| 1. |
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| 2. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Gregson, J., et al.
(author)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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In: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Journal article (peer-reviewed)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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| 4. |
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| 5. |
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| 6. |
- Kuderna, Lukas F. K., et al.
(author)
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Identification of constrained sequence elements across 239 primate genomes
- 2024
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
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Journal article (peer-reviewed)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 7. |
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| 8. |
- Graham, N. S. N., et al.
(author)
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Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury
- 2021
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:613
-
Journal article (peer-reviewed)abstract
- Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Gao, Hong, et al.
(author)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
-
Journal article (peer-reviewed)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 15. |
- Kuderna, Lukas F. K., et al.
(author)
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A global catalog of whole-genome diversity from 233 primate species
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
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Journal article (peer-reviewed)abstract
- The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
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| 16. |
- Rodriguez, Sébastien, et al.
(author)
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Science goals and new mission concepts for future exploration of Titan's atmosphere, geology and habitability : titan POlar scout/orbitEr and in situ lake lander and DrONe explorer (POSEIDON)
- 2022
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 54:2-3, s. 911-973
-
Journal article (peer-reviewed)abstract
- In response to ESA’s “Voyage 2050” announcement of opportunity, we propose an ambitious L-class mission to explore one of the most exciting bodies in the Solar System, Saturn’s largest moon Titan. Titan, a “world with two oceans”, is an organic-rich body with interior-surface-atmosphere interactions that are comparable in complexity to the Earth. Titan is also one of the few places in the Solar System with habitability potential. Titan’s remarkable nature was only partly revealed by the Cassini-Huygens mission and still holds mysteries requiring a complete exploration using a variety of vehicles and instruments. The proposed mission concept POSEIDON (Titan POlar Scout/orbitEr and In situ lake lander DrONe explorer) would perform joint orbital and in situ investigations of Titan. It is designed to build on and exceed the scope and scientific/technological accomplishments of Cassini-Huygens, exploring Titan in ways that were not previously possible, in particular through full close-up and in situ coverage over long periods of time. In the proposed mission architecture, POSEIDON consists of two major elements: a spacecraft with a large set of instruments that would orbit Titan, preferably in a low-eccentricity polar orbit, and a suite of in situ investigation components, i.e. a lake lander, a “heavy” drone (possibly amphibious) and/or a fleet of mini-drones, dedicated to the exploration of the polar regions. The ideal arrival time at Titan would be slightly before the next northern Spring equinox (2039), as equinoxes are the most active periods to monitor still largely unknown atmospheric and surface seasonal changes. The exploration of Titan’s northern latitudes with an orbiter and in situ element(s) would be highly complementary in terms of timing (with possible mission timing overlap), locations, and science goals with the upcoming NASA New Frontiers Dragonfly mission that will provide in situ exploration of Titan’s equatorial regions, in the mid-2030s.
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| 17. |
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| 18. |
- Bakesiima, Ritah, et al.
(author)
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Modern contraceptive use among female refugee adolescents in northern Uganda : prevalence and associated factors
- 2020
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In: Reproductive Health. - : BioMed Central. - 1742-4755. ; 17:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Adolescent pregnancies are persistently high among refugees. The pregnancies have been attributed to low contraceptive use in this population. The aim of this study was to determine the prevalence and factors associated with modern contraceptive use among female refugee adolescents in northern Uganda.METHODS: This was a cross sectional study using both descriptive and analytical techniques. The study was carried out in Palabek refugee settlement in Northern Uganda from May to July 2019. A total of 839 refugee adolescents who were sexually active or in-union were consecutively enrolled. Interviewer administered questionnaires were used for data collection.RESULTS: Modern contraceptive prevalence was 8.7% (95% CI: 7.0 to 10.8). The injectable was the most commonly used modern contraceptive method [42.5% (95% CI: 31.5 to 54.3)], and most of the participants had used the contraceptives for 6 months or less (59.7%). Reasons for not using modern contraceptives included fear of side effects (39.3%), partner prohibition (16.4%), and the desire to become pregnant (7.0%). Participants who were married (OR = 0.11, 95% CI: 0.04 to 0.35, p < 0.001), cohabiting (OR = 0.43, 95% CI: 0.20 to 0.93, p = 0.032) or having an older partner (OR = 0.93, 95% CI: 0.86 to 0.99, p = 0.046) were less likely to use modern contraceptives.CONCLUSION: Modern contraceptive use among female refugee adolescents was very low, and few reported a desire to become pregnant, leaving them vulnerable to unplanned pregnancies. Least likely to use modern contraceptives were participants who were married/cohabiting and those having older partners implying a gender power imbalance in fertility decision making. There is an urgent need for innovations to address the gender and power imbalances within relationships, which could shape fertility decision-making and increase modern contraceptive use among refugee adolescents.
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| 19. |
- Callaghan, TV, et al.
(author)
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Key findings and extended summaries
- 2004
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In: Ambio: a Journal of Human Environment. - 0044-7447. ; 33:7, s. 386-392
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Journal article (peer-reviewed)
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| 20. |
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| 21. |
- Eapen, Mathew Suji, et al.
(author)
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Chronic Obstructive Pulmonary Disease and Lung Cancer : Underlying Pathophysiology and New Therapeutic Modalities
- 2018
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In: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 78:16, s. 1717-1740
-
Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship.
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| 22. |
- Gerstung, M, et al.
(author)
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The evolutionary history of 2,658 cancers
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 122-
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Journal article (peer-reviewed)abstract
- Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
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| 23. |
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| 24. |
- Johnson, Candice, et al.
(author)
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Skin sensitization in silico protocol
- 2020
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In: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 116
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Journal article (peer-reviewed)abstract
- The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducing a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.
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| 25. |
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| 26. |
- Jones, C. A., et al.
(author)
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A mathematical examination of the impact of mould transparency to infrared radiation on solidification during the investment casting process
- 2023
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In: IOP Conference Series. - : Institute of Physics (IOP). - 1757-8981 .- 1757-899X. ; 1281:1
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Journal article (peer-reviewed)abstract
- Investment casting is a highly dynamic process during which multiple competing physical phenomena are at work. Those seeking to understand and simulate such processes computationally are confronted with a considerable task, balancing accuracy with efficiency. Approximations and models based on well-understood and documented fundamental physics are powerful tools in a modeller’s arsenal. Driven by observed discrepancies between experimental thermocouple measurements and simulation predictions of casting temperatures, this work explores the additional alloy cooling mechanism of mould transparency to infrared radiation, targeting a new mathematical approximation applicable in such situations. Direct attenuation, scattering from coarse sand, sand distribution in the mould and material temperatures play a role in the extent of radiation transparency that must be considered. From this model, estimation of the additional cooling rate resulting from expected mould transparency can be determined and applied as a corrective measure to computation fluid dynamics (CFD) simulation results that do not capture this phenomenon.
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| 27. |
- Jones, C. A., et al.
(author)
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A verification of thermophysical properties of a porous ceramic investment casting mould using commercial computational fluid dynamics software
- 2020
-
In: IOP Conference Series. - : Institute of Physics Publishing.
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Conference paper (peer-reviewed)abstract
- Defects in cast metals remain a common problem in many areas of the foundry industry, particularly in the investment casting of large area, thin-walled components for aerospace applications. During previous research, the thermophysical properties, density and porosity of a fibre reinforced ceramic investment casting mould were determined using several experimental techniques. Without verification, these experimental results remain nothing more than educated guesswork. The purpose of this study is to verify previous results and to more fully characterise the ceramic mould material with complementary measurements. A commercially available computational fluid dynamic (CFD) simulation package, Flow-3D®, was used in conjunction with a full-scale Ni-superalloy (IN718) casting to assess the accuracy of these results. By placing thermocouples strategically across the mould thickness, temperature profiles were determined and compared directly to predicted profiles extracted from the simulation by a custom-written Python script.
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| 28. |
- Jones, C. A., et al.
(author)
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An experimental characterization of thermophysical properties of a porous ceramic shell used in the investment casting process
- 2020
-
In: TMS 2020 149th Annual Meeting & Exhibition Supplemental Proceedings. - Cham : Springer. - 9783030362959 ; , s. 1095-1105
-
Conference paper (peer-reviewed)abstract
- This study presents the results of an investigation that characterises the thermophysical properties of an investment casting mould, comprising of a Zirconium dioxide/Cobalt aluminate prime slurry and a fused Silica/fibre reinforced backup slurry. Growing prevalence of successful computer simulations within the foundry industry enables defects that emerge during the casting process to become increasingly predictable, providing cost-effective alternatives to trial castings. The viability of these simulations as predictors is heavily dependent upon the facilitation of accurate material property data, as attained through this investigation. Differential scanning calorimetry (DSC) and laser flash analysis (LFA) were utilized to determine the specific heat capacity and thermal diffusivity, respectively. These values, in combination with the material density and linear coefficient of thermal expansion, have been used to determine the thermal conductivity of the mould. With the aim of verifying these parameters, initial studies in Flow-3D® simulation software have been performed to determine the constraints needed to reduce variability in simulation parameters. Due to the diversity of casting moulds used throughout the industry, ensuring the material database is kept as comprehensively populated as possible is a crucial undertaking.
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| 29. |
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| 30. |
- Ruggeri, Kai, et al.
(author)
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The globalizability of temporal discounting
- 2022
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In: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397
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Journal article (peer-reviewed)abstract
- Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
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| 31. |
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| 32. |
- Scott, Gregory, et al.
(author)
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Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration.
- 2018
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 1460-2156. ; 141:2, s. 459-471
-
Journal article (peer-reviewed)abstract
- Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = -23.30%, 95% confidence interval -40.9 to -5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.
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| 33. |
- Sun, Fengwu, et al.
(author)
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Extensive Lensing Survey of Optical and Near-infrared Dark Objects (El Sonido): HST H-faint Galaxies behind 101 Lensing Clusters
- 2021
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 922:2
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Journal article (peer-reviewed)abstract
- We present a Spitzer/IRAC survey of H-faint (H-160 greater than or similar to 26.4, < 5 sigma) sources in 101 lensing cluster fields. Across a CANDELS/Wide-like survey area of similar to 648 arcmin(2) (effectively similar to 221 arcmin(2) in the source plane), we have securely discovered 53 sources in the IRAC Channel-2 band (CH2, 4.5 mu m; median CH2 = 22.46 +/- 0.11 AB mag) that lack robust HST/WFC3-IR F160W counterparts. The most remarkable source in our sample, namely ES-009 in the field of Abell 2813, is the brightest H-faint galaxy at 4.5 mu m known so far (CH2 = 20.48 +/- 0.03 AB mag). We show that the H-faint sources in our sample are massive (median M-star = 10 10.3 +/- 0.3 M-circle dot, star-forming (median star formation rate =1001 M-circle dot yr(-1)), and dust-obscured (A(v) = 2.6 +/- 0.3) galaxies around a median photometric redshift of z = 3.9 +/- 0.4. The stellar continua of 14 H-faint galaxies can be resolved in the CH2 band, suggesting a median circularized effective radius (R-e,R-circ; lensing corrected) of 1.9 +/- 0.2 kpc and <1.5 kpc for the resolved and whole samples, respectively. This is consistent with the sizes of massive unobscured galaxies at z similar to 4, indicating that H-faint galaxies represent the dusty tail of the distribution of a wider galaxy population. Comparing with the ALMA dust continuum sizes of similar galaxies reported previously, we conclude that the heavy dust obscuration in H-faint galaxies is related to the compactness of both stellar and dust continua (R-e,R-circ similar to 1 kpc). These H-faint galaxies make up 161 3 % of the galaxies in the stellar-mass range of 10(10) - 10(11.2) M-circle dot at z = 3 similar to 5, contributing to 8(-4)(+8)% of the cosmic star formation rate density in this epoch and likely tracing the early phase of massive galaxy formation.
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| 34. |
- Zwickl, Craig M., et al.
(author)
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Principles and procedures for assessment of acute toxicity incorporating in silico methods
- 2022
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In: COMPUTATIONAL TOXICOLOGY. - : Elsevier. - 2468-1113. ; 24
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Journal article (peer-reviewed)abstract
- Acute toxicity in silico models are being used to support an increasing number of application areas including (1) product research and development, (2) product approval and registration as well as (3) the transport, storage and handling of chemicals. The adoption of such models is being hindered, in part, because of a lack of guidance describing how to perform and document an in silico analysis. To address this issue, a framework for an acute toxicity hazard assessment is proposed. This framework combines results from different sources including in silico methods and in vitro or in vivo experiments. In silico methods that can assist the prediction of in vivo outcomes (i.e., LD50) are analyzed concluding that predictions obtained using in silico approaches are now well-suited for reliably supporting assessment of LD50- based acute toxicity for the purpose of the Globally Harmonized System (GHS) classification. A general overview is provided of the endpoints from in vitro studies commonly evaluated for predicting acute toxicity (e.g., cytotoxicity/cytolethality as well as assays targeting specific mechanisms). The increased understanding of pathways and key triggering mechanisms underlying toxicity and the increased availability of in vitro data allow for a shift away from assessments solely based on endpoints such as LD50, to mechanism-based endpoints that can be accurately assessed in vitro or by using in silico prediction models. This paper also highlights the importance of an expert review of all available information using weight-of-evidence considerations and illustrates, using a series of diverse practical use cases, how in silico approaches support the assessment of acute toxicity.
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