Showing papers by "Kyushu University published in 2015"
National University of Cordoba1, Addis Ababa University2, National Autonomous University of Mexico3, State University of Campinas4, United Nations Environment Programme5, UNESCO6, United States Department of Agriculture7, Indiana University8, University of British Columbia9, Commonwealth Scientific and Industrial Research Organisation10, University of Paris-Sud11, Landcare Research12, University College London13, Autonomous University of Madrid14, University of Cambridge15, Council for Scientific and Industrial Research16, University of Southern Denmark17, United Nations University18, Virginia Tech College of Natural Resources and Environment19, The Nature Conservancy20, University of the South Pacific21, University of East Anglia22, Kyushu University23, King Abdulaziz City for Science and Technology24, University of Washington25, Budapest University of Technology and Economics26, Environmental Law Institute27, Ankara University28, University of Portsmouth29, Chinese Academy of Sciences30, Indian Institute of Technology Bombay31, Kyoto University32, Joseph Fourier University33, National Scientific and Technical Research Council34, University of Yaoundé35, Polish Academy of Sciences36, University of São Paulo37, École Normale Supérieure38, University of Otago39, Stanford University40, University of Queensland41, Azim Premji University42, Helmholtz Centre for Environmental Research - UFZ43, University of Ghana44, Corvinus University of Budapest45, Stockholm University46, Lakehead University47, Indian Institute of Forest Management48, Seoul National University49, Sofia University50
TL;DR: The first public product of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) is its Conceptual Framework as discussed by the authors, which will underpin all IPBES functions and provide structure and comparability to the syntheses that will produce at different spatial scales, on different themes, and in different regions.
1,585 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
23 Aug 2015
TL;DR: A new Challenge 4 on Incidental Scene Text has been added to the Challenges on Born-Digital Images, Focused Scene Images and Video Text and tasks assessing End-to-End system performance have been introduced to all Challenges.
Abstract: Results of the ICDAR 2015 Robust Reading Competition are presented. A new Challenge 4 on Incidental Scene Text has been added to the Challenges on Born-Digital Images, Focused Scene Images and Video Text. Challenge 4 is run on a newly acquired dataset of 1,670 images evaluating Text Localisation, Word Recognition and End-to-End pipelines. In addition, the dataset for Challenge 3 on Video Text has been substantially updated with more video sequences and more accurate ground truth data. Finally, tasks assessing End-to-End system performance have been introduced to all Challenges. The competition took place in the first quarter of 2015, and received a total of 44 submissions. Only the tasks newly introduced in 2015 are reported on. The datasets, the ground truth specification and the evaluation protocols are presented together with the results and a brief summary of the participating methods.
1,224 citations
TL;DR: Associations between inherited cellular transport gene variants and risk of EOC histologic subtypes are revealed on a large cohort of women.
Abstract: BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
1,100 citations
TL;DR: It is shown that a large delocalization of the highest occupied molecular orbital and lowest unoccupied molecular orbital in these charge-transfer compounds enhances the rate of radiative decay considerably by inducing a large oscillator strength even when there is a small overlap between the two wavefunctions.
Abstract: Organic compounds that exhibit highly efficient, stable blue emission are required to realize inexpensive organic light-emitting diodes for future displays and lighting applications. Here, we define the design rules for increasing the electroluminescence efficiency of blue-emitting organic molecules that exhibit thermally activated delayed fluorescence. We show that a large delocalization of the highest occupied molecular orbital and lowest unoccupied molecular orbital in these charge-transfer compounds enhances the rate of radiative decay considerably by inducing a large oscillator strength even when there is a small overlap between the two wavefunctions. A compound based on our design principles exhibited a high rate of fluorescence decay and efficient up-conversion of triplet excitons into singlet excited states, leading to both photoluminescence and internal electroluminescence quantum yields of nearly 100%.
1,007 citations
Emory University1, Harvard University2, University of Tennessee3, Wakayama Medical University4, University of British Columbia5, Mayo Clinic6, University of Verona7, Tokyo Medical University8, Ohio State University9, Tokyo Metropolitan Komagome Hospital10, Shinshu University11, Kanazawa University12, University of Ulsan13, Kyoto University14, Yokohama City University15, University of Greifswald16, Karolinska Institutet17, Kanazawa Medical University18, University of Toyama19, Kyushu University20, Nagoya City University21, Kansai Medical University22, Aix-Marseille University23, Tohoku University24, Sapporo Medical University25, Teikyo University26, University College London27, Peking Union Medical College28
TL;DR: A. H. Wallace, J. L. Carruthers, S. L€ ohr, Y. Khosroshahi, Z. Chari, E. Della-Torre, L. Frulloni, H.
Abstract: A. Khosroshahi, Z. S. Wallace, J. L. Crowe, T. Akamizu, A. Azumi, M. N. Carruthers, S. T. Chari, E. Della-Torre, L. Frulloni, H. Goto, P. A. Hart, T. Kamisawa, S. Kawa, M. Kawano, M. H. Kim, Y. Kodama, K. Kubota, M. M. Lerch, M. L€ ohr, Y. Masaki, S. Matsui, T. Mimori, S. Nakamura, T. Nakazawa, H. Ohara, K. Okazaki, J. H. Ryu, T. Saeki, N. Schleinitz, A. Shimatsu, T. Shimosegawa, H. Takahashi, M. Takahira, A. Tanaka, M. Topazian, H. Umehara, G. J. Webster, T. E. Witzig, M. Yamamoto, W. Zhang, T. Chiba, and J. H. Stone
728 citations
TL;DR: A thermally activated delayed fluorescence material for organic light-emitting diodes is shown, which realizes both approximately 100% photoluminescence quantum yield and Approximately 100% up-conversion of the triplet to singlet excited state.
Abstract: Efficient organic light-emitting diodes have been developed using emitters containing rare metals, such as platinum and iridium complexes. However, there is an urgent need to develop emitters composed of more abundant materials. Here we show a thermally activated delayed fluorescence material for organic light-emitting diodes, which realizes both approximately 100% photoluminescence quantum yield and approximately 100% up-conversion of the triplet to singlet excited state. The material contains electron-donating diphenylaminocarbazole and electron-accepting triphenyltriazine moieties. The typical trade-off between effective emission and triplet-to-singlet up-conversion is overcome by fine-tuning the highest occupied molecular orbital and lowest unoccupied molecular orbital distributions. The nearly zero singlet–triplet energy gap, smaller than the thermal energy at room temperature, results in an organic light-emitting diode with external quantum efficiency of 29.6%. An external quantum efficiency of 41.5% is obtained when using an out-coupling sheet. The external quantum efficiency is 30.7% even at a high luminance of 3,000 cd m−2. Organic light-emitting diodes promise a more environment-friendly future for light sources, but many use rare metals. Here, the authors present an approach that achieves external quantum efficiency over 40% by realising 100% up-conversion from triplet to singlet excitons and thus 100% radiative emission.
718 citations
TL;DR: In this article, the authors delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors, suggesting that there is functional interplay between the mutations that drive clonal selection.
Abstract: Grade II and III gliomas are generally slowly progressing brain cancers, many of which eventually transform into more aggressive tumors Despite recent findings of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis is still incomplete Here, combining two large sets of high-throughput sequencing data, we delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection Extensive serial and multi-regional sampling analyses further supported this finding and also identified a high degree of temporal and spatial heterogeneity generated during tumor expansion and relapse, which is likely shaped by the complex but ordered processes of multiple clonal selection and evolutionary events
675 citations
Kyriaki Michailidou1, Jonathan Beesley2, Sara Lindström3, Sander Canisius +280 more•Institutions (76)
TL;DR: 15 new loci associated with breast cancer at P < 5 × 10−8 are identified, and one association appears to be driven by an amino acid substitution encoded in EXO1, which is found in women of European ancestry.
Abstract: Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.
523 citations
TL;DR: The connection between hydrogen-enhanced plasticity and the hydrogen-induced fracture mechanism and pathway is established through examination of the evolved microstructural state immediately beneath fracture surfaces including voids, quasi-cleavage, and intergranular surfaces as discussed by the authors.
Abstract: The connection between hydrogen-enhanced plasticity and the hydrogen-induced fracture mechanism and pathway is established through examination of the evolved microstructural state immediately beneath fracture surfaces including voids, “quasi-cleavage,” and intergranular surfaces. This leads to a new understanding of hydrogen embrittlement in which hydrogen-enhanced plasticity processes accelerate the evolution of the microstructure, which establishes not only local high concentrations of hydrogen but also a local stress state. Together, these factors establish the fracture mechanism and pathway.
519 citations
Royal Free Hospital1, Institut Gustave Roussy2, University of Perugia3, University of Turin4, Imperial College London5, University of Milan6, University of Bern7, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico8, Memorial Sloan Kettering Cancer Center9, University of Marburg10, Autonomous University of Barcelona11, Erasmus University Rotterdam12, Uppsala University13, University of Genoa14, Churchill Hospital15, Kyushu University16, National Institutes of Health17, National and Kapodistrian University of Athens18, University of Reims Champagne-Ardenne19, University of Copenhagen20, Medical University of Silesia21, Curie Institute22, Aberdeen Royal Infirmary23, University College Dublin24, Charité25, Charles University in Prague26, University College London27, University of Freiburg28, Peking Union Medical College29
TL;DR: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up, and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC.
Kyushu University1, University of California, San Diego2, Keio University3, National Cheng Kung University4, Fox Chase Cancer Center5, Lamar University6, Fudan University7, United States Department of Veterans Affairs8, San Diego State University9, Medical University of South Carolina10, French Institute of Health and Medical Research11, University of Paris12
TL;DR: It is shown in mice and human cells that gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the gp130 effector STAT3.
Abstract: Inflammation promotes regeneration of injured tissues through poorly understood mechanisms, some of which involve interleukin (IL)-6 family members, the expression of which is elevated in many diseases including inflammatory bowel diseases and colorectal cancer. Here we show in mice and human cells that gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the gp130 effector STAT3. Through YAP and Notch, intestinal gp130 signalling stimulates epithelial cell proliferation, causes aberrant differentiation and confers resistance to mucosal erosion. gp130 associates with the related tyrosine kinases Src and Yes, which are activated on receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signalling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.
TL;DR: Blue and green organic light-emitting diodes containing a hole-transport layer, an undoped TADF emissive layer, and an electron-trans transport layer achieve maximum external quantum efficiencies of 19%, which is comparable to the best doped OLEDs.
Abstract: The design of efficient and concentration-insensitive metal-free thermally activateddelayed fluorescence (TADF) materials is reported. Blue and green organic light-emitting diodes (OLEDs) containing a hole-transport layer, an undoped TADF emissive layer, and an electron-transport layer achieve maximum external quantum efficiencies of 19%, which is comparable to the best doped OLEDs.
TL;DR: In this article, the authors provide a detailed account of these improvements, focusing specifically on microstructure evolution during processing, and expander expansion during the fabrication of dual-phase alloys.
Abstract: Dual-phase (DP) steel is the flagship of advanced high-strength steels, which were the first among various candidate alloy systems to find application in weight-reduced automotive components. On the one hand, this is a metallurgical success story: Lean alloying and simple thermomechanical treatment enable use of less material to accomplish more performance while complying with demanding environmental and economic constraints. On the other hand, the enormous literature on DP steels demonstrates the immense complexity of microstructure physics in multiphase alloys: Roughly 50 years after the first reports on ferrite-martensite steels, there are still various open scientific questions. Fortunately, the last decades witnessed enormous advances in the development of enabling experimental and simulation techniques, significantly improving the understanding of DP steels. This review provides a detailed account of these improvements, focusing specifically on (a) microstructure evolution during processing, (b) exp...
TL;DR: It is discussed how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies and pitfalls which might be faced by researchers in the field.
Environment Canada1, European Centre for Medium-Range Weather Forecasts2, Royal Meteorological Institute3, Royal Netherlands Meteorological Institute4, Leibniz Association5, National Institute for Environmental Studies6, National Institute of Information and Communications Technology7, Kyushu University8, European Space Research and Technology Centre9
TL;DR: The EarthCARE satellite mission as discussed by the authors provides global profiles of cloud, aerosol, precipitation, and associated radiative properties inferred from a combination of measurements made by collocated active and passive sensors.
Abstract: The collective representation within global models of aerosol, cloud, precipitation, and their radiative properties remains unsatisfactory. They constitute the largest source of uncertainty in predictions of climatic change and hamper the ability of numerical weather prediction models to forecast high-impact weather events. The joint ESA-JAXA EarthCARE satellite mission, scheduled for launch in 2017, will help to resolve these weaknesses by providing global profiles of cloud, aerosol, precipitation, and associated radiative properties inferred from a combination of measurements made by its collocated active and passive sensors. EarthCARE will improve our understanding of cloud and aerosol processes by extending the invaluable dataset acquired by the A-Train satellites CloudSat, CALIPSO, and Aqua. Specifically, EarthCARE's Cloud Profling Radar, with 7 dB more sensitivity than CloudSat, will detect more thin clouds and its Doppler capability will provide novel information on convection, precipitating ice particle and raindrop fall speeds. EarthCARE's 355-nm High Spectral Resolution Lidar will measure directly and accurately cloud and aerosol extinction and optical depth. Combining this with backscatter and polarization information should lead to an unprecedented ability to identify aerosol type. The Multi-Spectral Imager will provide a context for, and the ability to construct the cloud and aerosol distribution in 3D domains around the narrow 2D retrieved cross-section. The consistency of the retrievals will be assessed to within a target of ±10 W m−2 on the (10 km2) scale by comparing the multi-view Broad-Band Radiometer observations to the top-of-atmosphere fluxes estimated by 3D radiative transfer models acting on retrieved 3D domains.
TL;DR: In this paper, the authors proposed new universal scaling parameters for the dilemma strength, and proved universality by showing that the conditions for an ESS and the expressions for the internal equilibriums in an infinite, well-mixed population subjected to any of the five reciprocity mechanisms depend only on the new scaling parameters.
TL;DR: Investigation of the role of dynamin-related protein 1 (Drp1), a GTPase that mediates mitochondrial fission, in mediating mitochondrial autophagy, ventricular function, and stress resistance in the heart found disruption of Drp1 induces mitochondrial elongation, inhibits mitochondrial autophileagy, and causes mitochondrial dysfunction, thereby promoting cardiac dysfunction and increased susceptibility to ischemia/reperfusion.
Abstract: Rationale: Both fusion and fission contribute to mitochondrial quality control. How unopposed fusion affects survival of cardiomyocytes and left ventricular function in the heart is poorly understood. Objective: We investigated the role of dynamin-related protein 1 (Drp1), a GTPase that mediates mitochondrial fission, in mediating mitochondrial autophagy, ventricular function, and stress resistance in the heart. Methods and Results: Drp1 downregulation induced mitochondrial elongation, accumulation of damaged mitochondria, and increased apoptosis in cardiomyocytes at baseline. Drp1 downregulation also suppressed autophagosome formation and autophagic flux at baseline and in response to glucose deprivation in cardiomyocytes. The lack of lysosomal translocation of mitochondrially targeted Keima indicates that Drp1 downregulation suppressed mitochondrial autophagy. Mitochondrial elongation and accumulation of damaged mitochondria were also observed in tamoxifen-inducible cardiac-specific Drp1 knockout mice. After Drp1 downregulation, cardiac-specific Drp1 knockout mice developed left ventricular dysfunction, preceded by mitochondrial dysfunction, and died within 13 weeks. Autophagic flux is significantly suppressed in cardiac-specific Drp1 knockout mice. Although left ventricular function in cardiac-specific Drp1 heterozygous knockout mice was normal at 12 weeks of age, left ventricular function decreased more severely after 48 hours of fasting, and the infarct size/area at risk after ischemia/reperfusion was significantly greater in cardiac-specific Drp1 heterozygous knockout than in control mice. Conclusions: Disruption of Drp1 induces mitochondrial elongation, inhibits mitochondrial autophagy, and causes mitochondrial dysfunction, thereby promoting cardiac dysfunction and increased susceptibility to ischemia/reperfusion.
TL;DR: In this article, a search for new phenomena in final states with an energetic jet and large missing transverse momentum was performed using 20.3 fb(-1) of root s = 8 TeV data collected in 2012.
Abstract: Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb(-1) of root s = 8 TeV data collected in 2012 ...
TL;DR: Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients and showed poorer prognoses than the low expression group.
Abstract: Background Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the early detection of recurrence in human colorectal cancer (CRC). Methods Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT-PCR. Results Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P Conclusions Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.
University of Oxford1, The George Institute for Global Health2, Johns Hopkins University3, Colef4, University of Edinburgh5, University College London6, Imperial College London7, Boston University8, University of South Florida9, University of Washington10, University of California, San Francisco11, University of Gothenburg12, Wake Forest University13, Kyushu University14, Group Health Cooperative15, National Cheng Kung University16, NHS Scotland17, Norwegian Institute of Public Health18, Stockholm University19, Tianjin Medical University20, Curtin University21, University of Sydney22
TL;DR: A meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia found individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes.
Abstract: OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45–1.80]; men: pooled RR 1.58 [95% CI 1.38–1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86–2.94) in women and 1.73 (95% CI 1.61–1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35–1.73) in women and 1.49 (95% CI 1.31–1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08–1.30]; P CONCLUSIONS Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.
TL;DR: Patients with PD-L1(+) DLBCL had inferior overall survival (OS) compared with that in patients withPD-L 1(-)DLBCL (P = .0009); in contrast, there was no significant difference in OS between mPD- L1(+) and mPD/PAX5(+), and the expression of PD- l1 maintained prognostic value for OS in multivariate analysis.
TL;DR: Findings that both EML4–ALK and mutant EGFR upregulate PD-L1 by activating PI3K–AKT and MEK–ERK signaling pathways in NSCLC reveal a direct link between oncogenic drivers and PD- L1 expression.
Abstract: Purpose:Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in a subset of patients with non-small cell lung cancer (NSCLC). We have now examined PD-L1 expression and its regulation in NSCLC positive for the EML4-ALK fusion gene.
Experimental Design:The expression of PD-L1 at the protein and mRNA levels in NSCLC cell lines was examined by flow cytometry and by reverse transcription and real-time PCR analysis, respectively. The expression of PD-L1 in 134 surgically resected NSCLC specimens was evaluated by immunohistochemical analysis.
Results:The PD-L1 expression level was higher in NSCLC cell lines positive for EML4-ALK than in those negative for the fusion gene. Forced expression of EML4-ALK in Ba/F3 cells markedly increased PD-L1 expression, whereas endogenous PD-L1 expression in EML4-ALK-positive NSCLC cells was attenuated by treatment with the specific ALK inhibitor alectinib or by RNA interference with ALK siRNAs. Furthermore, expression of PD-L1 was down-regulated by inhibitors of the MEK-ERK and PI3K-AKT signaling pathways in NSCLC cells positive for either EML4-ALK or activating mutations of the epidermal growth factor receptor (EGFR). Finally, the expression level of PD-L1 was positively associated with the presence of EML4-ALK in NSCLC specimens.
Conclusions:Our findings that both EML4-ALK and mutant EGFR up-regulate PD-L1 by activating PI3K-AKT and MEK-ERK signaling pathways in NSCLC reveal a direct link between oncogenic drivers and PD-L1 expression.
TL;DR: Parallel studies in cultured murine embryonic fibroblasts and in vivo mouse hearts revealed that Mfn1/Mfn2 deletion provoked accumulation of defective mitochondria exhibiting an unfolded protein response, without appropriately increasing mitophagy, and interrupting mitochondrial fission by Drp1 ablation increased mitophileagy and caused a generalized loss of mitochondria.
Teikyo University1, University of Occupational and Environmental Health Japan2, International University of Health and Welfare3, Mie University4, Tokyo Medical University5, Jichi Medical University6, Kanazawa University7, Kyushu University8, Kyoto Prefectural University of Medicine9, Shinshu University10, Sapporo Medical University11, Kindai University12, Tohoku University13, University of Tokyo14, Yokohama City University Medical Center15
TL;DR: Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006, and following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, the development of a minimally invasive method for local complications of pancreatitis spread was developed.
Abstract: Background
Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines.
Methods
A comprehensive evaluation was carried out on the evidence for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on the concepts of the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). With the graded recommendations, where the evidence was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional new meta-analysis, the results of which were included in the guidelines.
Results
Thirty-nine questions were prepared in 17 subject areas, for which 43 recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy, Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor, Nutritional support, Intensive care, management of Biliary Pancreatitis, management of Abdominal Compartment Syndrome, Interventions for the local complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis Bundles 2015). Meta-analysis was conducted in the following four subject areas based on randomized controlled trials: (1) prophylactic antibiotics use; (2) prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the results of the meta-analysis, recommendations were graded to create useful information. In addition, a mobile application was developed, which made it possible to diagnose, assess severity and check pancreatitis bundles.
Conclusions
The JPN Guidelines 2015 were prepared using the most up-to-date methods, and including the latest recommended medical treatments, and we are confident that this will make them easy for many clinicians to use, and will provide a useful tool in the decision-making process for the treatment of patients, and optimal medical support. The free mobile application and calculator for the JPN Guidelines 2015 is available via http://www.jshbps.jp/en/guideline/jpn-guideline2015.html
Stanford University1, University of Minnesota2, Center for International Blood and Marrow Transplant Research3, Medical College of Wisconsin4, University of Michigan5, Harvard University6, Fred Hutchinson Cancer Research Center7, University of Wisconsin Hospital and Clinics8, University of Pennsylvania9, Temple University10, Memorial Sloan Kettering Cancer Center11, Karolinska University Hospital12, Vanderbilt University Medical Center13, University of British Columbia14, Kyushu University15, Ottawa Hospital16, Washington University in St. Louis17, Vanderbilt University18, University of Texas MD Anderson Cancer Center19, Alberta Children's Hospital20, Imperial College London21, Duke University22, Gulf Coast Regional Blood Center23, University of Florida24, Florida Hospital Orlando25, Roswell Park Cancer Institute26, Spanish National Research Council27, Mayo Clinic28, Royal Adelaide Hospital29, Nagoya University30, Karolinska Institutet31, Uppsala University32, Emory University33, Columbia University Medical Center34
TL;DR: In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods and the mounting need for addressing this major late complication of transplantation in future research is underscores.
TL;DR: In this article, the authors conducted real-time measurements of non-refractory submicron aerosol (NR-PM1) species (sulfate, nitrate, ammonium, chloride, and organics) in Beijing using an Aerodyne Aerosol Chemical Speciation Monitor for 1 year, from July 2011 to June 2012.
Abstract: . High concentrations of fine particles (PM2.5) are frequently observed during all seasons in Beijing, China, leading to severe air pollution and human health problems in this megacity. In this study, we conducted real-time measurements of non-refractory submicron aerosol (NR-PM1) species (sulfate, nitrate, ammonium, chloride, and organics) in Beijing using an Aerodyne Aerosol Chemical Speciation Monitor for 1 year, from July 2011 to June 2012. This is the first long-term, highly time-resolved (~ 15 min) measurement of fine particle composition in China. The seasonal average (±1σ) mass concentration of NR-PM1 ranged from 52 (±49) μg m−3 in the spring season to 62 (±49) μg m−3 in the summer season, with organics being the major fraction (40–51 %), followed by nitrate (17–25 %) and sulfate (12–17 %). Organics and chloride showed pronounced seasonal variations, with much higher concentrations in winter than in the other seasons, due to enhanced coal combustion emissions. Although the seasonal variations of secondary inorganic aerosol (SIA, i.e., sulfate + nitrate + ammonium) concentrations were not significant, higher contributions of SIA were observed in summer (57–61 %) than in winter (43–46 %), indicating that secondary aerosol production is a more important process than primary emissions in summer. Organics presented pronounced diurnal cycles that were similar among all seasons, whereas the diurnal variations of nitrate were mainly due to the competition between photochemical production and gas–particle partitioning. Our data also indicate that high concentrations of NR-PM1 (> 60 μg m−3) are usually associated with high ambient relative humidity (RH) (> 50 %) and that severe particulate pollution is characterized by different aerosol composition in different seasons. All NR-PM1 species showed evident concentration gradients as a function of wind direction, generally with higher values associated with wind from the south, southeast or east. This was consistent with their higher potential as source areas, as determined by potential source contribution function analysis. A common high potential source area, located to the southwest of Beijing along the Taihang Mountains, was observed during all seasons except winter, when smaller source areas were found. These results demonstrate a high potential impact of regional transport from surrounding regions on the formation of severe haze pollution in Beijing.
TL;DR: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity, and can be considered a standard treatment for inoperable stage INSCLC.
Abstract: Purpose To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC). Methods and Materials Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients. Results Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed. Conclusions Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.
TL;DR: The present study describes a new drug where molecular self-assembly acts as the mechanism of cytotoxicity, and reports cancer cell death initiated by the intracellular molecularSelf-assembly of a peptide lipid, which was derived from a gelator precursor.
Abstract: We report cancer cell death initiated by the intracellular molecular self-assembly of a peptide lipid, which was derived from a gelator precursor. The gelator precursor was designed to form nanofibers via molecular self-assembly, after cleavage by a cancer-related enzyme (matrix metalloproteinase-7, MMP-7), leading to hydrogelation. The gelator precursor exhibited remarkable cytotoxicity to five different cancer cell lines, while the precursor exhibited low cytotoxicity to normal cells. Cancer cells secrete excessive amounts of MMP-7, which converted the precursor into a supramolecular gelator prior to its uptake by the cells. Once inside the cells, the supramolecular gelator formed a gel via molecular self-assembly, exerting vital stress on the cancer cells. The present study thus describes a new drug where molecular self-assembly acts as the mechanism of cytotoxicity.
TL;DR: In this article, the jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton-proton collision data with a centre-of-mass energy of [Formula: see text]TeV corresponding to an integrated luminosity of [formula] see text][formula:see text].
Abstract: The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton-proton collision data with a centre-of-mass energy of [Formula: see text] TeV corresponding to an integrated luminosity of [Formula: see text][Formula: see text]. Jets are reconstructed from energy deposits forming topological clusters of calorimeter cells using the anti-[Formula: see text] algorithm with distance parameters [Formula: see text] or [Formula: see text], and are calibrated using MC simulations. A residual JES correction is applied to account for differences between data and MC simulations. This correction and its systematic uncertainty are estimated using a combination of in situ techniques exploiting the transverse momentum balance between a jet and a reference object such as a photon or a [Formula: see text] boson, for [Formula: see text] and pseudorapidities [Formula: see text]. The effect of multiple proton-proton interactions is corrected for, and an uncertainty is evaluated using in situ techniques. The smallest JES uncertainty of less than 1 % is found in the central calorimeter region ([Formula: see text]) for jets with [Formula: see text]. For central jets at lower [Formula: see text], the uncertainty is about 3 %. A consistent JES estimate is found using measurements of the calorimeter response of single hadrons in proton-proton collisions and test-beam data, which also provide the estimate for [Formula: see text] TeV. The calibration of forward jets is derived from dijet [Formula: see text] balance measurements. The resulting uncertainty reaches its largest value of 6 % for low-[Formula: see text] jets at [Formula: see text]. Additional JES uncertainties due to specific event topologies, such as close-by jets or selections of event samples with an enhanced content of jets originating from light quarks or gluons, are also discussed. The magnitude of these uncertainties depends on the event sample used in a given physics analysis, but typically amounts to 0.5-3 %.