Innovativer Fräsroboter mit Direktantrieben

Seit 2010 werden pro Jahr mehr als 100.000 Industrieroboterverkauft [IFR16]. Im Wesentlichen werden sie zur Steigerung des Automatisierungsgrades und der Qualität für Montage- und Schweißarbeiten eingesetzt. Nur ein Bruchteil von 1,7 % der Industrieroboter werden in Deutschland für spanende Verfahren eingesetzt [KAR16]. Dabei bieten Industrieroboter im Bereich der Zerspanung viele Vorteile. Gegenüber Werkzeugmaschinenhaben sie ein deutlichbesseres Verhältnis von Aufstellfläche zu Arbeitsraum, bessere Zugänglichkeit zum Werkstück und niedrigere Anschaffungskosten. Doch nicht nur die Fixkosten, auch die variablen Kosten sind bei der Betrachtung der Energieaufnahme der elektrischen Antriebe um den Faktor15 geringer als bei der Werkzeugmaschine[UHL16b].Trotz genannter Vorteile finden Industrieroboter für die Zerspanung in der Industrie kaum Relevanz. Hauptgründe sind unzureichende Genauigkeiten und die Bedienung [UHL16a]. Diese Kritikpunkte wurden bereits von Firmen und Forschungsinstituten aufgegriffen um z. B. Industrieroboter mittels CNC Steuerung zu verbessern [WU17], oder mittels Zusatzsystemen und Modellverbesserungen die Genauigkeit der Roboter zu steigern [WEI08]. Jene kosten intensiven Zusatzsysteme verbessern somit grundlegende Schwachstellen aktueller Roboter, beheben diese jedoch nicht

Gene therapy targets in heart failure: the path to translation

Heart failure (HF) is the common end point of cardiac diseases. Despite the optimization of therapeutic strategies and the consequent overall reduction in HF-related mortality, the key underlying intracellular signal transduction abnormalities have not been addressed directly. In this regard, the gaps in modern HF therapy include derangement of β-adrenergic receptor (β-AR) signaling, Ca(2+) disbalances, cardiac myocyte death, diastolic dysfunction, and monogenetic cardiomyopathies. In this review we discuss the potential of gene therapy to fill these gaps and rectify abnormalities in intracellular signaling. We also examine current vector technology and currently available vector-delivery strategies, and related to the transfer of successful preclinical gene therapy approaches to HF treatment in the clinic, as well as impending strategies aimed at overcoming these limitations

AAV6.βARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model

AIMS: G protein-coupled receptor kinase 2 (GRK2), which is markedly upregulated in failing human myocardium, has been implicated as a contributing factor or consequence of heart failure (HF). Importantly, cardiac-specific GRK2 knockout mice have recently proved the pathological nature of GRK2 in HF. Targeted inhibition of GRK2 is possible using a peptide inhibitor known as the βARKct, which has rescued several disparate small animal HF models. This study was designed to evaluate long-term βARKct expression in a clinically relevant large animal HF model, using stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). METHODS AND RESULTS: A porcine model of HF subsequent to left ventricular (LV) myocardial infarction (MI) was used to study the effects of retrograde injection into the anterior interventricular vein of either AAV6.βARKct or AAV6.luciferase as a control 2 weeks after MI. Echocardiography and LV hemodynamics were performed before and 6 weeks after gene transfer. Robust and long-term βARKct expression was found after AAV6-mediated delivery, leading to significant amelioration of LV haemodynamics and contractile function in HF pigs compared with AAV6.luciferase-treated control animals that showed a continued decline in cardiac function. Interestingly, the neurohormonal axis was virtually normalized in AVV6.βARKct-treated HF animals, represented by reductions in plasma norepinephrine levels, whereas AAV6.luciferase-treated pigs showed further increases in plasma catecholamine levels. As a result, LV remodelling and foetal gene expression was reversed by AVV6.βARKct gene therapy. CONCLUSION: These data—showing sustained amelioration of cardiac function in a post-MI pig HF model—demonstrate the therapeutic potential of βARKct gene therapy for HF