| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- Adhikari, Subash, et al.
(författare)
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A high-stringency blueprint of the human proteome
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 3. |
- Forslund, Tommie, et al.
(författare)
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Attachment goes to court : child protection and custody issues
- 2022
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Ingår i: Attachment & Human Development. - : Taylor & Francis Group. - 1461-6734 .- 1469-2988. ; 24:1, s. 1-52
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Tidskriftsartikel (refereegranskat)abstract
- Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. The article is divided into two parts. In the first, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child’s need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration.
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| 4. |
- Forslund, Tommie, et al.
(författare)
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El Apego Va a Juicio: Problemas de Custodia y Protección Infantil : [Attachment goes to court: Child protection and custody issues]
- 2021
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Ingår i: Anuario de psicología jurídica. - : Colegio Oficial de la Psicologia de Madrid. - 1133-0740 .- 2174-0542. ; 32:1, s. 115-139
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Tidskriftsartikel (refereegranskat)abstract
- Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. This article is divided into two parts. In the first part, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child's need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration.
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| 5. |
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| 6. |
- Windhorst, Rogier A., et al.
(författare)
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JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
- 2023
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Ingår i: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
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Tidskriftsartikel (refereegranskat)abstract
- We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
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| 7. |
- Berg, Danielle A., et al.
(författare)
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The COS Legacy Archive Spectroscopy Survey (CLASSY) Treasury Atlas
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 261:2
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Tidskriftsartikel (refereegranskat)abstract
- Far-ultraviolet (FUV; ∼1200–2000 Å) spectra are fundamental to our understanding of star-forming galaxies, providing a unique window on massive stellar populations, chemical evolution, feedback processes, and reionization. The launch of the James Webb Space Telescope will soon usher in a new era, pushing the UV spectroscopic frontier to higher redshifts than ever before; however, its success hinges on a comprehensive understanding of the massive star populations and gas conditions that power the observed UV spectral features. This requires a level of detail that is only possible with a combination of ample wavelength coverage, signal-to-noise, spectral-resolution, and sample diversity that has not yet been achieved by any FUV spectral database. We present the Cosmic Origins Spectrograph Legacy Spectroscopic Survey (CLASSY) treasury and its first high-level science product, the CLASSY atlas. CLASSY builds on the Hubble Space Telescope (HST) archive to construct the first high-quality (S/N1500 Å ≳ 5/resel), high-resolution (R ∼ 15,000) FUV spectral database of 45 nearby (0.002 < z < 0.182) star-forming galaxies. The CLASSY atlas, available to the public via the CLASSY website, is the result of optimally extracting and coadding 170 archival+new spectra from 312 orbits of HST observations. The CLASSY sample covers a broad range of properties including stellar mass (6.2 < log M⋆(M⊙) < 10.1), star formation rate (−2.0 < log SFR (M⊙ yr−1) < +1.6), direct gas-phase metallicity (7.0 < 12+log(O/H) < 8.8), ionization (0.5 < O32 < 38.0), reddening (0.02 < E(B − V) < 0.67), and nebular density (10 < ne (cm−3) < 1120). CLASSY is biased to UV-bright star-forming galaxies, resulting in a sample that is consistent with the z ∼ 0 mass–metallicity relationship, but is offset to higher star formation rates by roughly 2 dex, similar to z ≳ 2 galaxies. This unique set of properties makes the CLASSY atlas the benchmark training set for star-forming galaxies across cosmic time.
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| 8. |
- Bonate, Peter L., et al.
(författare)
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Training the next generation of pharmacometric modelers : a multisector perspective
- 2023
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Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Nature. - 1567-567X .- 1573-8744. ; 51:1, s. 5-31
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Tidskriftsartikel (refereegranskat)abstract
- The current demand for pharmacometricians outmatches the supply provided by academic institutions and considerable investments are made to develop the competencies of these scientists on-the-job. Even with the observed increase in academic programs related to pharmacometrics, this need is unlikely to change in the foreseeable future, as the demand and scope of pharmacometrics applications keep expanding. Further, the field of pharmacometrics is changing. The field largely started when Lewis Sheiner and Stuart Beal published their seminal papers on population pharmacokinetics in the late 1970’s and early 1980’s and has continued to grow in impact and use since its inception. Physiological-based pharmacokinetics and systems pharmacology have grown rapidly in scope and impact in the last decade and machine learning is just on the horizon. While all these methodologies are categorized as pharmacometrics, no one person can be an expert in everything. So how do you train future pharmacometricians? Leading experts in academia, industry, contract research organizations, clinical medicine, and regulatory gave their opinions on how to best train future pharmacometricians. Their opinions were collected and synthesized to create some general recommendations.
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| 9. |
- Gazagnes, Simon, et al.
(författare)
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Interpreting the Si ii and C ii Line Spectra from the COS Legacy Archive Spectroscopic SurveY Using a Virtual Galaxy from a High-resolution Radiation-hydrodynamic Simulation
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Tidskriftsartikel (refereegranskat)abstract
- Observations of low-ionization state metal lines provide crucial insights into the interstellar medium (ISM) of galaxies, yet, disentangling the physical processes responsible for the emerging line profiles is difficult. This work investigates how mock spectra generated using a single galaxy in a radiation-hydrodynamical simulation can help us interpret observations of a real galaxy. We create 22,500 C ii and Si ii spectra from the virtual galaxy at different times and through multiple lines of sight and compare them with the 45 observations of low-redshift star-forming galaxies from the COS Legacy Spectroscopic SurveY (classy). We find that the mock profiles provide accurate replicates of the observations of 38 galaxies with a broad range of stellar masses (106–109M⊙) and metallicities (0.02–0.55 Z⊙). Additionally, we highlight that aperture losses explain the weakness of the fluorescent emission in several classy spectra and must be accounted for when comparing simulations to observations. Overall, we show that the evolution of a single simulated galaxy can produce a large diversity of spectra whose properties are representative of galaxies of comparable or smaller masses. Building upon these results, we explore the origin of the continuum, residual flux, and fluorescent emission in the simulation. We find that these different spectral features all emerge from distinct regions in the galaxy's ISM, and their characteristics can vary as a function of the viewing angle. While these outcomes challenge simplified interpretations of down-the-barrel spectra, our results indicate that high-resolution simulations provide an optimal framework to interpret these observations.
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| 10. |
- James, Bethan L., et al.
(författare)
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CLASSY. II. A Technical Overview of the COS Legacy Archive Spectroscopic Survey
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 262:2
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Tidskriftsartikel (refereegranskat)abstract
- The COS Legacy Archive Spectroscopic SurveY (CLASSY) is designed to provide the community with a spectral atlas of 45 nearby star-forming galaxies that were chosen to cover similar properties to those seen at high z (z > 6). The prime high-level science product of CLASSY is accurately coadded UV spectra, ranging from ∼1000 to 2000 Å, derived from a combination of archival and new data obtained with HST's Cosmic Origins Spectrograph (COS). This paper details the multistage technical processes of creating this prime data product and the methodologies involved in extracting, reducing, aligning, and coadding far-ultraviolet and near-ultraviolet (NUV) spectra. We provide guidelines on how to successfully utilize COS observations of extended sources, despite COS being optimized for point sources, and best-practice recommendations for the coaddition of UV spectra in general. Moreover, we discuss the effects of our reduction and coaddition techniques in the scientific application of the CLASSY data. In particular, we find that accurately accounting for flux calibration offsets can affect the derived properties of the stellar populations, while customized extractions of NUV spectra for extended sources are essential for correctly diagnosing the metallicity of galaxies via C iii] nebular emission. Despite changes in spectral resolution of up to ∼25% between individual data sets (due to changes in the COS line-spread function), no adverse affects were observed on the difference in velocity width and outflow velocities of isolated absorption lines when measured in the final combined data products, owing in part to our signal-to-noise regime of S/N < 20.
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| 11. |
- Mingozzi, Matilde, et al.
(författare)
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CLASSY. VIII. Exploring the Source of Ionization with UV Interstellar Medium Diagnostics in Local High-z Analogs
- 2024
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 962:1
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Tidskriftsartikel (refereegranskat)abstract
- In the current JWST era, rest-frame UV spectra play a crucial role in enhancing our understanding of the interstellar medium (ISM) and stellar properties of the first galaxies in the epoch of reionization (z > 6). Here, we compare well-known and reliable optical diagrams sensitive to the main ionization source (i.e., star formation, SF; active galactic nuclei, AGN; and shocks) to UV counterparts proposed in the literature—the so-called "UV–BPT diagrams"—using the HST COS Legacy Archive Spectroscopic SurveY (CLASSY), which is the largest high-quality, high-resolution, and broad-wavelength range atlas of far-UV spectra for 45 local star-forming galaxies. In particular, we explore where CLASSY UV line ratios are located in the different UV diagnostic plots, taking into account state-of-the-art photoionization and shock models, and, for the first time, the measured ISM and stellar properties (e.g., gas-phase metallicity, ionization parameter, carbon abundance, and stellar age). We find that the combination of C iii] λλ1907,9 He iiλ1640 and O iii] λ1666 can be a powerful tool to separate between SF, shocks, and AGN at subsolar metallicities. We also confirm that alternative diagrams without O iii] λ1666 still allow us to define an SF-locus, with some caveats. Diagrams including C ivλλ1548,51 should be taken with caution given the complexity of this doublet profile. Finally, we present a discussion detailing the ISM conditions required to detect UV emission lines, visible only in low gas-phase metallicity (12 + log(O/H) ≲ 8.3) and high ionization parameter (log(U) ≳ −2.5) environments. Overall, CLASSY and our UV toolkit will be crucial in interpreting the spectra of the earliest galaxies that JWST is currently revealing.
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| 12. |
- Tuohimaa, Tomi, 1974-
(författare)
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Liquid-Jet-Target Microfocus X-Ray Sources : Electron Guns, Optics and Phase-Contrast Imaging
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This Thesis describes the development of an electron-impact microfocus x-ray source and its application for phase-contrast imaging. The source is based on a novel, liquid-jet target concept. Stable and continuous operation can be achieved at substantially higher electron-beam power densities than conventional solid target based systems. The maximum x-ray brightness can potentially be increased by a factor of 10-1000, which would provide significantly improved performance in applications such as imaging. In order to reach the high x-ray brightness, comparable performance from the electron gun is needed. A LaB6-cathode-based electron gun is analyzed in terms of achievable e-beam brightness and beam quality and is found capable to deliver power densities in the 10-100 MW/mm2 range using optimized electro-optics. A proof-of-principle microfocus source has been developed. Experiments show that the liquid-metal-jet target can be operated at more than an order of magnitude higher e-beam power densities than modern solid-metal targets. This brightness enhancement has been utilized to acquire in-line phase-contrast images of weakly absorbing objects. The source potentially enables the application of high-resolution phase-contrast x-ray imaging with short exposure times in clinics and laboratories. Different liquid-jet-target materials have been tested. The Sn-jet (Ka=25.3 keV) could be suitable for mammography, whereas the Ga-jet ((Ka=9.2 keV) may be utilized for x-ray diffraction studies. In addition, a non-metallic methanol jet has been the demonstrated in stable x-ray operation. All materials and compounds found in liquid form can, thus, potentially be used for electron-impact liquid-jet-target x-ray generation. Scaling to higher e-beam power density and x-ray brightness levels is discussed and is determined to be feasible. Potential difficulties, such as debris emission and instabilities of the x-ray emission spot, are investigated in some detail. Larger and/or faster jets could overcome the present limitations because of their inherently higher heat load capacities. Dynamic-similarity experiments show that liquid jets can in principle be operated in a stable manner at much higher speeds than previously shown.
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| 13. |
- Wilkins, Stephen M., et al.
(författare)
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First Light And Reionization Epoch Simulations (FLARES) VII : The star formation and metal enrichment histories of galaxies in the early Universe
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 518:3, s. 3935-3948
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Tidskriftsartikel (refereegranskat)abstract
- The star formation and metal enrichment histories of galaxies - at any epoch - constitute one of the key properties of galaxies, and their measurement is a core aim of observational extragalactic astronomy. The lack of deep rest-frame optical coverage at high redshift has made robust constraints elusive, but this is now changing thanks to JWST. In preparation for the constraints provided by JWST, we explore the star formation and metal enrichment histories of galaxies at z = 5-13 using the First Light And Reionization Epoch Simulations (FLARES) suite. Built on the EAGLE model, the unique strategy of FLARES allows us to simulate galaxies with a wide range of stellar masses (and luminosities) and environments. While we predict significant redshift evolution of average ages and specific star formation rates, our core result is mostly a flat relationship of age and specific star formation rate with stellar mass. We also find that galaxies in this epoch predominantly have strongly rising star formation histories, albeit with the normalization dropping with redshift and stellar mass. In terms of chemical enrichment, we predict a strong stellar mass-metallicity relation present at z = 10 and beyond alongside significant a-enhancement. Finally, we find no large-scale environmental dependence of the relationship between age, specific star formation rate, or metallicity with stellar mass.
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| 14. |
- Wilkins, Stephen M., et al.
(författare)
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First Light and Reionization Epoch Simulations (flares) - XIV. The Balmer/4000 Ã… breaks of distant galaxies
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 527:3, s. 7965-7973
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Tidskriftsartikel (refereegranskat)abstract
- With the successful launch and commissioning of JWST we are now able to routinely spectroscopically probe the rest-frame optical emission of galaxies at z > 6 for the first time. Among the most useful spectral diagnostics used in the optical is the Balmer/4000 & Aring; break; this is, in principle, a diagnostic of the mean ages of composite stellar populations. However, the Balmer break is also sensitive to the shape of the star formation history, the stellar (and gas) metallicity, the presence of nebular continuum emission, and dust attenuation. In this work, we explore the origin of the Balmer/4000 & Aring; break using the SYNTHESIZER synthetic observations package. We then make predictions of the Balmer/4000 & Aring; break using the First Light and Reionization Epoch Simulations at 5 < z < 10. We find that the average break strength weakly correlates with stellar mass and rest-frame far-ultraviolet luminosity, but that this is predominantly driven by dust attenuation. We also find that break strength provides a weak diagnostic of the age but performs better as a means to constrain star formation and stellar mass, alongside the ultraviolet and optical luminosity, respectively.
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