| 1. |
|
|
| 2. |
- Aamodt, K., et al.
(författare)
-
The ALICE experiment at the CERN LHC
- 2008
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
-
Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
|
|
| 3. |
- Bouyoucef, S E, et al.
(författare)
-
Poster Session 2 : Monday 4 May 2015, 08
- 2015
-
Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
|
| 5. |
- Helbig, K. L., et al.
(författare)
-
De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
-
Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Neumann, J. T., et al.
(författare)
-
Application of High-Sensitivity Troponin in Suspected Myocardial Infarction
- 2019
-
Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 380:26, s. 2529-2540
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundData regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. MethodsIn 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. ResultsAmong 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. ConclusionsA risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Bieser, Johannes, et al.
(författare)
-
The 3D biogeochemical marine mercury cycling model MERCY v2.0 – linking atmospheric Hg to methylmercury in fish
- 2023
-
Ingår i: Geoscientific Model Development. - 1991-959X .- 1991-9603. ; 16:9, s. 2649-2688
-
Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a pollutant of global concern. Due to anthropogenic emissions, the atmospheric and surface ocean Hg burden has increased substantially since preindustrial times. Hg emitted into the atmosphere gets transported on a global scale and ultimately reaches the oceans. There it is transformed into highly toxic methylmercury (MeHg) that effectively accumulates in the food web. The international community has recognized this serious threat to human health and in 2017 regulated Hg use and emissions under the UN Minamata Convention on Mercury. Currently, the first effectiveness evaluation of the Minamata Convention is being prepared, and, in addition to observations, models play a major role in understanding environmental Hg pathways and in predicting the impact of policy decisions and external drivers (e.g., climate, emission, and land-use change) on Hg pollution. Yet, the available model capabilities are mainly limited to atmospheric models covering the Hg cycle from emission to deposition. With the presented model MERCY v2.0 we want to contribute to the currently ongoing effort to improve our understanding of Hg and MeHg transport, transformation, and bioaccumulation in the marine environment with the ultimate goal of linking anthropogenic Hg releases to MeHg in seafood.Here, we present the equations and parameters implemented in the MERCY model and evaluate the model performance for two European shelf seas, the North and Baltic seas. With the model evaluation, we want to establish a set of general quality criteria that can be used for evaluation of marine Hg models. The evaluation is based on statistical criteria developed for the performance evaluation of atmospheric chemistry transport models. We show that the MERCY model can reproduce observed average concentrations of individual Hg species in water (normalized mean bias: HgT 17 %, Hg0 2 %, MeHg −28 %) in the two regions mentioned above. Moreover, it is able to reproduce the observed seasonality and spatial patterns. We find that the model error for HgT(aq) is mainly driven by the limitations of the physical model setup in the coastal zone and the availability of data on Hg loads in major rivers. In addition, the model error in calculating vertical mixing and stratification contributes to the total HgT model error. For the vertical transport we find that the widely used particle partitioning coefficient for organic matter of log(kd)=5.4 is too low for the coastal systems. For Hg0 the model performance is at a level where further model improvements will be difficult to achieve. For MeHg, our understanding of the processes controlling methylation and demethylation is still quite limited. While the model can reproduce average MeHg concentrations, this lack of understanding hampers our ability to reproduce the observed value range. Finally, we evaluate Hg and MeHg concentrations in biota and show that modeled values are within the range of observed levels of accumulation in phytoplankton, zooplankton, and fish. The model performance demonstrates the feasibility of developing marine Hg models with similar predictive capability to established atmospheric chemistry transport models. Our findings also highlight important knowledge gaps in the dynamics controlling methylation and bioaccumulation that, if closed, could lead to important improvements of the model performance.
|
|
| 15. |
- Capo, Eric, et al.
(författare)
-
Oxygen-deficient water zones in the Baltic Sea promote uncharacterized Hg methylating microorganisms in underlying sediments
- 2022
-
Ingår i: Limnology and Oceanography. - : Wiley. - 1939-5590 .- 0024-3590. ; 67:1, s. 135-146
-
Tidskriftsartikel (refereegranskat)abstract
- Human-induced expansion of oxygen-deficient zones can have dramatic impacts on marine systems and its resident biota. One example is the formation of the potent neurotoxic methylmercury (MeHg) that is mediated by microbial methylation of inorganic divalent Hg (HgII) under oxygen-deficient conditions. A negative consequence of the expansion of oxygen-deficient zones could be an increase in MeHg production due to shifts in microbial communities in favor of microorganisms methylating Hg. There is, however, limited knowledge about Hg-methylating microbes, i.e., those carrying hgc genes critical for mediating the process, from marine sediments. Here, we aim to study the presence of hgc genes and transcripts in metagenomes and metatranscriptomes from four surface sediments with contrasting concentrations of oxygen and sulfide in the Baltic Sea. We show that potential Hg methylators differed among sediments depending on redox conditions. Sediments with an oxygenated surface featured hgc-like genes and transcripts predominantly associated with uncultured Desulfobacterota (OalgD group) and Desulfobacterales (including Desulfobacula sp.) while sediments with a hypoxic-anoxic surface included hgc-carrying Verrucomicrobia, unclassified Desulfobacterales, Desulfatiglandales, and uncharacterized microbes. Our data suggest that the expansion of oxygen-deficient zones in marine systems may lead to a compositional change of Hg-methylating microbial groups in the sediments, where Hg methylators whose metabolism and biology have not yet been characterized will be promoted and expand.
|
|
| 16. |
- Chen, Long, et al.
(författare)
-
A decline in Arctic Ocean mercury suggested by differences in decadal trends of atmospheric mercury between the Arctic and northern midlatitudes
- 2015
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:14, s. 6076-6083
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric mercury (Hg) in the Arctic shows much weaker or insignificant annual declines relative to northern midlatitudes over the past decade (2000-2009) but with strong seasonality in trends. We use a global ocean-atmosphere model of Hg (GEOS-Chem) to simulate these observed trends and determine the driving environmental variables. The atmospheric decline at northern midlatitudes can largely be explained by decreasing North Atlantic oceanic evasion. The midlatitude atmospheric signal propagates to the Arctic but is countered by rapid Arctic warming and declining sea ice, which suppresses deposition and promotes oceanic evasion over the Arctic Ocean. The resulting simulation implies a decline of Hg in the Arctic surface ocean that we estimate to be -0.67%yr(-1) over the study period. Rapid Arctic warming and declining sea ice are projected for future decades and would drive a sustained decline in Arctic Ocean Hg, potentially alleviating the methylmercury exposure risk for northern populations.
|
|
| 17. |
- Dastoor, Ashu, et al.
(författare)
-
Arctic mercury cycling
- 2022
-
Ingår i: Nature Reviews Earth & Environment. - : Springer Nature. - 2662-138X. ; 3:4, s. 270-286
-
Forskningsöversikt (refereegranskat)abstract
- Anthropogenic mercury (Hg) emissions have driven marked increases in Arctic Hg levels,which are now being impacted by regional warming, with uncertain ecological consequences. This Review presents a comprehensive assessment of the present-day total Hg mass balance in the Arctic. Over 98% of atmospheric Hg is emitted outside the region and is transported to the Arctic via long-range air and ocean transport. Around two thirds of this Hg is deposited in terrestrial ecosystems, where it predominantly accumulates in soils via vegetation uptake. Rivers and coastal erosion transfer about 80 Mg year−1 of terrestrial Hg to the Arctic Ocean, in approximate balance with modelled net terrestrial Hg deposition in the region. The revised Arctic Ocean Hg mass balance suggests net atmospheric Hg deposition to the ocean and that Hg burial in inner-shelf sediments is underestimated (up to >100%), needing seasonal observations of sediment-oceanHg exchange. Terrestrial Hg mobilization pathways from soils and the cryosphere (permafrost, ice, snow and glaciers) remain uncertain. Improved soil, snowpack and glacial Hg inventories, transfer mechanisms of riverine Hg releases under accelerated glacier and soil thaw, coupled atmosphere– terrestrial modelling and monitoring of Hg in sensitive ecosystems such as fjords can help toanticipate impacts on downstream Arctic ecosystems.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Knot, J, et al.
(författare)
-
How to set up an effective national primary angioplasty network : Lessons learned from five European countries
- 2009
-
Ingår i: EuroIntervention. - 1774-024X. ; 3:299, s. 301-309
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Percutaneous coronary interventions (PCI) are used to treat acute and chronic forms of coronary artery disease. While in chronic forms the main goal of PCI is to improve the quality of life, in acute coronary syndromes (ACS) timely PCI is a life-saving procedure - especially in the setting of ST-elevation myocardial infarction (STEMI). The aim of this study was to describe the experience of countries with successful nationwide implementation of PCI in STEMI, and to provide general recommendations for other countries. METHODS AND RESULTS: The European Association of Percutaneous Cardiovascular Interventions (EAPCI) recenty launched the Stent For Life Initiative (SFLI). The initial phase of this pan-European project was focused on the positive experience of five countries to provide the best practice examples. The Netherlands, the Czech Republic, Sweden, Denmark and Austria were visited and the logistics of ACS treatment was studied. Public campaigns improved patient access to acute PCI. Regional networks involving emergency medical services (EMS), non-PCI hospitals and PCI centres are useful in providing access to acute PCI for most patients. Direct transfer from the first medical contact site to the cathlab is essential to minimise the time delays. Cathlab staff work is organised to provide acute PCI services 24 hours a day / seven days a week (24/7). Even in those regions where thrombolysis is still used due to long transfer distances to PCI, patients should still be transferred to a PCI centre (after thrombolysis). The highest risk non-ST elevation acute myocardial infarction patients should undergo emergency coronary angiography within two hours of hospital admission, i.e. similar to STEMI patients. CONCLUSIONS: Three realistic goals for other countries were defined based on these experiences: 1) primary PCI should be used for >70% of all STEMI patients, 2) primary PCI rates should reach >600 per million inhabitants per year and 3) existing PCI centres should treat all their STEMI patients by primary PCI, i.e. should offer a 24/7 service
|
|
| 21. |
|
|
| 22. |
- Rasmusson, Annica J., et al.
(författare)
-
Toll-like receptor 4 methylation grade is linked to depressive symptom severity
- 2021
-
Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores potential associations between the methylation of promoter-associated CpG sites of the toll-like receptor (TLR)-family, plasma levels of pro-inflammatory proteins and depressive symptoms in young female psychiatric patients. Ratings of depressive symptoms and blood samples were obtained from 92 young women seeking psychiatric care. Methylation of 32 promoter-associated CpG sites in TLR1 to TLR10 was analysed using the Illumina Infinium Methylation EPIC BeadChip. Expression levels of 91 inflammatory proteins were determined by proximity extension assay. Statistical correlations between depressive state, TLR1-10 methylation and inflammatory proteins were investigated. Four additional cohorts were studied to evaluate the generalizability of the findings. In the discovery cohort, methylation grade of cg05429895 (TLR4) in blood was inversely correlated with depressive symptoms score in young adults. After correction for multiple testing, plasma levels of macrophage inflammatory protein 1 beta (MIP-1 beta/CCL4) were associated with both TLR4 methylation and depressive symptom severity. A similar inverse association between TLR4 methylation in blood and affective symptoms score was also found in a cohort of 148 both males and females (<40 years of age) from the Danish Twin Registry. These findings were not, however, replicated in three other external cohorts; which differed from the first two cohorts by a higher age and mixed ethnicities, thus limiting the generalizability of our findings. However, TLR4 methylation inversely correlated with TLR4 mRNA expression in the Danish Twin Study indicating a functional significance of methylation at this particular CpG. Higher depression scores in young Scandinavian adults was associated with decreased methylation of TLR4 in blood.
|
|
| 23. |
- Sempreviva, A. M., et al.
(författare)
-
Observed development of the vertical structure of the marine boundary layer during the LASIE experiment in the Ligurian Sea
- 2010
-
Ingår i: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 28:1, s. 17-25
-
Tidskriftsartikel (refereegranskat)abstract
- In the marine environment, complete datasets describing the surface layer and the vertical structure of the Marine Atmospheric Boundary Layer (MABL), through its entire depth, are less frequent than over land, due to the high cost of measuring campaigns. During the seven days of the Ligurian Air-Sea Interaction Experiment (LASIE), organized by the NATO Undersea Research Centre (NURC) in the Mediterranean Sea, extensive in situ and remote sensing measurements were collected from instruments placed on a spar buoy and a ship. Standard surface meteorological measurements were collected by meteorological sensors mounted on the buoy ODAS Italia1 located in the centre of the Gulf of Genoa. The evolution of the height (z(i)) of the MABL was monitored using radiosondes and a ceilometer on board of the N/O Urania. Here, we present the database and an uncommon case study of the evolution of the vertical structure of the MABL, observed by two independent measuring systems: the ceilometer and radiosondes. Following the changes of surface flow conditions, in a sequence of onshore - offshore - onshore wind direction shifting episodes, during the mid part of the campaign, the overall structure of the MABL changed. Warm and dry air from land advected over a colder sea, induced a stably stratified Internal Boundary Layer (IBL) and a consequent change in the structure of the vertical profiles of potential temperature and relative humidity.
|
|
| 24. |
- Soerensen, Anne L., et al.
(författare)
-
A mass budget for mercury and methylmercury in the Arctic Ocean
- 2016
-
Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 30:4, s. 560-575
-
Tidskriftsartikel (refereegranskat)abstract
- Elevated biological concentrations of methylmercury (MeHg), a bioaccumulative neurotoxin, are observed throughout the Arctic Ocean, but major sources and degradation pathways in seawater are not well understood. We develop a mass budget for mercury species in the Arctic Ocean based on available data since 2004 and discuss implications and uncertainties. Our calculations show that high total mercury (Hg) in Arctic seawater relative to other basins reflect large freshwater inputs and sea ice cover that inhibits losses through evasion. We find that most net MeHg production (20Mga(-1)) occurs in the subsurface ocean (20-200m). There it is converted to dimethylmercury (Me2Hg: 17Mga(-1)), which diffuses to the polar mixed layer and evades to the atmosphere (14Mga(-1)). Me2Hg has a short atmospheric lifetime and rapidly degrades back to MeHg. We postulate that most evaded Me2Hg is redeposited as MeHg and that atmospheric deposition is the largest net MeHg source (8Mga(-1)) to the biologically productive surface ocean. MeHg concentrations in Arctic Ocean seawater are elevated compared to lower latitudes. Riverine MeHg inputs account for approximately 15% of inputs to the surface ocean (2.5Mga(-1)) but greater importance in the future is likely given increasing freshwater discharges and permafrost melt. This may offset potential declines driven by increasing evasion from ice-free surface waters. Geochemical model simulations illustrate that for the most biologically relevant regions of the ocean, regulatory actions that decrease Hg inputs have the capacity to rapidly affect aquatic Hg concentrations.
|
|
| 25. |
- Tulstrup, M, et al.
(författare)
-
TET2 mutations are associated with hypermethylation at key regulatory enhancers in normal and malignant hematopoiesis
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 6061-
-
Tidskriftsartikel (refereegranskat)abstract
- Mutations in the epigenetic modifier TET2 are frequent in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). Here, we investigate associations between TET2 mutations and DNA methylation in whole blood in 305 elderly twins, 15 patients with CCUS and 18 healthy controls. We find that TET2 mutations are associated with DNA hypermethylation at enhancer sites in whole blood in CHIP and in both granulocytes and mononuclear cells in CCUS. These hypermethylated sites are associated with leukocyte function and immune response and ETS-related and C/EBP-related transcription factor motifs. While the majority of TET2-associated hypermethylation sites are shared between CHIP and in AML, we find a set of AML-specific hypermethylated loci at active enhancer elements in hematopoietic stem cells. In summary, we show that TET2 mutations is associated with hypermethylated enhancers involved in myeloid differentiation in both CHIP, CCUS and AML patients.
|
|
