| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 9. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 11. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 12. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 13. |
- Poyatos, R., et al.
(författare)
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Global transpiration data from sap flow measurements: the SAPFLUXNET database
- 2021
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2607-2649
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Tidskriftsartikel (refereegranskat)abstract
- Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land-atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The "sapfluxnetr" R package - designed to access, visualize, and process SAPFLUXNET data - is available from CRAN.
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| 14. |
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| 16. |
- Adlarson, P., et al.
(författare)
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Isospin decomposition of the basic double-pionic fusion in the region of the ABC effect
- 2013
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 721:4-5, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive and kinematically complete high-statistics measurements of the basic double-pionic fusion reactions pn -> d pi(0)pi(0), pn -> d pi(+)pi(-) and pp -> d pi(+)pi(0) have been carried out simultaneously over the energy region of the ABC effect using the WASA detector setup at COSY. Whereas the isoscalar reaction part given by the d pi(0)pi(0) channel exhibits the ABC effect, i.e. a low-mass enhancement in the pi pi-invariant mass distribution, as well as the associated resonance structure in the total cross section, the isovector part given by the d pi(+)pi(0) channel shows a smooth behavior consistent with the conventional t-channel Delta Delta process. The d pi(+)pi(-) data are very well reproduced by combining the data for isovector and isoscalar contributions, if the kinematical consequences of the isospin violation due to different masses for charged and neutral pions are taken into account.
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| 17. |
- Adlarson, Patrik, et al.
(författare)
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Search for eta-mesic He-4 with the WASA-at-COSY detector
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:3, s. 035204-
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Tidskriftsartikel (refereegranskat)abstract
- An exclusive measurement of the excitation function for the dd -> (3)Hep pi(-) reaction was performed at the Cooler Synchrotron COSY-Julich with the WASA-at-COSY detection system. The data were taken during a slow acceleration of the beam from 2.185 to 2.400 GeV/c crossing the kinematic threshold for the eta-meson production in the dd -> He-4 eta reaction at 2.336 GeV/c. The corresponding excess energy with respect to the He-4-eta system varied from -51.4 to 22 MeV. The integrated luminosity in the experiment was determined using the dd -> (3)Hen reaction. The shape of the excitation function for the dd -> (3)Hep pi(-) reaction was examined. No signal of the He-4-eta bound state was observed. An upper limit for the cross section for the bound state formation and decay in the process dd -> (He-4-eta)(bound) -> (3)Hep pi(-) was determined on the 90% confidence level and it varies from 20 to 27 nb for the bound state width ranging from 5 to 35 MeV, respectively.
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| 18. |
- Adlarson, Patrik, et al.
(författare)
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Abashian-Booth-Crowe Effect in Basic Double-Pionic Fusion : A New Resonance?
- 2011
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:24, s. 242302-
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Tidskriftsartikel (refereegranskat)abstract
- We report on an exclusive and kinematically complete high-statistics measurement of the basic double-pionic fusion reaction pn -> d pi(0)pi(0) over the full energy region of the ABC effect, a pronounced low-mass enhancement in the pi pi-invariant mass spectrum. The measurements, which cover also the transition region to the conventional t- channel Delta Delta process, were performed with the upgraded WASA detector setup at COSY. The data reveal the Abashian-Booth-Crowe effect to be uniquely correlated with a Lorentzian energy dependence in the integral cross section. The observables are consistent with a narrow resonance with m = 2.37 GeV, Gamma approximate to 70 MeV and I(J(P)) = 0(3(+)) in both pn and Delta Delta systems. Necessary further tests of the resonance interpretation are discussed.
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| 19. |
- Adlarson, Patrik, et al.
(författare)
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Abashian-Booth-Crowe resonance structure in the double pionic fusion to He-4
- 2012
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 86:3, s. 032201-
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive and kinematically complete high-statistics measurements of the double pionic fusion reaction dd -> He-4 pi(0)pi(0) have been performed in the energy range 0.8-1.4 GeV covering thus the region of the Abashian-Booth-Crowe effect, which denotes a pronounced low-mass enhancement in the pi pi invariant mass spectrum. The experiments were carried out with the WASA detector setup at the cooler synchrotron at Forshungszentrum Julich GmbH. Similar to the observation in the basic pn -> d pi(0)pi(0) reaction, the data reveal a correlation between the ABC effect and a resonancelike energy dependence in the total cross section. The maximum occurs at m = 2.37 GeV + 2m(N), i.e., at the same position as in the basic reaction. The observed resonance width Gamma approximate to 160 MeV can be understood from broadening due to Fermi motion of the nucleons in initial and final nuclei together with collision damping. Differential cross sections are described equally well by the hypothesis of a pn resonance formation during the reaction process.
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| 20. |
- Adlarson, Patrik, et al.
(författare)
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Exclusive measurement of the eta -> pi(+) pi(-) gamma decay
- 2012
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 707:2, s. 243-249
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Tidskriftsartikel (refereegranskat)abstract
- An exclusive measurement of the decay eta -> pi(+) pi(-) gamma has been performed at the WASA facility at COSY. The eta mesons were produced in the fusion reaction pd -> He-3 X at a proton beam momentum of 1.7 GeV/c. Efficiency corrected differential distributions have been extracted based on 13 960 +/- 140 events after background subtraction. The measured pion angular distribution is consistent with a relative p-wave of the two-pion system, whereas the measured photon energy spectrum was found at variance with the simplest gauge invariant matrix element of eta -> pi(+) pi(-) gamma. A parameterization of the data can be achieved by the additional inclusion of the empirical pion vector form factor multiplied by a first-order polynomial in the squared invariant mass of the pi(+) pi(-) system.
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| 21. |
- Adlarson, Patrik, et al.
(författare)
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Investigation of the dd -> (3)Hen pi(0) reaction with the FZ Julich WASA-at-COSY facility
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:1, s. 014004-
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Tidskriftsartikel (refereegranskat)abstract
- An exclusive measurement of the dd -> (3)Hen pi(0) reaction was carried out at a beam momentum of p(d) = 1.2 GeV/c using the WASA-at-COSY facility. Information on the total cross section as well as differential distributions was obtained. The data are described by a phenomenological approach based on a combination of a quasifree model and a partial wave expansion for the three-body reaction. The total cross section is found to be sigma(tot) = ( 2.89 +/- 0.01(stat) +/- 0.06(sys) +/- 0.29(norm)) mu b. The contribution of the quasifree processes ( with the beam or target neutron being a spectator) accounts for 38% of the total cross section and dominates the differential distributions in specific regions of phase space. The remaining part of the cross section can be described by a partial wave decomposition indicating the significance of p-wave contributions in the final state.
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| 22. |
- Adlarson, Patrik, et al.
(författare)
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Measurement of the pn -> pp pi(0)pi(-) reaction in search for the recently observed resonance structure in d pi(0)pi(0) and d pi(+)pi(-) systems
- 2013
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 88:5, s. 055208-
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive measurements of the quasifree pn -> pp pi(0)pi(-) reaction have been performed by means of pd collisions at T-p = 1.2 GeV using the wide angle shower apparatus (WASA) detector setup at the cooler synchrotron COSY (Institut fur Kernphysik, Julich). Total and differential cross sections have been obtained covering the energy region root s = (2.35-2.46) GeV, which includes the region of the ABC effect and its associated resonance structure. NoABCeffect, i.e., low-mass enhancement is found in the pi(0)pi(-) -invariant mass spectrum, in agreement with the constraint from Bose statistics that the isovector pion pair can not be in relative s wave. At the upper end of the covered energy region t-channel processes for Roper, Delta(1600) and Delta Delta excitations provide a reasonable description of the data, but at low energies the measured cross sections are much larger than predicted by such processes. Adding a resonance amplitude for the resonance at m = 2.37 GeV with Gamma = 70 MeV and I (J(P)) = 0(3(+)) observed recently in pn -> d pi(0)pi(0) and pn -> d pi(+)pi(-) reactions leads to an agreement with the data also at low energies.
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| 23. |
- Adlarson, Patrik, et al.
(författare)
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pi(0)pi(0) Production in proton-proton collisions at T-p=1.4 GeV The WASA-at-COSY Collaboration
- 2012
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 706:4-5, s. 256-262
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Tidskriftsartikel (refereegranskat)abstract
- The reaction pp -> pp pi(0)pi(0) has been investigated at a beam energy of 1.4 GeV using the WASA-at-COSY facility. The total cross section is found to be (324 +/- 21(systematic) +/- 58(normalization)) mu b. In order to study the production mechanism, differential kinematic distributions have been evaluated. The differential distributions indicate that both initial state protons are excited into intermediate Delta(1232) resonances, each decaying into a proton and a single pion, thereby producing the pion pair in the final state. No significant contribution of the Roper resonance N*(1440) via its decay into a proton and two pions is found.
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| 24. |
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| 25. |
- Adlarson, Patrik, et al.
(författare)
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ABC effect and resonance structure in the double-pionic fusion to He-3
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 91:1, s. 015201-
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive and kinematically complete measurements of the double pionic fusion to He-3 have been performed in the energy region of the so-called ABC effect, which denotes a pronounced low-mass enhancement in the pi pi-invariant mass spectrum. The experiments were carried out with the WASA detector setup at COSY (the cooler synchrotron at Forschungszentrum Julich). Similar to the observations in the basic pn -> d pi(0)pi(0) reaction and in the dd -> He-4 pi(0)pi(0) reaction, the data reveal a correlation between the ABC effect and a resonance-like energy dependence in the total cross section. Differential cross sections are well described by the hypothesis of d* resonance formation during the reaction process in addition to the conventional t-channel Delta Delta mechanism. The deduced d* resonance width can be understood from collision broadening due to Fermi motion of the nucleons in initial and final nuclei.
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