| 1. |
|
|
| 2. |
|
|
| 3. |
- Bravo, L, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 4. |
- Tabiri, S, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 5. |
- Glasbey, JC, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 6. |
- Coenen, T., et al.
(författare)
-
The LOFAR pilot surveys for pulsars and fast radio transients
- 2014
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 570, s. 1-16
-
Tidskriftsartikel (refereegranskat)abstract
- We have conducted two pilot surveys for radio pulsars and fast transients with the Low-Frequency Array (LOFAR) around 140 MHz and here report on the first low-frequency fast-radio burst limit and the discovery of two new pulsars. The first survey, the LOFAR Pilot Pulsar Survey (LPPS), observed a large fraction of the northern sky, ~ 1.4 × 104 deg2, with 1 h dwell times. Each observation covered ~75 deg2 using 7 independent fields formed by incoherently summing the high-band antenna fields. The second pilot survey, the LOFAR Tied-Array Survey (LOTAS), spanned ~600 deg2, with roughly a 5-fold increase in sensitivity compared with LPPS. Using a coherent sum of the 6 LOFAR “Superterp” stations, we formed 19 tied-array beams, together covering 4 deg2 per pointing. From LPPS we derive a limit on the occurrence, at 142 MHz, of dispersed radio bursts of < 150 day-1 sky-1, for bursts brighter than S> 107 Jy for the narrowest searched burst duration of 0.66 ms. In LPPS, we re-detected 65 previously known pulsars. LOTAS discovered two pulsars, the first with LOFAR or any digital aperture array. LOTAS also re-detected 27 previously known pulsars. These pilot studies show that LOFAR can efficiently carry out all-sky surveys for pulsars and fast transients, and they set the stage for further surveying efforts using LOFAR and the planned low-frequency component of the Square Kilometer Array.
|
|
| 7. |
- Waszak, S. M., et al.
(författare)
-
Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
- 2018
-
Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798
-
Tidskriftsartikel (refereegranskat)abstract
- Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 4069) and 5-year overall survival was 65% (95% CI 5281); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.
|
|
| 8. |
- Waszak, S. M., et al.
(författare)
-
Germline Elongator mutations in Sonic Hedgehog medulloblastoma
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 580:7803
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children(1,2), and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma(3). Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHH alpha subtype(4) and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U-34) position(5,6). Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems(7-9). Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Johnson, Owen A., et al.
(författare)
-
A Simultaneous Dual-site Technosignature Search Using International LOFAR Stations
- 2023
-
Ingår i: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 166:5
-
Tidskriftsartikel (refereegranskat)abstract
- The Search for Extraterrestrial Intelligence aims to find evidence of technosignatures, which can point toward the possible existence of technologically advanced extraterrestrial life. Radio signals similar to those engineered on Earth may be transmitted by other civilizations, motivating technosignature searches across the entire radio spectrum. In this endeavor, the low-frequency radio band has remained largely unexplored; with prior radio searches primarily above 1 GHz. In this survey at 110-190 MHz, observations of 1,631,198 targets from TESS and Gaia are reported. Observations took place simultaneously with two international stations (noninterferometric) of the Low Frequency Array in Ireland and Sweden. We can reject the presence of any Doppler drifting narrowband transmissions in the barycentric frame of reference, with equivalent isotropic radiated power of 1017 W, for 0.4 million (or 1.3 million) stellar systems at 110 (or 190) MHz. This work demonstrates the effectiveness of using multisite simultaneous observations for rejecting anthropogenic signals in the search for technosignatures.
|
|
| 12. |
- Wandia, Kelvin, et al.
(författare)
-
An interferometric SETI observation of Kepler-111 b
- 2023
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 522:3, s. 3784-3794
-
Tidskriftsartikel (refereegranskat)abstract
- The application of very long baseline interferometry (VLBI) to the search for extraterrestrial intelligence (SETI) has been limited to date, despite the technique offering many advantages over traditional single-dish SETI observations. In order to further develop interferometry for SETI, we used the European VLBI network (EVN) at 21 cm to observe potential secondary phase calibrators in the Kepler field. Unfortunately, no secondary calibrators were detected. However, a VLBA primary calibrator in the field, J1926+4441, offset only ∼1.88 arcmin from a nearby exoplanet Kepler-111 b, was correlated with high temporal (0.25 s) and spectral (16384 × 488 Hz channels) resolution. During the analysis of the high-resolution data, we identified a spectral feature that was present in both the auto and cross-correlation data with a central frequency of 1420.424 ± 0.0002 MHz and a width of 0.25 MHz. We demonstrate that the feature in the cross-correlations is an artefact in the data, associated with a significant increase in each telescope's noise figure due to the presence of H I in the beam. This would typically go unnoticed in data correlated with standard spectral resolution. We flag (excluded from the subsequent analysis) these channels and phase rotate the data to the location of Kepler-111 b aided by the Gaia catalogue and search for signals with SNR > 7. At the time of our observations, we detect no transmitters with an equivalent isotropically radiated power ≳4 × 1015 W.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Northcott, Paul A, et al.
(författare)
-
Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
-
Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
|
|
| 16. |
|
|
| 17. |
- Rasmussen, RD, et al.
(författare)
-
BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 13398-
-
Tidskriftsartikel (refereegranskat)abstract
- Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM.
|
|
| 18. |
- Shaikh, Gaushiya A., et al.
(författare)
-
Assessing the Suitability of a-SiS Nanosheet as an Anode Material for Multivalent Metal-Ion Batteries
- 2023
-
Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 37:19, s. 15116-15126
-
Tidskriftsartikel (refereegranskat)abstract
- The search for suitable two-dimensional (2D) anode materials is crucial to drive the progress of multivalent metal-ion batteries capable of delivering exceptional performance, specifically with very fast charging and discharging rates. In this research, we have unveiled novel insights at the density functional theory level, with the workability of 2D puckered silicon monosulfide (a-SiS) as a probable anode material for multivalent metal-ion batteries using Na, Ca, and Al ions. Exploring the stability aspects of both structural and dynamic levels in the a-SiS nanosheet was estimated through the calculation of cohesive energy and non-imaginary phonon frequencies. The a-SiS nanosheet exhibited negative adsorption energies of -1.45, -0.92, and -2.67 eV for Na, Ca, and Al ions, respectively. Additionally, it was observed that the introduction of mono-, di-, and tri-metal atoms to the surface of the a-SiS nanosheet transformed its semiconducting nature into a metallic phase. Minimal activation energies for the active ion migration of Na (0.066 eV), Ca (0.067 eV), and Al (0.18 eV) on the surface of the a-SiS nanosheet suggest high diffusion and optimal charge/discharge functionality. Furthermore, diminished mean operating voltages of 0.44 V (Na), 0.43 V (Ca), and 0.55 V (Al) were attained and improved the theoretical storage performance of 2046.81 mAh/g (Na), 1643.02 mAh/g (Ca), and 2422.76 mAh/g (Al) for the a-SiS nanosheet. The results of this work suggest that the a-SiS nanosheet has the potential to play a crucial role as a hopeful anode material for the creation of budget-friendly, high-functioning metal-ion batteries using Na, Ca, and Al ions.
|
|
| 19. |
- Shaikh, Gaushiya A., et al.
(författare)
-
Prominent Electrode Material for Na-, K-, and Mg-ion Batteries : 2D beta-Sb Monolayer
- 2022
-
Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 36:13, s. 7087-7095
-
Tidskriftsartikel (refereegranskat)abstract
- The applicability of a two-dimensional beta-antimonene (beta-Sb) monolayer as a negative electrode material for Na-, K-, and Mg-ion batteries has been conducted through first-principles calculations based on density functional theory (DFT). Our findings propose that the hollow and top sites are the energetically most stable adsorption sites for Na, Mg, and K atoms. The chronological adsorption energy, charge transfer, open-circuit voltage, theoretical storage capacity, and metal-ion diffusion barrier energy are investigated. The semiconducting beta-Sb monolayer can provide inherent benefits for transportation of electrons through it, which can deliver tremendous mobility with lower barrier energies of 0.10 eV for Na, 0.09 eV for K, and 0.15 eV for Mg for the diffusion process. The double layers of beta-Sb can adsorb ions on both sides, which leads, at high concentrations (Na2Sb, K2Sb, and Mg2Sb), to theoretical storage capacities of 440.22, 440.22, and 880.45 mAh/gm for Na, K, and Mg ions, respectively. Besides, the electronic formation of beta-Sb changed the nature from semiconducting to metallic under metal-ion adsorption, which significantly enhanced the performance of metal-ion batteries. With the given advantages, we propose that the beta-Sb monolayer can be viewed as a potential material for negative electrodes in Na-, K-, and Mg-ion batteries.
|
|
