| 1. |
- Baum, Seth D., et al.
(författare)
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Long-term trajectories of human civilization
- 2019
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Ingår i: Foresight. - : Emerald Group Publishing Limited. - 1463-6689 .- 1465-9832. ; 21:11, s. 53-83
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This paper aims to formalize long-term trajectories of human civilization as a scientific and ethical field of study. The long-term trajectory of human civilization can be defined as the path that human civilization takes during the entire future time period in which human civilization could continue to exist. Design/methodology/approach: This paper focuses on four types of trajectories: status quo trajectories, in which human civilization persists in a state broadly similar to its current state into the distant future; catastrophe trajectories, in which one or more events cause significant harm to human civilization; technological transformation trajectories, in which radical technological breakthroughs put human civilization on a fundamentally different course; and astronomical trajectories, in which human civilization expands beyond its home planet and into the accessible portions of the cosmos. Findings: Status quo trajectories appear unlikely to persist into the distant future, especially in light of long-term astronomical processes. Several catastrophe, technological transformation and astronomical trajectories appear possible. Originality/value: Some current actions may be able to affect the long-term trajectory. Whether these actions should be pursued depends on a mix of empirical and ethical factors. For some ethical frameworks, these actions may be especially important to pursue.
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| 2. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 3. |
- Brum, Wagner S., et al.
(författare)
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Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:2, s. 1284-1297
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data. METHODS: We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CVI) and between-subject (CVG) BV, analytical variation, and reference change values (RCV). RESULTS: Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). DISCUSSION: BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.
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| 4. |
- Brunberg, Emma, et al.
(författare)
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A missense mutation in PMEL17 is associated with the Silver coat color in the horse
- 2006
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Ingår i: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 7, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Silver coat color, also called Silver dapple, in the horse is characterized by dilution of the black pigment in the hair. This phenotype shows an autosomal dominant inheritance. The effect of the mutation is most visible in the long hairs of the mane and tail, which are diluted to a mixture of white and gray hairs. Herein we describe the identification of the responsible gene and a missense mutation associated with the Silver phenotype. Results: Segregation data on the Silver locus (Z) were obtained within one half-sib family that consisted of a heterozygous Silver colored stallion with 34 offspring and their 29 non-Silver dams. We typed 41 genetic markers well spread over the horse genome, including one single microsatellite marker (TKY284) close to the candidate gene PMEL17 on horse chromosome 6 (ECA6q23). Significant linkage was found between the Silver phenotype and TKY284 (theta = 0, z = 9.0). DNA sequencing of PMEL17 in Silver and non-Silver horses revealed a missense mutation in exon 11 changing the second amino acid in the cytoplasmic region from arginine to cysteine (Arg618Cys). This mutation showed complete association with the Silver phenotype across multiple horse breeds, and was not found among non-Silver horses with one clear exception; a chestnut colored individual that had several Silver offspring when mated to different non-Silver stallions also carried the exon 11 mutation. In total, 64 Silver horses from six breeds and 85 non-Silver horses from 14 breeds were tested for the exon 11 mutation. One additional mutation located in intron 9, only 759 bases from the missense mutation, also showed complete association with the Silver phenotype. However, as one could expect to find several non-causative mutations completely associated with the Silver mutation, we argue that the missense mutation is more likely to be causative. Conclusion: The present study shows that PMEL17 causes the Silver coat color in the horse and enable genetic testing for this trait.
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| 5. |
- Hänninen, Kaj, et al.
(författare)
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Framework for Real-Time Analysis in Rubus-ICE
- 2008
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Ingår i: 2008 IEEE INTERNATIONAL CONFERENCE ON EMERGING TECHNOLOGIES AND FACTORY AUTOMATION, PROCEEDINGS. - 9781424415052 ; , s. 782-788
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Konferensbidrag (refereegranskat)abstract
- In this paper we present the development of a plug-in framework for integration of real-time analysis methods in the Rubus Integrated Component Environment (Rubus-ICE). We also present the implementation, and evaluate the integration, of two state of the art analysis techniques (i) response-time analysis for tasks with offsets and (ii) shared stack analysis, as plug-ins, in the Rubus-ICE framework. The paper shows that the proposed framework is well suited for integration of complex analysis methods. However experience also show that analysis methods are not easily transferred from an academic environment to industry. The main reason for this, we believe, originates from differences in requirements and assumptions between industry and academia.
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| 6. |
- Hänninen, Kaj, et al.
(författare)
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Introducing a Plug-In Framework for Real-Time Analysis in Rubus-ICE
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we present the development of a plug-in framework for integration of real-time analysis methods in the Rubus Integrated Component Environment (Rubus-ICE). We also present the implementation, and evaluate the integration, of two state of the art analysis techniques (i) response-time analysis for tasks with offsets and (ii) shared stack analysis, as plug-ins, in the Rubus-ICE framework.The paper shows that the proposed framework is well suited for integration of complex analysis methods. However, experience also show that analysis methods are not easily transferred from an academic environment to industry. The main reason for this, we believe, originates from differences in requirements and assumptions between industry and academia.
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| 7. |
- Lindgren, Gabriella, et al.
(författare)
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Limited number of patrilines in horse domestication.
- 2004
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 36:4
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies using mitochondrial DNA (mtDNA) have identified extensive matrilinear diversity among domestic horses. Here, we show that this high degree of polymorphism is not matched by a corresponding patrilinear diversity of the male-specific Y chromosome. In fact, a screening for single-nucleotide polymorphisms (SNPs) in 14.3 kb of noncoding Y chromosome sequence among 52 male horses of 15 different breeds did not identify a single segregation site. These observations are consistent with a strong sex-bias in the domestication process, with few stallions contributing genetically to the domestic horse.
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| 8. |
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| 9. |
- Pielberg, Gerli Rosengren, et al.
(författare)
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A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:8, s. 1004-1009
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Tidskriftsartikel (refereegranskat)abstract
- In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals.
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| 10. |
- Zackrisson, Erik, et al.
(författare)
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Hunting for dark halo substructure using submilliarcsecond-scale observations of macrolensed radio jets
- 2013
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 431:3, s. 2172-2183
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Tidskriftsartikel (refereegranskat)abstract
- Dark halo substructure may reveal itself through secondary, small-scale gravitational lensing effects on light sources that are macrolensed by a foreground galaxy. Here, we explore the prospects of using Very Long Baseline Interferometry (VLBI) observations of multiply-imaged quasar jets to search for submilliarcsecond-scale image distortions produced by various forms of dark substructures in the 10(3)-10(8) M-circle dot mass range. We present lensing simulations relevant for the angular resolutions attainable with the existing European VLBI Network, the global VLBI array and an upcoming observing mode in which the Atacama Large Millimeter Array (ALMA) is connected to the global VLBI array. While observations of this type would not be sensitive to standard cold dark matter subhaloes, they can be used to detect the more compact forms of halo substructure predicted in alternative structure formation scenarios. By mapping approximately five strongly lensed systems, it should be possible to detect or robustly rule out primordial black holes in the 10(3)-10(6) M-circle dot mass range if they constitute greater than or similar to 1 per cent of the dark matter in these lenses. Ultracompact minihaloes are harder to detect using this technique, but 10(6)-10(8) M-circle dot ultracompact minihaloes could in principle be detected if they constitute greater than or similar to 10 per cent of the dark matter.
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