| 191. |
- D’Ammando, F., et al.
(author)
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The most powerful flaring activity from the NLSy1 PMN J0948+0022
- 2015
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 446:3, s. 2456-2467
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Journal article (peer-reviewed)abstract
- We report on multifrequency observations performed during 2012 December–2013 August of the first narrow-line Seyfert 1 galaxy detected in γ-rays, PMN J0948+0022 (z = 0.5846). A γ-ray flare was observed by the Large Area Telescope on board Fermi during 2012 December–2013 January, reaching a daily peak flux in the 0.1–100 GeV energy range of (155 ± 31) × 10−8 ph cm−2 s−1 on 2013 January 1, corresponding to an apparent isotropic luminosity of ∼1.5 × 1048 erg s−1. The γ-ray flaring period triggered Swift and Very Energetic Radiation Imaging Telescope Array System (VERITAS) observations in addition to radio and optical monitoring by Owens Valley Radio Observatory, Monitoring Of Jets in Active galactic nuclei with VLBA Experiments, and Catalina Real-time Transient Survey. A strong flare was observed in optical, UV, and X-rays on 2012 December 30, quasi-simultaneously to the γ-ray flare, reaching a record flux for this source from optical to γ-rays. VERITAS observations at very high energy (E > 100 GeV) during 2013 January 6–17 resulted in an upper limit of F>0.2 TeV < 4.0 × 10−12 ph cm−2 s−1. We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
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| 192. |
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| 193. |
- Powell, Diana, et al.
(author)
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Sulfur dioxide in the mid-infrared transmission spectrum of WASP-39b
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 626:8001, s. 979-983
-
Journal article (peer-reviewed)abstract
- The recent inference of sulfur dioxide (SO2) in the atmosphere of the hot (approximately 1,100 K), Saturn-mass exoplanet WASP-39b from near-infrared JWST observations1–3 suggests that photochemistry is a key process in high-temperature exoplanet atmospheres4. This is because of the low (<1 ppb) abundance of SO2 under thermochemical equilibrium compared with that produced from the photochemistry of H2O and H2S (1–10 ppm)4–9. However, the SO2 inference was made from a single, small molecular feature in the transmission spectrum of WASP-39b at 4.05 μm and, therefore, the detection of other SO2 absorption bands at different wavelengths is needed to better constrain the SO2 abundance. Here we report the detection of SO2 spectral features at 7.7 and 8.5 μm in the 5–12-μm transmission spectrum of WASP-39b measured by the JWST Mid-Infrared Instrument (MIRI) Low Resolution Spectrometer (LRS)10. Our observations suggest an abundance of SO2 of 0.5–25 ppm (1σ range), consistent with previous findings4. As well as SO2, we find broad water-vapour absorption features, as well as an unexplained decrease in the transit depth at wavelengths longer than 10 μm. Fitting the spectrum with a grid of atmospheric forward models, we derive an atmospheric heavy-element content (metallicity) for WASP-39b of approximately 7.1–8.0 times solar and demonstrate that photochemistry shapes the spectra of WASP-39b across a broad wavelength range.
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| 194. |
- Schmit, Stephanie L, et al.
(author)
-
Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
-
Journal article (peer-reviewed)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 195. |
- Serwas, NK, et al.
(author)
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Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3106-
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Journal article (peer-reviewed)abstract
- Immune responses need to be controlled tightly to prevent autoimmune diseases, yet underlying molecular mechanisms remain partially understood. Here, we identify biallelic mutations in three patients from two unrelated families in differentially expressed in FDCP6 homolog (DEF6) as the molecular cause of an inborn error of immunity with systemic autoimmunity. Patient T cells exhibit impaired regulation of CTLA-4 surface trafficking associated with reduced functional CTLA-4 availability, which is replicated in DEF6-knockout Jurkat cells. Mechanistically, we identify the small GTPase RAB11 as an interactor of the guanine nucleotide exchange factor DEF6, and find disrupted binding of mutant DEF6 to RAB11 as well as reduced RAB11+CTLA-4+ vesicles in DEF6-mutated cells. One of the patients has been treated with CTLA-4-Ig and achieved sustained remission. Collectively, we uncover DEF6 as player in immune homeostasis ensuring availability of the checkpoint protein CTLA-4 at T-cell surface, identifying a potential target for autoimmune and/or cancer therapy.
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| 196. |
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| 197. |
- Wheeler, H, et al.
(author)
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The need for transformative changes in the use of Indigenous knowledge along with science for environmental decision‐making in the Arctic
- 2020
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In: People and Nature. - : John Wiley & Sons. - 2575-8314. ; 2:3, s. 544-556
-
Journal article (peer-reviewed)abstract
- 1. Recent attention to the role of Indigenous knowledge (IK) in environmental monitoring, research and decision‐making is likely to attract new people to this field of work.2. Advancing the bringing together of IK and science in a way that is desirable to IK holders can lead to successful and inclusive research and decision‐making.3. We used the Delphi technique with 18 expert participants who were IK holders or working closely with IK from across the Arctic to examine the drivers of progress and limitations to the use of IK along with science to inform decision‐making related to wildlife, reindeer herding and the environment. We also used this technique to identify participants' experiences of scientists' misconceptions concerning IK.4. Participants had a strong focus on transformative change relating to the structure of institutions, politics, rights, involvement, power and agency over technical issues advancing or limiting progress (e.g. new technologies and language barriers).5. Participants identified two modes of desirable research: coproducing knowledge with scientists and autonomous Indigenous‐led research. They highlighted the need for more collaborative and coproduction projects to allow further refinement of approaches and more funding to support autonomous, Indigenous‐led research.6. Most misconceptions held by scientists concerning IK that were identified by participants related to the spatial, temporal and conceptual scope of IK, and the perceived need to validate IK using Western science.7. Our research highlights some of the issues that need to be addressed by all participants in research and decision‐making involving IK and science. While exact approaches will need to be tailored to specific social‐ecological contexts, consideration of these broader concerns revealed by our analysis are likely to be central to effective partnerships.
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| 198. |
- Abazajian, Kevork, et al.
(author)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
-
Journal article (peer-reviewed)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 199. |
- Agha, R. A., et al.
(author)
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The SCARE 2018 statement: Updating consensus Surgical CAse REport (SCARE) guidelines
- 2018
-
In: International Journal of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1743-9191. ; 60, s. 132-136
-
Journal article (peer-reviewed)abstract
- Introduction: The SCARE Guidelines were published in 2016 to provide a structure for reporting surgical case reports. Since their publication, SCARE guidelines have been widely endorsed by authors, journal editors, and reviewers, and have helped to improve reporting transparency of case reports across a range of surgical specialties. In order to encourage further progress in reporting quality, the SCARE guidelines must themselves be kept up to date. We completed a Delphi consensus exercise to update the SCARE guidelines. Methods: A Delphi consensus exercise was undertaken. All members of the previous Delphi group were invited to participate, in addition to researchers who have previously studied case reports, and editors from the International Journal of Surgery Case Reports. The expert group was sent an online questionnaire where they were asked to rate their agreement with proposed changes to each of the 24 items. Results: 56 people agreed to participate and 45 (80%) invitees completed the survey which put forward modifications to the original guideline. The collated responses resulted in modifications. There was high agreement amongst the expert group. Conclusion: A modified and improved SCARE checklist is presented, after a Delphi consensus exercise was completed. The SCARE 2018 Statement: Updating Consensus Surgical CAse REport (SCARE) Guidelines. © 2018
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| 200. |
- Ali, Tahir, et al.
(author)
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Cellulose ether treatment inhibits amyloid beta aggregation, neuroinflammation and cognitive deficits in transgenic mouse model of Alzheimers disease
- 2023
-
In: Journal of Neuroinflammation. - : BMC. - 1742-2094. ; 20:1
-
Journal article (peer-reviewed)abstract
- Alzheimers disease (AD) is an incurable, progressive and devastating neurodegenerative disease. Pathogenesis of AD is associated with the aggregation and accumulation of amyloid beta (A & beta;), a major neurotoxic mediator that triggers neuroinflammation and memory impairment. Recently, we found that cellulose ether compounds (CEs) have beneficial effects against prion diseases by inhibiting protein misfolding and replication of prions, which share their replication mechanism with A & beta;. CEs are FDA-approved safe additives in foods and pharmaceuticals. Herein, for the first time we determined the therapeutic effects of the representative CE (TC-5RW) in AD using in vitro and in vivo models. Our in vitro studies showed that TC-5RW inhibits A & beta; aggregation, as well as neurotoxicity and immunoreactivity in A & beta;-exposed human and murine neuroblastoma cells. In in vivo studies, for the first time we observed that single and weekly TC-5RW administration, respectively, improved memory functions of transgenic 5XFAD mouse model of AD. We further demonstrate that TC-5RW treatment of 5XFAD mice significantly inhibited A & beta; oligomer and plaque burden and its associated neuroinflammation via regulating astrogliosis, microgliosis and proinflammatory mediator glial maturation factor beta (GMF & beta;). Additionally, we determined that TC-5RW reduced lipopolysaccharide-induced activated gliosis and GMF & beta; in vitro. In conclusion, our results demonstrate that CEs have therapeutic effects against A & beta; pathologies and cognitive impairments, and direct, potent anti-inflammatory activity to rescue neuroinflammation. Therefore, these FDA-approved compounds are effective candidates for developing therapeutics for AD and related neurodegenerative diseases associated with protein misfolding.
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