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2. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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8. |
- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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9. |
- Landén, Mikael, 1966, et al.
(författare)
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Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5124-5139
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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10. |
- Thoma, B, et al.
(författare)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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13. |
- Patel, Y., et al.
(författare)
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Virtual Ontogeny of Cortical Growth Preceding Mental Illness
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
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Tidskriftsartikel (refereegranskat)abstract
- Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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14. |
- Fernández, A., et al.
(författare)
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Reinterpretation of excited states in 212Po: Shell-model multiplets rather than α-cluster states
- 2021
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 104:5
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Tidskriftsartikel (refereegranskat)abstract
- A γ-ray spectroscopic study of 212Po was performed at the Grand Accélérateur National d'Ions Lourds, using the inverse kinematics α-transfer reaction 12C(208Pb,212Po)8Be and the AGATA spectrometer. A careful analysis based on γγ coincidence relations allowed us to establish 14 new excited states in the energy range between 1.9 and 3.3 MeV. None of these states, however, can be considered as candidates for the levels with spins and parities of 1− and 2− and excitation energies below 2.1 MeV, which have been predicted by recent α-cluster model calculations. A systematic comparison of the experimentally established excitation scheme of 212Po with shell-model calculations was performed. This comparison suggests that the six states with excitation energies (spins and parities) of 1744 (4−), 1751 (8−), 1787 (6−), 1946 (4−), 1986 (8−), and 2016 (6−) keV, which previously were interpreted as α-cluster states, may in fact be of positive parity and belong to low-lying shell-model multiplets. This reinterpretation of the structure of 212Po is supported by experimental information with respect to the linear polarization of γ rays, which suggests a magnetic character of the 432-keV γ ray decaying from the state at an excitation energy of 1787 keV to the 6+ yrast state, and exclusive reaction cross sections.
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16. |
- Avigo, R., et al.
(författare)
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Low-lying electric dipole gamma-continuum for the unstable Fe-62,64 nuclei : Strength evolution with neutron number
- 2020
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Ingår i: Physics Letters B. - : ELSEVIER. - 0370-2693 .- 1873-2445. ; 811
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Tidskriftsartikel (refereegranskat)abstract
- The gamma-ray emission from the nuclei Fe-62,Fe-64 following Coulomb excitation at bombarding energy of 400-440 AMeV was measured with special focus on E1 transitions in the energy region 4-8 MeV. The unstable neutron-rich nuclei Fe-62,Fe-64 were produced at the FAIR-GSI laboratories and selected with the FRS spectrometer. The gamma decay was detected with AGATA. From the measured gamma-ray spectra the summed E1 strength is extracted and compared to microscopic quasi-particle phonon model calculations. The trend of the E1 strength with increasing neutron number is found to be fairly well reproduced with calculations that assume a rather complex structure of the 1(-) states (three-phonon states) inducing a strong fragmentation of the E1 nuclear response below the neutron binding energy.
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18. |
- Cederwall, B., et al.
(författare)
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Isospin Properties of Nuclear Pair Correlations from the Level Structure of the Self-Conjugate Nucleus Ru-88
- 2020
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 124:6
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Tidskriftsartikel (refereegranskat)abstract
- The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N = Z) nuclide Ru-88(44)44 has been measured using the combination of the Advanced Gamma Tracking Array (AGATA) spectrometer, the NEDA and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in Ru-88 were populated via the Fe-54(Ar-36, 2n gamma)Ru-88* fusion-evaporation reaction at the Grand Accelerateur National d'Ions Lourds (GANIL) accelerator complex. The observed gamma-ray cascade is assigned to Ru-88 using clean prompt gamma-gamma-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N > Z nuclides. The direct observation of such a "delayed" rotational alignment in a deformed N = Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.
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19. |
- Cederwall, Bo, 1964-, et al.
(författare)
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Isospin Properties of Nuclear Pair Correlations from the Level Structure of the Self-Conjugate Nucleus Ru 88
- 2020
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 124:6
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Tidskriftsartikel (refereegranskat)abstract
- The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N = Z) nuclide 88Ru has been measured using the combination of the Advanced Gamma Tracking Array (AGATA)spectrometer, the NEDA, and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in 88 Ru were populated via the 54 Feð 36 Ar; 2nγÞ 88 Ru fusion-evaporationreaction at the Grand Accélérateur National d’Ions Lourds (GANIL) accelerator complex. The observed γ-ray cascade is assigned to 88 Ru using clean prompt γ-γ-2-neutron coincidences in anticoincidence with the detection of charged particles, confirming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N > Z nuclides. The direct observation of such a “delayed” rotational alignment in a deformed N 1⁄4 Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.
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20. |
- Liu, X., et al.
(författare)
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Evidence for enhanced neutron-proton correlations from the levelstructure of the N= Z+ 1 nucleus 8743Tc44
- 2021
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 104:2
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Tidskriftsartikel (refereegranskat)abstract
- The low-lying excited states in the neutron-deficient N = Z + 1 nucleus (87)(43)Tcc(44) have been studied via the fusion-evaporation reaction Fe-54(Ar-36, 2n1p)Tc-87 at the Grand Accelerateur National d'Ions Lourds (GANIL), France. The AGATA spectrometer was used in conjunction with the auxiliary NEDA, Neutron Wall, and DIAMANT detector arrays to measure coincident prompt gamma rays, neutrons, and charged particles emitted in the reaction. A level scheme of Tc-87 from the (9/2(g.s.)(+)) state to the (33/2(1)(+)) state was established based on six mutually coincident gamma-ray transitions. The constructed level structure exhibits a rotational behavior with a sharp backbending at (h) over bar omega approximate to 0.50 MeV. A decrease in alignment frequency and increase in alignment sharpness in the odd-mass isotonic chains around N = 44 is proposed as an effect of the enhanced isoscalar neutron-proton interactions in odd-mass nuclei when approaching the N = Z line.
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21. |
- Liu, Xiaoyu, et al.
(författare)
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Evidence for spherical-oblate shape coexistence in Tc-87
- 2022
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 106:3
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the neutron-deficient nucleus Tc-87 have been studied via the fusion-evaporation reaction 54Fe(36Ar, 2n1p) Tc-87 at 115 MeV beam energy. The AGATA gamma-ray spectrometer coupled to the DIAMANT, NEDA, and Neutron Wall detector arrays for light-particle detection was used to measure the prompt coincidence of gamma rays and light particles. Six transitions from the deexcitation of excited states belonging to a new band in Tc-87 were identified by comparing gamma-ray intensities in the spectra gated under different reaction channel selection conditions. The constructed level structure was compared with the shell model and total Routhian surface calculations. The results indicate that the new band structure in 87Tc is built on a spherical configuration, which is different from that assigned to the previously identified oblate yrast rotational band.
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23. |
- Siciliano, M., et al.
(författare)
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Pairing-quadrupole interplay in the neutron-deficient tin nuclei : First lifetime measurements of low-lying states in Sn-106,Sn-108
- 2020
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Ingår i: Physics Letters B. - : ELSEVIER. - 0370-2693 .- 1873-2445. ; 806
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Tidskriftsartikel (refereegranskat)abstract
- The lifetimes of the low-lying excited states 2(+) and 4(+) have been directly measured in the neutron-deficient Sn-106,Sn-108 isotopes. The nuclei were populated via a deep-inelastic reaction and the lifetime measurement was performed employing a differential plunger device. The emitted gamma rays were detected by the AGATA array, while the reaction products were uniquely identified by the VAMOS++ magnetic spectrometer. Large-Scale Shell-Model calculations with realistic forces indicate that, independently of the pairing content of the interaction, the quadrupole force is dominant in the B(E2; 2(1)(+) -> 0(g.s)(+)) values and it describes well the experimental pattern for Sn104-114 ; the B(E2;(+)(4) -> 2(1)(+)) values, measured here for the first time, depend critically on a delicate pairing-quadrupole balance, disclosed by the very precise results in Sn-108.
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24. |
- Belov, Vladimir, et al.
(författare)
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Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
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26. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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27. |
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28. |
- Carroll, R. J., et al.
(författare)
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γ -ray spectroscopy of a four-quasiparticle isomer band in Re 174
- 2020
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Ingår i: Physical Review C. - 2469-9985. ; 101:5
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in Re174 have been populated in fusion-evaporation reactions at the Australian National University, and γ-ray spectroscopy has been used to determine the level structure and to deduce the underlying nucleon configurations. The half-life of the bandhead of the Kπ=8- band has been measured to be 2.7(4) ns. A band built on an isomeric state of spin-parity (14-) and a half-life of 53(5) ns has been observed here for the first time, and has been determined to have a four-quasiparticle structure. Contrasting reduced-hindrance values for its decay are discussed in terms of deformation and configuration changes, as indicated by configuration-constrained potential energy surface calculations.
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29. |
- Ciemala, M., et al.
(författare)
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Testing ab initio nuclear structure in neutron-rich nuclei : Lifetime measurements of second 2(+) state in C-16 and O-20
- 2020
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Ingår i: Physical Review C. - : AMER PHYSICAL SOC. - 2469-9985 .- 2469-9993. ; 101:2
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Tidskriftsartikel (refereegranskat)abstract
- To test the predictive power of ab initio nuclear structure theory, the lifetime of the second 2(+) state in neutron-rich O-20, tau(2(2)(+)) = 150(-30)(+80) fs, and an estimate for the lifetime of the second 2(+) state in C-16 have been obtained for the first time. The results were achieved via a novel Monte Carlo technique that allowed us to measure nuclear state lifetimes in the tens-to-hundreds of femtoseconds range by analyzing the Doppler-shifted gamma-transition line shapes of products of low-energy transfer and deep-inelastic processes in the reaction O-18 (7.0 MeV/u) + Ta-181. The requested sensitivity could only be reached owing to the excellent performances of the Advanced gamma-Tracking Array AGATA, coupled to the PARIS scintillator array and to the VAMOS++ magnetic spectrometer. The experimental lifetimes agree with predictions of ab initio calculations using two- and three-nucleon interactions, obtained with the valence-space in-medium similarity renormalization group for O-20 and with the no-core shell model for C-16. The present measurement shows the power of electromagnetic observables, determined with high-precision gamma spectroscopy, to assess the quality of first-principles nuclear structure calculations, complementing common benchmarks based on nuclear energies. The proposed experimental approach will be essential for short lifetime measurements in unexplored regions of the nuclear chart, including r-process nuclei, when intense beams, produced by Isotope Separation On-Line (ISOL) techniques, become available.
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30. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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31. |
- Parr, E., et al.
(författare)
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Single-particle states and parity doublets in odd- Z Ac 221 and Pa 225 from α -decay spectroscopy
- 2022
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Ingår i: Physical Review C. - 2469-9985. ; 105:3
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Tidskriftsartikel (refereegranskat)abstract
- Low-lying states in the odd-Z isotopes Ac13289221 and Pa13491225 have been studied using α-particle and αγ-coincidence spectroscopy in the Pa225→Ac221→Fr217 decay chain. Ground-state spin and parity assignments of Iπ = 5/2- are proposed for both Ac221 and Pa225, with the odd proton occupying the ω = 5/2 orbital of the quadrupole-octupole deformed shell model in both nuclei. In Ac221, excited states in the bands based on the ω = 5/2 and ω = 3/2 orbitals have been identified, including proposed parity-doublet states. The results suggest that reflection-asymmetric deformation of the ground state persists in the odd-A members of the isotope chains down to N = 132 for Ac and N = 134 for Pa, before reaching the transitional region at N = 130.
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32. |
- Perez-Vidal, R. M., et al.
(författare)
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Evidence of Partial Seniority Conservation in the pi g9/2 Shell for the N=50 Isotones
- 2022
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 129:11
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Tidskriftsartikel (refereegranskat)abstract
- The reduced transition probabilities for the 4+1 -2+1 and 2+1 -0+1 transitions in 92Mo and 94Ru and for the 4+1 -2+1 and 6+1 -4+1 transitions in 90Zr have been determined in this experiment making use of a multinucleon transfer reaction. These results have been interpreted on the basis of realistic shell-model calculations in the f5=2, p3=2, p1=2, and g9=2 proton valence space. Only the combination of extensive lifetime information and large scale shell-model calculations allowed the extent of the seniority conservation in the N = 50 g9=2 orbital to be understood. The conclusion is that seniority is largely conserved in the first 71g9=2 orbital.
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33. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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34. |
- Bakalis, Serafim, et al.
(författare)
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Perspectives from CO+RE : How COVID-19 changed our food systems and food security paradigms.
- 2020
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Ingår i: Current Research in Food Science. - : Elsevier BV. - 2665-9271. ; 3, s. 166-172
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Tidskriftsartikel (refereegranskat)abstract
- Within a few weeks the world has changed, at the time this text is written (May 2020) more than 3.5 million people have been confirmed cases of COVID-19 and estimations propose up to a hundred times the number of actually infected. A third of the global population is on lockdown and a large part of our global economic activity has stopped. Food and access to food has played a visual role in portraying the impact of the outbreak on our society, with images of empty supermarket shelves appearing in mainstream media. In some countries closed schools resulted in many children not having access to free meals and mobilised a number of charities. While parts of the world are now exiting lockdown and measures start relaxing the near future remains uncertain with more waves of the pandemic expected. Given that there is currently no evidence to show that transmission of COVID-19 could occur through food or food packaging there has been limited discussion on the issue, implications and potential future scenarios within the wider food science community.Within the food research community, up to the pandemic crisis the discourse has been dominated with design and manufacture of healthy and safe foods. The main issues are relevant to sustainability, circular economy, energy and water efficiency, climate friendly practices of products and processes. Efficiency has been the focus, but resilience has not been a significant issue so far. The term food system resilience has been defined by Tendalla (Tendalla et al., 2015) as ‘capacity over time of a food system and its units at multiple levels, to provide sufficient, appropriate and accessible food to all, in the face of various and even unforeseen disturbances’. We believe that in the future we will continue to see similar pressures in the food system, e.g., comparable pandemics, effects of climate change on food production, and that resilience will become of major importance.This commentary aims to present a reflection from the past, considering the present situation to provide thoughts on the actions needed to ensure resilient food systems.
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35. |
- Brum, Wagner S., et al.
(författare)
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A two-step workflow based on plasma p-tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases
- 2023
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Ingår i: Nature Aging. - 2662-8465. ; 3:9, s. 1079-1090
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Tidskriftsartikel (refereegranskat)abstract
- Cost-effective strategies for identifying amyloid-beta (A beta) positivity in patients with cognitive impairment are urgently needed with recent approvals of anti-A beta immunotherapies for Alzheimer's disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow can reduce the number of confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests needed while accurately classifying patients. We evaluated a two-step workflow for determining A beta-PET status in patients with mild cognitive impairment (MCI) from two independent memory clinic-based cohorts (n = 348). A blood-based model including plasma tau protein 217 (p-tau217), age and APOE epsilon 4 status was developed in BioFINDER-1 (area under the curve (AUC) = 89.3%) and validated in BioFINDER-2 (AUC = 94.3%). In step 1, the blood-based model was used to stratify the patients into low, intermediate or high risk of A beta-PET positivity. In step 2, we assumed referral only of intermediate-risk patients to CSF A beta 42/A beta 40 testing, whereas step 1 alone determined A beta-status for low-and high-risk groups. Depending on whether lenient, moderate or stringent thresholds were used in step 1, the two-step workflow overall accuracy for detecting A beta-PET status was 88.2%, 90.5% and 92.0%, respectively, while reducing the number of necessary CSF tests by 85.9%, 72.7% and 61.2%, respectively. In secondary analyses, an adapted version of the BioFINDER-1 model led to successful validation of the two-step workflow with a different plasma p-tau217 immunoassay in patients with cognitive impairment from the TRIAD cohort (n = 84). In conclusion, using a plasma p-tau217-based model for risk stratification of patients with MCI can substantially reduce the need for confirmatory testing while accurately classifying patients, offering a cost-effective strategy to detect AD in memory clinic settings.
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36. |
- Cullen, Nicholas C., et al.
(författare)
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Test-retest variability of plasma biomarkers in Alzheimer's disease and its effects on clinical prediction models
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:3, s. 797-806
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION The effect of random error on the performance of blood-based biomarkers for Alzheimer's disease (AD) must be determined before clinical implementation. METHODS We measured test-retest variability of plasma amyloid beta (A beta)42/A beta 40, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (p-tau)217 and simulated effects of this variability on biomarker performance when predicting either cerebrospinal fluid (CSF) A beta status or conversion to AD dementia in 399 non-demented participants with cognitive symptoms. RESULTS Clinical performance was highest when combining all biomarkers. Among single-biomarkers, p-tau217 performed best. Test-retest variability ranged from 4.1% (A beta 42/A beta 40) to 25% (GFAP). This variability reduced the performance of the biomarkers (approximate to Delta AUC [area under the curve] -1% to -4%) with the least effects on models with p-tau217. The percent of individuals with unstable predicted outcomes was lowest for the multi-biomarker combination (14%). DISCUSSION Clinical prediction models combining plasma biomarkers-particularly p-tau217-exhibit high performance and are less effected by random error. Individuals with unstable predicted outcomes ("gray zone") should be recommended for further tests.
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37. |
- Koenig, Julian, et al.
(författare)
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Cortical thickness and resting-state cardiac function across the lifespan : A cross-sectional pooled mega-analysis
- 2021
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Ingår i: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986 .- 1540-5958. ; 58:7
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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38. |
- Leuzy, A., et al.
(författare)
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Robustness of CSF A beta 42/40 and A beta 42/P-tau181 measured using fully automated immunoassays to detect AD-related outcomes
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:7, s. 2994-3004
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThis study investigated the comparability of cerebrospinal fluid (CSF) cutoffs for Elecsys immunoassays for amyloid beta (A beta)42/A beta 40 or A beta 42/phosphorylated tau (p-tau)181 and the effects of measurement variability when predicting Alzheimer's disease (AD)-related outcomes (i.e., A beta-positron emission tomography [PET] visual read and AD neuropathology). MethodsWe studied 750 participants (BioFINDER study, Alzheimer's Disease Neuroimaging Initiative [ADNI], and University of California San Francisco [UCSF]). Youden's index was used to identify cutoffs and to calculate accuracy (A beta-PET visual read as outcome). Using longitudinal variability in A beta-negative controls, we identified a gray zone around cut-points where the risk of an inconsistent predicted outcome was >5%. ResultsFor A beta 42/A beta 40, cutoffs across cohorts were <0.059 (BioFINDER), <0.057 (ADNI), and <0.058 (UCSF). For A beta 42/p-tau181, cutoffs were <41.90 (BioFINDER), <39.20 (ADNI), and <46.02 (UCSF). Accuracy was approximate to 90% for both A beta 42/A beta 40 and A beta 42/p-tau181 using these cutoffs. Using A beta-PET as an outcome, 8.7% of participants fell within a gray zone interval for A beta 42/A beta 40, compared to 4.5% for A beta 42/p-tau181. Similar findings were observed using a measure of overall AD neuropathologic change (7.7% vs. 3.3%). In a subset with CSF and plasma A beta 42/40, the number of individuals within the gray zone was approximate to 1.5 to 3 times greater when using plasma A beta 42/40. DiscussionCSF A beta 42/p-tau181 was more robust to the effects of measurement variability, suggesting that it may be the preferred Elecsys-based measure in clinical practice and trials.
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39. |
- Neves, Joana B., et al.
(författare)
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Pattern, timing and predictors of recurrence after surgical resection of chromophobe renal cell carcinoma
- 2021
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Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 39:10, s. 3823-3831
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death. Methods: Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015–2019) and the international collaborative database RECUR (15 institutes, 2006–2011). Kaplan–Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source. Results: 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (< 24 months) was observed in 8 cases, all staged ≥ pT2b. 30 deaths occurred, of which 11 were attributed to chRCC. Sarcomatoid differentiation was rare (n = 4) but associated with recurrence and cancer-specific death on univariate analysis. On multivariate analysis, UICC/AJCC T-stage ≥ pT2b, presence of coagulative necrosis, and positive surgical margins were predictors of recurrence and cancer-specific death. Conclusion: Recurrence and death after surgically resected chRCC are rare. For completely excised lesions ≤ pT2a without coagulative necrosis or sarcomatoid features, prognosis is excellent. These patients should be reassured and follow-up intensity curtailed.
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40. |
- Novy, Vera, 1986, et al.
(författare)
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The characteristics of insoluble softwood substrates affect fungal morphology, secretome composition, and hydrolytic efficiency of enzymes produced by Trichoderma reesei
- 2021
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834 .- 1754-6834. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: On-site enzyme production using Trichoderma reesei can improve yields and lower the overall cost of lignocellulose saccharification by exploiting the fungal gene regulatory mechanism that enables it to continuously adapt enzyme secretion to the substrate used for cultivation. To harness this, the interrelation between substrate characteristics and fungal response must be understood. However, fungal morphology or gene expression studies often lack structural and chemical substrate characterization. Here, T. reesei QM6a was cultivated on three softwood substrates: northern bleached softwood Kraft pulp (NBSK) and lodgepole pine pretreated either by dilute-acid-catalyzed steam pretreatment (LP-STEX) or mild alkaline oxidation (LP-ALKOX). With different pretreatments of similar starting materials, we presented the fungus with systematically modified substrates. This allowed the elucidation of substrate-induced changes in the fungal response and the testing of the secreted enzymes’ hydrolytic strength towards the same substrates. Results: Enzyme activity time courses correlated with hemicellulose content and cellulose accessibility. Specifically, increased amounts of side-chain-cleaving hemicellulolytic enzymes in the protein produced on the complex substrates (LP-STEX; LP-ALKOX) was observed by secretome analysis. Confocal laser scanning micrographs showed that fungal micromorphology responded to changes in cellulose accessibility and initial culture viscosity. The latter was caused by surface charge and fiber dimensions, and likely restricted mass transfer, resulting in morphologies of fungi in stress. Supplementing a basic cellulolytic enzyme mixture with concentrated T. reesei supernatant improved saccharification efficiencies of the three substrates, where cellulose, xylan, and mannan conversion was increased by up to 27, 45, and 2800%, respectively. The improvement was most pronounced for proteins produced on LP-STEX and LP-ALKOX on those same substrates, and in the best case, efficiencies reached those of a state-of-the-art commercial enzyme preparation. Conclusion: Cultivation of T. reesei on LP-STEX and LP-ALKOX produced a protein mixture that increased the hydrolytic strength of a basic cellulase mixture to state-of-the-art performance on softwood substrates. This suggests that the fungal adaptation mechanism can be exploited to achieve enhanced performance in enzymatic hydrolysis without a priori knowledge of specific substrate requirements.
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41. |
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42. |
- Palmqvist, Sebastian, et al.
(författare)
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An accurate fully automated panel of plasma biomarkers for Alzheimer's disease
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:4, s. 1204-1215
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Tidskriftsartikel (refereegranskat)abstract
- Introduction There is a great need for fully automated plasma assays that can measure amyloid beta (A beta) pathology and predict future Alzheimer's disease (AD) dementia. Methods Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma A beta 42/A beta 40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results The best biomarker for discriminating A beta-positive versus A beta-negative participants was A beta 42/A beta 40 (are under the curve [AUC] 0.83-0.87). Combining A beta 42/A beta 40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (Delta AUC <= 0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and A beta 42/A beta 40 in MCI (AUC 0.87). Discussion The high accuracies for A beta pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.
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43. |
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44. |
- Salvadó, Gemma, et al.
(författare)
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Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients: A multi-cohort study
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:7, s. 2943-2955
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases.Methods: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of A beta 42, A beta 40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, alpha-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit).Results: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU) was best predicted by p-tau/A beta 42 alone (R-2 >= 0.31) or together with NfL (R-2 = 0.25), while p-tau/A beta 42 (R-2 >= 0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/A beta 42 (AUC >= 0.87) and p-tau/A beta 42 together with NfL (AUC >= 0.75) were the best predictors of conversion to AD and all-cause dementia, respectively.Discussion: P-tau/A beta 42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.
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45. |
- Spijkers, Jessica, et al.
(författare)
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Exploring the future of fishery conflict through narrative scenarios
- 2021
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 4:3, s. 386-396
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies suggest that the pervasive impacts on global fishery resources caused by stressors such as overfishing and climate change could dramatically increase the likelihood of fishery conflict. However, existing projections do not consider wider economic, social, or political trends when assessing the likelihood of, and influences on, future conflict trajectories. In this paper, we build four future fishery conflict scenarios by considering multiple fishery conflict drivers derived from an expert workshop, a longitudinal database of international fishery conflict, secondary data on conflict driver trends, and regional expert reviews. The scenarios take place between the years 2030 and 2060 in the North-East Atlantic (scramble for the Atlantic''), the East China Sea (the remodeled empire''), the coast of West Africa (oceanic decolonization''), and the Arctic (polar renaissance''). The scenarios explore the implications of ongoing trends in conflict-prone regions of the world and function as accessible, science-based communication tools that can help foster anticipatory governance capacity in the pursuit of future ocean security.
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46. |
- Zhang, Wei, et al.
(författare)
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Identification of excited states in Te55 52107
- 2021
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Ingår i: Physical Review C. Nuclear Physics. - : American Physical Society. - 0556-2813 .- 1089-490X. ; 104:6
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the extremely neutron-deficient nucleus Te107 have been identified from two separate experiments using the recoil-decay tagging technique. Two connected structures were observed on the basis of γγ-coincidence relations and tentatively assigned as built on the mixed-parentage νg7/2d5/2 and νh11/2 intruder configurations. The observed structures were compared with large-scale shell-model calculations and total Routhian surface calculations. Collective behavior was discovered to persist in the νh11/2 band of Te107 which highlights the shape-polarizing effect of a single valence neutron occupying the h11/2 intruder orbit as the N=50 shell closure is approached.
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