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5-HT1A targeting PARCEST agent DO3AM-MPP with potential for receptor imaging : Synthesis, physico-chemical and MR studies
- 2021
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Ingår i: Bioorganic chemistry. - : Elsevier. - 0045-2068. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- Contrast enhancement in MRI using magnetization or saturation transfer techniques promises better sensitivity, and faster acquisition compared to T-1 or T-2 contrast. This work reports the synthesis and evaluation of 5-HT1A targeted PARACEST MRI contrast agent using 1,4,7,10-tetraazacycloDOdecane-4,7,10-triacetAMide (DO3AM) as the bifunctional chelator, and 5-HT1A-antagonist methoxyphenyl piperazine (MPP) as a targeting unit. The multistep synthesis led to the MPP conjugated DO3AM with 60% yield. CEST-related physicochemical parameters were evaluated after loading DO3AM-MPP with paramagnetic MRI active lanthanides: Gadolinium (Gd-DO3AM-MPP) and Europium (Eu-DO3AM-MPP). Luminescence lifetime measurements with Eu-DO3AM-MPP and computational DFT studies using Gd-DO3AM-MPP revealed the coordination of one water molecule (q = 1.43) with metal-water distance (r(M)-H2O) of 2.7 angstrom and water residence time (tau(m)) of 0.23 ms. The dissociation constant of K-d 62 +/- 0.02 pM as evaluated from fluorescence quenching of 5-HT1A (protein) and docking score of -4.81 in theoretical evaluation reflect the binding potential of the complex Gd-DO3AM-MPP with the receptor 5-HT1A. Insights of the docked pose reflect the importance of NH2 (amide) and aromatic ring in Gd-DO3AM-MPP while interacting with Ser 374 and Phe 370 in the antagonist binding pocket of 5-HT1A. Gd-DO3AM-MPP shows longitudinal relaxivity 5.85 mM(-1)s(-1) with a water residence lifetime of 0.93 ms in hippocampal homogenate containing 5-HT1A. The potentiometric titration of DO3AM-MPP showed strong selectivity for Gd3+ over physiological metal ions such as Zn2+ and Cu2+. The in vitro and in vivo studies confirmed the minimal cytotoxicity and presential binding of Gd-DO3AM-MPP with 5-HT1A receptor in the hippocampus region of the mice. Summarizing, the complex Gd-DO3AM-MPP can have a potential for CEST imaging of 5-HT1A receptors.
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| 2. |
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A Constructive Critique of Religion. : Encounters between Christianity, Islam, and Non-religion in Secular Societies
- 2020. - 1
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- Why do some strategies for critique of religion seem to be more beneficial for constructive engagement, whereas others increase intolerance, polarization, and conflict?Through an analysis of the reasons underpinning a critique of religion in institutional contexts of secular democratic societies, A Constructive Critique of Religion explores how constructive interaction and critique can be developed across diverse interests. It shows how social and cultural conditions shaping these institutions enable and structure a critical and constructive engagement across diverging worldviews.A key argument running through the book is that to develop constructive forms of critique a more thorough and systematic investigation of resources for criticism located within religious worldviews themselves is needed. Chapters also address how critique of Islam and Christianity in particular is expressed in areas such as academia, the law, politics, media, education and parenting, with a focus on Northern Europe and North America. The interdisciplinary approach, which combines theoretical perspectives with empirical case studies, contributes to advancing studies of the complex and contentious character of religion in contemporary society.
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| 4. |
- Aad, G, et al.
(författare)
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Alignment of the ATLAS Inner Detector in Run 2
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:12
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Tidskriftsartikel (refereegranskat)abstract
- The performance of the ATLAS Inner Detector alignment has been studied using pp collision data at s=13TeV collected by the ATLAS experiment during Run 2 (2015–2018) of the Large Hadron Collider (LHC). The goal of the detector alignment is to determine the detector geometry as accurately as possible and correct for time-dependent movements. The Inner Detector alignment is based on the minimization of track-hit residuals in a sequence of hierarchical levels, from global mechanical assembly structures to local sensors. Subsequent levels have increasing numbers of degrees of freedom; in total there are almost 750,000. The alignment determines detector geometry on both short and long timescales, where short timescales describe movements within an LHC fill. The performance and possible track parameter biases originating from systematic detector deformations are evaluated. Momentum biases are studied using resonances decaying to muons or to electrons. The residual sagitta bias and momentum scale bias after alignment are reduced to less than ∼0.1TeV-1 and 0.9 × 10 - 3, respectively. Impact parameter biases are also evaluated using tracks within jets. © 2020, The Author(s).
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| 5. |
- Aad, G, et al.
(författare)
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ATLAS data quality operations and performance for 2015-2018 data-taking
- 2020
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS detector at the Large Hadron Collider reads out particle collision data from over 100 million electronic channels at a rate of approximately 100 kHz, with a recording rate for physics events of approximately 1 kHz. Before being certified for physics analysis at computer centres worldwide, the data must be scrutinised to ensure they are clean from any hardware or software related issues that may compromise their integrity. Prompt identification of these issues permits fast action to investigate, correct and potentially prevent future such problems that could render the data unusable. This is achieved through the monitoring of detector-level quantities and reconstructed collision event characteristics at key stages of the data processing chain. This paper presents the monitoring and assessment procedures in place at ATLAS during 2015-2018 data-taking. Through the continuous improvement of operational procedures, ATLAS achieved a high data quality efficiency, with 95.6% of the recorded proton-proton collision data collected at s=13 TeV certified for physics analysis.
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| 6. |
- Aad, G, et al.
(författare)
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Combination of searches for Higgs boson pairs in pp collisions at s=13TeV with the ATLAS detector
- 2020
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 800
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Tidskriftsartikel (refereegranskat)abstract
- This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb−1 of proton–proton collision data at a centre-of-mass energy s=13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the bb¯bb¯, bb¯W+W−, bb¯τ+τ−, W+W−W+W−, bb¯γγ and W+W−γγ final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (κλ) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to −5.0
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| 7. |
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| 8. |
- Aad, G, et al.
(författare)
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Combined measurements of Higgs boson production and decay using up to 80 fb-1 of proton-proton collision data at s =13 TeV collected with the ATLAS experiment
- 2020
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 1550-2368. ; 101:1
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Tidskriftsartikel (refereegranskat)abstract
- Combined measurements of Higgs boson production cross sections and branching fractions are presented. The combination is based on the analyses of the Higgs boson decay modes H→γγ, ZZ∗, WW∗, ττ, bb, μμ, searches for decays into invisible final states, and on measurements of off-shell Higgs boson production. Up to 79.8 fb-1 of proton-proton collision data collected at s=13 TeV with the ATLAS detector are used. Results are presented for the gluon-gluon fusion and vector-boson fusion processes, and for associated production with vector bosons or top-quarks. The global signal strength is determined to be μ=1.11-0.08+0.09. The combined measurement yields an observed (expected) significance for the vector-boson fusion production process of 6.5σ (5.3σ). Measurements in kinematic regions defined within the simplified template cross section framework are also shown. The results are interpreted in terms of modifiers applied to the Standard Model couplings of the Higgs boson to other particles, and are used to set exclusion limits on parameters in two-Higgs-doublet models and in the simplified minimal supersymmetric Standard Model. No significant deviations from Standard Model predictions are observed. © 2020 CERN. © 2020 CERN, for the ATLAS Collaboration. Published by the American Physical Society under the terms of the "https://creativecommons.org/licenses/by/4.0/" Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI. Funded by SCOAP3.
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| 9. |
- Aad, G, et al.
(författare)
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Differential cross-section measurements for the electroweak production of dijets in association with a Z boson in proton–proton collisions at ATLAS
- 2021
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 81:2
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Tidskriftsartikel (refereegranskat)abstract
- Differential cross-section measurements are presented for the electroweak production of two jets in association with a Z boson. These measurements are sensitive to the vector-boson fusion production mechanism and provide a fundamental test of the gauge structure of the Standard Model. The analysis is performed using proton–proton collision data collected by ATLAS at s=13TeV and with an integrated luminosity of 139fb-1. The differential cross-sections are measured in the Z→ ℓ+ℓ- decay channel (ℓ= e, μ) as a function of four observables: the dijet invariant mass, the rapidity interval spanned by the two jets, the signed azimuthal angle between the two jets, and the transverse momentum of the dilepton pair. The data are corrected for the effects of detector inefficiency and resolution and are sufficiently precise to distinguish between different state-of-the-art theoretical predictions calculated using Powheg+Pythia8, Herwig7+Vbfnlo and Sherpa 2.2. The differential cross-sections are used to search for anomalous weak-boson self-interactions using a dimension-six effective field theory. The measurement of the signed azimuthal angle between the two jets is found to be particularly sensitive to the interference between the Standard Model and dimension-six scattering amplitudes and provides a direct test of charge-conjugation and parity invariance in the weak-boson self-interactions. © 2020, The Author(s).
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| 10. |
- Aad, G, et al.
(författare)
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Dijet Resonance Search with Weak Supervision Using s =13 TeV pp Collisions in the ATLAS Detector
- 2020
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Ingår i: Physical Review Letters. - : American Physical Society (APS). - 1079-7114 .- 0031-9007. ; 125:13
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Tidskriftsartikel (refereegranskat)abstract
- This Letter describes a search for narrowly resonant new physics using a machine-learning anomaly detection procedure that does not rely on signal simulations for developing the analysis selection. Weakly supervised learning is used to train classifiers directly on data to enhance potential signals. The targeted topology is dijet events and the features used for machine learning are the masses of the two jets. The resulting analysis is essentially a three-dimensional search A→BC, for mA∼O(TeV), mB,mC∼O(100 GeV) and B, C are reconstructed as large-radius jets, without paying a penalty associated with a large trials factor in the scan of the masses of the two jets. The full run 2 s=13 TeV pp collision dataset of 139 fb-1 recorded by the ATLAS detector at the Large Hadron Collider is used for the search. There is no significant evidence of a localized excess in the dijet invariant mass spectrum between 1.8 and 8.2 TeV. Cross-section limits for narrow-width A, B, and C particles vary with mA, mB, and mC. For example, when mA=3 TeV and mBâ200 GeV, a production cross section between 1 and 5 fb is excluded at 95% confidence level, depending on mC. For certain masses, these limits are up to 10 times more sensitive than those obtained by the inclusive dijet search. These results are complementary to the dedicated searches for the case that B and C are standard model bosons. © 2020 CERN.
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