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- Aprile, E., et al.
(författare)
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Effective Field Theory and Inelastic Dark Matter Results from XENON1T
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this work we expand on the XENON1T nuclear recoil searches and study the individual signals of Dark Matter interactions from operators up to dimension-eight in a Chiral Effective Field Theory (ChEFT) as well as a model of inelastic Dark Matter using data from the two science runs of the detector totalling 1 tonne*year exposure. For these analyses we extended the region of interest from [4.9, 40.9]keVnr to [4.9, 54.4]keVnr to enhance our sensitivity for signals that peak at nonzero energies. We show that the data is consistent with a background only hypothesis, with small excesses in the models which peak between 20 and 50keVnr, obtaining a maximum local discovery significance of 1.7 for the VVs ChEFT model for a WIMP mass of 70GeV/c2, and 1.8 for an iDM particle of 50GeV/c2 with a mass splitting of 100keV/c2. For each model we report 90% confidence level upper limits. We also report limits on three benchmark models of WIMP interaction using ChEFT for which we investigate the effect of isospin breaking interactions, reporting up to 6 orders of magnitude weaker limits with respect to the isospin conserving case driven by cancellations in the expected rate.
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| 2. |
- Hoffmann, Thomas J, et al.
(författare)
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Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.
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| 3. |
- Martinsson, I, et al.
(författare)
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Aβ/APP-induced hyperexcitability and dysregulation of homeostatic synaptic plasticity in models of Alzheimer’s disease
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The proper function of the nervous system is dependent on the appropriate timing of neuronal firing. Synapses continually undergo rapid activity-dependent modifications that require feedback mechanisms to maintain network activity within a window in which communication is energy efficient and meaningful. Homeostatic synaptic plasticity (HSP) and homeostatic intrinsic plasticity (HIP) are such negative feedback mechanisms. Accumulating evidence implicates that Alzheimer’s disease (AD)-related amyloid precursor protein (APP) and its cleavage product amyloid-beta (Aβ) play a role in the regulation of neuronal network activity, and in particular HSP. AD features impaired neuronal activity with regional early hyper-activity and Aβ-dependent hyperexcitability has also been demonstrated in AD transgenic mice. We demonstrate similar hyper-activity in AD transgenic neurons in culture that have elevated levels of both human APP and Aβ. To examine the individual roles of APP and Aβ in promoting hyperexcitability we used an APP construct that does not generate Aβ, or elevated Aβ levels independently of APP. Increasing either APP or Aβ in wild type (WT) neurons leads to increased frequency and amplitude of calcium transients. Since HSP/HIP mechanisms normally maintain a setpoint of activity, we examined whether homeostatic synaptic/intrinsic plasticity was altered in AD transgenic neurons. Using methods known to induce HSP/HIP, we demonstrate that APP protein levels are regulated by chronic modulation of activity and show that AD transgenic neurons have an impaired response to global changes in activity. Further, AD transgenic compared to WT neurons failed to adjust the length of their axon initial segments (AIS), an adaptation known to alter excitability. Thus, we present evidence that both APP and Aβ influence neuronal activity and that mechanisms of HSP/HIP are disrupted in neuronal models of AD.Competing Interest StatementThe authors have declared no competing interest.
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| 4. |
- Cosar, Ahmet Kerem, et al.
(författare)
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What Drives Home Market Advantage?
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In the automobile industry, as in many tradable goods markets, firms earn their highest market share within their domestic market. This home market advantage persists despite substantial integration of international markets during the past several decades. The goal of this paper is to quantify the supply- and demand-driven sources of the home market advantage and to understand their implications for international trade and investment. Building on the random coefficients demand model developed by Berry, Levinsohn, and Pakes (1995), we estimate demand and supply in the automobile industry for nine countries across three continents, allowing for unobserved taste and cost variation at the car model and market levels. While trade and foreign production costs as well as taste heterogeneity matter for market outcomes, we find that preference for domestic brands is the single most important driver of home market advantage - even after controlling for brand histories and dealer networks.
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| 8. |
- Li, Zhe, 1987-, et al.
(författare)
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A strategic screening approach to identify transformation products of organic micropollutants along rivers
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Many transformation products (TPs) from organic micropollutants are not included in routine monitoring programs due to limited knowledge of their occurrence and fate. An efficient method to identify and prioritize critical compounds in terms of environmental relevance is needed. In this study we applied a strategic screening approach based on a case-control concept to identify TPs with an increasing trend along a stretch in four wastewater-impacted rivers. Time-integrated samples were taken over one week at both ends of a river stretch downstream of a wastewater treatment plant (WWTP) outfall. The screening procedure consisted of three major steps: i) screening for parent compounds (PCs) attenuating along the stretch; ii) prediction of TPs for these PCs; and iii) screening for TPs with an increasing trend along the stretch. In total, 48 organic micropollutants were tentatively identified, of which 32 were decreasing along the stretches. From these PCs, 1315 TPs were predicted and eight out of which were tentatively identified with increasing concentrations along the stretches. Generally, good correlations were observed between the suspect screening results from this study and previous target analysis results on the same samples, suggesting high confidence of our screening approach. The case-control concept was proven efficient and reliable for identifying environmental relevant TPs formed along rivers.
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| 9. |
- Repetto, Linda, et al.
(författare)
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Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
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