| 1. |
- Aprile, E., et al.
(författare)
-
Material radiopurity control in the XENONnT experiment
- 2022
-
Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:7
-
Tidskriftsartikel (refereegranskat)abstract
- The selection of low-radioactive construction materials is of the utmost importance for rare-event searches and thus critical to the XENONnT experiment. Results of an extensive radioassay program are reported, in which material samples have been screened with gamma-ray spectroscopy, mass spectrometry, and 222Rn emanation measurements. Furthermore, the cleanliness procedures applied to remove or mitigate surface contamination of detector materials are described. Screening results, used as inputs for a XENONnT Monte Carlo simulation, predict a reduction of materials background (∼∼17%) with respect to its predecessor XENON1T. Through radon emanation measurements, the expected 222Rn activity concentration in XENONnT is determined to be 4.2 (+0.5−0.7) μBq/kg, a factor three lower with respect to XENON1T. This radon concentration will be further suppressed by means of the novel radon distillation system.
|
|
| 2. |
- Hinrichsen, F., et al.
(författare)
-
Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis
- 2021
-
Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 33:12
-
Tidskriftsartikel (refereegranskat)abstract
- Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2(Delta IEC)). Hk2(Delta IEC) mice were less susceptible to acute colitis. Analyzing the epithelial transcriptome from Hk2(Delta IEC) mice during colitis and using HK2-deficient intestinal organoids and Caco-2 cells revealed reduced mitochondrial respiration and epithelial cell death in the absence of HK2. The microbiota strongly regulated HK2 expression and activity. The microbially derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression via histone deacetylase 8 (HDAC8) and reduced mitochondrial respiration in wild-type but not in HK2-deficient Caco-2 cells. Butyrate supplementation protected wild-type but not Hk2(Delta IEC) mice from colitis. Our findings define a mechanism how butyrate promotes intestinal homeostasis and suggest targeted HK2-inhibition as therapeutic avenue for inflammation.
|
|
| 3. |
- Chadburn, Sarah E., et al.
(författare)
-
Modeled Microbial Dynamics Explain the Apparent Temperature Sensitivity of Wetland Methane Emissions
- 2020
-
Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 34:11
-
Tidskriftsartikel (refereegranskat)abstract
- Methane emissions from natural wetlands tend to increase with temperature and therefore may lead to a positive feedback under future climate change. However, their temperature response includes confounding factors and appears to differ on different time scales. Observed methane emissions depend strongly on temperature on a seasonal basis, but if the annual mean emissions are compared between sites, there is only a small temperature effect. We hypothesize that microbial dynamics are a major driver of the seasonal cycle and that they can explain this apparent discrepancy. We introduce a relatively simple model of methanogenic growth and dormancy into a wetland methane scheme that is used in an Earth system model. We show that this addition is sufficient to reproduce the observed seasonal dynamics of methane emissions in fully saturated wetland sites, at the same time as reproducing the annual mean emissions. We find that a more complex scheme used in recent Earth system models does not add predictive power. The sites used span a range of climatic conditions, with the majority in high latitudes. The difference in apparent temperature sensitivity seasonally versus spatially cannot be recreated by the non-microbial schemes tested. We therefore conclude that microbial dynamics are a strong candidate to be driving the seasonal cycle of wetland methane emissions. We quantify longer-term temperature sensitivity using this scheme and show that it gives approximately a 12% increase in emissions per degree of warming globally. This is in addition to any hydrological changes, which could also impact future methane emissions.
|
|
| 4. |
- Peterziel, H, et al.
(författare)
-
Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
- 2022
-
Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 6:1, s. 94-
-
Tidskriftsartikel (refereegranskat)abstract
- The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.
|
|
| 5. |
- Qiu, Chunjing, et al.
(författare)
-
A strong mitigation scenario maintains climate neutrality of northern peatlands
- 2022
-
Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:1, s. 86-97
-
Tidskriftsartikel (refereegranskat)abstract
- Northern peatlands store 300–600 Pg C, of which approximately half are underlain by permafrost. Climate warming and, in some regions, soil drying from enhanced evaporation are progressively threatening this large carbon stock. Here, we assess future CO2 and CH4 fluxes from northern peatlands using five land surface models that explicitly include representation of peatland processes. Under Representative Concentration Pathways (RCP) 2.6, northern peatlands are projected to remain a net sink of CO2 and climate neutral for the next three centuries. A shift to a net CO2 source and a substantial increase in CH4 emissions are projected under RCP8.5, which could exacerbate global warming by 0.21°C (range, 0.09–0.49°C) by the year 2300. The true warming impact of peatlands might be higher owing to processes not simulated by the models and direct anthropogenic disturbance. Our study highlights the importance of understanding how future warming might trigger high carbon losses from northern peatlands.
|
|
| 6. |
|
|
| 7. |
- Haller, Paul M., et al.
(författare)
-
Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus
- 2023
-
Ingår i: European Journal of Preventive Cardiology. - 2047-4873 .- 2047-4881. ; 30:12, s. 1218-1226
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. 'METHODS AND RESULTS: We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81).CONCLUSION: Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.
|
|
| 8. |
- Renette, Cas, et al.
(författare)
-
Simulating the effect of subsurface drainage on the thermal regime and ground ice in blocky terrain in Norway
- 2023
-
Ingår i: Earth Surface Dynamics. - : Copernicus GmbH. - 2196-6311 .- 2196-632X. ; 11:1, s. 33-50
-
Tidskriftsartikel (refereegranskat)abstract
- Ground temperatures in coarse, blocky deposits such as mountain blockfields and rock glaciers have long been observed to be lower in comparison with other (sub)surface material. One of the reasons for this negative temperature anomaly is the lower soil moisture content in blocky terrain, which decreases the duration of the zero curtain in autumn. Here we used the CryoGrid community model to simulate the effect of drainage on the ground thermal regime and ground ice in blocky terrain permafrost at two sites in Norway. The model set-up is based on a one-dimensional model domain and features a surface energy balance, heat conduction and advection, as well as a bucket water scheme with adjustable lateral drainage. We used three idealized subsurface stratigraphies, blocks only, blocks with sediment and sediment only, which can be either drained (i.e. with strong lateral subsurface drainage) or undrained (i.e. without drainage), resulting in six scenarios. The main difference between the three stratigraphies is their ability to retain water against drainage: while the blocks only stratigraphy can only hold small amounts of water, much more water is retained within the sediment phase of the two other stratigraphies, which critically modifies the freeze-thaw behaviour. The simulation results show markedly lower ground temperatures in the blocks only, drained scenario compared to other scenarios, with a negative thermal anomaly of up to 2.2 degrees C. For this scenario, the model can in particular simulate the time evolution of ground ice, with build-up during and after snowmelt and spring and gradual lowering of the ice table in the course of the summer season. The thermal anomaly increases with larger amounts of snowfall, showing that well-drained blocky deposits are less sensitive to insulation by snow than other soils. We simulate stable permafrost conditions at the location of a rock glacier in northern Norway with a mean annual ground surface temperature of 2.0-2.5 degrees C in the blocks only, drained simulations. Finally, transient simulations since 1951 at the rock glacier site (starting with permafrost conditions for all stratigraphies) showed a complete loss of perennial ground ice in the upper 5 m of the ground in the blocks with sediment, drained run; a 1.6 m lowering of the ground ice table in the sediment only, drained run; and only 0.1 m lowering in the blocks only, drained run. The interplay between the subsurface water-ice balance and ground freezing/thawing driven by heat conduction can at least partly explain the occurrence of permafrost in coarse blocky terrain below the elevational limit of permafrost in non-blocky sediments. It is thus important to consider the subsurface water-ice balance in blocky terrain in future efforts in permafrost distribution mapping in mountainous areas. Furthermore, an accurate prediction of the evolution of the ground ice table in a future climate can have implications for slope stability, as well as water resources in arid environments.
|
|
| 9. |
- Sayedi, Sayedeh Sara, et al.
(författare)
-
Subsea permafrost carbon stocks and climate change sensitivity estimated by expert assessment
- 2020
-
Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 15:12
-
Tidskriftsartikel (refereegranskat)abstract
- The continental shelves of the Arctic Ocean and surrounding seas contain large stocks of organic matter (OM) and methane (CH4), representing a potential ecosystem feedback to climate change not included in international climate agreements. We performed a structured expert assessment with 25 permafrost researchers to combine quantitative estimates of the stocks and sensitivity of organic carbon in the subsea permafrost domain (i.e. unglaciated portions of the continental shelves exposed during the last glacial period). Experts estimated that the subsea permafrost domain contains similar to 560 gigatons carbon (GtC; 170-740, 90% confidence interval) in OM and 45 GtC (10-110) in CH4. Current fluxes of CH4 and carbon dioxide (CO2) to the water column were estimated at 18 (2-34) and 38 (13-110) megatons C yr(-1), respectively. Under Representative Concentration Pathway (RCP) RCP8.5, the subsea permafrost domain could release 43 Gt CO2-equivalent (CO(2)e) by 2100 (14-110) and 190 Gt CO(2)e by 2300 (45-590), with similar to 30% fewer emissions under RCP2.6. The range of uncertainty demonstrates a serious knowledge gap but provides initial estimates of the magnitude and timing of the subsea permafrost climate feedback.
|
|
| 10. |
|
|
| 11. |
- Vuori, Matti A., et al.
(författare)
-
Diabetes status-related differences in risk factors and mediators of heart failure in the general population : results from the MORGAM/BiomarCaRE consortium
- 2021
-
Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers.Methods: In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure.Results: Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49–2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59–2.69]; non-diabetes: HR 1.85 [1.68–2.02]), BMI (diabetes: HR 1.30 [1.18–1.42]; non-diabetes: HR 1.40 [1.35–1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55–2.75]; non-diabetes: HR 2.86 [2.50–3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82–2.80]; non-diabetes: HR 2.97 [2.21–4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19–1.34]; non-diabetes: HR 1.43 [1.39–1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04–1.16]; non-diabetes: HR 1.13 [1.10–1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03–1.24]; non-diabetes: HR 1.29 [1.25–1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9–52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3–16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7–17.4]), and hyperglycemia (glucose, 12.0% [4.2–19.9]).Conclusions: The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.
|
|
