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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 4. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 5. |
- Magg, Ekaterina, et al.
(författare)
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Observational constraints on the origin of the elements IV. Standard composition of the Sun
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 661
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Tidskriftsartikel (refereegranskat)abstract
- Context. The chemical composition of the Sun is required in the context of various studies in astrophysics, among them in the calculation of standard solar models (SSMs) used to describe the evolution of the Sun from the pre-main-sequence to its present age. Aims. In this work, we provide a critical re-analysis of the solar chemical abundances and corresponding SSMs. Methods. For the photospheric values, we employed new high-quality solar observational data collected with the IAG facility, state-of-the art non-equilibrium modelling, new oscillator strengths, and different atmospheric models, including the MARCS model, along with averages based on Stagger and CO5BOLD 3D radiation-hydrodynamics simulations of stellar convection. We performed new calculations of oscillator strengths for transitions in O I and N I. For O I, which is a critical element with regard to the interior models, calculations were carried out using several independent methods. We investigated our results in comparison with the previous estimates. Results. We find an unprecedented agreement between the new estimates of transition probabilities, thus supporting our revised solar oxygen abundance value. We also provide new estimates of the noble gas Ne abundance. In addition, we discuss the consistency of our photospheric measurements with meteoritic values, taking into account the systematic and correlated errors. Finally, we provide revised chemical abundances, leading to a new value proposed for the solar photospheric present-day metallicity of Z/X=0.0225, which we then employed in SSM calculations. We find that the puzzling mismatch between the helioseismic constraints on the solar interior structure and the model can be resolved thanks to this new chemical composition.
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| 6. |
- VandenBerg, Don A., et al.
(författare)
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Isochrones for Old (> 5 Gyr) Stars and Stelllar Populations. I. Models for-2.4 <= [Fe/H] <=+0.6, 0.25 <= Y <= 0.33, and-0.4 <= [alpha/Fe] <=+0.4
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 794:1, s. UNSP 72-
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Tidskriftsartikel (refereegranskat)abstract
- Canonical grids of stellar evolutionary sequences have been computed for the helium mass-fraction abundances Y = 0.25, 0.29, and 0.33, and for iron abundances that vary from 2.4 to +0.4 (in 0.2 dex increments) when [alpha/Fe] = +0.4, or for the ranges 2.0 <= [Fe/H] <= +0.6, 1.8 <= [Fe/H] <= +0.6 when [alpha/Fe] = 0.0 and -0.4, respectively. The grids, which consist of tracks for masses from 0.12 M-circle dot to 1.1-1.5 M-circle dot (depending on the metallicity) are based on up-to-date physics, including the gravitational settling of helium (but not metals diffusion). Interpolation software is provided to generate isochrones for arbitrary ages between approximate to 5 and 15 Gyr and any values of Y, [alpha/Fe], and [Fe/H] within the aformentioned ranges. Comparisons of isochrones with published color magnitude diagrams (CMDs) for the open clusters M67 ([Fe/H] approximate to 0.0) and NGC 6791 ([Fe/H] approximate to 0.3) and for four of the metal-poor globular clusters (47 Tuc, M3, M5, and M92) indicate that the models for the observed metallicities do a reasonably good job of reproducing the locations and slopes of the cluster main sequences and giant branches. The same conclusion is reached from a consideration of plots of nearby subdwarfs that have accurate Hipparcos parallaxes and metallicities in the range -2.0 <= [Fe/H] <= -1.0 on various CMDs and on the (log T-eff, M-V) diagram. A relatively hot temperature scale similar to that derived in recent calibrations of the infrared flux method is favored by both the isochrones and the adopted color transformations, which are based on the latest MARCS model atmospheres.
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| 7. |
- VandenBerg, Don A., et al.
(författare)
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Models of metal-poor stars with different initial abundances of C, N, O, Mg, and Si - I. Bolometric corrections derived from new MARCS synthetic spectra and their implications for observed colour-magnitude diagrams
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 509:3, s. 4189-4207
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Tidskriftsartikel (refereegranskat)abstract
- New, high-resolution MARCS synthetic spectra have been calculated for more than a dozen mixtures of the metals allowing, in turn, for variations in C:N:O, [CNO/Fe], and enhanced abundances of C, O, Mg, and Si. Bolometric corrections (BCs) for many of the broad-band filters currently in use have been generated from these spectra. Due to improved treatments of molecules that involve atoms of C, N, and O, the BCs for UV and blue passbands, in particular, differ substantially from those derived from previous MARCS models. These differences, and the effects on the BCs of varying the abundances of the metals, are shown in a number of instructive plots. Stellar evolutionary grids for -2.5 <= [Fe/H] <=-0.5 have also been computed for the different mixtures. Isochrones based on these tracks are intercompared on the theoretical H-R diagram and on a few of the colour-magnitude diagrams that can be constructed from HST Wide Field Camera 3 (WFC3) F336W, F438W, F606W, F814W, F110W, and F160W observations. For the first application of these models, isochrones have been fitted to WFC3 photometry of the globular cluster NGC 6496 from the HST UV Legacy Survey, with very encouraging results.
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| 8. |
- Vandenberg, Don A., et al.
(författare)
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On Stellar Models with Blanketed Atmospheres as Boundary Conditions
- 2007
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Ingår i: Stellar Populations as Building Blocks of Galaxies. ; , s. 23-27
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The impact on the predicted Teff scale of using the latest MARCS model atmospheres, instead of a fixed atmospheric structure (e.g., the gray T–τ relation) is examined. The former were fitted to stellar interior models at both the photosphere and at τ = 100 to determine the sensitivity of evolutionary tracks and isochrones for [Fe/H] = 0.0 and −2.0 to the chosen fitting point. In the case of solar abundances, the Teff of the giant branch varied by up to 100–150 K, depending on how the outer layers were treated. Much smaller variations were found for metal-poor giants (or main-sequence stars). Interestingly, models for the low solar Z favored by Asplund et al. (Z=0.0125) were unable to reproduce the gap near the turnoff in the C-M diagram of the old open cluster M 67, in contrast to models that assume Z=0.0188.
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