| 1. |
- Fenstermacher, M.E., et al.
(författare)
-
DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
|
|
| 2. |
|
|
| 3. |
- Barucca, G., et al.
(författare)
-
The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
-
Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
|
|
| 4. |
- Barucca, G., et al.
(författare)
-
Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
-
Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
|
|
| 5. |
|
|
| 6. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 7. |
- Abdo, A. A., et al.
(författare)
-
Gamma-ray emission concurrent with the nova in the symbiotic binary V407 cygni
- 2010
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5993, s. 817-821
-
Tidskriftsartikel (refereegranskat)abstract
- Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce x-ray emission, but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable γ-ray emission (0.1 to 10 billion electron volts) from the recently detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary and that particles can be accelerated effectively to produce π0 decay γ-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.
|
|
| 8. |
- Abdo, A. A., et al.
(författare)
-
DISCOVERY OF HIGH-ENERGY GAMMA-RAY EMISSION FROM THE BINARY SYSTEM PSR B1259-63/LS 2883 AROUND PERIASTRON WITH FERMI
- 2011
-
Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 736:1, s. L11-
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of >= 100 MeV gamma-rays from the binary system PSR B1259-63/LS 2883 using the Large Area Telescope (LAT) on board Fermi. The system comprises a radio pulsar in orbit around a Be star. We report on LAT observations from near apastron to similar to 128 days after the time of periastron, t(p), on 2010 December 15. No gamma-ray emission was detected from this source when it was far from periastron. Faint gamma-ray emission appeared as the pulsar approached periastron. At similar to t(p) + 30 days, the >= 100 MeV gamma-ray flux increased over a period of a few days to a peak flux 20-30 times that seen during the pre-periastron period, but with a softer spectrum. For the following month, it was seen to be variable on daily timescales, but remained at similar to(1-4) x 10(-6) cm(-2) s(-1) before starting to fade at similar to t(p) + 57 days. The total gamma-ray luminosity observed during this period is comparable to the spin-down power of the pulsar. Simultaneous radio and X-ray observations of the source showed no corresponding dramatic changes in radio and X-ray flux between the pre-periastron and post-periastron flares. We discuss possible explanations for the observed gamma-ray-only flaring of the source.
|
|
| 9. |
|
|
| 10. |
- Abdo, A. A., et al.
(författare)
-
The second Fermi large area telescope catalog of gamma-ray pulsars
- 2013
-
Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 208:2, s. 17-
-
Tidskriftsartikel (refereegranskat)abstract
- This catalog summarizes 117 high-confidence ≥0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.
|
|
| 11. |
|
|
| 12. |
- Abdo, A. A., et al.
(författare)
-
Fermi large area telescope observations of PSR J1836+5925
- 2010
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 712:2, s. 1209-1218
-
Tidskriftsartikel (refereegranskat)abstract
- The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8 million years, a spindown luminosity of 1.1 x 10(34) erg s(-1), and a large off-peak (OP) emission component, making it quite unusual among the known gamma-ray pulsar population. We present an analysis of one year of LAT data, including an updated timing solution, detailed spectral results, and a long-term light curve showing no indication of variability. No evidence for a surrounding pulsar wind nebula is seen and the spectral characteristics of the OP emission indicate it is likely magnetospheric. Analysis of recent XMM-Newton observations of the X-ray counterpart yields a detailed characterization of its spectrum, which, like Geminga, is consistent with that of a neutron star showing evidence for both magnetospheric and thermal emission.
|
|
| 13. |
|
|
| 14. |
- Abdo, A. A., et al.
(författare)
-
Detection of 16 Gamma-Ray Pulsars Through Blind Frequency Searches Using the Fermi LAT
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5942, s. 840-844
-
Tidskriftsartikel (refereegranskat)abstract
- Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently only seven were observed to pulse in gamma rays, and these were all discovered at other wavelengths. The Fermi Large Area Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma-ray pulsations. We report the detection of 16 gamma-ray pulsars in blind frequency searches using the LAT. Most of these pulsars are coincident with previously unidentified gamma-ray sources, and many are associated with supernova remnants. Direct detection of gamma-ray pulsars enables studies of emission mechanisms, population statistics, and the energetics of pulsar wind nebulae and supernova remnants.
|
|
| 15. |
- Ackermann, M., et al.
(författare)
-
A STATISTICAL APPROACH TO RECOGNIZING SOURCE CLASSES FOR UNASSOCIATED SOURCES IN THE FIRST FERMI-LAT CATALOG
- 2012
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 753:1, s. 83-
-
Tidskriftsartikel (refereegranskat)abstract
- The Fermi Large Area Telescope (LAT) First Source Catalog (1FGL) provided spatial, spectral, and temporal properties for a large number of gamma-ray sources using a uniform analysis method. After correlating with the most-complete catalogs of source types known to emit gamma rays, 630 of these sources are unassociated (i.e., have no obvious counterparts at other wavelengths). Here, we employ two statistical analyses of the primary gamma-ray characteristics for these unassociated sources in an effort to correlate their gamma-ray properties with the active galactic nucleus (AGN) and pulsar populations in 1FGL. Based on the correlation results, we classify 221 AGN-like and 134 pulsar-like sources in the 1FGL unassociated sources. The results of these source classifications appear to match the expected source distributions, especially at high Galactic latitudes. While useful for planning future multiwavelength follow-up observations, these analyses use limited inputs, and their predictions should not be considered equivalent to probable source classes for these sources. We discuss multiwavelength results and catalog cross-correlations to date, and provide new source associations for 229 Fermi-LAT sources that had no association listed in the 1FGL catalog. By validating the source classifications against these new associations, we find that the new association matches the predicted source class in similar to 80% of the sources.
|
|
| 16. |
- Ackermann, M., et al.
(författare)
-
Fermi establishes classical novae as a distinct class of gamma-ray sources
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 345:6196, s. 554-558
-
Tidskriftsartikel (refereegranskat)abstract
- A classical nova results from runaway thermonuclear explosions on the surface of a white dwarf that accretes matter from a low-mass main-sequence stellar companion. In 2012 and 2013, three novae were detected in gamma rays and stood in contrast to the first gamma-ray-detected nova V407 Cygni 2010, which belongs to a rare class of symbiotic binary systems. Despite likely differences in the compositions and masses of their white dwarf progenitors, the three classical novae are similarly characterized as soft-spectrum transient gamma-ray sources detected over 2- to 3-week durations. The gamma-ray detections point to unexpected high-energy particle acceleration processes linked to the mass ejection from thermonuclear explosions in an unanticipated class of Galactic gamma-ray sources.
|
|
| 17. |
- Dahl-Jensen, D., et al.
(författare)
-
Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
-
Tidskriftsartikel (refereegranskat)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Maas, R. R., et al.
(författare)
-
Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases
- 2017
-
Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 82:6, s. 1004-1015
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: 3-Methylglutaconic aciduria, dystonia–deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1. Methods: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. Results: Sixty-seven individuals (39 previously unreported) from 59 families were included (age range = 5 days–33.4 years, median age = 9 years). A total of 41 different SERAC1 variants were identified, including 20 that have not been reported before. With the exception of 2 families with a milder phenotype, all affected individuals showed a strikingly homogeneous phenotype and time course. Severe, reversible neonatal liver dysfunction and hypoglycemia were seen in >40% of all cases. Starting at a median age of 6 months, muscular hypotonia (91%) was seen, followed by progressive spasticity (82%, median onset = 15 months) and dystonia (82%, 18 months). The majority of affected individuals never learned to walk (68%). Seventy-nine percent suffered hearing loss, 58% never learned to speak, and nearly all had significant intellectual disability (88%). Magnetic resonance imaging features were accordingly homogenous, with bilateral basal ganglia involvement (98%); the characteristic “putaminal eye” was seen in 53%. The urinary marker 3-methylglutaconic aciduria was present in virtually all patients (98%). Supportive treatment focused on spasticity and drooling, and was effective in the individuals treated; hearing aids or cochlear implants did not improve communication skills. Interpretation: MEGDHEL syndrome is a progressive deafness–dystonia syndrome with frequent and reversible neonatal liver involvement and a strikingly homogenous course of disease. Ann Neurol 2017;82:1004–1015. © 2017 American Neurological Association
|
|
| 21. |
- Schüpbach, S., et al.
(författare)
-
Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.
|
|
| 22. |
|
|
| 23. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
|
|
| 24. |
- Ombrello, MJ, et al.
(författare)
-
Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications
- 2017
-
Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:5, s. 906-913
-
Tidskriftsartikel (refereegranskat)abstract
- Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA.MethodsWe performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes.ResultsThe major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes.ConclusionsThe lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
|
|
| 25. |
- Wagner-Drouet, E, et al.
(författare)
-
Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation
- 2021
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:2, s. 363-374
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediate- and high-risk allogeneic hematopoietic stem cell transplant recipients under preemptive antiviral therapy. Cytomegalovirus-specific cellular immunity was measured using a standardized IFN-γ ELISpot assay (T-Track® CMV). Primary aim was to evaluate the suitability of measuring cytomegalovirus-specific immunity after end of treatment for a first cytomegalovirus reactivation to predict recurrent reactivation. 40/101 (39.6%) patients with a first cytomegalovirus reactivation experienced recurrent reactivations, mainly in the high-risk group (cytomegalovirus-seronegative donor/cytomegalovirus-seropositive recipient). The positive predictive value of T-Track® CMV (patients with a negative test after the first reactivation experienced at least one recurrent reactivation) was 84.2% in high-risk patients. Kaplan-Meier analysis revealed a higher probability of recurrent cytomegalovirus reactivation in high-risk patients with a negative test after the first reactivation (hazard ratio 2.73; p=0.007). Interestingly, a post-hoc analysis considering T-Track® CMV measurements at day 100 post-transplantation, a time point highly relevant for outpatient care, showed a positive predictive value of 90.0% in high-risk patients. Our results indicate that standardized cytomegalovirus-specific cellular immunity monitoring may allow improved risk stratification and management of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. This study was registered at www.clinicaltrials.gov as #NCT02156479.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Kaput, J, et al.
(författare)
-
The case for strategic international alliances to harness nutritional genomics for public and personal health
- 2005
-
Ingår i: The British journal of nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 94:5, s. 623-632
-
Tidskriftsartikel (refereegranskat)abstract
- Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Abdel-Aziz, MI, et al.
(författare)
-
A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma
- 2021
-
Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
-
Tidskriftsartikel (refereegranskat)abstract
- There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the “Systems Pharmacology Approach to Uncontrolled Pediatric Asthma” (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case–control study, moderate-to-severe asthmatic children (age; 6–17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.
|
|
| 35. |
|
|
| 36. |
- Arvidson, R. E., et al.
(författare)
-
Opportunity Mars Rover mission : Overview and selected results from Purgatory ripple to traverses to Endeavour crater
- 2011
-
Ingår i: Journal of Geophysical Research. - Hoboken : Wiley-Blackwell. - 0148-0227 .- 2156-2202. ; 116, s. E00F15-
-
Tidskriftsartikel (refereegranskat)abstract
- Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony-iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional-scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour's rim that will be markedly different from anything examined to date. Copyright 2011 by the American Geophysical Union.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Di Fatta, G., et al.
(författare)
-
Preface
- 2011
-
Ingår i: IEEE International Conference on Data Mining. Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 1550-4786. ; , s. xlviii-xlvix
-
Tidskriftsartikel (refereegranskat)
|
|
| 42. |
- Halappanavar, S, et al.
(författare)
-
Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale
- 2020
-
Ingår i: Particle and fibre toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 17:1, s. 16-
-
Tidskriftsartikel (refereegranskat)abstract
- Toxicity testing and regulation of advanced materials at the nanoscale, i.e. nanosafety, is challenged by the growing number of nanomaterials and their property variants requiring assessment for potential human health impacts. The existing animal-reliant toxicity testing tools are onerous in terms of time and resources and are less and less in line with the international effort to reduce animal experiments. Thus, there is a need for faster, cheaper, sensitive and effective animal alternatives that are supported by mechanistic evidence. More importantly, there is an urgency for developing alternative testing strategies that help justify the strategic prioritization of testing or targeting the most apparent adverse outcomes, selection of specific endpoints and assays and identifying nanomaterials of high concern. The Adverse Outcome Pathway (AOP) framework is a systematic process that uses the available mechanistic information concerning a toxicological response and describes causal or mechanistic linkages between a molecular initiating event, a series of intermediate key events and the adverse outcome. The AOP framework provides pragmatic insights to promote the development of alternative testing strategies. This review will detail a brief overview of the AOP framework and its application to nanotoxicology, tools for developing AOPs and the role of toxicogenomics, and summarize various AOPs of relevance to inhalation toxicity of nanomaterials that are currently under various stages of development. The review also presents a network of AOPs derived from connecting all AOPs, which shows that several adverse outcomes induced by nanomaterials originate from a molecular initiating event that describes the interaction of nanomaterials with lung cells and involve similar intermediate key events. Finally, using the example of an established AOP for lung fibrosis, the review will discuss various in vitro tests available for assessing lung fibrosis and how the information can be used to support a tiered testing strategy for lung fibrosis. The AOPs and AOP network enable deeper understanding of mechanisms involved in inhalation toxicity of nanomaterials and provide a strategy for the development of alternative test methods for hazard and risk assessment of nanomaterials.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
- Kerzenmacher, T., et al.
(författare)
-
Validation of NO2 and NO from the Atmospheric Chemistry Experiment (ACE)
- 2008
-
Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:19, s. 5801--5841-
-
Tidskriftsartikel (refereegranskat)abstract
- Vertical profiles of NO2 and NO have been obtained from solar occultation measurements by the Atmospheric Chemistry Experiment (ACE), using an infrared Fourier Transform Spectrometer (ACE-FTS) and (for NO2) an ultraviolet-visible-near-infrared spectrometer, MAESTRO (Measurement of Aerosol Extinction in the Stratosphere and Troposphere Retrieved by Occultation). In this paper, the quality of the ACE-FTS version 2.2 NO2 and NO and the MAESTRO version 1.2 NO2 data are assessed using other solar occultation measurements (HALOE, SAGE II, SAGE III, POAM III, SCIAMACHY), stellar occultation measurements (GOMOS), limb measurements (MIPAS, OSIRIS), nadir measurements (SCIAMACHY), balloon-borne measurements (SPIRALE, SAOZ) and ground-based measurements (UV-VIS, FTIR). Time differences between the comparison measurements were reduced using either a tight coincidence criterion, or where possible, chemical box models. ACE-FTS NO2 and NO and the MAESTRO NO2 are generally consistent with the correlative data. The ACE-FTS and MAESTRO NO2 volume mixing ratio (VMR) profiles agree with the profiles from other satellite data sets to within about 20% between 25 and 40 km, with the exception of MIPAS ESA (for ACE-FTS) and SAGE II (for ACE-FTS (sunrise) and MAESTRO) and suggest a negative bias between 23 and 40 km of about 10%. MAESTRO reports larger VMR values than the ACE-FTS. In comparisons with HALOE, ACE-FTS NO VMRs typically (on average) agree to ±8% from 22 to 64 km and to +10% from 93 to 105 km, with maxima of 21% and 36%, respectively. Partial column comparisons for NO2 show that there is quite good agreement between the ACE instruments and the FTIRs, with a mean difference of +7.3% for ACE-FTS and +12.8% for MAESTRO.
|
|
| 46. |
|
|
| 47. |
- Kisand, Kai, et al.
(författare)
-
Interferon autoantibodies associated with AIRE-deficiency decrease the expression of IFN-stimulated genes
- 2008
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 112:7, s. 2657-2666
-
Tidskriftsartikel (refereegranskat)abstract
- Neutralizing autoantibodies to type I, but not type II, interferons (IFNs) are found at high titers in almost every patient with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a disease caused by AIRE gene mutations that lead to defects in thymic T-cell selection. Combining genome-wide expression array with real time RT-PCR assays, we here demonstrate that antibodies against IFN-alpha cause highly significant down-regulation of interferon-stimulated gene expression in cells from APECED patients' blood by blocking their highly dilute endogenous IFNs. This down-regulation was lost progressively as these APECED cells matured in cultures without neutralizing autoantibodies. Most interestingly, a rare APECED patient with autoantibodies to IFN-omega but not IFN-alpha showed a marked increase in expression of the same interferon-stimulated genes. We also report unexpected increases in serum CXCL10 levels in APECED. Our results argue that the breakdown of tolerance to IFNs in AIRE deficiency is associated with impaired responses to them in thymus, and highlight APECED as another autoimmune disease with associated dysregulation of IFN activity.
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
