| 1. |
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| 2. |
- Sun, W. J., et al.
(författare)
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A Comparative Study of the Proton Properties of Magnetospheric Substorms at Earth and Mercury in the Near Magnetotail
- 2018
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 45:16, s. 7933-7941
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Tidskriftsartikel (refereegranskat)abstract
- The variations of plasma sheet proton properties during magnetospheric substorms at Earth and Mercury are comparatively studied. This study utilizes kappa distributions to interpret proton properties at both planets. Proton number densities are found to be around an order of magnitude higher, temperatures several times smaller, and kappa values broader at Mercury than at Earth. Protons become denser and cooler during the growth phase, and are depleted and heated after the dipolarizations in both magnetospheres. The changes of kappa at Earth are generally small (<20%), indicating that spectrum-preserving processes, like adiabatic betatron acceleration, play an important role there, while variations of kappa at Mercury are large (>60%), indicating the importance of spectrum-altering processes there, such as acceleration due to nonadiabatic cross-tail particle motions and wave-particle interactions. This comparative study reveals important intrinsic properties on the energization of protons in both magnetospheres. Plain Language Summary Earth and Mercury are the only two planets possessing global intrinsic magnetic fields among the four inner planets, which are Mercury, Venus, Earth, and Mars, within the solar system. The interactions between the intrinsic magnetic fields and the continual flow of high-speed solar wind from the Sun form similar magnetospheres at the two planets, although the scale of the magnetosphere is much smaller at Mercury than at Earth. Magnetospheric substorms, a result of solar wind-magnetosphere coupling, occur in both magnetospheres. Comparative study of a similar process between different planets is meaningful as it can help us in understanding the specific process further as well as help us in understanding the intrinsic properties of the magnetospheres. This research paper characterizes the proton properties of magnetospheric substorms of both planets, revealing that different mechanisms control the behavior of protons during the magnetospheric substorms of the two planets.
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| 3. |
- Actis, M., et al.
(författare)
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Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
- 2011
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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| 4. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 5. |
- Cawthon, P. M., et al.
(författare)
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Putative Cut-Points in Sarcopenia Components and Incident Adverse Health Outcomes: AnSDOCAnalysis
- 2020
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1429-1437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht(2)); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality). DESIGN Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 +/- 2.3 years for mortality. SETTING Eight prospective observational cohort studies. PARTICIPANTS A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA. RESULTS Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness. CONCLUSION Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia.
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| 6. |
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| 7. |
- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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| 8. |
- De Leoz, M. L. A., et al.
(författare)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 9. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 10. |
- Jones, G., et al.
(författare)
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Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n=48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p=4x10(-17)), arthritis (GDF5p=4x10(-13)), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.
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| 11. |
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| 12. |
- Nyberg, Joakim, 1978-, et al.
(författare)
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Edoxaban Exposure-Response Analysis and Clinical Utility Index Assessment in Patients With Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism
- 2016
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 5:4, s. 222-232
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Tidskriftsartikel (refereegranskat)abstract
- Edoxaban exposure-response relationships from the phase III study evaluating edoxaban for prevention and treatment of venous thromboembolism (VTE) in patients with acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were assessed by parametric time-to-event analysis. Statistical significant exposure-response relationships were recurrent VTE with hazard ratio (HR) based on average edoxaban concentration at steady state (C-av) (HRCav) 50.98 (i.e., change in the HR with every 1 ng/mL increase of C-av); the composite of recurrent DVT and nonfatal PE with HRC(av)50.99; and the composite of recurrent DVT, nonfatal PE, and all-cause mortality HRC(av)50.98, and all death using maximal edoxaban concentration (C-max) with HR (C-max) 50.99. No statistical significant exposure-response relationships were found for clinically relevant bleeding or major adverse cardiovascular event. Results support the recommendation of once-daily edoxaban 60 mg, and a reduced 30 mg dose in patients with moderate renal impairment, body weight <= 60 kg, or use of P-glycoprotein inhibitors verapamil or quinidine.
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| 13. |
- Pitkänen, Timo, 1979-, et al.
(författare)
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Statistical Survey of Magnetic Forces Associated With Earthward Bursty Bulk Flows Measured by MMS 2017-2021
- 2023
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 128:5
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the magnetic forces (the magnetic pressure gradient force, the curvature force, and their sum the j x B-force) associated with earthward bursty bulk flows (BBFs) using Magnetospheric Multiscale (MMS) data from five tail seasons (2017-2021). For the first time, the magnetic forces are inferred downtail of XGSM = -20 R-E and in the GSM XY and YZ planes. The results suggest that BBFs tend to be accelerated earthward by the magnetic pressure gradient force tailward of similar to 19 R-E and decelerated closer to that distance in the 2017-2018 data. The force magnitudes increase with distance. This is in accordance with earlier Cluster results. In the 2019-2021 data, the pressure gradient force magnitudes are generally smaller and no clear distance for the acceleration reversal can be determined. The curvature forces for both 2017-2018 and 2019-2021 BBFs indicate earthward acceleration independent of distance, consistent with the Cluster measurements. The sum, the j x B-force, suggests for the 2017-2018 BBFs earthward acceleration tailward of XGSM similar to 15 R-E and deceleration within that distance, also consistent with Cluster. In contrast, the 2019-2021 BBFs show general earthward acceleration by j x B independent of distance. In the GSM XY plane, the average (j x B)(xy) vectors are earthward, and in the premidnight and postmidnight dawnward for the 2017-2018 BBFs. For 2019-2021, the average (j x B)(xy) vectors have components toward the tail center. In the GSM YZ plane, the average (j x B)(yz) vectors are toward the neutral sheet.
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| 14. |
- Teumer, A., et al.
(författare)
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Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits
- 2016
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 15:5, s. 811-824
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Tidskriftsartikel (refereegranskat)abstract
- The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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| 15. |
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| 16. |
- Abolhassani, H, et al.
(författare)
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Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency
- 2017
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 214:1, s. 91-106
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)–related diseases. Three patients presented with EBV-associated Hodgkin’s lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal, but the proportions of memory B cells and EBV-specific effector memory CD8+ T cells were reduced. Furthermore, although T cell proliferation was normal, in vitro–generated EBV-specific cytotoxic T cell activity was reduced because of CD70 deficiency. This reflected impaired activation by, rather than effects during killing of, EBV-transformed B cells. Notably, expression of 2B4 and NKG2D, receptors implicated in controlling EBV infection, on memory CD8+ T cells from CD70-deficient individuals was reduced, consistent with their impaired killing of EBV-infected cells. Thus, autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70–CD27 interactions therefore play a nonredundant role in T and B cell–mediated immunity, especially for protection against EBV and humoral immunity.
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| 17. |
- Abramowski, A., et al.
(författare)
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The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
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Tidskriftsartikel (refereegranskat)abstract
- The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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| 18. |
- Aliu, E., et al.
(författare)
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Discovery of High-energy and Very High Energy γ-Ray Emission from the Blazar RBS 0413
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 750:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of high-energy (HE; E > 0.1 GeV) and very high energy (VHE; E > 100 GeV) γ-ray emission from the high-frequency-peaked BL Lac object RBS 0413. VERITAS, a ground-based γ-ray observatory, detected VHE γ rays from RBS 0413 with a statistical significance of 5.5 standard deviations (σ) and a γ-ray flux of (1.5 ± 0.6stat ± 0.7syst) × 10–8 photons m–2 s–1 (~1% of the Crab Nebula flux) above 250 GeV. The observed spectrum can be described by a power law with a photon index of 3.18 ± 0.68stat ± 0.30syst. Contemporaneous observations with the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope detected HE γ rays from RBS 0413 with a statistical significance of more than 9σ, a power-law photon index of 1.57 ± 0.12stat +0.11 – 0.12sys, and a γ-ray flux between 300 MeV and 300 GeV of (1.64 ± 0.43stat +0.31 – 0.22sys) × 10–5photons m–2 s–1. We present the results from Fermi-LAT and VERITAS, including a spectral energy distribution modeling of the γ-ray, quasi-simultaneous X-ray (Swift-XRT), ultraviolet (Swift-UVOT), and R-band optical (MDM) data. We find that, if conditions close to equipartition are required, both the combined synchrotron self-Compton/external-Compton and the lepto-hadronic models are preferred over a pure synchrotron self-Compton model.
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| 19. |
- Aliu, E., et al.
(författare)
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Discovery of TeV Gamma-Ray Emission from CTA 1 by VERITAS
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 764:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of TeV gamma-ray emission coincident with the shell-type radio supernova remnant (SNR) CTA 1 using the VERITAS gamma-ray observatory. The source, VER J0006+729, was detected as a 6.5 standard deviation excess over background and shows an extended morphology, approximated by a two-dimensional Gaussian of semimajor (semiminor) axis 030 (024) and a centroid 5' from the Fermi gamma-ray pulsar PSR J0007+7303 and its X-ray pulsar wind nebula (PWN). The photon spectrum is well described by a power-law dN/dE = N 0(E/3 TeV)–Γ, with a differential spectral index of Γ = 2.2 ± 0.2stat ± 0.3sys, and normalization N 0 = (9.1 ± 1.3stat ± 1.7sys) × 10–14 cm–2 s–1 TeV–1. The integral flux, F γ = 4.0 ×10–12 erg cm–2 s–1 above 1 TeV, corresponds to 0.2% of the pulsar spin-down power at 1.4 kpc. The energetics, colocation with the SNR, and the relatively small extent of the TeV emission strongly argue for the PWN origin of the TeV photons. We consider the origin of the TeV emission in CTA 1.
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| 20. |
- Aliu, E., et al.
(författare)
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Discovery of TeV Gamma-Ray Emission toward Supernova Remnant SNR G78.2+2.1
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 770:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of an unidentified, extended source of very-high-energy gamma-ray emission, VER J2019+407, within the radio shell of the supernova remnant SNR G78.2+2.1, using 21.4 hr of data taken by the VERITAS gamma-ray observatory in 2009. These data confirm the preliminary indications of gamma-ray emission previously seen in a two-year (2007-2009) blind survey of the Cygnus region by VERITAS. VER J2019+407, which is detected at a post-trials significance of 7.5 standard deviations in the 2009 data, is localized to the northwestern rim of the remnant in a region of enhanced radio and X-ray emission. It has an intrinsic extent of and its spectrum is well-characterized by a differential power law (dN/dE = N 0 × (E/TeV)–Γ) with a photon index of Γ = 2.37 ± 0.14stat ± 0.20sys and a flux normalization of N 0 = 1.5 ± 0.2stat ± 0.4sys × 10–12 photon TeV–1 cm–2 s–1. This yields an integral flux of 5.2 ± 0.8stat ± 1.4sys × 10–12 photon cm–2 s–1above 320 GeV, corresponding to 3.7% of the Crab Nebula flux. We consider the relationship of the TeV gamma-ray emission with the GeV gamma-ray emission seen from SNR G78.2+2.1 as well as that seen from a nearby cocoon of freshly accelerated cosmic rays. Multiple scenarios are considered as possible origins for the TeV gamma-ray emission, including hadronic particle acceleration at the SNR shock.
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| 21. |
- Aliu, E., et al.
(författare)
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Multiwavelength Observations of the Previously Unidentified Blazar RX J0648.7+1516
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 742:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the VERITAS discovery of very high energy (VHE) gamma-ray emission above 200 GeV from the high-frequency-peaked BL Lac (HBL) object RX J0648.7+1516 (GB J0648+1516), associated with 1FGL J0648.8+1516. The photon spectrum above 200 GeV is fitted by a power law dN/dE = F 0(E/E 0)–Γ with a photon index Γ of 4.4 ± 0.8stat ± 0.3syst and a flux normalization F 0 of (2.3 ± 0.5stat ± 1.2sys) × 10–11 TeV–1 cm–2 s–1 with E 0 = 300 GeV. No VHE variability is detected during VERITAS observations of RX J0648.7+1516 between 2010 March 4 and April 15. Following the VHE discovery, the optical identification and spectroscopic redshift were obtained using the Shane 3 m Telescope at the Lick Observatory, showing the unidentified object to be a BL Lac type with a redshift of z = 0.179. Broadband multiwavelength observations contemporaneous with the VERITAS exposure period can be used to subclassify the blazar as an HBL object, including data from the MDM observatory, Swift-UVOT, and X-Ray Telescope, and continuous monitoring at photon energies above 1 GeV from the FermiLarge Area Telescope (LAT). We find that in the absence of undetected, high-energy rapid variability, the one-zone synchrotron self-Compton (SSC) model overproduces the high-energy gamma-ray emission measured by the Fermi-LAT over 2.3 years. The spectral energy distribution can be parameterized satisfactorily with an external-Compton or lepto-hadronic model, which have two and six additional free parameters, respectively, compared to the one-zone SSC model.
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| 22. |
- Aliu, E., et al.
(författare)
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Search for a Correlation between Very-high-energy Gamma Rays and Giant Radio Pulses in the Crab Pulsar
- 2012
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 760:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results of a joint observational campaign between the Green Bank radio telescope and the VERITAS gamma-ray telescope, which searched for a correlation between the emission of very-high-energy (VHE) gamma rays (E γ > 150 GeV) and giant radio pulses (GRPs) from the Crab pulsar at 8.9 GHz. A total of 15,366 GRPs were recorded during 11.6 hr of simultaneous observations, which were made across four nights in 2008 December and in 2009 November and December. We searched for an enhancement of the pulsed gamma-ray emission within time windows placed around the arrival time of the GRP events. In total, eight different time windows with durations ranging from 0.033 ms to 72 s were positioned at three different locations relative to the GRP to search for enhanced gamma-ray emission which lagged, led, or was concurrent with, the GRP event. Furthermore, we performed separate searches on main pulse GRPs and interpulse GRPs and on the most energetic GRPs in our data sample. No significant enhancement of pulsed VHE emission was found in any of the preformed searches. We set upper limits of 5-10 times the average VHE flux of the Crab pulsar on the flux simultaneous with interpulse GRPs on single-rotation-period timescales. On ~8 s timescales around interpulse GRPs, we set an upper limit of 2-3 times the average VHE flux. Within the framework of recent models for pulsed VHE emission from the Crab pulsar, the expected VHE-GRP emission correlations are below the derived limits.
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| 23. |
- Aliu, E., et al.
(författare)
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VERITAS deep observations of the dwarf spheroidal galaxy Segue 1
- 2012
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 85:6
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Tidskriftsartikel (refereegranskat)abstract
- The VERITAS array of Cherenkov telescopes has carried out a deep observational program on the nearby dwarf spheroidal galaxy Segue 1. We report on the results of nearly 48 hours of good quality selected data, taken between January 2010 and May 2011. No significant γ-ray emission is detected at the nominal position of Segue 1, and upper limits on the integrated flux are derived. According to recent studies, Segue 1 is the most dark matter-dominated dwarf spheroidal galaxy currently known. We derive stringent bounds on various annihilating and decaying dark matter particle models. The upper limits on the velocity-weighted annihilation cross-section are ⟨σv⟩95% CL≲10−23 cm3 s−1, improving our limits from previous observations of dwarf spheroidal galaxies by at least a factor of 2 for dark matter particle masses mχ≳300 GeV. The lower limits on the decay lifetime are at the level of τ95% CL≳1024 s. Finally, we address the interpretation of the cosmic ray lepton anomalies measured by ATIC and PAMELA in terms of dark matter annihilation, and show that the VERITAS observations of Segue 1 disfavor such a scenario.
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| 24. |
- Aliu, E., et al.
(författare)
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VERITAS Observations of Six Bright, Hard-spectrum Fermi-LAT Blazars
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 759:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on VERITAS very high energy (VHE; E ≥ 100 GeV) observations of six blazars selected from the Fermi Large Area Telescope First Source Catalog (1FGL). The gamma-ray emission from 1FGL sources was extrapolated up to the VHE band, taking gamma-ray absorption by the extragalactic background light into account. This allowed the selection of six bright, hard-spectrum blazars that were good candidate TeV emitters. Spectroscopic redshift measurements were attempted with the Keck Telescope for the targets without Sloan Digital Sky Survey spectroscopic data. No VHE emission is detected during the observations of the six sources described here. Corresponding TeV upper limits are presented, along with contemporaneousFermi observations and non-concurrent Swift UVOT and X-Ray Telescope data. The blazar broadband spectral energy distributions (SEDs) are assembled and modeled with a single-zone synchrotron self-Compton model. The SED built for each of the six blazars shows a synchrotron peak bordering between the intermediate- and high-spectrum-peak classifications, with four of the six resulting in particle-dominated emission regions.
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| 25. |
- Aliu, E., et al.
(författare)
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VERITAS Observations of the Nova in V407 Cygni
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 754:1
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Tidskriftsartikel (refereegranskat)abstract
- We report on very high energy (E > 100 GeV) gamma-ray observations of V407 Cygni, a symbiotic binary that underwent a nova outburst producing 0.1-10 GeV gamma rays during 2010 March 10-26. Observations were made with the Very Energetic Radiation Imaging Telescope Array System during 2010 March 19-26 at relatively large zenith angles due to the position of V407 Cyg. An improved reconstruction technique for large zenith angle observations is presented and used to analyze the data. We do not detect V407 Cygni and place a differential upper limit on the flux at 1.6 TeV of 2.3 × 10–12 erg cm–2 s–1 (at the 95% confidence level). When considered jointly with data from Fermi-LAT, this result places limits on the acceleration of very high energy particles in the nova.
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| 26. |
- Alsén, Samuel, et al.
(författare)
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Antigen-Presenting B Cells Program the Efferent Lymph T Helper Cell Response
- 2022
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T-B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined intervals post-immunization. Focusing on gut-draining mesenteric lymph nodes (MLNs), we show that antigen-specific alpha(4)beta(+)(7) gut-homing effector Th cells enter the circulation prior to CXCR5(+)PD-1(+) Tfh-like cells. B cells appear to have no or limited impact on the early generation and egress of gut-homing Th cells but are critical for the subsequent appearance of Tfh-like cells that peak in the lymph before GCs have developed. At this stage, antigen-presenting B cells also reduce the proportion of alpha(4)beta(+)(7) Th cells in the MLN and efferent lymph. Furthermore, cognate B-cell interaction drives a broad transcriptional program in Th cells, including IL-4 that is confined to the Tfh cell lineage. The IL-4-producing Tfh-like cells originate from Bcl6(+) precursors in the LNs and have gut-homing capacity. Hence, B cells program the efferent lymph Th cell response within a limited window of time after antigenic challenge.
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| 27. |
- Antoniou, A. C., et al.
(författare)
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Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2009
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Ingår i: Human Molecular Genetics. - [Antoniou, Antonis C.; McGuffog, Lesley; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Pooley, Karen A.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England. [Sinilnikova, Olga M.; Leone, Melanie] Univ Lyon, CNRS, Hosp Civils Lyon,Ctr Leon Berard,UMR5201, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canada Res Chair Oncogenet, Canc Genom Lab, Quebec City, PQ, Canada. Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary] Mayo Clin, Rochester, MN USA. [Peterlongo, Paolo; Peissel, Bernard; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Molecolare, Milan, Italy. [Bonanni, Bernardo; Bernard, Loris] Ist Europeo Oncol, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Aviano, Italy. [Bernard, Loris] Cogentech, Consortium Genom Technol, Milan, Italy. [Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Zikan, Michal] Charles Univ Prague, Dept Biochem & Expt Oncol, Fac Med 1, Prague, Czech Republic. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Greene, Mark H.; Mai, Phuong L.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad; Lejbkowicz, Flavio] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] B Rappaport Fac Med, Haifa, Israel. [Andrulis, Irene L.; Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Gerdes, Anne-Marie; Thomassen, Mads] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, DK-5000 Odense, Denmark. [Sunde, Lone] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Caligo, Maria A.] Univ Pisa, Div Surg Mol & Ultrastructural Pathol, Dept Oncol, Pisa, Italy. [Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy. [Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella; Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Dagan, Efrat; Baruch, Ruth Gershoni] Rambam Med Ctr, Genet Inst, Haifa, Israel. [Harbst, Katja] Lund Univ, Dept Oncol, S-22100 Lund, Sweden. [Barbany-Bustinza, Gisela; Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrenska Univ, Dept Oncol, Gothenburg, Sweden. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Philadelphia, PA 19104 USA. [Osorio, Ana; Benitez, Javier] Ctr Invest Biomed Red Enfermedades Raras CIBERERE, Inst Salud Carlos III, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Blanco, Ignacio] Catalan Inst Oncol ICO, Canc Genet Counseling Program, Barcelona, Spain. [Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, Neuenheimer Feld 580 69120, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Rotterdam Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Devilee, Peter] Dept Genet Epidemiol, Leiden, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Utrecht, Med Ctr, Dept Clin Mol Genet, NL-3508 TC Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van Roozendaal, Cornelis E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Rosalind] Inst Canc Res, Translat Canc Genet Team, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys Hosp, Clin Genet, London SE1 9RT, England. [Davidson, Rosemarie] Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare, NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Hodgson, Shirley] Univ London, Dept Canc Genet, St Georges Hosp, London, England. [Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM U509, Serv Genet Oncol, Paris, France. [Buecher, Bruno] Inst Curie, Dept Genet, Paris, France. [Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Lenoir, Gilbert M.] Inst Cancrol Gustave Roussy, Dept Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, INSERM U946, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Lenoir, Gilbert M.] Inst Cancerol Gustave Roussy, CNRS FRE2939, Villejuif, France. [Sevenet, Nicolas; Longy, Michel] Inst Bergonie, Lab Genet Constitutionnelle, Bordeaux, France. [Longy, Michel] Inst Bergonie, INSERM U916, Bordeaux, France. [Ferrer, Sandra Fert] Hop Hotel Dieu, Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Prieur, Fabienne] CHU St Etienne, Serv Genet Clin Chromosom, St Etienne, France. [Goldgar, David] Univ Utah, Dept Dermatol, Salt Lake City, UT 84112 USA. [Miron, Alexander; Yassin, Yosuf] Dana Farber Canc Inst, Boston, MA 02115 USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Hopper, John L.] Univ Melbourne, Melbourne, Australia. [Terry, Mary Beth] Columbia Univ, New York, NY USA. [Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine] Med Univ Vienna, Div Special Gynecol, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. [Barkardottir, Rosa Bjork] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Evanston NW Healthcare, NorthShore Univ Hlth Syst, Evanston, IL 60201 USA. [Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. [Boggess, John F.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Basil, Jack] St Elizabeth Hosp, Edgewood, KY 41017 USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Blank, Stephanie V.] New York Univ, Sch Med, New York, NY 10016 USA. [Toland, Amanda E.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Montagna, Marco; Casella, Cinzia] IRCCS, Ist Oncologico Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Res Inst, St Petersburg, Russia. [Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Schmutzler, Rita K.; Versmold, Beatrix; Arnold, Norbert] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaeco Oncol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynecol, Munich, Germany. Univ Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, Germany. [Niederacher, Dieter] Univ Duesseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, Dusseldorf, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Suttner, Christian] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Schoenbuchner, Ines] Univ Wurzburg, Inst Human Genet, D-8700 Wurzburg, Germany. [Gadzicki, Dorothea] Med Univ, Inst Cellular & Mol Pathol, Hannover, Germany. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clinico San Carlos 28040, Madrid, Spain. : Oxford University Press. - 0964-6906 .- 1460-2083. ; 18:22, s. 4442-4456
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 × 10-4]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.
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| 28. |
- Arlen, T., et al.
(författare)
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Constraints on Cosmic Rays, Magnetic Fields, and Dark Matter from Gamma-Ray Observations of the Coma Cluster of Galaxies with VERITAS and Fermi
- 2012
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 757:2
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of TeV gamma-ray emission coincident with the shell-type radio supernova remnant (SNR) CTA 1 using the VERITAS gamma-ray observatory. The source, VER J0006+729, was detected as a 6.5 standard deviation excess over background and shows an extended morphology, approximated by a two-dimensional Gaussian of semimajor (semiminor) axis 030 (024) and a centroid 5' from the Fermi gamma-ray pulsar PSR J0007+7303 and its X-ray pulsar wind nebula (PWN). The photon spectrum is well described by a power-law dN/dE = N 0(E/3 TeV)–Γ, with a differential spectral index of Γ = 2.2 ± 0.2stat ± 0.3sys, and normalization N 0 = (9.1 ± 1.3stat ± 1.7sys) × 10–14 cm–2 s–1 TeV–1. The integral flux, F γ = 4.0 ×10–12 erg cm–2 s–1 above 1 TeV, corresponds to 0.2% of the pulsar spin-down power at 1.4 kpc. The energetics, colocation with the SNR, and the relatively small extent of the TeV emission strongly argue for the PWN origin of the TeV photons. We consider the origin of the TeV emission in CTA 1.
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| 29. |
- Arlen, T., et al.
(författare)
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Rapid TeV Gamma-Ray Flaring of BL Lacertae
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 762:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the detection of a very rapid TeV gamma-ray flare from BL Lacertae on 2011 June 28 with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The flaring activity was observed during a 34.6 minute exposure, when the integral flux above 200 GeV reached (3.4 ± 0.6) × 10–6 photons m–2 s–1, roughly 125% of the Crab Nebula flux measured by VERITAS. The light curve indicates that the observations missed the rising phase of the flare but covered a significant portion of the decaying phase. The exponential decay time was determined to be 13 ± 4 minutes, making it one of the most rapid gamma-ray flares seen from a TeV blazar. The gamma-ray spectrum of BL Lacertae during the flare was soft, with a photon index of 3.6 ± 0.4, which is in agreement with the measurement made previously by MAGIC in a lower flaring state. Contemporaneous radio observations of the source with the Very Long Baseline Array revealed the emergence of a new, superluminal component from the core around the time of the TeV gamma-ray flare, accompanied by changes in the optical polarization angle. Changes in flux also appear to have occurred at optical, UV, and GeV gamma-ray wavelengths at the time of the flare, although they are difficult to quantify precisely due to sparse coverage. A strong flare was seen at radio wavelengths roughly four months later, which might be related to the gamma-ray flaring activities. We discuss the implications of these multiwavelength results.
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| 30. |
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| 31. |
- Boulanger, B., et al.
(författare)
-
Focus issue introduction: nonlinear optics
- 2011
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Ingår i: Optics Express. - 1094-4087 .- 1094-4087. ; 19:23, s. 23561-23566
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Tidskriftsartikel (refereegranskat)abstract
- It is now fifty years since the original observation of second harmonic generation ushered in the field of nonlinear optics, close on the heels of the invention of the laser. This feature issue celebrates this anniversary with papers that span the range from new nonlinear optical materials, through the increasingly novel methods that have been developed for phase matching, to emerging areas such as nonlinear metamaterials and plasmonic enhancement of optical properties. It is clear that the next fifty years of nonlinear optics will witness a proliferation of new applications with increasing technological impact.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- He, Z Q, et al.
(författare)
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As overlayer on GaAs(110) studied with photoemission
- 1995
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 52:23, s. 16602-16607
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Tidskriftsartikel (refereegranskat)abstract
- As-terminated GaAs(110) surfaces were prepared on ex situ cleaved substrates by molecular-beam epitaxy. The surface stoichiometry was controlled by postgrowth As deposition. Photoemission from a surface covered with a monolayer As was investigated in detail using synchrotron radiation. Two different surface components were found in core-level spectra, which are interpreted as due to adatoms bonding to the surface anions and cations. In the valence-band spectra several surface states were identified, in analogy with previous reports on the isoelectronic Sb/GaAs(110) system. The polarization dependence is not the same, however, which leads us to the conclusion that the adlayer bonding mechanisms are different in the two cases.
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| 41. |
- He, Z Q, et al.
(författare)
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Band structure evolution in InAs overlayers on GaAs(110)
- 1996
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Ingår i: Applied Surface Science. - 0169-4332 .- 1873-5584. ; 104, s. 608-614
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Tidskriftsartikel (refereegranskat)abstract
- An angle-resolved photoemission study of MBE grown InAs/GaAs(110) hetero-structures was carried out to investigate the establishment of valence bands as a function of overlayer thickness. The valence band spectra were found to change gradually up to thicknesses well above 10 nm. The data are interpreted in terms of excitations within the overlayer from a combination of substrate and overlayer initial states, the former tailing into the overlayer.
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| 42. |
- Hou, JH, et al.
(författare)
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Polygenic resilience scores capture protective genetic effects for Alzheimer's disease
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 296-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.
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| 43. |
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| 44. |
- Ito, H., et al.
(författare)
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Comparison of analytical methods for profiling N- and O-linked glycans from cultured cell lines
- 2016
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Ingår i: Glycoconjugate Journal. - : Springer Science and Business Media LLC. - 0282-0080 .- 1573-4986. ; 33:3, s. 405-415
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Tidskriftsartikel (refereegranskat)abstract
- The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. Since 2004, the initiative has conducted three pilot studies. The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples.
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| 45. |
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| 48. |
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| 49. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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- Karlsson, Christofer A.Q., et al.
(författare)
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Streptococcus pyogenes Infection and the Human Proteome with a Special Focus on the Immunoglobulin G-cleaving Enzyme IdeS
- 2018
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Ingår i: Molecular and Cellular Proteomics. - 1535-9476. ; 17:6, s. 1097-1111
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Tidskriftsartikel (refereegranskat)abstract
- Infectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a combined mass spectrometry-based proteomics strategy to investigate how the human proteome is transiently modified by the pathogen Streptococcus pyogenes, with a particular focus on bacterial cleavage of IgG in vivo. In invasive diseases, S. pyogenes evokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG. S. pyogenes produces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments. The results show that IdeS contributes to the adaptation of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection.
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