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The peculiar metallic electronic states observed in the Kondo insulator, samarium hexaboride (SmB6), has stimulated considerable attention among those studying non-trivial electronic phenomena. However, experimental studies of these states have led to controversial conclusions mainly due to the difficulty and inhomogeneity of the SmB6 crystal surface. Here, we show the detailed electronic structure of SmB6 with angle-resolved photoelectron spectroscopy measurements of the three-fold (111) surface where only two inequivalent time-reversal-invariant momenta (TRIM) exist. We observe the metallic two-dimensional state was dispersed across the bulk Kondo gap. Its helical in-plane spin polarisation around the surface TRIM indicates that SmB6 is topologically non-trivial, according to the topological classification theory for weakly correlated systems. Based on these results, we propose a simple picture of the controversial topological classification of SmB6. [ABSTRACT FROM AUTHOR]

This report describes the clinical course of a 41 year-old African woman who presented with an episode of acute alcoholic pancreatitis followed next by severe alcoholic hepatitis (SAH). Initially admitted for pancreatitis, the patient responded promptly to comprehensive treatment with strict abstinence from alcohol. However, remarkable elevations in white blood cell count to 44,000/µL and total bilirubin level to 12.4 mg/dL were observed 5–7 weeks later. Contrast-enhanced computed tomography revealed rapidly progressing hepatosplenomegaly. Histological analysis of a liver biopsy detected ballooned hepatocytes with Mallory–Denk bodies and significant neutrophilic infiltration in the hepatic parenchyma, which confirmed the diagnosis of SAH. The patient's hepatosplenomegaly and overall condition improved with supportive care alone. The reported case reveals the unexpected fact that SAH can develop after alcoholic acute pancreatitis. [ABSTRACT FROM AUTHOR]

Among several secreted glycoproteins belonging to the thrombospondin family, thrombospondin 2 (TSP2) is involved in various functions, including collagen/fibrin formation. Liver/serum TSP2 levels have been correlated to liver fibrosis stage and disease activity in nonalcoholic fatty liver disease. This study investigated whether serum TSP2 was associated with clinicopathological features in hepatitis C virus (HCV)-infected patients as well. A total of 350 patients with HCV who had undergone liver biopsy were retrospectively enrolled and divided into a discovery cohort (n = 270) and a validation cohort (n = 80). In the discovery cohort, serum TSP2 levels were moderately correlated with both liver fibrosis stage (r = 0.426, P < 0.0001) and activity grade (r = 0.435, P < 0.0001). The area under the receiver operating characteristic curve of TSP2 for predicting severe fibrosis (≥ F3) was 0.78 and comparable to or better than those of autotaxin (0.78), FIB-4 index (0.78), and APRI (0.76). The discovery cohort findings were closely replicated in the validation cohort. Moreover, comprehensive liver genetic analysis of HCV-infected patients confirmed that the expression of the THBS2 gene encoding TSP2 was significantly higher in severely fibrotic F4 than in F1 patients. Circulating TSP2 levels may reflect the severity of hepatic fibrosis/inflammation in HCV-infected patients. [ABSTRACT FROM AUTHOR]

Peptide–major histocompatibility complex (pMHC) multimers enable the detection of antigen-specific T cells in studies ranging from vaccine efficacy to cancer immunotherapy. However, this technology is unreliable when applied to pMHC class II for the detection of CD4+ T cells. Here, using a combination of molecular biological and immunological techniques, we cloned sequences encoding human leukocyte antigen (HLA)-DP, HLA-DQ and HLA-DR molecules with enhanced CD4 binding affinity (with a Kd of 8.9 ± 1.1 µM between CD4 and affinity-matured HLA-DP4) and produced affinity-matured class II dimers that stain antigen-specific T cells better than conventional multimers in both in vitro and ex vivo analyses. Using a comprehensive library of dimers for HLA-DP4, which is the most frequent HLA allele in many ancestry groups, we mapped 103 HLA-DP4-restricted epitopes derived from diverse tumor-associated antigens and cloned the cognate T-cell antigen receptor (TCR) genes from in vitro-stimulated CD4+ T cells. The availability of affinity-matured class II dimers across HLA-DP, HLA-DQ and HLA-DR alleles will aid in the investigation of human CD4+ T-cell responses. CD4+ T cells are readily detected with class II MHC dimers. [ABSTRACT FROM AUTHOR]

Trichosporon asahii is a pathogenic fungus that causes deep mycosis in patients with neutropenia. Establishing an experimental animal model for quantitatively evaluating pathogenicity and developing a genetic recombination technology will help to elucidate the infection mechanism of T. asahii and promote the development of antifungal drugs. Here we established a silkworm infection model with a transgenic T. asahii strain expressing eGFP. Injecting T. asahii into silkworms eventually killed the silkworms. Moreover, the administration of antifungal agents, such as amphotericin B, fluconazole, and voriconazole, prolonged the survival time of silkworms infected with T. asahii. A transgenic T. asahii strain expressing eGFP was obtained using a gene recombination method with Agrobacterium tumefaciens. The T. asahii strain expressing eGFP showed hyphal formation in the silkworm hemolymph. Both hyphal growth and the inhibition of hyphal growth by the administration of antifungal agents were quantitatively estimated by monitoring fluorescence. Our findings suggest that a silkworm infection model using T. asahii expressing eGFP is useful for evaluating both the pathogenicity of T. asahii and the efficacy of antifungal drugs. [ABSTRACT FROM AUTHOR]

We report a retrospective analysis of 38 patients (age ≤ 30 years) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) for relapsed or refractory anaplastic large-cell lymphoma (ALCL). Median follow-up for survivors after undergoing allo-SCT was 72 months (range, 35-96 months). Eight patients received reduced-intensity conditioning (RIC) regimens, including three patients with fludarabine plus melphalan-based regimens and five patients with fludarabine plus busulfan-based regimens. The remaining 30 patients received myeloablative conditioning (MAC) regimens. Median ages in the RIC and MAC groups were 24 and 15 years, respectively. The 5-year overall survival rates in the RIC and MAC groups were 100% and 49%, respectively (P = 0.018). The 5-year event-free survival rates in the RIC and MAC groups were 88% and 43%, respectively (P = 0.039). In the RIC group, four of the eight patients showed residual disease at allo-SCT, but all eight patients survived with complete remission (CR), including one patient with relapse. This result suggests that allo-SCT using the RIC regimen may be effective for relapsed or refractory ALCL in children, adolescents, and young adults, even in non-CR cases. [ABSTRACT FROM AUTHOR]

Physical human-robot interaction plays an important role in social robotics, and touch is one of the key factors that influence a human's impression of robots. However, very few studies have explored different conditions pertaining to such interactions, and therefore, only few systematic results have been reported. As the first step toward addressing this issue, we studied the types of impressions of a robot's personality that humans may experience when they touch a soft part of the robot. In the study, the left forearm of a child-like android robot named "Affetto" was exposed; the original forearm was made of silicone rubber and can be replaced with any one of three other forearms that provide different sensations of hardness upon touching. Participants were asked to touch the robot's forearm and answer evaluation questionnaires on 19 touch sensations and 46 personality impressions for each of the four conditions associated with the different forearms. Four impression factors for touch sensations and three for personality impressions were extracted from the evaluation scores by the factor analysis method. The causal relationships between these factors were analyzed by the path analysis method. Several significant causal relationships were found, for example, between preferable touch sensations and likable personality impressions. The study results are expected to help in the design of the personality impressions of robots by facilitating a more systematic design of touch sensations. Furthermore, the results of an analysis of variance suggested that the most preferable touch sensation is possibly related to the robot's appearance and that designers of social robots should understand the complex touch sensation properties of humans. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We previously found that intestine-specific homeobox (ISX) mRNA expression increased in organoids cultured from Helicobacter-infected mouse mucosa. In this study, we elucidate the role of ISX in the development of IM and gastric carcinogenesis.Methods: ISX expression was assessed in Helicobacter-infected mouse and human gastric mucosa. MKN45 gastric cancer cells were co-cultured with H. pylori to determine whether Helicobacter infection induced ISX expression. We established stable MKN45 transfected cells expressing ISX (Stable-ISX MKN45) and performed a spheroid colony formation assay and a xenograft model. We performed ISX immunohistochemistry in cancer and adjacent gastric tissues.Results: ISX expression was increased in mouse and human gastric mucosa infected with Helicobacter. The presence of IM and H. pylori infection in human stomach was correlated with ISX expression. H. pylori induced ISX mRNA and protein expression. CDX1/2, cyclinD1, and MUC2 were upregulated in Stable-ISX MKN45, whereas MUC5AC was downregulated. Stable-ISX MKN45 cells formed more spheroid colonies, and had high tumorigenic ability. ISX expression in gastric cancer and adjacent mucosa were correlated.Conclusions: ISX expression induced by H. pylori infection may lead to IM and hyperproliferation of gastric mucosa through CDX1/2 and cyclinD1 expression, contributing to gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

Main Conclusion: A rice glutaredoxin isoform (OsGrxC2;2) with antioxidant capacity is expressed abundantly in seed tissues and is localized to storage vacuoles in aleurone layers in developing and mature seeds. Seed tissues undergo drastic water loss at the late stage of seed development, and thus need to tolerate oxidative injuries associated with desiccation. We previously found a rice glutaredoxin isoform, OsGrxC2; 2, as a gene expressed abundantly in developing seeds. Since glutaredoxin is involved in antioxidant defense, in the present study we investigated the subcellular localization and expression profile of OsGrxC2;2 and whether OsGrxC2;2 has a role in the defense against reactive oxygen species. Western blotting and immunohistochemistry revealed that the OsGrxC2;2 protein accumulated at a high level in the embryo and aleurone layers of developing and mature seeds. The OsGrxC2;2 in developing seeds was particularly localized to aleurone grains, which are storage organelles derived from vacuoles. Overexpression of OsGrxC2;2 resulted in an enhanced tolerance to menadione in yeast and methyl viologen in green leaves of transgenic rice plants. These results suggest that OsGrxC2;2 participates in the defense against oxidative stress in developing and mature seeds. [ABSTRACT FROM AUTHOR]

The goal of Human-Computer Interface (or called Human-Robot interface) research is to provide humans with a new communication channel that allows translating people's intention states via a computer into performing specific actions. This paper presents a novel hands-free control system for controlling the electric wheelchair, which is based on Bio-signals just as surface electromyogram signals. The Bioelectric signals are picked up from facial muscles, then the Bio-signals are passed through an amplifier and a high pass filter. Motion control commands (Forward, Left, Right, Forward to the Right, Forward to the left and Stop) are classified by simple rule, and these commands are used for controlling the electric wheelchair. However, it is difficult to realize safety control and fine control using the biological signal only. In addition, we introduce the semi-automatic control system using the laser range scanner. In this paper, we report the introduction of our proposal systems and our experimental results. [ABSTRACT FROM AUTHOR]

Aortic aneurysm and/or dissection (AAD) is a life-threatening condition, and several syndromes are known to be related to AAD. In this study, two new technologies, resequencing array technology (ResAT) and next-generation sequencing (NGS), were used to analyze eight genes associated with syndromic AAD in 70 patients with non-syndromic AAD. Eighteen sequence variants were detected using both ResAT and NGS. In addition one of these sequence variants was detected by ResAT only and two additional variants by NGS only. Three of the 18 variants are likely to be pathogenic (in 4.3% of AAD patients and in 8.6% of a subset of patients with thoracic AAD), highlighting the importance of genetic analysis in non-syndromic AAD. ResAT and NGS similarly detected most, but not all, of the variants. Resequencing array technology was a rapid and efficient method for detecting most nucleotide substitutions, but was unable to detect short insertions/deletions, and it is impractical to update custom arrays frequently. Next-generation sequencing was able to detect almost all types of mutation, but requires improved informatics methods. [ABSTRACT FROM AUTHOR]

Although enrichment culture is typically employed to isolate cellulolytic microbes, this approach tends to favor fast-growing species and discriminates against all others. Therefore, efforts to prevent the overgrowth of fast-growing species are necessary to isolate novel cellulase-producing strains. In this study, we developed a simple culture method for isolating hitherto-uncultured microbes that possess cellulase activity, particularly exocellulase. In this method, the microbial source (a forest soil) was suspended in sterilized water and inoculated onto a mineral salts agar medium, which was then overlaid with filter paper to sandwich the microbial suspension between the agar surface and paper. The filter paper fibers served to immobilize the microbial cells and were the dominant carbon source. Following cultivation at 30°C for 2 weeks, emerging colonies were isolated based on their morphology and were then subjected to phylogenetic and enzyme analyses. Using this method, 2,150 CFUs/g dry soil were obtained, and the ratio of fungal to bacterial isolates was approximately 4:1. Phylogenetic analyses revealed that most fungal and bacterial isolates belong to ten and two genera, respectively. Notably, all isolates possessed exocellulase activity, and several strains showed strong activity that was comparable to Trichoderma cellulase. Many isolates also exhibited cellulase and xylanase activity, and several strains possessed laccase activity. It is expected that the culture method described here will be useful for the isolation of hitherto-uncultured cellulolytic microbes and the identification of novel cellulases. [ABSTRACT FROM AUTHOR]

A FAD-dependent glucose dehydrogenase (FADGDH) mutant with narrow substrate specificity was constructed by site-directed mutagenesis. Several characteristics of FADGDH, such as high catalytic activity and high electron transfer ability, make this enzyme suitable for application to glucose sensors. However, for further applications, improvement of the broad substrate specificity is needed. In this paper, we mutated two residues, Asn475 and Ala472, which are located near the putative active site of the catalytic subunit of FADGDH and have been predicted from the alignment with the active site of glucose oxidase. Of the 38 mutants constructed, Ala472Phe and Asn475Asp were purified and their activities were analyzed. Both mutants showed a higher specificity toward glucose compared to the wild type enzyme. [ABSTRACT FROM AUTHOR]

Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5′-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5′-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs. [ABSTRACT FROM AUTHOR]