chromatography-mass spectrometry (LC-MS) was applied to non-targeted metabolic analyses to discover new metabolic markers in animal plasma. Principle component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) were used to analyse LC-MS multivariate data. PCA clearly generated two separate clusters for artificially induced diabetic mice and healthy control mice. PLS-DA of time-course changes in plasma metabolites of chicks after feeding generated three clusters (pre- and immediately after feeding, 0.5-3 h after feeding and 4 h after feeding). Two separate clusters were also generated for plasma metabolites of pregnant Angus heifers with differing live-weight change profiles (gaining or losing). The accompanying PLS-DA loading plot detailed the metabolites that contribute the most to the cluster separation. In each case, the same highly hydrophilic metabolite was strongly correlated to the group separation. The metabolite was identified as betaine by LC-MS/MS. This result indicates that betaine and its metabolic precursor, choline, may be useful biomarkers to evaluate the nutritional and metabolic status of animals.

Selective down-regulation of Th2 cell-mediated airway inflammation in mice by pharmacological intervention of CCR4.

BACKGROUND: The chemokine receptor CCR4 has been implicated in Th2 cell-mediated immune responses. However, other T cell subsets are also known to participate in allergic inflammation. OBJECTIVE: The role of CCR4 in Th1, Th2, and Th17 cell-mediated allergic airway inflammation was investigated. METHOD: We generated an allergic airway inflammation model by adoptive transfer of in vitro-polarized ovalbumin (OVA)-specific Th1, Th2, and Th17 cells. The effect of a low-molecular weight CCR4 antagonist, Compound 22, on this model was examined. RESULTS: Upon in vitro polarization of DO11.10 naïve T cells, Th1- and Th2-polarized cells dominantly expressed CXCR3 and CCR4, respectively, while Th17-polarized cells expressed CCR6 and CCR4. Intranasal OVA-challenge of mice transferred with each T cell subset induced accumulation of T cells in the lungs. Eosinophils were also massively accumulated in Th2-transferred mice, whereas neutrophils were preferentially recruited in Th1- and Th17-transferred mice. Compound 22, as well as anti-CCL17 or anti-CCL22 antibody selectively suppressed accumulation of Th2 cells and eosinophils in the lungs of Th2-transferred and OVA-challenged mice. Compound 22 also inhibited bronchial hyperresponsiveness but had little effect on goblet cell hyperplasia in Th2-transferred and OVA-challenged mice. CONCLUSIONS AND CLINICAL RELEVANCE: There were notable differences in allergic lung inflammation mediated by different T cell subsets. CCR4 blockage was selectively effective for suppression of Th2-mediated allergic inflammation by blocking infiltration of Th2 cells.

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities.

Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

Genetic diversity of genogroup IV noroviruses in wastewater in Japan.

AIMS: To investigate the prevalence, seasonality and genetic diversity of genogroup IV noroviruses (GIV NoVs) in wastewater in Japan. METHODS AND RESULTS: Untreated and treated wastewater samples were collected monthly for a year from a wastewater treatment plant in Japan. The concentrated wastewater samples were examined for the presence of GIV NoV genomes with seminested RT-PCR assay targeting partial capsid gene. Among 12 untreated and 12 treated wastewater samples tested, GIV NoV genomes were detected in three (25%) untreated and two (17%) treated wastewater samples with a high positive ratio in winter season. Genetic analysis revealed that the GIV NoVs in the wastewater samples were genetically diverse and were classified into three different genetic clusters. CONCLUSIONS: Frequent detection of GIV NoVs in winter season, which is a common epidemic period of human NoVs in Japan, indicates that GIV NoVs exhibit temporal trends similar to GI and GII NoVs. Based on the partial capsid gene sequences, we identified several unique GIV NoV strains belonging to the novel genetic cluster, demonstrating that GIV NoVs are more genetically diverse than previously appreciated. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings provide novel evidence of considerable genetic diversity among the GIV NoV strains.

A meta-analysis of the impact of IVF and ICSI on major malformations after adjusting for the effect of subfertility.

OBJECTIVE: To estimate the effect of assisted reproductive technology (ART) on major malformation (MM) rate in ART offspring independent of the effect of subfertility on MM. DESIGN: Meta-analysis. METHODS: This meta-analysis is based on our previously published meta-analysis of observational studies evaluating the relationship between ART treatment and MM rates, as well as recent research by Zhu et al. to estimate the impact of subfertility alone on MM in subfertile couples conceiving spontaneously. RESULTS: The overall odds ratio for MM in our original meta-analysis, in which all studies used apparently inappropriate control groups of "normal" populations, was 1.29 (95% CI 1.01-1.67). Here we attempted to estimate the risk of subfertility and used this estimate to perform an adjusted meta-analysis. Zhu et al. found that about 40% of the odds of MM was due to subfertility. When we took Zhu's finding into account, the adjusted odds ratio in the meta-analysis was 1.01 (95% CI 0.82-1.23). CONCLUSIONS: Our study suggests ART does not increase the risk of MM as much as previously reported. More research is needed to quantify the underlying risk of subfertility and separate it from the risk associated with ART. Physicians who counsel subfertile couples should recognize that previous studies of MM rates in ART patients probably overestimated the risk.

Effects of metformin on plasma concentrations of glucose and mannose, G6Pase and PEPCK activity, and mRNA expression in the liver and kidney of chickens.

1. The objective of this study was to determine the effects of the gluconeogenesis inhibitor metformin on 21-d old chickens. The following parameters were measured in the liver and kidney: plasma glucose, plasma mannose, enzyme activities and mRNA expression levels of glucose-6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK). 2. Chickens were divided into two groups, and received either metformin (300 mg/kg body weight) or water. Plasma glucose and mannose concentrations were analysed by high performance liquid chromatography (HPLC). G6Pase and PEPCK activities were determined by glucose 6-phosphate and malic acid substrate methods, respectively. The expression levels of mRNA were determined by real-time PCR. 3. Plasma glucose and mannose reached their lowest concentrations 1 h after metformin administration. At 0·5 h-1 h after metformin administration, the enzyme activities and mRNA expression levels of G6Pase and PEPCK reached their lowest point in the kidney and their highest point in the liver. The decrease observed in the kidney may have been associated with reductions in both plasma glucose and mannose concentrations. 4. In conclusion, the effect of metformin on the kidney of chickens is similar to its effect in mammals. In contrast, no suppression of enzyme activity or mRNA expression was observed in chicken liver. Therefore, the mode of action of metformin, via AMPK activation, may be different in the chicken liver.

Living with COVID-19: mass gatherings and minimizing risk.

During the COVID-19 pandemic, it has been important to both minimize the risk of infection and restore daily life. As a typical example, mass gathering events, such as sporting events, are gradually becoming more common, thanks to the measures taken to contain COVID-19. Some pilot studies have been launched at governments' initiative to investigate the risk of infection without measures such as face masks and physical distancing at mass gathering events, but the ethics of these studies should be carefully considered. On the other hand, it is still beneficial to implement infection control measures at mass gathering events and, in parallel, to estimate the risk of infection with measures in place, especially under a lack of vaccination progress or the spread of mutant strains possibly resistant to vaccines. To help improve compliance with measures taken by spectators and organizers and to ensure their effectiveness, we have conducted quantitative evaluations of the implementation of such measures by monitoring CO2 concentrations, assessing the proportion of people wearing face masks and analysing human flow at the event. This approach allows us to share our observations with stakeholders and participants, enabling us to protect the culture of mass gathering events, minimize the risk of infection and restore a sense of well-being in daily life.

Splenectomy and antiviral treatment for thrombocytopenic patients with chronic hepatitis C virus infection.

Thrombocytopenic patients with chronic hepatitis C virus (HCV) infection are poor candidates for antiviral treatment with interferon (IFN), but no standard treatment for thrombocytopenia has yet been established. We evaluated the safety of splenectomy and its efficacy for the initiation and continuation of antiviral therapy. From March 2003 to April 2006, 10 patients (mean age 62.5 years) with HCV-related cirrhosis, low platelet count (<==106 000/mm(3)) and splenomegaly (spleen size >==10 cm) underwent splenectomy. Platelet counts significantly increased at 4-8 weeks after splenectomy [pre: 64 200 +/- 6900/mm(3)vs post 209 000 +/- 40 600/mm(3) (P = 0.004)]. No severe operative complications were observed. All patients subsequently received antiviral therapy. Of the eight patients who were infected with HCV genotype 1 and had a high viral load (>==100 KIU/mL), four received combination therapy with pegylated IFNalpha-2b plus ribavirin, and the other four received standard IFNalpha-2b plus ribavirin. One patient infected with HCV genotype 2 and another with HCV genotype 1 and a low viral load (<100 KIU/mL) were treated with pegylated IFNalpha-2a. Six patients achieved sustained virologic response (SVR). Among four patients who failed to achieve SVR, one was given retreatment with pegylated IFN plus ribavirin, and the other three received low-dose long-term IFN therapy. Although this study was small, the treatment results were similar to those for patients without thrombocytopenia and suggested that splenectomy would not reduce the antiviral efficacy of IFNalpha-based treatment.

Uterine sperm-egg transfer: a cost-effective alternative to IVF?

Direct transcervical transfer of spermatozoa and oocytes to the uterine cavity has been carried out in the past. This procedure could be a more appropriate approach than IVF for some anovulatory patients who require gonadotrophin stimulation, since the number of oocytes could be limited, thus reducing the occurrence of multiple gestations. However, most of the clinical pregnancy rates reported in the literature for gamete intrauterine transfer appear to be inferior to IVF pregnancy rates. This study attempted to improve the outcome of gamete intrauterine transfer by modifying some aspects of the procedure. This procedure is referred to as uterine sperm-egg transfer (U-SET) to imply that U (you the patient) set (determine) the number of oocytes to be transferred to the uterus. In this study's series of 16 anovulatory patients under the age of 36 years, the clinical pregnancy rate was 69% and the live birth rate was 50%.

Effects of deconditioning on the initial ventilatory and circulatory responses at the onset of exercise in man.

In order to elucidate the effects of deconditioning (inactivity) on the ventilatory and circulatory responses at the onset of exercise within 20 s, we initiated head-down bed rest and unilateral lower limb suspension experiments, and measured these responses to dynamic voluntary leg exercise and passive movements. Initial ventilatory and heart rate responses to voluntary exercise were attenuated after bed rest but showed no change after suspension or during passive movements, suggesting the minimal role of peripheral neural reflex.

Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV.

The development of a safe and effective mucosal vaccine adjuvant is a crucial step for the development of vaccines against human immunodeficiency virus type-1 (HIV). We have previously reported that a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, possessed strong mucosal vaccine adjuvant activities in mice. Here, we evaluated the potential of mTNF-K90R as a mucosal vaccine adjuvant for the induction of systemic and mucosal immune responses against HIV. Nasal immunization of BALB/c mice with 5 microg of an HIV gp120 env protein immunogen together with mTNF-K90R induced higher serum anti-HIV gp120 protein immunoglobulin G (IgG) responses than gp120 alone. Furthermore, mTNF-K90R induced anti-gp120 IgA responses in nasal as well as vaginal washes from immunized mice, although these were not administration sites. Again, responses with mTNF-K90R were higher than with gp120 alone. These results indicate that mTNF-K90R may be applicable as amucosal adjuvant for HIV vaccination to induce both systemic and mucosal immune responses.

Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin.

The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis (P = 0.002), the timing of HCV RNA negativiation (P < 0.001) and the mean doses of ribavirin (P < 0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given > or = 12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 microg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (> or = 12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.