| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Fazey, Ioan, et al.
(författare)
-
Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
-
Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
-
Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
|
|
| 3. |
- Singh, Tejas P., et al.
(författare)
-
Association between aortic peak wall stress and rupture index with abdominal aortic aneurysm–related events
- 2023
-
Ingår i: European Radiology. - : Springer Nature. - 0938-7994 .- 1432-1084. ; 33:8, s. 5698-5706
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to assess whether aortic peak wall stress (PWS) and peak wall rupture index (PWRI) were associated with the risk of abdominal aortic aneurysm (AAA) rupture or repair (defined as AAA events) among participants with small AAAs. Methods: PWS and PWRI were estimated from computed tomography angiography (CTA) scans of 210 participants with small AAAs (≥ 30 and ≤ 50 mm) prospectively recruited between 2002 and 2016 from two existing databases. Participants were followed for a median of 2.0 (inter-quartile range 1.9, 2.8) years to record the incidence of AAA events. The associations between PWS and PWRI with AAA events were assessed using Cox proportional hazard analyses. The ability of PWS and PWRI to reclassify the risk of AAA events compared to the initial AAA diameter was examined using net reclassification index (NRI) and classification and regression tree (CART) analysis. Results: After adjusting for other risk factors, one standard deviation increase in PWS (hazard ratio, HR, 1.56, 95% confidence intervals, CI 1.19, 2.06; p = 0.001) and PWRI (HR 1.74, 95% CI 1.29, 2.34; p < 0.001) were associated with significantly higher risks of AAA events. In the CART analysis, PWRI was identified as the best single predictor of AAA events at a cut-off value of > 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. Conclusion: PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. Key Points: • Aortic diameter is an imperfect measure of abdominal aortic aneurysm (AAA) rupture risk. • This observational study of 210 participants found that peak wall stress (PWS) and peak wall rupture index (PWRI) predicted the risk of aortic rupture or AAA repair. • PWRI, but not PWS, significantly improved the risk stratification for AAA events compared to aortic diameter alone.
|
|
| 4. |
- Singh, Tejas P., et al.
(författare)
-
Effect of Telmisartan on the Peak Wall Stress and Peak Wall Rupture Index of Small Abdominal Aortic Aneurysms : An Exploratory Analysis of the TEDY Trial
- 2022
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 64:4, s. 396-404
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: This study was an unplanned exploratory analysis of a subset of participants from the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial. It aimed to assess the efficacy of the angiotensin 1 receptor blocker telmisartan in reducing abdominal aortic aneurysm (AAA) peak wall stress (PWS) and peak wall rupture index (PWRI) among individuals with small AAAs. Methods: Participants with AAAs measuring 35 - 49 mm in maximum diameter were randomised to receive telmisartan 40 mg or identical placebo in the TEDY trial. Participants who had computed tomography angiography performed at entry and at least one other time point during the trial (12 or 24 months) were included in the current study. Orthogonal AAA diameter, PWS, and PWRI were measured using previously validated methods. The annual change in PWS and PWRI from baseline was compared between participants allocated telmisartan or placebo using linear mixed effects models. These models were either unadjusted or adjusted for risk factors that were different in the groups at entry (p <.100) or systolic blood pressure (SBP) at one year. Results: Of the 207 participants recruited to TEDY, 124 were eligible for inclusion in this study. This study included 65 and 59 participants from the telmisartan and placebo groups, respectively. The PWS and PWRI were not significantly different in the two groups at baseline. Participants allocated telmisartan had a slower annual increase in PWS (-4.19; 95% CI -8.24, -0.14 kPa/year; p = .043) and PWRI (-0.014; 95% CI -0.026, -0.001; p = .032) compared with those allocated placebo after adjusting for risk factors. After adjustment for SBP at one year, telmisartan did not significantly reduce annual increases in PWS or PWRI. Conclusion: The findings of this study suggest that telmisartan limits the rate of increase in PWS and PWRI of small AAAs by reducing blood pressure.
|
|
| 5. |
- Anderson, Marin M., et al.
(författare)
-
Simultaneous Search for Prompt Radio Emission Associated with the Short GRB 170112A Using the All-sky Imaging Capability of the OVRO-LWA
- 2018
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 864:1
-
Tidskriftsartikel (refereegranskat)abstract
- We have conducted the most sensitive low-frequency (below 100 MHz) search to date for prompt, low-frequency radio emission associated with short-duration gamma-ray bursts (GRBs), using the Owens Valley Radio Observatory Long Wavelength Array (OVRO-LWA). The OVRO-LWA's nearly full-hemisphere field of view (similar to 20,000 square degrees) allows us to search for low-frequency (sub-100 MHz) counterparts for a large sample of the subset of GRB events for which prompt radio emission has been predicted. Following the detection of short GRB 170112A by Swift, we used all-sky OVRO-LWA images spanning one hour prior to and two hours following the GRB event to search for a transient source coincident with the position of GRB 170112A. We detect no transient source to within a 3 sigma flux density limit of 4.5. Jy at 13 s timescales for frequencies spanning 27-84. MHz. We place constraints on a number of models predicting prompt, low-frequency radio emission accompanying short GRBs and their potential binary neutron star merger progenitors, and place an upper limit of L-radio/L gamma less than or similar to 3.5 x 10(-6) on the fraction of energy released in the prompt radio emission, under the assumptions of negligible scattering of the radio pulse and beaming of emission along the line of sight. These observations serve as a pilot effort for a program targeting a wider sample of both short and long GRBs with the OVRO-LWA, including bursts with confirmed redshift measurements that are critical to placing constraining limits on prompt radio emission models, as well as a program for the follow-up of gravitational wave compact binary coalescence events detected by advanced LIGO and Virgo.
|
|
| 6. |
- Arzoumanian, Doris, et al.
(författare)
-
Dust polarized emission observations of NGC 6334: BISTRO reveals the details of the complex but organized magnetic field structure of the high-mass star-forming hub-filament network
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 647
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Molecular filaments and hubs have received special attention recently thanks to new studies showing their key role in star formation. While the (column) density and velocity structures of both filaments and hubs have been carefully studied, their magnetic field (B-field) properties have yet to be characterized. Consequently, the role of B-fields in the formation and evolution of hub-filament systems is not well constrained. Aims. We aim to understand the role of the B-field and its interplay with turbulence and gravity in the dynamical evolution of the NGC 6334 filament network that harbours cluster-forming hubs and high-mass star formation. Methods. We present new observations of the dust polarized emission at 850 μm toward the 2 pc × 10 pc map of NGC 6334 at a spatial resolution of 0.09 pc obtained with the James Clerk Maxwell Telescope (JCMT) as part of the B-field In STar-forming Region Observations (BISTRO) survey. We study the distribution and dispersion of the polarized intensity (PI), the polarization fraction (PF), and the plane-of-The-sky B-field angle (χB_POS) toward the whole region, along the 10 pc-long ridge and along the sub-filaments connected to the ridge and the hubs. We derived the power spectra of the intensity and χBPOS along the ridge crest and compared them with the results obtained from simulated filaments. Results. The observations span 3 orders of magnitude in Stokes I and PI and 2 orders of magnitude in PF (from 0.2 to 20%). A large scatter in PI and PF is observed for a given value of I. Our analyses show a complex B-field structure when observed over the whole region ( 10 pc); however, at smaller scales (1 pc), χBPOS varies coherently along the crests of the filament network. The observed power spectrum of χBPOS can be well represented with a power law function with a slope of-1.33 ± 0.23, which is 20% shallower than that of I. We find that this result is compatible with the properties of simulated filaments and may indicate the physical processes at play in the formation and evolution of star-forming filaments. Along the sub-filaments, χBPOS rotates frombeing mostly perpendicular or randomly oriented with respect to the crests to mostly parallel as the sub-filaments merge with the ridge and hubs. This variation of the B-field structure along the sub-filaments may be tracing local velocity flows of infalling matter in the ridge and hubs. Our analysis also suggests a variation in the energy balance along the crests of these sub-filaments, from magnetically critical or supercritical at their far ends to magnetically subcritical near the ridge and hubs. We also detect an increase in PF toward the high-column density (NH2 â 1023 cm-2) star cluster-forming hubs. These latter large PF values may be explained by the increase in grain alignment efficiency due to stellar radiation from the newborn stars, combined with an ordered B-field structure. Conclusions. These observational results reveal for the first time the characteristics of the small-scale (down to 0.1 pc) B-field structure of a 10 pc-long hub-filament system. Our analyses show variations in the polarization properties along the sub-filaments that may be tracing the evolution of their physical properties during their interaction with the ridge and hubs. We also detect an impact of feedback from young high-mass stars on the local B-field structure and the polarization properties, which could put constraints on possible models for dust grain alignment and provide important hints as to the interplay between the star formation activity and interstellar B-fields.
|
|
| 7. |
- Brown, James A L, et al.
(författare)
-
Targeting cancer using KAT inhibitors to mimic lethal knockouts.
- 2016
-
Ingår i: Biochemical Society transactions. - 1470-8752. ; 44:4, s. 979-86
-
Forskningsöversikt (refereegranskat)abstract
- Two opposing enzyme classes regulate fundamental elements of genome maintenance, gene regulation and metabolism, either through addition of an acetyl moiety by histone acetyltransferases (HATs) or its removal by histone de-acetyltransferases (HDAC), and are exciting targets for drug development. Importantly, dysfunctional acetylation has been implicated in numerous diseases, including cancer. Within the HAT superfamily the MYST family holds particular interest, as its members are directly involved in the DNA damage response and repair pathways and crucially, several members have been shown to be down-regulated in common cancers (such as breast and prostate). In the present study we focus on the development of lysine (K) acetyltransferase inhibitors (KATi) targeting the MYST family member Tip60 (Kat5), an essential protein, designed or discovered through screening libraries. Importantly, Tip60 has been demonstrated to be significantly down-regulated in many cancers which urgently require new treatment options. We highlight current and future efforts employing these KATi as cancer treatments and their ability to synergize and enhance current cancer treatments. We investigate the different methods of KATi production or discovery, their mechanisms and their validation models. Importantly, the utility of KATi is based on a key concept: using KATi to abrogate the activity of an already down-regulated essential protein (effectively creating a lethal knockout) provides another innovative mechanism for targeting cancer cells, while significantly minimizing any off-target effects to normal cells. This approach, combined with the rapidly developing interest in KATi, suggests that KATi have a bright future for providing truly personalized therapies.
|
|
| 8. |
- Collins, David H., et al.
(författare)
-
Gene expression during larval caste determination and differentiation in intermediately eusocial bumblebees, and a comparative analysis with advanced eusocial honeybees
- 2021
-
Ingår i: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 30:3, s. 718-735
-
Tidskriftsartikel (refereegranskat)abstract
- The queen-worker caste system of eusocial insects represents a prime example of developmental polyphenism (environmentally-induced phenotypic polymorphism) and is intrinsic to the evolution of advanced eusociality. However, the comparative molecular basis of larval caste determination and subsequent differentiation in the eusocial Hymenoptera remains poorly known. To address this issue within bees, we profiled caste-associated gene expression in female larvae of the intermediately eusocial bumblebee Bombus terrestris. In B. terrestris, female larvae experience a queen-dependent period during which their caste fate as adults is determined followed by a nutrition-sensitive period also potentially affecting caste fate but for which the evidence is weaker. We used mRNA-seq and qRT-PCR validation to isolate genes differentially expressed between each caste pathway in larvae at developmental stages before and after each of these periods. We show that differences in gene expression between caste pathways are small in totipotent larvae, then peak after the queen-dependent period. Relatively few novel (i.e. taxonomically-restricted) genes were differentially expressed between castes, though novel genes were significantly enriched in late-instar larvae in the worker pathway. We compared sets of caste-associated genes in B. terrestris with those reported from the advanced eusocial honeybee, Apis mellifera, and found significant but relatively low levels of overlap of gene lists between the two species. These results suggest both the existence of low numbers of shared toolkit genes and substantial divergence in caste-associated genes between Bombus and the advanced eusocial Apis since their last common eusocial ancestor.
|
|
| 9. |
- Deane, R. P., et al.
(författare)
-
The VLBA CANDELS GOODS-North Survey -I. survey design, processing, data products, and source counts
- 2024
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 529:3, s. 2428-2442
-
Tidskriftsartikel (refereegranskat)abstract
- The past decade has seen significant advances in wide-field cm-wave very long baseline interferometry (VLBI), which is timely given the wide-area, synoptic survey-driven strategy of major facilities across the electromagnetic spectrum. While wide-field VLBI poses significant post-processing challenges that can severely curtail its potential scientific yield, man y dev elopments in the km-scale connected-element interferometer sphere are directly applicable to addressing these. Here we present the design, processing, data products, and source counts from a deep (11 μJy beam -1 ), quasi-uniform sensitivity, contiguous wide-field (160 arcmin 2 ) 1.6 GHz VLBI surv e y of the CANDELS GOODS-North field. This is one of the best-studied extragalactic fields at milli-arcsecond resolution and, therefore, is well-suited as a comparative study for our Tera-pixel VLBI image. The derived VLBI source counts show consistency with those measured in the COSMOS field, which broadly traces the AGN population detected in arcsecond-scale radio surv e ys. Ho we ver, there is a distinctive flattening in the S 1.4GHz ∼100-500 μJy flux density range, which suggests a transition in the population of compact faint radio sources, qualitatively consistent with the excess source counts at 15 GHz that is argued to be an unmodelled population of radio cores. This surv e y approach will assist in deriving robust VLBI source counts and broadening the disco v ery space for future wide-field VLBI surv e ys, including VLBI with the Square Kilometre Array, which will include new large field-of-view antennas on the African continent at ≲1000 km baselines. In addition, it may be useful in the design of both monitoring and/or rapidly triggered VLBI transient programmes.
|
|
| 10. |
- Eastwood, Michael W., et al.
(författare)
-
The Radio Sky at Meter Wavelengths: M-mode Analysis Imaging with the OVRO-LWA
- 2018
-
Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 156:1
-
Tidskriftsartikel (refereegranskat)abstract
- A host of new low-frequency radio telescopes seek to measure the 21 cm transition of neutral hydrogen from the early universe. These telescopes have the potential to directly probe star and galaxy formation at redshifts 20 ≳ z ≳ 7 but are limited by the dynamic range they can achieve against foreground sources of low-frequency radio emission. Consequently, there is a growing demand for modern, high-fidelity maps of the sky at frequencies below 200 MHz for use in foreground modeling and removal. We describe a new wide-field imaging technique for drift-scanning interferometers: Tikhonov-regularized m-mode analysis imaging. This technique constructs images of the entire sky in a single synthesis imaging step with exact treatment of wide-field effects. We describe how the CLEAN algorithm can be adapted to deconvolve maps generated by m-mode analysis imaging. We demonstrate Tikhonov-regularized m-mode analysis imaging using the Owens Valley Radio Observatory Long Wavelength Array (OVRO-LWA) by generating eight new maps of the sky north of δ = -30° with 15′ angular resolution at frequencies evenly spaced between 36.528 and 73.152 MHz and ∼800 mJy beam-1thermal noise. These maps are a 10-fold improvement in angular resolution over existing full-sky maps at comparable frequencies, which have angular resolutions ≥2°. Each map is constructed exclusively from interferometric observations and does not represent the globally averaged sky brightness. Future improvements will incorporate total power radiometry, improved thermal noise, and improved angular resolution due to the planned expansion of the OVRO-LWA to 2.6 km baselines. These maps serve as a first step on the path to the use of more sophisticated foreground filters in 21 cm cosmology incorporating the measured angular and frequency structure of all foreground contaminants.
|
|
