| 1. |
|
|
| 2. |
- Ajello, M., et al.
(författare)
-
Fermi and Swift Observations of GRB 190114C : Tracing the Evolution of High-energy Emission from Prompt to Afterglow
- 2020
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 890:1
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the observations of gamma-ray burst (GRB) 190114C by the Fermi Gamma -ray Space Telescope and the Neil Gehrels Swift Observatory. The prompt gamma-ray emission was detected by the Fermi GRB Monitor (GBM), the Fermi Large Area Telescope (LAT), and the Swift Burst Alert Telescope (BAT) and the long-lived afterglow emission was subsequently observed by the GBM, LAT, Swift X-ray Telescope (XRT), and Swift UV Optical Telescope. The early -time observations reveal multiple emission components that evolve independently, with a delayed power-law component that exhibits significant spectral attenuation above 40 MeV in the first few seconds of the burst. This power-law component transitions to a harder spectrum that is consistent with the afterglow emission observed by the XRT at later times. This afterglow component is clearly identifiable in the GBM and BAT light curves as a slowly fading emission component on which the rest of the prompt emission is superimposed. As a result, we are able to observe the transition from internal-shock- to external-shock-dominated emission. We find that the temporal and spectral evolution of the broadband afterglow emission can be well modeled as synchrotron emission from a forward shock propagating into a wind -like circumstellar environment. We estimate the initial bulk Lorentz factor using the observed high-energy spectral cutoff. Considering the onset of the afterglow component, we constrain the deceleration radius at which this forward shock begins to radiate in order to estimate the maximum synchrotron energy as a function of time. We find that even in the LAT energy range, there exist high-energy photons that are in tension with the theoretical maximum energy that can be achieved through synchrotron emission from a shock. These violations of the maximum synchrotron energy are further compounded by the detection of very high-energy (VHE) emission above 300 GeV by MAGIC concurrent with our observations. We conclude that the observations of VHE photons from GRB 190114C necessitates either an additional emission mechanism at very high energies that is hidden in the synchrotron component in the LAT energy range, an acceleration mechanism that imparts energy to the particles at a rate that is faster than the electron synchrotron energy -loss rate, or revisions of the fundamental assumptions used in estimating the maximum photon energy attainable through the synchrotron process.
|
|
| 3. |
|
|
| 4. |
- Lin, HY, et al.
(författare)
-
KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 9264-
-
Tidskriftsartikel (refereegranskat)abstract
- Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP–SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10–9) and 3145 (P < 1 × 10–5) SNP–SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene–gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP–SNP interactions were supported by gene expression and protein–protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
|
|
| 5. |
- Allen, K. D., et al.
(författare)
-
Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative
- 2023
-
Ingår i: Osteoarthritis and Cartilage. - : ELSEVIER SCI LTD. - 1063-4584 .- 1522-9653. ; 31:7, s. 954-965
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). Design: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by & GE;80% of participants were retained, and participants could suggest addi-tional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if & GE;80% rated it & GE;6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if & GE;80% of participants rated it & GE;9 and as "optional" if & GE;80% rated it & GE;7. Results: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. Conclusion: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
|
|
| 6. |
|
|
| 7. |
- Gatenby, Robert A., et al.
(författare)
-
Lung adenocarcinomas without driver genes converge to common adaptive strategies through diverse genetic, epigenetic, and niche construction evolutionary pathways
- 2024
-
Ingår i: Medical Oncology. - 1357-0560. ; 41:6
-
Tidskriftsartikel (refereegranskat)abstract
- Somatic evolution selects cancer cell phenotypes that maximize survival and proliferation in dynamic environments. Although cancer cells are molecularly heterogeneous, we hypothesized convergent adaptive strategies to common host selection forces can be inferred from patterns of epigenetic and genetic evolutionary selection in similar tumors. We systematically investigated gene mutations and expression changes in lung adenocarcinomas with no common driver genes (n = 313). Although 13,461 genes were mutated in at least one sample, only 376 non-synonymous mutations evidenced positive evolutionary selection with conservation of 224 genes, while 1736 and 2430 genes exhibited ≥ two-fold increased and ≥ 50% decreased expression, respectively. Mutations under positive selection are more frequent in genes with significantly altered expression suggesting they often “hardwire” pre-existing epigenetically driven adaptations. Conserved genes averaged 16-fold higher expression in normal lung tissue compared to those with selected mutations demonstrating pathways necessary for both normal cell function and optimal cancer cell fitness. The convergent LUAD phenotype exhibits loss of differentiated functions and cell–cell interactions governing tissue organization. Conservation with increased expression is found in genes associated with cell cycle, DNA repair, p53 pathway, epigenetic modifiers, and glucose metabolism. No canonical driver gene pathways exhibit strong positive selection, but extensive down-regulation of membrane ion channels suggests decreased transmembrane potential may generate persistent proliferative signals. NCD LUADs perform niche construction generating a stiff, immunosuppressive microenvironment through selection of specific collagens and proteases. NCD LUADs evolve to a convergent phenotype through a network of interconnected genetic, epigenetic, and ecological pathways.
|
|
