| 1. |
- Abbasi, R., et al.
(författare)
-
Solar energetic particle spectrum on 2006 December 13 determined by IceTop
- 2008
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 689:1, s. L65-L68
-
Tidskriftsartikel (refereegranskat)abstract
- On 2006 December 13 the IceTop air shower array at the South Pole detected a major solar particle event. By numerically simulating the response of the IceTop tanks, which are thick Cerenkov detectors with multiple thresholds deployed at high altitude with no geomagnetic cutoff, we determined the particle energy spectrum in the energy range 0.6-7.6 GeV. This is the first such spectral measurement using a single instrument with a well-defined viewing direction. We compare the IceTop spectrum and its time evolution with previously published results and outline plans for improved resolution of future solar particle spectra.
|
|
| 2. |
|
|
| 3. |
- Pluta, J, et al.
(författare)
-
Identification of 22 susceptibility loci associated with testicular germ cell tumors
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 4487-
-
Tidskriftsartikel (refereegranskat)abstract
- Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation.
|
|
| 4. |
|
|
| 5. |
- Raap, A. K., et al.
(författare)
-
Non-Random mtDNA Segregation Patterns Indicate a Metastable Heteroplasmic Segregation Unit in m.3243A>G Cybrid Cells
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12, s. e52080-
-
Tidskriftsartikel (refereegranskat)abstract
- Many pathogenic mitochondrial DNA mutations are heteroplasmic, with a mixture of mutated and wild-type mtDNA present within individual cells. The severity and extent of the clinical phenotype is largely due to the distribution of mutated molecules between cells in different tissues, but mechanisms underpinning segregation are not fully understood. To facilitate mtDNA segregation studies we developed assays that measure m.3243A>G point mutation loads directly in hundreds of individual cells to determine the mechanisms of segregation over time. In the first study of this size, we observed a number of discrete shifts in cellular heteroplasmy between periods of stable heteroplasmy. The observed patterns could not be parsimoniously explained by random mitotic drift of individual mtDNAs. Instead, a genetically metastable, heteroplasmic mtDNA segregation unit provides the likely explanation, where stable heteroplasmy is maintained through the faithful replication of segregating units with a fixed wild-type/m.3243A>G mutant ratio, and shifts occur through the temporary disruption and re-organization of the segregation units. While the nature of the physical equivalent of the segregation unit remains uncertain, the factors regulating its organization are of major importance for the pathogenesis of mtDNA diseases.
|
|
| 6. |
- Hathazi, D., et al.
(författare)
-
Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency
- 2020
-
Ingår i: Embo Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 39:23
-
Tidskriftsartikel (refereegranskat)abstract
- Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only similar to 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.
|
|
| 7. |
- Peter, Bradley, et al.
(författare)
-
Defective mitochondrial protease LonP1 can cause classical mitochondrial disease
- 2018
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1743-1753
-
Tidskriftsartikel (refereegranskat)abstract
- LonP1 is a mitochondrial matrix protease whose selective substrate specificity is essential for maintaining mitochondrial homeostasis. Recessively inherited, pathogenic defects in LonP1 have been previously reported to underlie cerebral, ocular, dental, auricular and skeletal anomalies (CODAS) syndrome, a complex multisystemic and developmental disorder. Intriguingly, although classical mitochondrial disease presentations are well-known to exhibit marked clinical heterogeneity, the skeletal and dental features associated with CODAS syndrome are pathognomonic. We have applied whole exome sequencing to a patient with congenital lactic acidosis, muscle weakness, profound deficiencies in mitochondrial oxidative phosphorylation associated with loss of mtDNA copy number and MRI abnormalities consistent with Leigh syndrome, identifying biallelic variants in the LONP1 (NM_004793.3) gene; c.1693T > C predicting p.(Tyr565His) and c.2197G > A predicting p.(Glu733Lys); no evidence of the classical skeletal or dental defects observed in CODAS syndrome patients were noted in our patient. In vitro experiments confirmed the p.(Tyr565His) LonP1 mutant alone could not bind or degrade a substrate, consistent with the predicted function of Tyr565, whilst a second missense [p.(Glu733Lys)] variant had minimal effect. Mixtures of p.(Tyr565His) mutant and wild-type LonP1 retained partial protease activity but this was severely depleted when the p.(Tyr565His) mutant was mixed with the p.(Glu733Lys) mutant, data consistent with the compound heterozygosity detected in our patient. In summary, we conclude that pathogenic LONP1 variants can lead to a classical mitochondrial disease presentations associated with severe biochemical defects in oxidative phosphorylation in clinically relevant tissues.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Dittrich, Christian, et al.
(författare)
-
ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
-
Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
-
Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
|
|
| 11. |
|
|
| 12. |
- Fisher, Rebecca E., et al.
(författare)
-
Measurement of the C-13 isotopic signature of methane emissions from northern European wetlands
- 2017
-
Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:3, s. 605-623
-
Tidskriftsartikel (refereegranskat)abstract
- Isotopic data provide powerful constraints on regional and global methane emissions and their source profiles. However, inverse modeling of spatially resolved methane flux is currently constrained by a lack of information on the variability of source isotopic signatures. In this study, isotopic signatures of emissions in the Fennoscandian Arctic have been determined in chambers over wetland, in the air 0.3 to 3m above the wetland surface and by aircraft sampling from 100m above wetlands up to the stratosphere. Overall, the methane flux to atmosphere has a coherent delta C-13 isotopic signature of -71 +/- 1%, measured in situ on the ground in wetlands. This is in close agreement with delta C-13 isotopic signatures of local and regional methane increments measured by aircraft campaigns flying through air masses containing elevated methane mole fractions. In contrast, results from wetlands in Canadian boreal forest farther south gave isotopic signatures of -67 +/- 1%. Wetland emissions dominate the local methane source measured over the European Arctic in summer. Chamber measurements demonstrate a highly variable methane flux and isotopic signature, but the results from air sampling within wetland areas show that emissions mix rapidly immediately above the wetland surface and methane emissions reaching the wider atmosphere do indeed have strongly coherent C isotope signatures. The study suggests that for boreal wetlands (>60 degrees N) global and regional modeling can use an isotopic signature of -71 parts per thousand to apportion sources more accurately, but there is much need for further measurements over other wetlands regions to verify this.
|
|
| 13. |
- Ljunggren, Philip, et al.
(författare)
-
Reduced brachial artery distensibility in patients with type 1 diabetes
- 2016
-
Ingår i: Journal of diabetes and its complications. - : ELSEVIER SCIENCE INC. - 1056-8727 .- 1873-460X. ; 30:5, s. 893-897
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: In patients with type 1 diabetes mellitus (T1D), cardiovascular disease (CVD) events are more common and occur earlier in life than in non-diabetics. Reduced brachial artery distensibility (BrachD) is an independent risk factor for development of CVD. Our aim was to determine if adults with T1D have lower BrachD compared to adults without diabetes and also to determine how age and gender affect the relationship of BrachD with T1D status. Materials and methods: BrachD was measured using the Dynapulse instrument in 829 participants (352 with T1D, 477 non-diabetics). An ANCOVA model was used to test the association of BrachD with age, sex, and T1D, and the significance of an age*sex*T1D interaction. Results: Mean BrachD was lower in T1D patients vs. controls (6.43 +/- 1.46 vs. 7.16 +/- 1.48 % change per mmHg, p amp;lt; 0.0001). In a model adjusted for age, T1D, and sex, the interaction of age*T1D*sex was significant (p = 0.0045). Younger women both with and without T1D had higher BrachD than men with and without T1D, but older women with and without T1D had lower BrachD compared to older men with and without T1D. Women with T1D had a steeper decline in BrachD with age than nondiabetic women. Conclusions: BrachD is lower in T1D patients than in non-diabetics, indicating increased vascular stiffness. Younger females have higher BrachD than males, but the decline with age in BrachD is steeper for women, particularly among those with T1D. BrachD may be an inexpensive, non-invasive method to ascertain increased CVD risk in this population. (C) 2016 Elsevier Inc. All rights reserved.
|
|
| 14. |
- Nuntiyakul, W., et al.
(författare)
-
Direct Determination of a Bare Neutron Counter Yield Function
- 2020
-
Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 125:4
-
Tidskriftsartikel (refereegranskat)abstract
- Ground-based neutron counters are a standard tool for detecting atmospheric showers from GeV range primary cosmic rays of either solar or galactic origin. Bare neutron counters, a type of lead-free neutron monitor, function much like standard neutron monitors but have different yield functions primarily because they are more sensitive to neutrons of lower energy. When operated together with standard monitors, the different yield functions allow estimates to be made of the energy spectrum of galactic or solar particles. In 2010 a new array of 12 bare neutron detectors was installed at the South Pole to operate together with the neutron monitor there. Prior to installation, two of the detectors were operated on a ship that traveled from Sweden to Antarctica and back from November 2009 to April 2010. The purpose of this latitude survey was to use Earth's magnetic field as a spectrometer, blocking cosmic rays below the local cutoff rigidity (momentum per unit charge), from which we determined the response function versus rigidity of these bare counters. By comparing that measured response function to direct measurements of the cosmic ray spectrum taken by the PAMELA spacecraft, we were able to make a direct determination of the yield function for these detectors.
|
|
| 15. |
- Nuntiyakul, W., et al.
(författare)
-
Direct Determination of a Bare Neutron Counter Yield Function
- 2022
-
Ingår i: 37th International Cosmic Ray Conference, ICRC2021. - Trieste, Italy : Proceedings of Science.
-
Konferensbidrag (refereegranskat)abstract
- Ground based neutron counters are a standard tool for detecting atmospheric showers from GeV-range primary cosmic rays of either solar or galactic origin. Bare neutron counters, a type of lead-free neutron monitor, function much like standard neutron monitors but have different yield functions primarily because they are more sensitive to neutrons of lower energy. When operated together with standard monitors the different yield functions allow estimates to be made of the energy spectrum of galactic or solar particles. In 2010 a new array of twelve bare neutron detectors was installed at the South Pole to operate together with the neutron monitor there. Prior to installation, two of the detectors were operated on a ship that traveled from Sweden to Antarctica and back from November 2009 to April 2010. The purpose of this latitude survey was to use Earth's magnetic field as a spectrometer, blocking cosmic rays below the local cutoff rigidity (momentum per unit charge), from which we determined the response function vs. rigidity of these bare counters. By comparing that measured response function to direct measurements of the cosmic ray spectrum taken by the PAMELA spacecraft, we were able to make a direct determination of the yield function for these detectors.
|
|
