| 1. |
- Algaba, Juan-Carlos, et al.
(författare)
-
Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
-
Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
|
|
| 2. |
- Adams, C. B., et al.
(författare)
-
Observation of the Gamma-Ray Binary HESS J0632+057 with the HESS, MAGIC, and VERITAS Telescopes
- 2021
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 923:2
-
Tidskriftsartikel (refereegranskat)abstract
- The results of gamma-ray observations of the binary system HESS J0632 + 057 collected during 450 hr over 15 yr, between 2004 and 2019, are presented. Data taken with the atmospheric Cherenkov telescopes H.E.S.S., MAGIC, and VERITAS at energies above 350 GeV were used together with observations at X-ray energies obtained with Swift-XRT, Chandra, XMM-Newton, NuSTAR, and Suzaku. Some of these observations were accompanied by measurements of the H alpha emission line. A significant detection of the modulation of the very high-energy gamma-ray fluxes with a period of 316.7 +/- 4.4 days is reported, consistent with the period of 317.3 +/- 0.7 days obtained with a refined analysis of X-ray data. The analysis of data from four orbital cycles with dense observational coverage reveals short-timescale variability, with flux-decay timescales of less than 20 days at very high energies. Flux variations observed over a timescale of several years indicate orbit-to-orbit variability. The analysis confirms the previously reported correlation of X-ray and gamma-ray emission from the system at very high significance, but cannot find any correlation of optical H alpha parameters with fluxes at X-ray or gamma-ray energies in simultaneous observations. The key finding is that the emission of HESS J0632 + 057 in the X-ray and gamma-ray energy bands is highly variable on different timescales. The ratio of gamma-ray to X-ray flux shows the equality or even dominance of the gamma-ray energy range. This wealth of new data is interpreted taking into account the insufficient knowledge of the ephemeris of the system, and discussed in the context of results reported on other gamma-ray binary systems.
|
|
| 3. |
- Balkenhol, Maschenka C. A., et al.
(författare)
-
Optimized tumour infiltrating lymphocyte assessment for triple negative breast cancer prognostics
- 2021
-
Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 56, s. 78-87
-
Tidskriftsartikel (refereegranskat)abstract
- The tumour microenvironment has been shown to be a valuable source of prognostic information for different cancer types. This holds in particular for triple negative breast cancer (TNBC), a breast cancer subtype for which currently no prognostic biomarkers are established. Although different methods to assess tumour infiltrating lymphocytes (TILs) have been published, it remains unclear which method (marker, region) yields the most optimal prognostic information. In addition, to date, no objective TILs assessment methods are available. For this proof of concept study, a subset of our previously described TNBC cohort (n = 94) was stained for CD3, CD8 and FOXP3 using multiplex immunohistochemistry and subsequently imaged by a multispectral imaging system. Advanced whole-slide image analysis algorithms, including convolutional neural networks (CNN) were used to register unmixed multispectral images and corresponding H&E sections, to segment the different tissue compartments (tumour, stroma) and to detect all individual positive lymphocytes. Densities of positive lymphocytes were analysed in different regions within the tumour and its neighbouring environment and correlated to relapse free survival (RFS) and overall survival (OS). We found that for all TILs markers the presence of a high density of positive cells correlated with an improved survival. None of the TILs markers was superior to the others. The results of TILs assessment in the various regions did not show marked differences between each other. The negative correlation between TILs and survival in our cohort are in line with previous studies. Our results provide directions for optimizing TILs assessment methodology. (C) 2021 The Author(s). Published by Elsevier Ltd.
|
|
| 4. |
- Breznau, Nate, et al.
(författare)
-
Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
|
|
| 5. |
|
|
| 6. |
- Otte, J, et al.
(författare)
-
MYCN Function in Neuroblastoma Development
- 2021
-
Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 10, s. 624079-
-
Tidskriftsartikel (refereegranskat)abstract
- Dysregulated expression of the transcription factor MYCN is frequently detected in nervous system tumors such as childhood neuroblastoma. Here, gene amplification ofMYCNis a single oncogenic driver inducing neoplastic transformation in neural crest-derived cells. This abnormalMYCNexpression is one of the strongest predictors of poor prognosis. It is present at diagnosis and is never acquired during later tumorigenesis ofMYCNnon-amplified neuroblastoma. This suggests that increasedMYCNexpression is an early event in these cancers leading to a peculiar dysregulation of cells that results in embryonal or cancer stem-like qualities, such as increased self-renewal, apoptotic resistance, and metabolic flexibility.
|
|
| 7. |
- Saba, Karim H., et al.
(författare)
-
Disruption of the TP53 locus in osteosarcoma leads to TP53 promoter gene fusions and restoration of parts of the TP53 signalling pathway
- 2023
-
Ingår i: Journal of Pathology. - 0022-3417. ; , s. 147-160
-
Tidskriftsartikel (refereegranskat)abstract
- TP53 is the most frequently mutated gene in human cancer. This gene shows not only loss-of-function mutations but also recurrent missense mutations with gain-of-function activity. We have studied the primary bone malignancy osteosarcoma, which harbours one of the most rearranged genomes of all cancers. This is odd since it primarily affects children and adolescents who have not lived the long life thought necessary to accumulate massive numbers of mutations. In osteosarcoma, TP53 is often disrupted by structural variants. Here, we show through combined whole-genome and transcriptome analyses of 148 osteosarcomas that TP53 structural variants commonly result in loss of coding parts of the gene while simultaneously preserving and relocating the promoter region. The transferred TP53 promoter region is fused to genes previously implicated in cancer development. Paradoxically, these erroneously upregulated genes are significantly associated with the TP53 signalling pathway itself. This suggests that while the classical tumour suppressor activities of TP53 are lost, certain parts of the TP53 signalling pathway that are necessary for cancer cell survival and proliferation are retained. In line with this, our data suggest that transposition of the TP53 promoter is an early event that allows for a new normal state of genome-wide rearrangements in osteosarcoma.
|
|
| 8. |
- Saba, Karim H., et al.
(författare)
-
Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma
- 2020
-
Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 6:4, s. 231-237
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases. These rearrangements modify the terminal exon of the gene and are believed to stabilise both the FOS transcript and the encoded protein, resulting in high expression levels. Here, we applied in-depth genetic analyses to a series of 29 osteoblastomas, including five classified as epithelioid osteoblastoma. We found recurrent homozygous deletions of the NF2 gene in three of the five epithelioid cases and in one conventional osteoblastoma. These events were mutually exclusive from FOS mutations. Structural variations were determined by deep whole genome sequencing and the number of FOS-rearranged cases was less than previously reported (10/23, 43%). One conventional osteoblastoma displayed a novel mechanism of FOS upregulation; bringing the entire FOS gene under the control of the WNT5A enhancer that is itself activated by FOS. Taken together, we show that NF2 loss characterises a subgroup of osteoblastomas, distinct from FOS-rearranged cases. Both NF2 and FOS are involved in regulating bone homeostasis, thereby providing a mechanistic link to the excessive bone growth of osteoblastoma.
|
|
