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Yvonne Nitschke,Yan Yan,Insa Buers,Kristina Kintziger,Kim Askew,Frank Rutsch 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Generalized arterial calcification of infancy (GACI) is associated with widespread arterial calcification and stenoses and is caused by mutations in ENPP1. ENPP1 encodes for ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which cleaves ATP to generate inorganic pyrophosphate (PPi) and adenosine monophosphate (AMP) extracellularly. The current study was designed to define the prevalence of arterial stenoses in GACI individuals and to identify the mechanism through which ENPP1 deficiency causes intimal proliferation. Furthermore, we aimed to effectively prevent and treat neointima formation in an animal model of GACI through the systemic administration of recombinant human (rh)ENPP1-Fc protein. Based on a literature review, we report that arterial stenoses are present in at least 72.4% of GACI cases. We evaluated the effect of rhENPP1-Fc on ENPP1-silenced human vascular smooth muscle cells (VSMCs) and on induced intimal proliferation in Enpp1-deficient ttw/ttw mice treated with carotid ligation. We demonstrate that silencing ENPP1 in VSMCs resulted in a tenfold increase in proliferation relative to that of cells transfected with negative control siRNA. The addition of rhENPP1-Fc, AMP or adenosine restored the silenced ENPP1- associated proliferation. In contrast, neither PPi nor etidronate, a current off-label treatment for GACI, had an effect on VSMC proliferation. Furthermore, subcutaneous rhENPP1-Fc protein replacement was effective in preventing and treating intimal hyperplasia induced by carotid ligation in an animal model of GACI. We conclude that ENPP1 inhibits neointima formation by generating AMP. RhENPP1-Fc may serve as an approach for the effective prevention and treatment of arterial stenoses in GACI.
A Quadrocopter Automatic Control Contest as an Example of Interdisciplinary Design Education
Christian Nitschke,Yuki Minami,Masayuki Hiromoto,Hiroaki Ohshima,Takashi Sato 제어로봇시스템학회 2014 제어로봇시스템학회 국제학술대회 논문집 Vol.2014 No.10
Unmanned aerial vehicles (UAVs) have many applications and quickly gain popularity with the availability of low-cost micro aerial vehicles (MAVs). Robotics is a popular interdisciplinary education target as it involves understanding and collaboration of several disciplines. Thus, UAVs can serve as an ideal study platform. However, as robotics requires technical background, skills and initial efforts, it is commonly applied in long-term courses. In this paper we successfully exploit the opposite case of robotics in short-term education for students without background, in form of a one-day contest on automatic visual UAV navigation. We provide an extensive survey, and show that existing material and tools do not fit the task and lack in technical aspects. We introduce a novel open-source programming library that comprises programs to guide learning by experience and allow rapid development. It makes contributions to marker-based tracking, with a novel nested-marker design and accurate calibration parameters estimated from 14 Parrot AR.Drone 2.0 front cameras. We show a detailed discussion of the contest results, which represents an extensive user study regarding robotics in education and the effectiveness of the library. The achievement of a steep learning curve for a complex subject has important implications in interdisciplinary design education, as it allows deep understanding of potentials and limitations to facilitate decision-making, unconventional problem solutions and novel applications.
Ousaka, Naoki,Grunder, Sergio,Castilla, Ana M.,Whalley, Adam C.,Stoddart, J. Fraser,Nitschke, Jonathan R. American Chemical Society 2012 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.134 No.37
<P>A series of large, optically active Fe<SUB>4</SUB>L<SUB>6</SUB> cages was prepared from linear 5,5′-bis(2-formylpyridines) incorporating varying numbers (<I>n</I> = 0–3) of oligo-<I>p</I>-xylene spacers, chiral amines, and Fe<SUP>II</SUP>. When a cage was constructed from the ligand bridged by one <I>p</I>-xylene spacer (<I>n</I> = 1) and a bulky chiral amine, both a homochiral Fe<SUB>2</SUB>L<SUB>3</SUB> helicate and Fe<SUB>4</SUB>L<SUB>6</SUB> cage were observed to coexist in solution due to a delicate balance between steric factors. In contrast, when a less bulky chiral amine was used, only the Fe<SUB>4</SUB>L<SUB>6</SUB> cage was observed. In the case of larger cages (<I>n</I> = 2, 3), long-range (>2 nm) stereochemical coupling between metal centers was observed, which was minimally diminished as the ligands were lengthened. This communication was mediated by the ligands’ geometries and rigidity, as opposed to gearing effects between xylene methyl groups: the metal-centered stereochemistry was not observed to affect the axial stereochemistry of the ligands.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2012/jacsat.2012.134.issue-37/ja306615d/production/images/medium/ja-2012-06615d_0014.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja306615d'>ACS Electronic Supporting Info</A></P>