| 1. |
- Ahmadi, M., et al.
(författare)
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Investigation of the fine structure of antihydrogen
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7795, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- At the historic Shelter Island Conference on the Foundations of Quantum Mechanics in 1947, Willis Lamb reported an unexpected feature in the fine structure of atomic hydrogen: a separation of the 2S(1/2) and 2P(1/2) states(1). The observation of this separation, now known as the Lamb shift, marked an important event in the evolution of modern physics, inspiring others to develop the theory of quantum electrodynamics(2-5). Quantum electrodynamics also describes antimatter, but it has only recently become possible to synthesize and trap atomic antimatter to probe its structure. Mirroring the historical development of quantum atomic physics in the twentieth century, modern measurements on anti-atoms represent a unique approach for testing quantum electrodynamics and the foundational symmetries of the standard model. Here we report measurements of the fine structure in the n = 2 states of antihydrogen, the antimatter counterpart of the hydrogen atom. Using optical excitation of the 1S-2P Lyman-alpha transitions in antihydrogen(6), we determine their frequencies in a magnetic field of 1 tesla to a precision of 16 parts per billion. Assuming the standard Zeeman and hyperfine interactions, we infer the zero-field fine-structure splitting (2P(1/2)-2P(3/2)) in antihydrogen. The resulting value is consistent with the predictions of quantum electrodynamics to a precision of 2 per cent. Using our previously measured value of the 1S-2S transition frequency(6,7), we find that the classic Lamb shift in antihydrogen (2S(1/2)-2P(1/2) splitting at zero field) is consistent with theory at a level of 11 per cent. Our observations represent an important step towards precision measurements of the fine structure and the Lamb shift in the antihydrogen spectrum as tests of the charge-parity-time symmetry(8) and towards the determination of other fundamental quantities, such as the antiproton charge radius(9,10), in this antimatter system. Precision measurements of the 1S-2P transition in antihydrogen that take into account the standard Zeeman and hyperfine effects confirm the predictions of quantum electrodynamics.
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| 2. |
- Olin, JW, et al.
(författare)
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A plasma proteogenomic signature for fibromuscular dysplasia
- 2020
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Ingår i: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 116:1, s. 63-77
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Tidskriftsartikel (refereegranskat)abstract
- AimsFibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test.Methods and resultsFemales with ‘multifocal’ FMD and matched healthy controls underwent clinical phenotyping, dermal biopsy, and blood draw. Using dual-capture proximity extension assay and nuclear magnetic resonance-spectroscopy, we evaluated plasma levels of 981 proteins and 31 lipid sub-classes, respectively. In a discovery cohort (Ncases = 90, Ncontrols = 100), we identified 105 proteins and 16 lipid sub-classes (predominantly triglycerides and fatty acids) with differential plasma abundance in FMD cases vs. controls. In an independent cohort (Ncases = 23, Ncontrols = 28), we successfully validated 37 plasma proteins and 10 lipid sub-classes with differential abundance. Among these, 5/37 proteins exhibited genetic control and Bayesian analyses identified 3 of these as potential upstream drivers of FMD. In a 3rd cohort (Ncases = 506, Ncontrols = 876) the genetic locus of one of these upstream disease drivers, CD2-associated protein (CD2AP), was independently validated as being associated with risk of having FMD (odds ratios = 1.36; P = 0.0003). Immune-fluorescence staining identified that CD2AP is expressed by the endothelium of medium-large arteries. Finally, machine learning trained on the discovery cohort was used to develop a test for FMD. When independently applied to the validation cohort, the test showed a c-statistic of 0.73 and sensitivity of 78.3%.ConclusionFMD exhibits a plasma proteogenomic and lipid signature that includes potential causative disease drivers, and which holds promise for developing a blood-based test for this disease.
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| 3. |
- Ghaderi, A, et al.
(författare)
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ROR1 Is Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of Lymphoma Cells
- 2020
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- The receptor tyrosine kinase ROR1 is absent in most normal adult tissues, but overexpressed in several malignancies. In this study, we explored clinical and functional inhibitory aspects of ROR1 in diffuse large B-cell lymphoma (DLBCL). ROR1 expression in tumor cells was more often observed in primary refractory DLBCL, Richter’s syndrome and transformed follicular lymphoma than in relapsed and non-relapsed DLBCL patients (p < 0.001). A survival effect of ROR1 expression was preliminarily observed in relapsed/refractory patients independent of gender and stage but not of age, cell of origin and international prognostic index. A second generation small molecule ROR1 inhibitor (KAN0441571C) induced apoptosis of ROR1+ DLBCL cell lines, similar to venetoclax (BCL-2 inhibitor) but superior to ibrutinib (BTK inhibitor). The combination of KAN0441571C and venetoclax at EC50 concentrations induced almost complete killing of DLBCL cell lines. Apoptosis was accompanied by the downregulation of BCL-2 and MCL-1 and confirmed by the cleavage of PARP and caspases 3, 8, 9. PI3Kδ/AKT/mTOR (non-canonical Wnt pathway) as well as β-catenin and CK1δ (canonical pathway) were inactivated. In zebra fishes transplanted with a ROR1+ DLBCL cell line, KAN0441571C induced a significant tumor reduction. New drugs with mechanisms of action other than those available for DLBCL are warranted. ROR1 inhibitors might represent a novel promising approach.
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| 4. |
- Zhou, Zheng, et al.
(författare)
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Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens : a CIBMTR report
- 2020
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:13, s. 3180-3190
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Tidskriftsartikel (refereegranskat)abstract
- There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
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| 5. |
- Amid Hägg, Shadi, et al.
(författare)
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Smokers with insomnia symptoms are less likely to stop smoking
- 2020
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 170
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Smoking is associated with sleep disturbances. The aim of this study was to analyze whether sleep disturbances are predictors of smoking cessation and whether continued smoking is associated with the development of sleep disturbances. Methods: A questionnaire was sent to randomly selected men and women in Northern Europe in 1999-2001 (RHINE II) and was followed up by a questionnaire in 2010-2012 (RHINE III). The study population consisted of 2568 participants who were smokers at baseline and provided data on smoking at follow-up. Insomnia symptoms were defined as having difficulty initiating and/or maintaining sleep and/or early morning awakening >= 3 nights/week. Multiple logistic regression analyses were performed to calculate odds ratios (OR). Results: Subjects with difficulty initiating sleep (adjusted odds ratio; 95% confidence interval: 0.6; 0.4-0.8), difficulty maintaining sleep (0.7; 0.5-0.9), early morning awakening (0.6; 0.4-0.8), any insomnia symptom (0.6; 0.5-0.8) or excessive daytime sleepiness (0.7; 0.5-0.8) were less likely to achieve long-term smoking cessation after adjustment for age, BMI, pack-years, hypertension, diabetes, chronic bronchitis, rhinitis, asthma, gender and BMI difference. There was no significant association between snoring and smoking cessation. In subjects without sleep disturbance at baseline, continued smoking increased the risk of developing difficulty initiating sleep during the follow-up period compared with those that had quit smoking (adj. OR 1.7, 95% CI 1.2-2.3). Conclusions: Insomnia symptoms and excessive daytime sleepiness negatively predict smoking cessation. Smoking is a risk factor for the development of difficulty initiating sleep. Treatment for sleep disturbances should be included in smoking-cessation programs.
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| 6. |
- Bergqvist, Joel, et al.
(författare)
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Non-infectious rhinitis is more strongly associated with early-rather than late-onset of COPD: data from the European Community Respiratory Health Survey (ECRHS)
- 2020
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 277, s. 1353-1359
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity. The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time. The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD. Methods This study is part of the European Community Respiratory Health Survey (ECRHS). A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998-2002 (ECRHS II) and in 2008-2013 (ECRHS III). Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported. Subjects reporting asthma were excluded. COPD was defined as a spirometry ratio of FEV1/FVC < 0.7. A total of 5901 subjects were included. Results Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p < 0.001) in ECRHS II (mean age 43) but not in ECHRS III (mean age 54). In the multivariable regression model adjusted for COPD, smoking, age, BMI, and gender, non-infectious rhinitis was associated with COPD in both ECRHS II and III. Conclusion Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43. Ten years later, the association was weaker. The findings indicate that NIR could be associated with the early onset of COPD.
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| 7. |
- Franke, James A., et al.
(författare)
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The GGCMI Phase 2 emulators : Global gridded crop model responses to changes in CO2, temperature, water, and nitrogen (version 1.0)
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 13:9, s. 3995-4018
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Tidskriftsartikel (refereegranskat)abstract
- Statistical emulation allows combining advantageous features of statistical and process-based crop models for understanding the effects of future climate changes on crop yields. We describe here the development of emulators for nine process-based crop models and five crops using output from the Global Gridded Model Intercomparison Project (GGCMI) Phase 2. The GGCMI Phase 2 experiment is designed with the explicit goal of producing a structured training dataset for emulator development that samples across four dimensions relevant to crop yields: Atmospheric carbon dioxide (CO2) concentrations, temperature, water supply, and nitrogen inputs (CTWN). Simulations are run under two different adaptation assumptions: That growing seasons shorten in warmer climates, and that cultivar choice allows growing seasons to remain fixed. The dataset allows emulating the climatological-mean yield response of all models with a simple polynomial in mean growing-season values. Climatological-mean yields are a central metric in climate change impact analysis; we show here that they can be captured without relying on interannual variations. In general, emulation errors are negligible relative to differences across crop models or even across climate model scenarios; errors become significant only in some marginal lands where crops are not currently grown. We demonstrate that the resulting GGCMI emulators can reproduce yields under realistic future climate simulations, even though the GGCMI Phase 2 dataset is constructed with uniform CTWN offsets, suggesting that the effects of changes in temperature and precipitation distributions are small relative to those of changing means. The resulting emulators therefore capture relevant crop model responses in a lightweight, computationally tractable form, providing a tool that can facilitate model comparison, diagnosis of interacting factors affecting yields, and integrated assessment of climate impacts.
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| 8. |
- Franke, James A., et al.
(författare)
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The GGCMI Phase 2 experiment : Global gridded crop model simulations under uniform changes in CO2, temperature, water, and nitrogen levels (protocol version 1.0)
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 13:5, s. 2315-2336
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Tidskriftsartikel (refereegranskat)abstract
- Concerns about food security under climate change motivate efforts to better understand future changes in crop yields. Process-based crop models, which represent plant physiological and soil processes, are necessary tools for this purpose since they allow representing future climate and management conditions not sampled in the historical record and new locations to which cultivation may shift. However, process-based crop models differ in many critical details, and their responses to different interacting factors remain only poorly understood. The Global Gridded Crop Model Intercomparison (GGCMI) Phase 2 experiment, an activity of the Agricultural Model Intercomparison and Improvement Project (AgMIP), is designed to provide a systematic parameter sweep focused on climate change factors and their interaction with overall soil fertility, to allow both evaluating model behavior and emulating model responses in impact assessment tools. In this paper we describe the GGCMI Phase 2 experimental protocol and its simulation data archive. A total of 12 crop models simulate five crops with systematic uniform perturbations of historical climate, varying CO2, temperature, water supply, and applied nitrogen ("CTWN") for rainfed and irrigated agriculture, and a second set of simulations represents a type of adaptation by allowing the adjustment of growing season length. We present some crop yield results to illustrate general characteristics of the simulations and potential uses of the GGCMI Phase 2 archive. For example, in cases without adaptation, modeled yields show robust decreases to warmer temperatures in almost all regions, with a nonlinear dependence that means yields in warmer baseline locations have greater temperature sensitivity. Inter-model uncertainty is qualitatively similar across all the four input dimensions but is largest in high-latitude regions where crops may be grown in the future.
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| 9. |
- Lakshmikanth, T., et al.
(författare)
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Human Immune System Variation during 1 Year
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal cum. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.
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| 10. |
- Rhodes, Olin E., et al.
(författare)
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Integration of ecosystem science into radioecology : A consensus perspective
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 740
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Tidskriftsartikel (refereegranskat)abstract
- In the Fall of 2016 a workshop was held which brought together over 50 scientists from the ecological and radiological fields to discuss feasibility and challenges of reintegrating ecosystem science into radioecology. There is a growing desire to incorporate attributes of ecosystem science into radiological risk assessment and radioecological research more generally, fueled by recent advances in quantification of emergent ecosystem attributes and the desire to accurately reflect impacts of radiological stressors upon ecosystem function. This paper is a synthesis of the discussions and consensus of the workshop participant's responses to three primary questions, which were: 1) How can ecosystem science support radiological risk assessment? 2) What ecosystem level endpoints potentially could be used for radiological risk assessment? and 3) What inference strategies and associated methods would be most appropriate to assess the effects of radionuclides on ecosystem structure and function? The consensus of the participants was that ecosystem science can and should support radiological risk assessment through the incorporation of quantitative metrics that reflect ecosystem functions which are sensitive to radiological contaminants. The participants also agreed that many such endpoints exit or are thought to exit and while many are used in ecological risk assessment currently, additional data need to be collected that link the causal mechanisms of radiological exposure to these endpoints. Finally, the participants agreed that radiological risk assessments must be designed and informed by rigorous statistical frameworks capable of revealing the causal inference tying radiological exposure to the endpoints selected for measurement.
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