Showing papers by "Kyushu University published in 2011"

Everolimus for Advanced Pancreatic Neuroendocrine Tumors

Abstract: A B S T R AC T BACKGROUND Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study. METHODS We randomly assigned 410 patients who had advanced, low-grade or intermediategrade pancreatic neuroendocrine tumors with radiologic progression within the previous 12 months to receive everolimus, at a dose of 10 mg once daily (207 patients), or placebo (203 patients), both in conjunction with best supportive care. The primary end point was progression-free survival in an intention-to-treat analysis. In the case of patients in whom radiologic progression occurred during the study, the treatment assignments could be revealed, and patients who had been randomly assigned to placebo were offered open-label everolimus. Results The median progression-free survival was 11.0 months with everolimus as compared with 4.6 months with placebo (hazard ratio for disease progression or death from any cause with everolimus, 0.35; 95% confidence interval [CI], 0.27 to 0.45; P<0.001), representing a 65% reduction in the estimated risk of progression or death. Estimates of the proportion of patients who were alive and progression-free at 18 months were 34% (95% CI, 26 to 43) with everolimus as compared with 9% (95% CI, 4 to 16) with placebo. Drug-related adverse events were mostly grade 1 or 2 and included stomatitis (in 64% of patients in the everolimus group vs. 17% in the placebo group), rash (49% vs. 10%), diarrhea (34% vs. 10%), fatigue (31% vs. 14%), and infections (23% vs. 6%), which were primarily upper respiratory. Grade 3 or 4 events that were more frequent with everolimus than with placebo included anemia (6% vs. 0%) and hyperglycemia (5% vs. 2%). The median exposure to everolimus was longer than exposure to placebo by a factor of 2.3 (38 weeks vs. 16 weeks). Conclusions Everolimus, as compared with placebo, significantly prolonged progression-free survival among patients with progressive advanced pancreatic neuroendocrine tumors and was associated with a low rate of severe adverse events. (Funded by Novartis Oncology; RADIANT-3 ClinicalTrials.gov number, NCT00510068.)

TRY - a global database of plant traits

Abstract: Plant traits – the morphological, anatomical, physiological, biochemical and phenological characteristics of plants and their organs – determine how primary producers respond to environmental factors, affect other trophic levels, influence ecosystem processes and services and provide a link from species richness to ecosystem functional diversity. Trait data thus represent the raw material for a wide range of research from evolutionary biology, community and functional ecology to biogeography. Here we present the global database initiative named TRY, which has united a wide range of the plant trait research community worldwide and gained an unprecedented buy-in of trait data: so far 93 trait databases have been contributed. The data repository currently contains almost three million trait entries for 69 000 out of the world's 300 000 plant species, with a focus on 52 groups of traits characterizing the vegetative and regeneration stages of the plant life cycle, including growth, dispersal, establishment and persistence. A first data analysis shows that most plant traits are approximately log-normally distributed, with widely differing ranges of variation across traits. Most trait variation is between species (interspecific), but significant intraspecific variation is also documented, up to 40% of the overall variation. Plant functional types (PFTs), as commonly used in vegetation models, capture a substantial fraction of the observed variation – but for several traits most variation occurs within PFTs, up to 75% of the overall variation. In the context of vegetation models these traits would better be represented by state variables rather than fixed parameter values. The improved availability of plant trait data in the unified global database is expected to support a paradigm shift from species to trait-based ecology, offer new opportunities for synthetic plant trait research and enable a more realistic and empirically grounded representation of terrestrial vegetation in Earth system models.

Evidence for osteocyte regulation of bone homeostasis through RANKL expression

Abstract: Osteocytes embedded in bone have been postulated to orchestrate bone homeostasis by regulating both bone-forming osteoblasts and bone-resorbing osteoclasts. We find here that purified osteocytes express a much higher amount of receptor activator of nuclear factor-κB ligand (RANKL) and have a greater capacity to support osteoclastogenesis in vitro than osteoblasts and bone marrow stromal cells. Furthermore, the severe osteopetrotic phenotype that we observe in mice lacking RANKL specifically in osteocytes indicates that osteocytes are the major source of RANKL in bone remodeling in vivo.

Microbiota regulates immune defense against respiratory tract influenza A virus infection

Abstract: Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro–IL-1β and pro–IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.

An Expanded Palette of Genetically Encoded Ca2+ Indicators

Abstract: Engineered fluorescent protein (FP) chimeras that modulate their fluorescence in response to changes in calcium ion (Ca2+) concentration are powerful tools for visualizing intracellular signaling activity. However, despite a decade of availability, the palette of single FP-based Ca2+ indicators has remained limited to a single green hue. We have expanded this palette by developing blue, improved green, and red intensiometric indicators, as well as an emission ratiometric indicator with an 11,000% ratio change. This series enables improved single-color Ca2+ imaging in neurons and transgenic Caenorhabditis elegans. In HeLa cells, Ca2+ was imaged in three subcellular compartments, and, in conjunction with a cyan FP–yellow FP–based indicator, Ca2+ and adenosine 5′-triphosphate were simultaneously imaged. This palette of indicators paints the way to a colorful new era of Ca2+ imaging.

Long Noncoding RNA HOTAIR Regulates Polycomb-Dependent Chromatin Modification and Is Associated with Poor Prognosis in Colorectal Cancers

Abstract: The functional impact of recently discovered long noncoding RNAs (ncRNAs) in human cancer remains to be clarified. One long ncRNA which has attracted attention is the Hox transcript antisense intergenic RNA termed HOTAIR, a long ncRNA expressed from the developmental HOXC locus located on chromosome 12q13.13. In cooperation with Polycomb complex PRC2, the HOTAIR long ncRNA is reported to reprogram chromatin organization and promote breast cancer metastasis. In this study, we examined the status and function of HOTAIR in patients with stage IV colorectal cancer (CRC) who have liver metastases and a poor prognosis. HOTAIR expression levels were higher in cancerous tissues than in corresponding noncancerous tissues and high HOTAIR expression correlated tightly with the presence of liver metastasis. Moreover, patients with high HOTAIR expression had a relatively poorer prognosis. In a subset of 32 CRC specimens, gene set enrichment analysis using cDNA array data revealed a close correlation between expression of HOTAIR and members of the PRC2 complex (SUZ12, EZH2, and H3K27me3). Our findings suggest that HOTAIR expression is associated with a genome-wide reprogramming of PRC2 function not only in breast cancer but also in CRC, where upregulation of this long ncRNA may be a critical element in metastatic progression.

MIROC-ESM 2010: model description and basic results of CMIP5-20c3m experiments

Abstract: . An earth system model (MIROC-ESM 2010) is fully described in terms of each model component and their interactions. Results for the CMIP5 (Coupled Model Intercomparison Project phase 5) historical simulation are presented to demonstrate the model's performance from several perspectives: atmosphere, ocean, sea-ice, land-surface, ocean and terrestrial biogeochemistry, and atmospheric chemistry and aerosols. An atmospheric chemistry coupled version of MIROC-ESM (MIROC-ESM-CHEM 2010) reasonably reproduces transient variations in surface air temperatures for the period 1850–2005, as well as the present-day climatology for the zonal-mean zonal winds and temperatures from the surface to the mesosphere. The historical evolution and global distribution of column ozone and the amount of tropospheric aerosols are reasonably simulated in the model based on the Representative Concentration Pathways' (RCP) historical emissions of these precursors. The simulated distributions of the terrestrial and marine biogeochemistry parameters agree with recent observations, which is encouraging to use the model for future global change projections.

Efficient up-conversion of triplet excitons into a singlet state and its application for organic light emitting diodes

Abstract: A material possessing a very small energy gap between its singlet and triplet excited states, ΔE1−3, which allows efficient up-conversion of triplet excitons into a singlet state and leads to efficient thermally activated delayed fluorescence (TADF), is reported. The compound, 2-biphenyl-4,6-bis(12-phenylindolo[2,3-a] carbazole-11-yl)-1,3,5-triazine, breaks the restriction of a large energy gap, with a ΔE1−3 of just 0.11 eV, while maintaining a high fluorescent radiative decay rate (kr∼107). The intense TADF provides a pathway for highly efficient electroluminescence.

Stem cell gene expression programs influence clinical outcome in human leukemia

Abstract: Xenograft studies indicate that some solid tumors and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSCs). Despite the promise of the CSC model, its relevance in humans remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model on the basis of sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSCs) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSCs and HSCs, revealing the molecular machinery underlying 'stemness' properties. Both stem cell programs were highly significant independent predictors of patient survival and were found in existing prognostic signatures. Thus, determinants of stemness influence the clinical outcome of AML, establishing that LSCs are clinically relevant and not artifacts of xenotransplantation.

Global dust model intercomparison in AeroCom phase I

Abstract: . This study presents the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project. Each model is compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth (AOD) and dust deposition. Additional comparisons to Angstrom exponent (AE), coarse mode AOD and dust surface concentrations are included to extend the assessment of model performance and to identify common biases present in models. These data comprise a benchmark dataset that is proposed for model inspection and future dust model development. There are large differences among the global models that simulate the dust cycle and its impact on climate. In general, models simulate the climatology of vertically integrated parameters (AOD and AE) within a factor of two whereas the total deposition and surface concentration are reproduced within a factor of 10. In addition, smaller mean normalized bias and root mean square errors are obtained for the climatology of AOD and AE than for total deposition and surface concentration. Characteristics of the datasets used and their uncertainties may influence these differences. Large uncertainties still exist with respect to the deposition fluxes in the southern oceans. Further measurements and model studies are necessary to assess the general model performance to reproduce dust deposition in ocean regions sensible to iron contributions. Models overestimate the wet deposition in regions dominated by dry deposition. They generally simulate more realistic surface concentration at stations downwind of the main sources than at remote ones. Most models simulate the gradient in AOD and AE between the different dusty regions. However the seasonality and magnitude of both variables is better simulated at African stations than Middle East ones. The models simulate the offshore transport of West Africa throughout the year but they overestimate the AOD and they transport too fine particles. The models also reproduce the dust transport across the Atlantic in the summer in terms of both AOD and AE but not so well in winter-spring nor the southward displacement of the dust cloud that is responsible of the dust transport into South America. Based on the dependency of AOD on aerosol burden and size distribution we use model bias with respect to AOD and AE to infer the bias of the dust emissions in Africa and the Middle East. According to this analysis we suggest that a range of possible emissions for North Africa is 400 to 2200 Tg yr−1 and in the Middle East 26 to 526 Tg yr−1.

Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors

Abstract: The location and timing of cellular differentiation must be stringently controlled for proper organ formation. Normally, hepatocytes differentiate from hepatic progenitor cells to form the liver during development. However, previous studies have shown that the hepatic program can also be activated in non-hepatic lineage cells after exposure to particular stimuli or fusion with hepatocytes. These unexpected findings suggest that factors critical to hepatocyte differentiation exist and become activated to induce hepatocyte-specific properties in different cell types. Here, by screening the effects of twelve candidate factors, we identify three specific combinations of two transcription factors, comprising Hnf4α plus Foxa1, Foxa2 or Foxa3, that can convert mouse embryonic and adult fibroblasts into cells that closely resemble hepatocytes in vitro. The induced hepatocyte-like (iHep) cells have multiple hepatocyte-specific features and reconstitute damaged hepatic tissues after transplantation. The generation of iHep cells may provide insights into the molecular nature of hepatocyte differentiation and potential therapies for liver diseases.

Structure of the human histamine H1 receptor complex with doxepin.

Abstract: The biogenic amine histamine is an important pharmacological mediator involved in pathophysiological processes such as allergies and inflammations. Histamine H1 receptor (H1R) antagonists are very effective drugs alleviating the symptoms of allergic reactions. Here we show the crystal structure of the H1R complex with doxepin, a first-generation H1R antagonist. Doxepin sits deep in the ligand-binding pocket and directly interacts with Trp 4286.48, a highly conserved key residue in G-protein-coupled-receptor activation. This well-conserved pocket with mostly hydrophobic nature contributes to the low selectivity of the first-generation compounds. The pocket is associated with an anion-binding region occupied by a phosphate ion. Docking of various second-generation H1R antagonists reveals that the unique carboxyl group present in this class of compounds interacts with Lys 1915.39 and/or Lys 179ECL2, both of which form part of the anion-binding region. This region is not conserved in other aminergic receptors, demonstrating how minor differences in receptors lead to pronounced selectivity differences with small molecules. Our study sheds light on the molecular basis of H1R antagonist specificity against H1R. The common antihistamines are antagonists of histamine H1 receptor (H1R), a G-protein-coupled receptor (GPCR) that is expressed in various tissues including airway, intestinal smooth muscle and brain. The X-ray crystal structure of human H1R in the presence of doxepin, a first-generation H1R antagonist, is now reported. It shows that the drug resides in a much deeper pocket than in other aminergic GPCR structures. Analysis of drug–protein interactions should facilitate the development of antihistamines that are more selective and less likely to cause side effects than those currently available.

SCF FBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction

Abstract: This is one of two papers demonstrating that in several cancer types including ovarian cancer and T-cell leukaemias, the apoptosis regulator MCL1 is targeted for degradation by the FBW7 tumour suppressor. This study finds that this mechanism can determine the response to drugs targeting BCL2 family apoptosis factors. Deletion or mutation of FBW7 found in cancer patients therefore can render tumours resistant to these therapies.

Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians

Abstract: We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 × 10(-8)) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 × 10(-31) and P = 1.3 × 10(-35) for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention.

Wide control of proton conductivity in porous coordination polymers.

Abstract: The proton conductivities of the porous coordination polymers M(OH)(bdc−R) [H2bdc = 1,4-benzenedicarboxylic acid; M = Al, Fe; R = H, NH2, OH, (COOH)2] were investigated under humid conditions. Good correlations among pKa, proton conductivity, and activation energy were observed. Fe(OH)(bdc−(COOH)2), having carboxy group and the lowest pKa, showed the highest proton conductivity and the lowest activation energy in this system. This is the first example in which proton conductivity has been widely controlled by substitution of ligand functional groups in an isostructural series.

Repeatable photoinduced self-healing of covalently cross-linked polymers through reshuffling of trithiocarbonate units

Abstract: Self-healing materials are the subject of increasing interest, because they can repair the internal and external damage thereby extending the lifetime of the material in numerous applications. The initial polymeric self-healing materials relied on microencapsulated healing agents within the bulk polymer. When the system was stressed, the microcapsules were ruptured releasing agents that reacted with the polymer matrix to repair the damage. This reaction was based on covalent bond formation. The covalent bonds provided the desirable mechanical properties at the site of rupture of the microcapsules, but the repair could not be repeated owing to the consumption of the encapsulated agents. On the other hand, systems based on noncovalent bond formation, such as hydrogen bonds and p–p stacking interactions, can provide a repeatable healing response as a consequence of their reversible reactivity. For example, self-healing rubbers and hydrogels were reported as examples of self-healing materials, based on noncovalent bond systems. The challenge for such systems is to enhance the structural stability and mechanical strength of the materials. 10] Recently, dynamic covalent chemistry 12] has attracted much attention. These systems employ the reversible covalent bonds that control the structure of the material by modifying the thermodynamic equilibrium position. The concept has been applied to stimuli responsive polymer networks, systems based on reversible cross-linking reactions, and size-control of covalent networks. Most recently, self-healing systems based on dynamic covalent chemistry have been developed [23,24] where the reversible covalent bonds enable the polymeric material to undergo repetitive self-repair, while providing mechanically stable structures. Typical approaches rely on multiple equilibrium states with functional groups that respond to external stimuli such as thermal stimulation 20, 25] and chemical stimulation. 24] Photostimulation is an especially powerful technique because the stimulation can occur at room temperature, it is easy to handle, and exposure can be limited to targeted areas. Although some photostimulation of covalent selfhealing systems have been reported, 27] no macroscopic selfhealing polymeric systems that depend on photostimulation have been reported. In a previous report, our research group demonstrated self-healing reactions of polymer gels based on reshuffling reactions of trithiocarbonate (TTC) units through chemical stimulation procedures. The TTC units have the potential to undergo photostimulated reshuffling reactions because they can act as photoinitiators in RAFT polymerizations. Herein, we show that systems based on TTC are photoresponsive and can indeed undergo repeatable self-healing resulting from dynamic covalent reshuffling of TTC units, as shown in Figure 1. To the best of our knowledge, this is the first example that achieves both a repeatable self-healing of covalently cross-linked polymers through photostimuli and macroscopic fusion of separate pieces, simultaneously. Model reactions using low-molecular-weight TTC compounds 1 and 2 through UV irradiation were performed to investigate and confirm the photoresponsive reshuffling

Itokawa Dust Particles: A Direct Link Between S-Type Asteroids and Ordinary Chondrites

Abstract: The Hayabusa spacecraft successfully recovered dust particles from the surface of near-Earth asteroid 25143 Itokawa. Synchrotron-radiation x-ray diffraction and transmission and scanning electron microscope analyses indicate that the mineralogy and mineral chemistry of the Itokawa dust particles are identical to those of thermally metamorphosed LL chondrites, consistent with spectroscopic observations made from Earth and by the Hayabusa spacecraft. Our results directly demonstrate that ordinary chondrites, the most abundant meteorites found on Earth, come from S-type asteroids. Mineral chemistry indicates that the majority of regolith surface particles suffered long-term thermal annealing and subsequent impact shock, suggesting that Itokawa is an asteroid made of reassembled pieces of the interior portions of a once larger asteroid.

Transdifferentiation of glioblastoma cells into vascular endothelial cells

Abstract: Glioblastoma (GBM) is the most malignant brain tumor and is highly resistant to intensive combination therapies and anti-VEGF therapies. To assess the resistance mechanism to anti-VEGF therapy, we examined the vessels of GBMs in tumors that were induced by the transduction of p53+/− heterozygous mice with lentiviral vectors containing oncogenes and the marker GFP in the hippocampus of GFAP-Cre recombinase (Cre) mice. We were surprised to observe GFP+ vascular endothelial cells (ECs). Transplantation of mouse GBM cells revealed that the tumor-derived endothelial cells (TDECs) originated from tumor-initiating cells and did not result from cell fusion of ECs and tumor cells. An in vitro differentiation assay suggested that hypoxia is an important factor in the differentiation of tumor cells to ECs and is independent of VEGF. TDEC formation was not only resistant to an anti-VEGF receptor inhibitor in mouse GBMs but it led to an increase in their frequency. A xenograft model of human GBM spheres from clinical specimens and direct clinical samples from patients with GBM also showed the presence of TDECs. We suggest that the TDEC is an important player in the resistance to anti-VEGF therapy, and hence a potential target for GBM therapy.

Recent Progress in Metal Borohydrides for Hydrogen Storage

Abstract: The prerequisite for widespread use of hydrogen as an energy carrier is the development of new materials that can safely store it at high gravimetric and volumetric densities. Metal borohydrides M(BH4)n (n is the valence of metal M), in particular, have high hydrogen density, and are therefore regarded as one such potential hydrogen storage material. For fuel cell vehicles, the goal for on-board storage systems is to achieve reversible store at high density but moderate temperature and hydrogen pressure. To this end, a large amount of effort has been devoted to improvements in their thermodynamic and kinetic aspects. This review provides an overview of recent research activity on various M(BH4)n, with a focus on the fundamental dehydrogenation and rehydrogenation properties and on providing guidance for material design in terms of tailoring thermodynamics and promoting kinetics for hydrogen storage.

Complete electric dipole response and the neutron skin in 208Pb.

Abstract: A benchmark experiment on Pb-208 shows that polarized proton inelastic scattering at very forward angles including 0 degrees is a powerful tool for high-resolution studies of electric dipole (E1) and spin magnetic dipole (M1) modes in nuclei over a broad excitation energy range to test up-to-date nuclear models. The extracted E1 polarizability leads to a neutron skin thickness r(skin) = 0.156(-0.021)(+0.025) fm in Pb-208 derived within a mean-field model [Phys. Rev. C 81, 051303 (2010)], thereby constraining the symmetry energy and its density dependence relevant to the description of neutron stars.

Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus.

Abstract: Genomic imprinting causes parental origin–specific monoallelic gene expression through differential DNA methylation established in the parental germ line. However, the mechanisms underlying how specific sequences are selectively methylated are not fully understood. We have found that the components of the PIWI-interacting RNA (piRNA) pathway are required for de novo methylation of the differentially methylated region (DMR) of the imprinted mouse Rasgrf1 locus, but not other paternally imprinted loci. A retrotransposon sequence within a noncoding RNA spanning the DMR was targeted by piRNAs generated from a different locus. A direct repeat in the DMR, which is required for the methylation and imprinting of Rasgrf1, served as a promoter for this RNA. We propose a model in which piRNAs and a target RNA direct the sequence-specific methylation of Rasgrf1.

Open-Ended, N-Doped Carbon Nanotube-Graphene Hybrid Nanostructures as High-Performance Catalyst Support

Abstract: A hierarchical N-doped carbon nanotube-graphene hybrid nanostructure (NCNT-GHN), in which the graphene layers are distributed inside the CNT inner cavities, was designed to efficiently support noble metal (e.g., PtRu) nanoparticles. Well-dispersed PtRu nanoparticles with diameters of 2–4 nm were immobilized onto these NCNT-GHN supports by a low-temperature chemical reduction method without any pretreatment. Compared to conventional CNTs and commercial catalysts. a much better catalytic performance was achieved by a synergistic effect of the hierarchical structure (graphene-CNT hybrid) and electronic modulation (N-doping) during the methanol electrooxidation reaction. Improved single-cell performances with long-term stability are also demonstrated using NCNT-GHN as catalyst support.

Electrochemical Properties of NaTi2(PO4)3 Anode for Rechargeable Aqueous Sodium-Ion Batteries

Abstract: The charge/discharge characteristics of NaTi2(PO4)3 as an anode active material for aqueous sodium-ion battery containing 2 M Na2SO4 aqueous electrolyte were examined. Cyclic voltammograms, galvanostatic discharge/charge and XRD data of the material indicated that sodium can be reversibly intercalated into NASICON-type NaTi2(PO4)3 without serious degradation of the host structure. The best reversible capacity at rate of 2.0 mA cm−2 was 93% of the theoretical capacity of 133 mAh g−1 and the plateau voltage was 2.1 V versus Na/Na+.

Glucose tolerance status and risk of dementia in the community: The Hisayama Study

Abstract: Objective: We investigated the association between glucose tolerance status defined by a 75-g oral glucose tolerance test (OGTT) and the development of dementia. Methods: A total of 1,017 community-dwelling dementia-free subjects aged ≥60 years who underwent the OGTT were followed up for 15 years. Outcome measure was clinically diagnosed dementia. Results: The age- and sex-adjusted incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) were significantly higher in subjects with diabetes than in those with normal glucose tolerance. These associations remained robust even after adjustment for confounding factors for all-cause dementia and AD, but not for VaD (all-cause dementia: adjusted hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.19 to 2.53, p = 0.004; AD: adjusted HR = 2.05, 95% CI = 1.18 to 3.57, p = 0.01; VaD: adjusted HR = 1.82, 95% CI = 0.89 to 3.71, p = 0.09). Moreover, the risks of developing all-cause dementia, AD, and VaD significantly increased with elevated 2-hour postload glucose (PG) levels even after adjustment for covariates, but no such associations were observed for fasting plasma glucose (FPG) levels: compared with those with 2-hour PG levels of Conclusions: Our findings suggest that diabetes is a significant risk factor for all-cause dementia, AD, and probably VaD. Moreover, 2-hour PG levels, but not FPG levels, are closely associated with increased risk of all-cause dementia, AD, and VaD.