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  • Abe, O, et al. (författare)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • 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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  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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  • Wang, F., et al. (författare)
  • Reinvestigation of the excited states in the proton emitter Lu-151 : Particle-hole excitations across the N = Z=64 subshell
  • 2017
  • Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 96:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The excited states of the proton emitter Lu-151 were reinvestigated in a recoil-decay tagging experiment at the Accelerator Laboratory of the University of Jyvaskyla (JYFL). The level scheme built on the ground state of 151Lu was updated with five new y-ray transitions. Large-scale shell model calculations were carried out in the model space consisting of the neutron and proton orbitals 0g(7/2), Id(5/2), Id(3/2), 2s(1/2), and Oh(1/2) with the optimized monopole interaction in order to interpret the experimental level scheme of Lu-151. It is found that the excitation energies of states above the 27/2(-) and 23/2(+) isomeric levels in Lu-151 can be sensitive to excitations from g(7/2) and d(5/2) to single-particle orbitals above N = Z = 64.
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  • Wang, F., et al. (författare)
  • Spectroscopic factor and proton formation probability for the d3/2 proton emitter 151mLu
  • 2017
  • Ingår i: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 770, s. 83-87
  • Tidskriftsartikel (refereegranskat)abstract
    • The quenching of the experimental spectroscopic factor for proton emission from the short-lived d3/2 isomeric state in 151mLu was a long-standing problem. In the present work, proton emission from this isomer has been reinvestigated in an experiment at the Accelerator Laboratory of the University of Jyväskylä. The proton-decay energy and half-life of this isomer were measured to be 1295(5) keV and 15.4(8) μs, respectively, in agreement with another recent study. These new experimental data can resolve the discrepancy in the spectroscopic factor calculated using the spherical WKB approximation. Using the R-matrix approach it is found that the proton formation probability indicates no significant hindrance for the proton decay of 151mLu.
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  • Antalic, S., et al. (författare)
  • The new isotopes in Po-Rn region
  • 2007
  • Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 38:4, s. 1557-1560
  • Tidskriftsartikel (refereegranskat)abstract
    • This contribution reviews the results of the recent experiments at the velocity filter SHIP in GSI Darmstadt obtained in the region of neutron deficient isotopes from lead to radon. The data for new very neutron-deficient isotopes Po-187, Rn-193,Rn-194 and their decay properties are presented. The isotopes were produced and identified in the complete fusion reactions Ti-46+Sm-144 -> Po-187+3n and Cr-52+Sm-144 -> Rn-194,Rn-193+2,3n.
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  • Andreyev, A. N., et al. (författare)
  • alpha decay of the new isotopes Rn-193,Rn-194
  • 2006
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 74:6, s. 064303-
  • Tidskriftsartikel (refereegranskat)abstract
    • The new neutron-deficient isotopes Rn-193,Rn-194 have been identified in the complete fusion reaction Cr-52+Sm-144 -> Rn-196(*) at the velocity filter SHIP. The alpha-decay energy and half-life value of Rn-194 were determined to be E-alpha=7700(10) keV and T-1/2=0.78(16) ms, respectively. For Rn-193 the half-life of T-1/2=1.15(27) ms and two alpha lines at E-alpha 1=7685(15) keV, I-alpha 1=74(20)% and E-alpha 2=7875(20) keV, I-alpha 2=26(12)% were found. The decay pattern of Rn-193, which is substantially different from that of the heavier odd-A Rn isotopes, provides first experimental evidence for the long-predicted deformation in the very neutron-deficient Rn nuclei.
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13.
  • Bianco, L., et al. (författare)
  • Discovery of W-157 and Os-161
  • 2010
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 690:1, s. 15-18
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclides W-157 and Os-161 have been discovered ill reactions of Ni-58 ion beams with a Cd-106 target. The Os-161 alpha-decay energy and half-life were 6890 +/- 12 keV and 640 +/- 60 mu s. The daughter W-157 nuclei beta-decayed with a half-life of 275 +/- 40 ms, populating both low-lying alpha-decaying states in Ta-157, which is consistent with a 7/2(-) ground state in W-157. Fine structure observed in the alpha decay of Os-161 places the lowest excited state in W-157 with 1(pi) = 9/2(-) at 318 +/- 30 key. The branching ratio of 5.5(-2.2)(+3.1)% indicates that Os-161 also has a 7/2(-) ground state. Shell-model calculations analysing the effects of monopole shifts and a tensor force on the relative energies of 2f(7/2) and 1h(9/2) neutron states in N = 83 isotones are presented. (C) 2010 Elsevier B.V. All rights reserved.
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14.
  • Darby, I. G., et al. (författare)
  • Decay of the high-spin isomer in Re-160 : Changing single-particle structure beyond the proton drip line
  • 2011
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 695:1-4, s. 78-81
  • Tidskriftsartikel (refereegranskat)abstract
    • A new high-spin isomeric state (t(1/2) = 2.8 +/- 0.1 mu s) in Re-160 has been identified. This high-spin isomer is unique in that it only decays by gamma-decay and not by proton or alpha-particle emission as is the case in every other proton emitter between Z = 64 and 80. Shell model calculations indicate how the convergence of the h(9/2) and f(7/2) neutron levels in this region could open up a gamma-decay path from the high-spin isomer to the low-spin ground state of 160Re. providing a natural explanation for this anomalous absence of charged-particle emission. The consequences of these observations for future searches for proton emission from even more exotic nuclei and in-beam spectroscopic studies are considered.
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15.
  • Darby, I. G., et al. (författare)
  • Precision measurements of proton emission from the ground states of Ta-156 and Re-160
  • 2011
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 83:6, s. 064320-
  • Tidskriftsartikel (refereegranskat)abstract
    • The decays of the pi d(3/2) ground states of Ta-156 and Re-160 have been studied in detail using the GREAT spectrometer. More than 7000 Re-160 nuclei were produced in reactions of 290- and 300-MeV Ni-58 ions with an isotopically enriched Cd-106 target and separated in flight using the RITU separator. The proton and alpha decays of the pi d(3/2) level were confirmed and the half-life and branching ratios of this state were determined with improved precision to be t(1/2) = 611 +/- 7 mu s and b(p) = 89 +/- 1% and b(alpha) = 11 +/- 1%, respectively. The alpha-decay branch populated the ground state of Ta-156, allowing improved values for the proton-decay energy and half-life to be obtained (E-p = 1011 +/- 5 keV; t(1/2) = 106 +/- 4 ms). The beta decay of this level was identified for the first time and a branching ratio of b(beta) = 29 +/- 3% was deduced. The spectroscopic factors deduced from these measurements are compared with predictions.
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  • Davis-Merry, T. R., et al. (författare)
  • Collective excitations in the transitional nuclei Re-163 and Re-165
  • 2015
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 91:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states in the neutron-deficient nuclei (163)(75) Re-88 and (165)(75) Re-90 were populated in the Cd-106(Ni-60, p2n gamma) and Mo-92(Kr-78, 3p2n gamma) fusion-evaporation reactions at bombarding energies of 270 and 380 MeV, respectively.. rays were detected at the target position using the JUROGAM spectrometer while recoiling ions were separated in-flight by the RITU gas-filled recoil separator and implanted in the GREAT spectrometer. The energy level schemes for Re-163 and Re-165 were identified using recoil-decay correlation techniques. At low spin, the yrast bands of these isotopes consist of signature partner bands based on a single pi h(11/2) quasiproton configuration. The bands display large energy splitting consistent with the soft triaxial shape typical of transitional nuclei above N = 82. The configurations of the excited states are proposed within the framework of the cranked shell model.
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17.
  • Hartley, D. J., et al. (författare)
  • Wobbling mode in Ta-167
  • 2009
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The collective wobbling mode, the strongest signature for the rotation of a triaxial nucleus, has previously been seen only in a few Lu isotopes in spite of extensive searches in nearby isotopes. A sequence of transitions in the N = 94 Ta-167 nucleus exhibiting features similar to those attributed to the wobbling bands in the Lu nuclei has now been found. This band feeds into the pi i(13/2) band at a relative energy similar to that seen in the established wobbling bands and its dynamic moment of inertia and alignment properties are nearly identical to the i(13/2) structure over a significant frequency range. Given these characteristics, it is likely that the wobbling mode has been observed for the first time in a nucleus other than Lu, making this collective motion a more general phenomenon.
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18.
  • Joss, D. T., et al. (författare)
  • Discovery of the proton emitting nucleus 159Re
  • 2007
  • Ingår i: Proton Emitting Nuclei and Related Topics. - : American Institute of Physics (AIP). - 9780735404755 ; , s. 28-33
  • Konferensbidrag (refereegranskat)abstract
    • The observation of the new nuclide 159Re provides important insights into the evolution of single-particle structure in heavy nuclei beyond the proton drip line. The nuclide 159Re was synthesised in the reaction 106Cd(58Ni, p4n) and identified via its proton radioactivity using the RITU gas-filled separator and the GREAT focal-plane spectrometer. Comparisons of the measured proton energy (Ep = 1805±20 keV) and decay half-life (t1/2 = 21±4 μs) with values calculated using the WKB method indicate that the proton is emitted from an h11/2 state. The implications of these results for future experimental investigations into even more proton unbound Re isotopes using in-flight separation techniques are considered.
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19.
  • Joss, D. T., et al. (författare)
  • Evolving collective structures in the transitional nuclei W-162 and W-164
  • 2016
  • Ingår i: PHYSICAL REVIEW C. - : American Physical Society. - 2469-9985. ; 93:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states in the neutron-deficient nuclides(74)(162)W(88) and W-164(74)90 were investigated by using the gamma-ray spectrometer Jurogam. A change in structure is apparent from the first rotational alignments in W-162 and W-164, whose rotationally aligned bands are interpreted as nu(h(9/2))(2) and nu(i(13/2))(2) configurations, respectively. The level schemes have been extended using recoil (-decay) correlations with the observation of excited collective structures. Configuration assignments have been made on the basis of comparisons of the deduced aligned angular momentum, as a function of rotational frequency, with the predictions of the cranked shell model.
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20.
  • Joss, D. T., et al. (författare)
  • Probing the limit of nuclear existence : Proton emission from Re-159
  • 2006
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 641:1, s. 34-37
  • Tidskriftsartikel (refereegranskat)abstract
    • The observation of the new nuclide Re-159(75)84 provides important insights into the evolution of single-particle structure and the mass surface in heavy nuclei beyond the proton drip line. This nuclide, 26 neutrons away from the nearest stable rhenium isotope, was synthesised in the reaction Cd-106(Ni-58, p4n) and identified via its proton radioactivity using the RITU gas-filled separator and the GREAT focal-plane spectrometer. Comparisons of the measured proton energy (E-p = 1805 +/- 20 keV) and decay half-life (t(1/2) = 21 +/- 4 mu s) with values calculated using the WKB method indicate that the proton is emitted from an h(11/2) state. The implications of these results for future experimental investigations into even more proton unbound nuclei using in-flight separation techniques are considered.
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21.
  • Joss, D. T., et al. (författare)
  • The influence of quasineutron configurations on 161Ta and nearby odd-A nuclei
  • 2011
  • Ingår i: AIP Conf. Proc.. - : AIP. - 9780735409835 ; , s. 43-48
  • Konferensbidrag (refereegranskat)abstract
    • Several strongly coupled bands in the neutron-deficient nucleus 161Ta have been identified and quasiparticle configuration assignments have been made on the basis of rotational alignments and cranked shell model calculations. The level scheme elucidated for 161Ta highlights the competition between the ν(h 9/2) and ν(i 13/2) orbitals to form the yrast spectrum. The band structures in 161Ta also provide new insights into the structural features of other heavy odd-A nuclei populated with much lower reaction cross sections in this region at the proton drip line.
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22.
  • Ketelhut, S., et al. (författare)
  • gamma-Ray Spectroscopy at the Limits : First Observation of Rotational Bands in Lr-255
  • 2009
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:21, s. 212501-
  • Tidskriftsartikel (refereegranskat)abstract
    • The rotational band structure of Lr-255 has been investigated using advanced in-beam gamma-ray spectroscopic techniques. To date, Lr-255 is the heaviest nucleus to be studied in this manner. One rotational band has been unambiguously observed and strong evidence for a second rotational structure was found. The structures are tentatively assigned to be based on the 1/2(-)[521] and 7/2(-)[514] Nilsson states, consistent with assignments from recently obtained alpha decay data. The experimental rotational band dynamic moment of inertia is used to test self-consistent mean-field calculations using the Skyrme SLy4 interaction and a density-dependent pairing force.
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23.
  • Page, R. D., et al. (författare)
  • alpha decay of Re-159 and proton emission from Ta-155
  • 2007
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 75:6, s. 061302-
  • Tidskriftsartikel (refereegranskat)abstract
    • The alpha decay of Re-159 has been observed for the first time in reactions of 300 MeV Ni-58 ions with an isotopically enriched Cd-106 target. The Re-159 ions were separated in-flight using the RITU separator and implanted into the GREAT spectrometer. The alpha decay emanates from the proton-emitting pi h(11/2) state in Re-159 with an energy of E-alpha=6776 +/- 26 keV and a branching ratio of 7.5 +/- 3.5%. This alpha decay populates a state in the closed neutron shell nucleus Ta-155, which decays by emitting 1444 +/- 15 keV protons with a half-life of 2.9(-1.1)(+1.5) ms. These values are consistent with the emission of the proton from a pi h(11/2) orbital. These results fit in with the systematics of proton and alpha-particle separation energies in the region, but disagree with the previously reported decay properties of Ta-155.
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24.
  • Page, R. D., et al. (författare)
  • Probing single-particle structures beyond the proton drip line
  • 2007
  • Ingår i: Proton Emitting Nuclei and Related Topics. - : American Institute of Physics (AIP). - 9780735404755 ; , s. 137-142
  • Konferensbidrag (refereegranskat)abstract
    • Single-particle energies have been investigated in the closed neutron shell proton emitter 155Ta. The 155Ta nuclei were populated through the α decay of 159Re, which has been observed for the first time. The 159Re nuclei were produced in reactions of 300 MeV 58Ni ions with an isotopically enriched 106Cd target, separated in-flight using the RITU separator and implanted into the GREAT spectrometer. The 159Re α decay emanates from the proton-emitting πh11/2 state and populates a state in 155Ta which decays by the emission of a proton from a πh 11/2 orbital. The results fit in with the systematics of proton and α-particle separation energies in the region, but disagree with the previously reported decay properties of 155Ta.
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25.
  • Thomson, J., et al. (författare)
  • Competing quasiparticle configurations in W-163
  • 2010
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 81:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states in the neutron-deficient nuclide W-163 were investigated using the Cd-106(Ni-60, 2pn)W-163 reaction at a beam energy of 270 MeV. The level scheme for W-163 was extended significantly with the observation of five new band structures. The yrast band based on a 13/2(+) isomeric state is extended up to (57/2(+)). Two band structures were established on the 7/2(-) ground state. Quasiparticle configuration assignments for the new band structures were made on the basis of cranked Woods-Saxon shell-model calculations. The results reported in this article suggest that the negative-parity nu(f(7/2), h(9/2)) orbitals are responsible for the first rotational alignment in the yrast band.
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26.
  • Cocolios, T. E., et al. (författare)
  • Early onset of deformation in the neutron-deficient polonium isotopes
  • 2012
  • Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 381:1, s. 012072-
  • Tidskriftsartikel (refereegranskat)abstract
    • In-source laser spectroscopy has been performed at CERN-ISOLDE with the RILIS laser ion source on 191-204,206,208-211,216,218Po. New information on the β decay of 199Po were extracted in the process, challenging previous results. Large-scale atomic calculations were performed to extract the changes in the mean-square charge radius δr 2 from the isotope shifts. The δ«r» 2 for the even-A isotopes reveal a large deviation from the spherical droplet model for N < 116.
  •  
27.
  • Cocolios, T. E., et al. (författare)
  • Early Onset of Ground State Deformation in Neutron Deficient Polonium Isotopes
  • 2011
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 106:5, s. 052503-
  • Tidskriftsartikel (refereegranskat)abstract
    • In-source resonant ionization laser spectroscopy of the even-A polonium isotopes Po-192-210,Po-216,Po-218 has been performed using the 6p(3)7s S-5(2) to (6)p(3)7p P-5(2) (lambda = 843.38 nm) transition in the polonium atom (Po-I) at the CERN ISOLDE facility. The comparison of the measured isotope shifts in Po200-210 with a previous data set allows us to test for the first time recent large-scale atomic calculations that are essential to extract the changes in the mean-square charge radius of the atomic nucleus. When going to lighter masses, a surprisingly large and early departure from sphericity is observed, which is only partly reproduced by beyond mean field calculations.
  •  
28.
  • Eratne, D., et al. (författare)
  • Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders
  • 2023
  • Ingår i: Australian and New Zealand Journal of Psychiatry. - 0004-8674. ; 58:1, s. 70-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. Methods: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). Results: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. Conclusions: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
  •  
29.
  • Hadinia, Baharak, et al. (författare)
  • First identification of gamma-rays in Te-106 using recoil decay tagging technique
  • 2006
  • Ingår i: Frontiers in Nuclear Structure Astrophysics, and Reactions: FINUSTAR. - MELVILLE, NY : AMER INST PHYSICS. - 0735403236 - 9780735403239 ; , s. 457-459
  • Konferensbidrag (refereegranskat)abstract
    • Gamma-ray transitions from excited states in Te-106 have been identified using the recoil decay tagging technique. The experiment which was the reaction Fe-54(Fe-54,2n)Te-106* was performed at the JYFL accelerator facility at the University of Jyvaskyla, Finland. The production cross section was estimated at 25 nb, a new limit for in-beam gamma-ray spectroscopy. A tentative level structure for the ground state band of Te-106 is proposed.
  •  
30.
  • Herzberg, R-D, et al. (författare)
  • Isomer spectroscopy in No-254
  • 2006
  • Ingår i: Physica Scripta. - 0031-8949 .- 1402-4896. ; T125, s. 73-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Isomeric states in No-254 were investigated using a calorimetric method. Two different isomers were found with half-lives of T-1/2 = 266 +/- 2 ms and T-1/2 = 184 +/- 3 mu s, respectively. The dominant decay path of the 184 mu s isomer proceeds via states feeding the longer-lived 266 ms isomer. The 266 ms isomer in turn decays via a two-quasi-particle K = 3 band to the ground-state band. The full decay path was observed with the GREAT spectrometer located at the focal plane of the gas-filled separator RITU at the Accelerator Laboratory in Jyvskyl. This work sheds light on the two-quasi-particle structure in this transfermium nucleus.
  •  
31.
  • Petri, M., et al. (författare)
  • Nuclear levels in proton-unbound I-109 : Relative single-particle energies beyond the proton drip line
  • 2007
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 76:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A level scheme has been constructed for the proton-unbound, T-z=3/2 nuclide I-109(53)56 following a recoil-decay-tagging experiment using the Ni-58(Fe-54, p2n gamma) reaction at a beam energy of 195 MeV. The experiment was performed using the highly efficient JUROGAM gamma-ray spectrometer in conjunction with the RITU gas-filled recoil separator and the GREAT focal-plane spectrometer. Cranking calculations are used to interpret band structures built on pi g(7/2) and pi h(11/2) states in a weakly deformed, triaxial nucleus.
  •  
32.
  • Seliverstov, M. D., et al. (författare)
  • Charge radii of odd-A Po191-211 isotopes
  • 2013
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 719:4-5, s. 362-366
  • Tidskriftsartikel (refereegranskat)abstract
    • Isotope shifts have been measured for the odd-A polonium isotopes Po191-211 and changes in the nuclear mean square charge radii delta < r(2 >) have been deduced. The measurements were performed at CERN-ISOLDE using the in-source resonance-ionization spectroscopy technique. The combined analysis of these data and our recent results for even-A polonium isotopes indicates an onset of deformation already at Po-197,Po-198, when going away from stability. This is significantly earlier than was suggested by previous theoretical and experimental studies of the polonium isotopes. Moreover and in contrast to the mercury isotopes, where a strong odd-even staggering of the charge radii of the ground states was observed by approaching the neutron mid-shell at N = 104, no such effect is present in polonium down to Po-191. Consequently the charge radii of both isomeric and ground states of the odd-A polonium isotopes follow the same trend as the even-A isotopes.
  •  
33.
  •  
34.
  •  
35.
  • Cocolios, T. E., et al. (författare)
  • Structure of Pb-191 from alpha- and beta-decay spectroscopy
  • 2010
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 37:12, s. 125103-
  • Tidskriftsartikel (refereegranskat)abstract
    • Complementary studies of Pb-191 have been made in the beta decay of Bi-191 at LISOL (CRC) and in the alpha decay of Po-195 at ISOLDE (CERN). Fine structures in the alpha decay of the low-spin and high-spin isomers of 195Po have been fully resolved. Identification of the parent state is made possible via isomer selection based on narrow-band laser frequency scanning. The alpha-particle and gamma-ray energies have been determined with greater precision. New alpha-particle and. gamma-ray energies are identified. Branching ratios in the decay of Po-195 and Pb-191 have been examined.
  •  
36.
  • Drummond, M. C., et al. (författare)
  • Low-lying excited states in the neutron-deficient isotopes Os-163 and Os-165
  • 2013
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:5, s. 054309-
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states in the neutron-deficient isotopes Os-163 and Os-165 were identified using the JUROGAM and GREAT spectrometers in conjunction with the RITU gas-filled separator. The Os-163 and Os-165 nuclei were populated via the Cd-106(Ni-60,3n) and Mo-92(Kr-78,2p3n) reactions at bombarding energies of 270 MeV and 357 MeV, respectively. Gamma-ray emissions from these nuclei have been established unambiguously using the recoil-decay tagging technique and a coincidence analysis has allowed level schemes to be established. These results suggest that the yrast states are based upon negative-parity configurations originating from the f(7/2) and h(9/2) orbitals.
  •  
37.
  • Grahn, T., et al. (författare)
  • Collectivity and configuration mixing in Pb186,188 and Po194
  • 2006
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Lifetimes of prolate intruder states in Pb186 and oblate intruder states in Po194 have been determined by employing, for the first time, the recoil-decay tagging technique in recoil distance Doppler-shift lifetime measurements. In addition, lifetime measurements of prolate states in Pb188 up to the 8+ state were carried out using the recoil-gating method. The B(E2) values have been deduced from which deformation parameters |β2|=0.29(5) and |β2|=0.17(3) for the prolate and the oblate bands, respectively, have been extracted. The results also shed new light on the mixing between different shapes.
  •  
38.
  • Mustafa, M., et al. (författare)
  • Diverse collective excitations in Er-159 up to high spin
  • 2011
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A spectroscopic investigation of the gamma decays from excited states in Er-159 has been performed to study the changing structural properties exhibited as ultrahigh spins (I > 60 (h) over bar) are approached. The nucleus of Er-159 was populated by the reaction Cd-116(Ca-48, 5n gamma) at a beam energy of 215 MeV, and the resulting gamma decays were studied using the Gammasphere spectrometer. New rotational bands and extensions to existing sequences were observed, which are discussed in terms of the cranked shell model, revealing a diverse range of quasiparticle configurations. At spins around 50 (h) over bar, there is evidence for a change from dominant prolate collective motion at the yrast line to oblate non-collective structures via the mechanism of band termination. A possible strongly deformed triaxial band occurs at these high spins, which indicates collectivity beyond 50 (h) over bar. The high-spin data are interpreted within the framework of cranked Nilsson-Strutinsky calculations.
  •  
39.
  • Ollier, J., et al. (författare)
  • Structure changes in Er-160 from low to ultrahigh spin
  • 2011
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 83:4
  • Tidskriftsartikel (refereegranskat)abstract
    • A spectroscopic investigation of the gamma decays from excited states in Er-160 has been performed in order to study the changing structural properties exhibited from low spin up toward ultrahigh spin (I similar to 60 h). The nucleus Er-160 was populated by the reaction Cd-116(Ca-48,4n gamma) at a beam energy of 215 MeV, and resulting gamma decays were studied using the Gammasphere spectrometer. New rotational structures and extensions to existing bands were observed, revealing a diverse range of quasiparticle configurations, which are discussed in terms of the cranked shell model. At spins around 50h there is evidence for oblate states close to the yrast line. Three rotational bands that have the characteristics of strongly deformed triaxial structures are observed, marking a return to collectivity at even higher spin. The high-spin data are interpreted within the framework of cranked Nilsson-Strutinsky calculations.
  •  
40.
  • Ollier, J., et al. (författare)
  • Ultrahigh-spin spectroscopy of Er-159,Er-160: Observation of triaxial strongly deformed structures
  • 2009
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Three weakly populated high-spin rotational bands associated with the gamma decay of Er-159 and Er-160 were observed in fusion-evaporation reactions involving a beam of Ca-48 at an energy of 215 MeV incident on a Cd-116 target. The gamma decays were detected using the highly efficient Gammasphere spectrometer. The discovery of these bands, which extend discrete-line spectroscopy in these nuclei to ultrahigh spin of similar to 60h, is consistent with recent observations of high-spin collective structures in isotopes of Er, Yb, and Tm around N=90. Cranked Nilsson-Strutinsky calculations suggest that these bands may arise from well-deformed triaxial configurations with either positive or negative gamma deformation.
  •  
41.
  • Riley, M. A., et al. (författare)
  • Strongly Deformed Nuclear Shapes at Ultra-High Spin and Shape Coexistence in N\sim 90 Nuclei
  • 2009
  • Ingår i: Acta Physica Polonica B. - 0587-4254. ; 40:3, s. 513-522
  • Tidskriftsartikel (refereegranskat)abstract
    • The N similar to 90 region of the nuclear chart has featured prominently as the spectroscopy of nuclei at extreme spin has progressed. This talk will present recent discoveries from investigations of high spin behavior in the N similar to 90 Er, Tm and Yb nuclei utilizing the Gammasphere gamma-ray spectrometer. In particular it will include discussion of the beautiful shape evolution and coexistence observed in these nuclei along with the identification of a remarkable new family of band structures. The latter are very weakly populated rotational sequences with high moment of inertia that bypass the classic terminating configurations near spin 40-50 (h) over bar, marking a return to collectivity that extends discrete gamma-ray spectroscopy to well over 60 (h) over bar. Establishing the nature of the yrast states in these nuclei beyond the oblate band-termination states has been a major goal for the past two decades. Cranking calculations suggest that these new structures most likely represent stable triaxial strongly deformed bands that lie in a valley of favored shell energy in deformation and particle-number space.
  •  
42.
  • Scholey, C., et al. (författare)
  • In-beam and decay spectroscopy of very neutron deficient iridium nuclei
  • 2005
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 31:10, s. S1719-S1722
  • Tidskriftsartikel (refereegranskat)abstract
    • Iridium nuclei at and beyond the proton drip line have been studied via fusion evaporation reactions. A reaction of Mo-92(Kr-78, p2n) at a beam energy of 360 MeV and target thickness 500 mu g cm(-2) was employed to study (167,167m) Ir. A reaction of Sn-112(Ni-58, p2n) at a beam energy of 266 MeV and target thickness 500 mu g cm(-2) was used to study (169,169m) Ir. The experiments were performed at the University of Jyvaskyla utilizing the RITU separator in conjunction with the focal plane GREAT spectrometer and the JUROGAM Ge array at the target position. Excited states feeding. both the ground state and isomeric state in Ir-169, excited states feeding the ground state of Ir-167 and the ground state alpha decay of Re-165 have been observed for the first time along with excited states feeding (167)m Ir Experimental spectroscopic factors and reduced widths have been obtained for the proton and alpha decay of these nuclei.
  •  
43.
  • Seliverstov, M. D., et al. (författare)
  • Electromagnetic moments of odd-A Po-193-203,Po-211 isotopes
  • 2014
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 89:3, s. 034323-
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyperfine splitting parameters have been measured for the neutron-deficient odd-mass polonium isotopes and isomers Po-193-203(g,m), Po-209,Po-211. The measurement was performed at the ISOLDE (CERN) online mass separator using the in-source resonance ionization spectroscopy technique. The magnetic dipole moments mu and spectroscopic electric quadrupole moments Q(S) have been deduced. Their implication for the understanding of nuclear structure in the vicinity of the closed proton shell at Z = 82 and the neutron mid-shell at N = 104 is discussed. For the most neutron-deficient nuclei (A = 193,195,197), a deviation of mu and QS from the nearly constant values for heavier polonium nuclei was observed. Particle-plus-rotor calculations with static oblate deformation describe the electromagnetic moments for these nuclei well, provided a gradual increase of a mean deformation when going to lighter masses is assumed for the polonium nuclei with A < 198.
  •  
44.
  • Blasch, J., et al. (författare)
  • New clean energy communities in polycentric settings : Four avenues for future research
  • 2021
  • Ingår i: Energy Research and Social Science. - : Elsevier BV. - 2214-6296. ; 82
  • Tidskriftsartikel (refereegranskat)abstract
    • Given the gaps between EU ambitions regarding energy community development and the current reality of clean energy communities in Europe, we explore a research framework enabling viable multi- and interdisciplinary research into new clean energy communities. We offer a definition of new clean energy communities, discuss their potential for wider dissemination and identify four factors that contribute to the current mismatch between ambitions and reality in energy community development. As a broader framework for interdisciplinary research into the field of new clean energy communities, we propose polycentric governance theory, considering the fact that the area of community energy systems is essentially multi-scalar, and that the rules of engagement in such systems are of great significance. This opens up four avenues for research on energy communities, which we outline in terms of enabling institutional contexts, potential for learning and transferability, business models and value propositions, and evaluation of outcomes and processes.
  •  
45.
  •  
46.
  • Carroll, R. J., et al. (författare)
  • Blurring the Boundaries : Decays of Multiparticle Isomers at the Proton Drip Line
  • 2014
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 112:9, s. 092501-
  • Tidskriftsartikel (refereegranskat)abstract
    • A multiparticle spin-trap isomer has been discovered in the proton-unbound nucleus 158 73 Ta 85. The isomer mainly decays by (h) over bar -ray emission with a half-life of 6.1d(1) mu s. Analysis of the gamma-ray data shows that the isomer lies 2668 keV above the known 9(+) state and has a spin 10h higher and negative parity. This 19(-) isomer also has an 8644(11) keV, 1.4(2)% alpha-decay branch that populates the 9(+) state in Lu-154. No proton-decay branch from the isomer was identified, despite the isomer being unbound to proton emission by 3261(14) keV. This remarkable stability against proton emission is compared with theoretical predictions, and the implications for the extent of observable nuclides are considered.
  •  
47.
  • Carroll, R. J., et al. (författare)
  • Competing decay modes of a high-spin isomer in the proton-unbound nucleus 158Ta
  • 2015
  • Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 46:3, s. 695-698
  • Tidskriftsartikel (refereegranskat)abstract
    • An isomeric state at high spin and excitation energy was recently observed in the proton-unbound nucleus 158Ta. This state was observed to decay by both α and γ decay modes. The large spin change required to decay via γ-ray emission incurs a lifetime long enough for α decay to compete. The α decay has an energy of 8644(11) keV, which is among the highest observed in the region, a partial half-life of 440(70) μs and changes the spin by 11h. In this paper, additional evidence supporting the assignment of this α decay to the high-spin isomer in 158Ta will be presented.
  •  
48.
  • Carroll, R. J., et al. (författare)
  • Multiparticle configurations of excited states in Lu-155
  • 2016
  • Ingår i: PHYSICAL REVIEW C. - 2469-9985. ; 94:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states in the neutron-deficient N = 84 nuclide Lu-155 have been populated by using the Pd-102(Ni-58, alpha p) reaction. The Lu-155 nuclei were separated by using the gas-filled recoil ion transport unit (RITU) separator and implanted into the Si detectors of the gamma recoil electron alpha tagging (GREAT) spectrometer. Prompt gamma-ray emissions measured at the target position using the JUROGAM Ge detector array were assigned to Lu-155 through correlations with alpha decays measured in GREAT. Structures feeding the (11/2(-)) and (25/2(-)) alpha-decaying states have been revised and extended. Shell-model calculations have been performed and are found to reproduce the excitation energies of several of the low-lying states observed to within an average of 71 keV. In particular, the seniority inversion of the 25/2(-) and 27/2(-) states is reproduced.
  •  
49.
  • Cartwright, S. P., et al. (författare)
  • Constitutively-stressed yeast strains are high-yielding for recombinant Fps1: implications for the translational regulation of an aquaporin
  • 2017
  • Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We previously selected four strains of Saccharomyces cerevisiae for their ability to produce the aquaporin Fps1 in sufficient yield for further study. Yields from the yeast strains spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline) that had been transformed with an expression plasmid containing 249 base pairs of 5' untranslated region (UTR) in addition to the primary FPS1 open reading frame (ORF) were 10-80 times higher than yields from wild-type cells expressing the same plasmid. One of the strains increased recombinant yields of the G protein-coupled receptor adenosine receptor 2a (A(2a)R) and soluble green fluorescent protein (GFP). The specific molecular mechanisms underpinning a high-yielding Fps1 phenotype remained incompletely described. Results: Polysome profiling experiments were used to analyze the translational state of spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline); all but gcn5 Delta. were found to exhibit a clear block in translation initiation. Four additional strains with known initiation blocks (rpl31a Delta., rpl22a Delta., ssf1 Delta. and nop1 Delta.) also improved the yield of recombinant Fps1 compared to wild-type. Expression of the eukaryotic transcriptional activator GCN4 was increased in spt3 Delta, srb5 Delta, gcn5 Delta. and yTHCBMS1 (supplemented with 0.5 mu g/mL doxycycline); these four strains also exhibited constitutive phosphorylation of the eukaryotic initiation factor, eIF2 alpha. Both responses are indicative of a constitutively-stressed phenotype. Investigation of the 5' UTR of FPS1 in the expression construct revealed two untranslated ORFs (uORF1 and uORF2) upstream of the primary ORF. Deletion of either uORF1 or uORF1 and uORF2 further improved recombinant yields in our four strains; the highest yields of the uORF deletions were obtained from wild-type cells. Frame-shifting the stop codon of the native uORF (uORF2) so that it extended into the FPS1 ORF did not substantially alter Fps1 yields in spt3. or wild-type cells, suggesting that high-yielding strains are able to bypass 5' uORFs in the FPS1 gene via leaky scanning, which is a known stress-response mechanism. Yields of recombinant A2aR, GFP and horseradish peroxidase could be improved in one or more of the yeast strains suggesting that a stressed phenotype may also be important in high-yielding cell factories. Conclusions: Regulation of Fps1 levels in yeast by translational control may be functionally important; the presence of a native uORF (uORF2) may be required to maintain low levels of Fps1 under normal conditions, but higher levels as part of a stress response. Constitutively-stressed yeast strains may be useful high-yielding microbial cell factories for recombinant protein production.
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50.
  • Clarke, M, et al. (författare)
  • Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer : patient-level meta-analysis of randomised trials
  • 2008
  • Ingår i: The Lancet. - 0140-6736. ; 371:9606, s. 29-40
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast cancer in 46 trials of polychemotherapy versus not (non-taxane-based polychemotherapy, typically about six cycles; trial start dates 1975-96, median 1984) and about 14 000 women with ER-poor breast cancer in 50 trials of tamoxifen versus not (some trials in the presence and some in the absence of polychemotherapy; trial start dates 1972-93, median 1982).FINDINGS: In women with ER-poor breast cancer, polychemotherapy significantly reduced recurrence, breast cancer mortality, and death from any cause, in those younger than 50 years and those aged 50-69 years at entry into trials of polychemotherapy versus not. In those aged younger than 50 years (1907 women, 15% node-positive), the 10-year risks were: recurrence 33% versus 45% (ratio of 10-year risks 0.73, 2p<0.00001), breast cancer mortality 24% versus 32% (ratio 0.73, 2p=0.0002), and death from any cause 25% versus 33% (ratio 0.75, 2p=0.0003). In women aged 50-69 years (3965 women, 58% node-positive), the 10-year risks were: recurrence 42% versus 52% (ratio 0.82, 2p<0.00001), breast cancer mortality 36% versus 42% (ratio 0.86, 2p=0.0004), and death from any cause 39% versus 45% (ratio 0.87, 2p=0.0009). Few were aged 70 years or older. Tamoxifen had little effect on recurrence or death in women who were classified in these trials as having ER-poor disease, and did not significantly modify the effects of polychemotherapy.INTERPRETATION: In women who had ER-poor breast cancer, and were either younger than 50 years or between 50 and 69 years, these older adjuvant polychemotherapy regimens were safe (ie, had little effect on mortality from causes other than breast cancer) and produced substantial and definite reductions in the 10-year risks of recurrence and death. Current and future chemotherapy regimens could well yield larger proportional reductions in breast cancer mortality.
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