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  • Result 1-12 of 12
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1.
  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
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  • Jack, C. R., et al. (author)
  • Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2
  • 2015
  • In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:7, s. 740-756
  • Journal article (peer-reviewed)abstract
    • Introduction: Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. Methods: We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. Results: Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. Discussion: Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
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  • Lindblad-Toh, Kerstin, et al. (author)
  • A high-resolution map of human evolutionary constraint using 29 mammals
  • 2011
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482
  • Journal article (peer-reviewed)abstract
    • The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
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  • Nüchel, Julian, et al. (author)
  • TGFB1 is secreted through an unconventional pathway dependent on the autophagic machinery and cytoskeletal regulators
  • 2018
  • In: Autophagy. - : Informa UK Limited. - 1554-8627 .- 1554-8635. ; 14:3, s. 465-486
  • Journal article (peer-reviewed)abstract
    • TGFB1 (transforming growth factor beta 1) is a potent cytokine playing a driving role in development, fibrosis and cancer. It is synthesized as prodomain-growth factor complex that requires tethering to LTBP (latent transforming growth factor beta binding protein) for efficient secretion into the extracellular space. Upon release, this large latent complex is sequestered by anchorage to extracellular matrix (ECM) networks, from which the mature growth factor needs to be activated in order to reach its receptors and initiate signaling. Here, we uncovered a novel intracellular secretion pathway by which the latent TGFB1 complex reaches the plasma membrane and is released from fibroblasts, the key effector cells during tissue repair, fibrosis and in the tumor stroma. We show that secretion of latent TGFB1, but not of other selected cytokines or of bulk cargo, is regulated by fibroblast-ECM communication through ILK (integrin linked kinase) that restricts RHOA activity by interacting with ARHGAP26/GRAF1. Latent TGFB1 interacts with GORASP2/GRASP55 and is detected inside MAP1LC3-positive autophagosomal intermediates that are secreted by a RAB8A-dependent pathway. Interestingly, TGFB1 secretion is fully abrogated in human and murine fibroblasts and macrophages that lack key components of the autophagic machinery. Our data demonstrate an unconventional secretion mode of TGFB1 adding another level of control of its bioavailability and activity in order to effectively orchestrate cellular programs prone to dysregulation as seen in fibrosis and cancer.
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  • Yastrubchak, O., et al. (author)
  • Influence of Ion Implantation on Magnetic, Structural and Optical Properties of (Ga,Mn)As Epitaxial Films
  • 2008
  • In: ACTA PHYSICA POLONICA A. - 0587-4246. ; 114:5, s. 1445-1450
  • Conference paper (peer-reviewed)abstract
    • We performed implantation experiments; applying both the chemically active oxygen ions and inactive ions of neon noble gas, to thin epitaxial films of (Ga,Mn)As ferromagnetic semiconductor. Inspection of their magnetic properties by means of a superconducting quantum interference device magnetometer revealed that the implantation with a low dose of either O or Ne ions completely suppressed ferromagnetism in the films. Both the high resolution X-ray diffraction technique and the Raman spectroscopy showed significant changes in the structural and optical properties of the films caused by oxygen and neon implantation.
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  • Yastrubchak, O., et al. (author)
  • Ion-Implantation Control of Ferromagnetism in (Ga,Mn)As Epitaxial Layers
  • 2010
  • In: Journal Of Electronic Materials. - : Springer Science and Business Media LLC. - 0361-5235 .- 1543-186X. ; 39:6, s. 794-798
  • Conference paper (peer-reviewed)abstract
    • Epitaxial layers of (Ga,Mn)As ferromagnetic semiconductor have been subjected to low-energy ion implantation by applying a very low fluence of either chemically active, oxygen ions or inactive ions of neon noble gas. Several complementary characterization techniques have been used with the aim of studying the effect of ion implantation on the layer properties. Investigation of their electrical and magnetic properties revealed that implantation with either O or Ne ions completely suppressed both the conductivity and ferromagnetism in the layers. On the other hand, Raman spectroscopy measurements evidenced that O ion implantation influenced optical properties of the layers noticeably stronger than did Ne ion implantation. Moreover, structural modifications of the layers caused by ion implantation were investigated using high-resolution x-ray diffraction technique. A mechanism responsible for ion-implantation-induced suppression of the conductivity and ferromagnetism in (Ga,Mn)As layers, which could be applied as a method for tailoring nanostructures in the layers, is discussed in terms of defects created in the layers by the two implanted elements.
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