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Sökning: WAKA:ref > Uppsala universitet

  • Resultat 1-10 av 160357
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  • 5-HT1A targeting PARCEST agent DO3AM-MPP with potential for receptor imaging : Synthesis, physico-chemical and MR studies
  • 2021
  • Ingår i: Bioorganic chemistry. - : Elsevier. - 0045-2068. ; 106
  • 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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  • A Constructive Critique of Religion. : Encounters between Christianity, Islam, and Non-religion in Secular Societies
  • 2020. - 1
  • 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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  • A design of high performance gas sensor array withdiscrete islands of Au catalyst for increasing of ZnO nanowire junctions
  • 2013
  • Proceedings (redaktörskap) (refereegranskat)abstract
    • In this study, an effective design for growth of ZnO nanowires directly on gas sensor chips is introduced. The design utilizes the dendrite islands of Au catalyst deposited between and on the Pt electrodes for the nanowires to grow on instead of a continuous seed layer or Au film. This lead to an increase of the nanowirenanowire junctions in the devices, as well as a reduction of the leak current that would occur through the mentioned alternative seed layer; resulting in a higher sensitivity. The results showed that the developed gas sensors could be used for monitoring of NO2 at low concentration.
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