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1.
  • Acharya, B. S., et al. (författare)
  • Introducing the CTA concept
  • 2013
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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  • Actis, M., et al. (författare)
  • Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
  • 2011
  • Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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  • Imanishi, T., et al. (författare)
  • Integrative annotation of 21,037 human genes validated by full-length cDNA clones
  • 2004
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
  • Tidskriftsartikel (refereegranskat)abstract
    • The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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4.
  • Silventoinen, K., et al. (författare)
  • The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
  • 2019
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
  • Tidskriftsartikel (refereegranskat)abstract
    • The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status. 
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  • Nakajima, K., et al. (författare)
  • Enhanced diagnostic accuracy for quantitative bone scan using an artificial neural network system: A Japanese multi-center database project
  • 2013
  • Ingår i: EJNMMI Research. - 2191-219X. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Artificial neural network (ANN)-based bone scan index (BSI), a marker of the amount of bone metastasis, has been shown to enhance diagnostic accuracy and reproducibility but is potentially affected by training databases. The aims of this study were to revise the software using a large number of Japanese databases and to validate its diagnostic accuracy compared with the original Swedish training database. Methods The BSI was calculated with EXINIbone (EB; EXINI Diagnostics) using the Swedish training database (n = 789). The software using Japanese training databases from a single institution (BONENAVI version 1, BN1, n = 904) and the revised version from nine institutions (version 2, BN2, n = 1,532) were compared. The diagnostic accuracy was validated with another 503 multi-center bone scans including patients with prostate (n = 207), breast (n = 166), and other cancer types. The ANN value (probability of abnormality) and BSI were calculated. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) analyses were performed. Results The ROC analysis based on the ANN value showed significant improvement from EB to BN1 and BN2. In men (n = 296), the area under the curve (AUC) was 0.877 for EB, 0.912 for BN1 (p = not significant (ns) vs. EB) and 0.934 for BN2 (p = 0.007 vs. EB). In women (n = 207), the AUC was 0.831 for EB, 0.910 for BN1 (p = 0.016 vs. EB), and 0.932 for BN2 (p < 0.0001 vs. EB). The optimum sensitivity and specificity based on BN2 was 90% and 84% for men and 93% and 85% for women. In patients with prostate cancer, the AUC was equally high with EB, BN1, and BN2 (0.939, 0.949, and 0.957, p = ns). In patients with breast cancer, the AUC was improved from EB (0.847) to BN1 (0.910, p = ns) and BN2 (0.924, p = 0.039). The NRI using ANN between EB and BN1 was 17.7% (p = 0.0042), and that between EB and BN2 was 29.6% (p < 0.0001). With respect to BSI, the NRI analysis showed downward reclassification with total NRI of 31.9% (p < 0.0001). Conclusion In the software for calculating BSI, the multi-institutional database significantly improved identification of bone metastasis compared with the original database, indicating the importance of a sufficient number of training databases including various types of cancers. © 2013 Nakajima et al.
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  • Stoop, Thomas F., et al. (författare)
  • Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy
  • 2024
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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12.
  • Aharonian, Felix, et al. (författare)
  • Atmospheric gas dynamics in the Perseus cluster observed with Hitomi
  • 2018
  • Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Extending the earlier measurements reported in Hitomi collaboration (2016, Nature, 535, 117), we examine the atmospheric gas motions within the central 100 kpc of the Perseus cluster using observations obtained with the Hitomi satellite. After correcting for the point spread function of the telescope and using optically thin emission lines, we find that the line-of-sight velocity dispersion of the hot gas is remarkably low and mostly uniform. The velocity dispersion reaches a maxima of approximately 200 km s(-1) toward the central active galactic nucleus (AGN) and toward the AGN inflated northwestern ghost bubble. Elsewhere within the observed region, the velocity dispersion appears constant around 100 km s(-1). We also detect a velocity gradient with a 100 km s(-1) amplitude across the cluster core, consistent with large-scale sloshing of the core gas. If the observed gas motions are isotropic, the kinetic pressure support is less than 10% of the thermal pressure support in the cluster core. The well-resolved, optically thin emission lines have Gaussian shapes, indicating that the turbulent driving scale is likely below 100 kpc, which is consistent with the size of the AGN jet inflated bubbles. We also report the first measurement of the ion temperature in the intracluster medium, which we find to be consistent with the electron temperature. In addition, we present a new measurement of the redshift of the brightest cluster galaxy NGC 1275.
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  • Rolland, J., et al. (författare)
  • Conceptual and empirical bridges between micro- and macroevolution
  • 2023
  • Ingår i: Nature Ecology and Evolution. - 2397-334X. ; 7, s. 1181-1193
  • Tidskriftsartikel (refereegranskat)abstract
    • This Perspective discusses four questions of evolutionary biology that bridge macro and microevolution perspectives and proposes future research avenues to link evolutionary mechanisms and processes. Explaining broad molecular, phenotypic and species biodiversity patterns necessitates a unifying framework spanning multiple evolutionary scales. Here we argue that although substantial effort has been made to reconcile microevolution and macroevolution, much work remains to identify the links between biological processes at play. We highlight four major questions of evolutionary biology whose solutions require conceptual bridges between micro and macroevolution. We review potential avenues for future research to establish how mechanisms at one scale (drift, mutation, migration, selection) translate to processes at the other scale (speciation, extinction, biogeographic dispersal) and vice versa. We propose ways in which current comparative methods to infer molecular evolution, phenotypic evolution and species diversification could be improved to specifically address these questions. We conclude that researchers are in a better position than ever before to build a synthesis to understand how microevolutionary dynamics unfold over millions of years.
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18.
  • SUGAWARA, M, et al. (författare)
  • HIGH-SPIN STATES IN RB-79
  • 1995
  • Ingår i: JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN. - : PHYSICAL SOCIETY JAPAN KIKAI-SHINKO BUILDING. ; 64:1
  • Annan publikation (övrigt vetenskapligt/konstnärligt)
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19.
  • Sugawara, Toshitaka, et al. (författare)
  • Neoadjuvant chemotherapy versus upfront surgery for resectable pancreatic adenocarcinoma : an updated nationwide study
  • 2024
  • Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 279:2, s. 331-339
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). BACKGROUND: The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear.METHODS: Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery.RESULTS: In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages.CONCLUSIONS: The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.
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