| 1. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 2. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 3. |
- Reyer, Christopher P. O., et al.
(författare)
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A plant's perspective of extremes : terrestrial plant responses to changing climatic variability
- 2013
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Ingår i: Global Change Biology. - HOBOKEN 07030-5774, NJ USA : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 19:1, s. 75-89
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Forskningsöversikt (refereegranskat)abstract
- We review observational, experimental, and model results on how plants respond to extreme climatic conditions induced by changing climatic variability. Distinguishing between impacts of changing mean climatic conditions and changing climatic variability on terrestrial ecosystems is generally underrated in current studies. The goals of our review are thus (1) to identify plant processes that are vulnerable to changes in the variability of climatic variables rather than to changes in their mean, and (2) to depict/evaluate available study designs to quantify responses of plants to changing climatic variability. We find that phenology is largely affected by changing mean climate but also that impacts of climatic variability are much less studied, although potentially damaging. We note that plant water relations seem to be very vulnerable to extremes driven by changes in temperature and precipitation and that heatwaves and flooding have stronger impacts on physiological processes than changing mean climate. Moreover, interacting phenological and physiological processes are likely to further complicate plant responses to changing climatic variability. Phenological and physiological processes and their interactions culminate in even more sophisticated responses to changing mean climate and climatic variability at the species and community level. Generally, observational studies are well suited to study plant responses to changing mean climate, but less suitable to gain a mechanistic understanding of plant responses to climatic variability. Experiments seem best suited to simulate extreme events. In models, temporal resolution and model structure are crucial to capture plant responses to changing climatic variability. We highlight that a combination of experimental, observational, and/or modeling studies have the potential to overcome important caveats of the respective individual approaches.
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| 4. |
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| 5. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 6. |
- Bayha, Luca, et al.
(författare)
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Observing the emergence of a quantum phase transition shell by shell
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7835, s. 583-587
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Tidskriftsartikel (refereegranskat)abstract
- Many-body physics describes phenomena that cannot be understood by looking only at the constituents of a system1. Striking examples are broken symmetry, phase transitions and collective excitations2. To understand how such collective behaviour emerges as a system is gradually assembled from individual particles has been a goal in atomic, nuclear and solid-state physics for decades3–6. Here we observe the few-body precursor of a quantum phase transition from a normal to a superfluid phase. The transition is signalled by the softening of the mode associated with amplitude vibrations of the order parameter, usually referred to as a Higgs mode7. We achieve fine control over ultracold fermions confined to two-dimensional harmonic potentials and prepare closed-shell configurations of 2, 6 and 12 fermionic atoms in the ground state with high fidelity. Spectroscopy is then performed on our mesoscopic system while tuning the pair energy from zero to a value larger than the shell spacing. Using full atom counting statistics, we find the lowest resonance to consist of coherently excited pairs only. The distinct non-monotonic interaction dependence of this many-body excitation, combined with comparison with numerical calculations allows us to identify it as the precursor of the Higgs mode. Our atomic simulator provides a way to study the emergence of collective phenomena and the thermodynamic limit, particle by particle.
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| 7. |
- Billawa, Priyanka, et al.
(författare)
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SoK: Security of Microservice Applications: A Practitioners' Perspective on Challenges and Best Practices
- 2022
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Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM.
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Konferensbidrag (refereegranskat)abstract
- Cloud-based application deployment is becoming increasingly popular among businesses, thanks to the emergence of microservices. However, securing such architectures is a challenging task since traditional security concepts cannot be directly applied to microservice architectures due to their distributed nature. The situation is exacerbated by the scattered nature of guidelines and best practices advocated by practitioners and organizations in this field. In this research paper we aim to shay light over the current microservice security discussions hidden within Grey Literature (GL) sources. Particularly, we identify the challenges that arise when securing microservice architectures, as well as solutions recommended by practitioners to address these issues. For this, we conducted a systematic GL study on the challenges and best practices of microservice security present in the Internet with the goal of capturing relevant discussions in blogs, white papers, and standards. We collected 312 GL sources from which 57 were rigorously classified and analyzed. This analysis on the one hand validated past academic literature studies in the area of microservice security, but it also identified improvements to existing methodologies pointing towards future research directions.
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| 8. |
- Eitel-Amor, Georg, et al.
(författare)
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Hairpin vortices in turbulent boundary layers
- 2015
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Ingår i: Physics of fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 27:2
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Tidskriftsartikel (refereegranskat)abstract
- The present work presents a number of parallel and spatially developing simulations of boundary layers to address the question of whether hairpin vortices are a dominant feature of near-wall turbulence, and which role they play during transition. In the first part, the parent-offspring regeneration mechanism is investigated in parallel (temporal) simulations of a single hairpin vortex introduced in a mean shear flow corresponding to either turbulent channels or boundary layers (Re-tau less than or similar to 590). The effect of a turbulent background superimposed on the mean flow is considered by using an eddy viscosity computed from resolved simulations. Tracking the vortical structure downstream, it is found that secondary hairpins are only created shortly after initialization, with all rotational structures decaying for later times. For hairpins in a clean (laminar) environment, the decay is relatively slow, while hairpins in weak turbulent environments (10% of nu(t)) dissipate after a couple of eddy turnover times. In the second part, the role of hairpin vortices in laminar-turbulent transition is studied using simulations of spatial boundary layers tripped by hairpin vortices. These vortices are generated by means of specific volumetric forces representing an ejection event, creating a synthetic turbulent boundary layer initially dominated by hairpin-like vortices. These hairpins are advected towards the wake region of the boundary layer, while a sinusoidal instability of the streaks near the wall results in rapid development of a turbulent boundary layer. For Re-theta > 400, the boundary layer is fully developed, with no evidence of hairpin vortices reaching into the wall region. The results from both the parallel and spatial simulations strongly suggest that the regeneration process is rather short-lived and may not sustain once a turbulent background is developed. From the transitional flow simulations, it is conjectured that the forest of hairpins reported in former direct numerical simulation studies is reminiscent of the transitional boundary layer and may not be connected to some aspects of the dynamics of the fully developed wall-bounded turbulence.
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| 9. |
- Eitel-Amor, Georg, et al.
(författare)
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Hairpin vortices in turbulent boundary layers
- 2014
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Ingår i: Proceedings 1st Multiflow Summer Workshop. - : IOP Publishing. ; , s. 012008-
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Konferensbidrag (refereegranskat)abstract
- The present work addresses the question whether hairpin vortices are a dominant feature of near-wall turbulence and which role they play during transition. First, the parent-offspring mechanism is investigated in temporal simulations of a single hairpin vortex introduced in a mean shear flow corresponding to turbulent channels and boundary layers up to Re-tau = 590. Using an eddy viscosity computed from resolved simulations, the effect of a turbulent background is also considered. Tracking the vortical structure downstream, it is found that secondary hairpins are created shortly after initialization. Thereafter, all rotational structures decay, whereas this effect is enforced in the presence of an eddy viscosity. In a second approach, a laminar boundary layer is tripped to transition by insertion of a regular pattern of hairpins by means of defined volumetric forces representing an ejection event. The idea is to create a synthetic turbulent boundary layer dominated by hairpin-like vortices. The flow for Re-tau < 250 is analysed with respect to the lifetime of individual hairpin-like vortices. Both the temporal and spatial simulations demonstrate that the regeneration process is rather short-lived and may not sustain once a turbulent background has formed. From the transitional flow simulations, it is conjectured that the forest of hairpins reported in former DNS studies is an outer layer phenomenon not being connected to the onset of near-wall turbulence.
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| 10. |
- Eitel-Amor, Georg, et al.
(författare)
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Simulation and validation of a spatially evolving turbulent boundary layer up to Reθ = 8300
- 2014
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Ingår i: International Journal of Heat and Fluid Flow. - : Elsevier BV. - 0142-727X .- 1879-2278. ; 47, s. 57-69
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Tidskriftsartikel (refereegranskat)abstract
- Results of a finely resolved large-eddy simulation (LES) of a spatially developing zero-pressure-gradient turbulent boundary layer up to a Reynolds number of Reθ = 8300 are presented. The very long computational domain provides substantial assessment for suggested high Reynolds number (Re) trends. Statistics, integral quantities and spectral data are validated using high quality direct numerical simulation (DNS) ranging up to Reθ = 4300 and hot-wire measurements covering the remaining Re-range. The mean velocity, turbulent fluctuations, skin friction, and shape factor show excellent agreement with the reference data. Through utilisation of filtered DNS, subtle differences between the LES and DNS could to a large extent be explained by the reduced spanwise resolution of the LES. Spectra and correlations for the streamwise velocity and the wall-shear stress evidence a clear scale-separation and a footprint of large outer scales on the near-wall small scales. While the inner peak decreases in importance and reduces to 4% of the total energy at the end of the domain, the energy of the outer peak scales in outer units. In the near-wall region a clear k - 1 region emerges. Consideration of the two-dimensional spectra in time and spanwise space reveals that an outer time scale λt ≈ 10δ99 / U∞, with the boundary layer thickness δ99 and free-stream velocity U∞, is the correct scale throughout the boundary layer rather than the transformed streamwise wavelength multiplied by a (scale independent) convection velocity. Maps for the covariance of small scale energy and large scale motions exhibit a stronger linear Re dependence for the amplitude of the off-diagonal peak compared to the diagonal one, thereby indicating that the strength of the amplitude modulation can only qualitatively be assessed through the diagonal peak. In addition, the magnitude of the wall-pressure fluctuations confirms mixed scaling, and pressure spectra at the highest Re give a first indication of a -7/3 wave number dependence.
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