83 research outputs found

    On the stability of high-speed milling with spindle speed variation

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    Spindle speed variation is a well-known technique to suppress regenerative machine tool vibrations, but it is usually considered to be effective only for low spindle speeds. In this paper, the effect of spindle speed variation is analyzed in the high-speed domain for spindle speeds corresponding to the first flip (period doubling) and to the first Hopf lobes. The optimal amplitudes and frequencies of the speed modulations are computed using the semidiscre- tization method. It is shown that period doubling chatter can effectively be suppressed by spindle speed variation, although, the technique is not effective for the quasiperiodic chatter above the Hopf lobe. The results are verified by cutting tests. Some special cases are also discussed where the practical behavior of the system differs from the predicted one in some ways. For these cases, it is pointed out that the concept of stability is understood on the scale of the principal period of the system—that is, the speed modulation period for variable spindle speed machining and the tooth passing period for constant spindle speed machining

    Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

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    Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

    The Role of Glypicans in Wnt Inhibitory Factor-1 Activity and the Structural Basis of Wif1's Effects on Wnt and Hedgehog Signaling

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    Proper assignment of cellular fates relies on correct interpretation of Wnt and Hedgehog (Hh) signals. Members of the Wnt Inhibitory Factor-1 (WIF1) family are secreted modulators of these extracellular signaling pathways. Vertebrate WIF1 binds Wnts and inhibits their signaling, but its Drosophila melanogaster ortholog Shifted (Shf) binds Hh and extends the range of Hh activity in the developing D. melanogaster wing. Shf activity is thought to depend on reinforcing interactions between Hh and glypican HSPGs. Using zebrafish embryos and the heterologous system provided by D. melanogaster wing, we report on the contribution of glypican HSPGs to the Wnt-inhibiting activity of zebrafish Wif1 and on the protein domains responsible for the differences in Wif1 and Shf specificity. We show that Wif1 strengthens interactions between Wnt and glypicans, modulating the biphasic action of glypicans towards Wnt inhibition; conversely, glypicans and the glypican-binding “EGF-like” domains of Wif1 are required for Wif1's full Wnt-inhibiting activity. Chimeric constructs between Wif1 and Shf were used to investigate their specificities for Wnt and Hh signaling. Full Wnt inhibition required the “WIF” domain of Wif1, and the HSPG-binding EGF-like domains of either Wif1 or Shf. Full promotion of Hh signaling requires both the EGF-like domains of Shf and the WIF domains of either Wif1 or Shf. That the Wif1 WIF domain can increase the Hh promoting activity of Shf's EGF domains suggests it is capable of interacting with Hh. In fact, full-length Wif1 affected distribution and signaling of Hh in D. melanogaster, albeit weakly, suggesting a possible role for Wif1 as a modulator of vertebrate Hh signaling

    Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1

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    Wnt morphogens control embryonic development and homeostasis in adult tissues. In vertebrates the N-terminal WIF domain (WIF-1 WD) of Wnt inhibitory factor 1 (WIF-1) binds Wnt ligands. Our crystal structure of WIF-1 WD reveals a previously unidentified binding site for phospholipid; two acyl chains extend deep into the domain, and the head group is exposed to the surface. Biophysical and cellular assays indicate that there is a WIF-1 WD Wnt-binding surface proximal to the lipid head group but also implicate the five epidermal growth factor (EGF)-like domains (EGFs I-V) in Wnt binding. The six-domain WIF-1 crystal structure shows that EGFs I-V are wrapped back, interfacing with WIF-1 WD at EGF III. EGFs II-V contain a heparan sulfate proteoglycan (HSPG)-binding site, consistent with conserved positively charged residues on EGF IV. This combination of HSPG-and Wnt-binding properties suggests a modular model for the localization of WIF-1 and for signal inhibition within morphogen gradients. © 2011 Nature America, Inc. All rights reserved

    Visuelle Aufmerksamkeitsmechanismen auf bimodalen Laserdaten

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    Aufmerksamkeit hilft Menschen dabei, relevante Punkte der Umgebung mit den Augen zu fixieren, um wesentliche Informationen aus der Menge an Sinneseindrücken herauszufiltern. Obwohl menschliche Aufmerksamkeit durch verschiedene Sinnesorgane beeinflußt wird, simulieren bestehende Aufmerksamkeitsmodelle gewöhnlich nur visuelle Aufmerksamkeit und deren Implementierungen nutzen meist nur Kameradaten. Im Gegensatz dazu wenden wir Aufmerksamkeitsmechanismen auf bimodale Daten eines 3D-Laserscanners an, der auf einem autonomen mobilen Roboter montiert ist. Der 3D-Laserscanner deckt eine große Bildfläche ab und liefert mit einem einzigen Scan sowohl Tiefen- als auch Intensitätswerte. Diese Daten wurden als Bilder dargestellt, so dass ein Scan-Durchgang ein Tiefen- und ein Intensitätsbild der Umgebung erzeugt. Auf diese Bilder wurde das Aufmerksamkeitsmodell von Itti et al. angewendet. Der Vorteil dieses Ansatzes ist die zusätzliche Tiefeninformation, die bei rein Kamera-gesteuerten Modellen nur durch den aufwändigen Einsatz von Stereo-Bilddatenverarbeitung zu gewinnen ist. Dadurch können Objekte mit gewissem Abstand zu ihrem Hintergrund leicht detektiert werden. In unseren Experimenten wurde der Ansatz sowohl innerhalb von Gebäuden als auch im Freien getestet, so dass die Szenen von Büroumgebungen bis zu Straßenverkehrsszenen reichen. Die Ergebnisse belegen die Eignung des 3D-Laserscanners zur Detektion auffälliger Bereiche: 86% der zuerst fokussierten Bereiche zeigen ein Objekt von potenziellem Interesse. Vorteilhaft ist dabei die Multimodalität des Scanners, da Intensitäts- und Tiefeninformation verschiedene Arten von Auffälligkeit detektieren und sich so gegenseitig ergänzen können. In Zukunft sollen diese Ergebnisse genutzt werden, um Robotern bei diversen Aufgaben behilflich zu sein, zum Beispiel bei der Manipulation von Objekten, der Hindernisvermeidung oder der Selbst-Lokalisierung anhand von Landmarken
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