Austrian Drug Screening Institute ADSI

Innsbruck, Austria

Austrian Drug Screening Institute ADSI

Innsbruck, Austria
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Bonn G.,Austrian Drug Screening Institute ADSI | Bonn G.,University of Innsbruck | Gjerde D.T.,PhyNexus Inc
LC-GC Europe | Year: 2017

Dual flow chromatography (DFC) separations are performed with back and forth flow for rapid method development, design of experiments (DOE), quality-by-design (QbD), or high-throughput chromatographic purification. Although different than conventional unidirectional flow through chromatography, chromatographic principles still control the separations. Selectivity coefficients and Langmuir adsorption isotherms control the separation chemistry properties of the column and dictate the mobile phase conditions needed to achieve separation. However, the kinetic rates of diffusion and interaction of mobile phase molecules with the stationary phase, column channeling, and other column properties are not germane to the practice of DFC. Chromatographic conditions developed with DFC can be scaled to any size, including laboratory and industrial preparative columns. One practical use of DFC is in the pharmaceutical industry where multidimensional method development and high-throughput, parallel processing has been used to improve R&D productivity and decrease the time to manufacturing of biopharmaceutical drugs. © 2017, LC-GC Europe. All rights reserved.


Scheffler J.M.,Innsbruck Medical University | Sparber F.,Innsbruck Medical University | Tripp C.H.,Innsbruck Medical University | Herrmann C.,Innsbruck Medical University | And 6 more authors.
Nature Communications | Year: 2014

The receptor tyrosine kinase Flt3 and its ligand are crucial for dendritic cell (DC) homeostasis by activating downstream effectors including mammalian target of Rapamycin (mTOR) signalling. LAMTOR2 is a member of the Ragulator/LAMTOR complex known to regulate mTOR and extracellular signal-regulated kinase activation on the late endosome as well as endosomal biogenesis. Here we show in mice that conditional ablation of LAMTOR2 in DCs results in a severe disturbance of the DC compartment caused by accumulation of Flt3 on the cell surface. This results in an increased downstream activation of the AKT/mTOR signalling pathway and subsequently to a massive expansion of conventional DCs and plasmacytoid DCs in ageing mice. Finally, we can revert the symptoms in vivo by inhibiting the activation of Flt3 and its downstream target mTOR. © 2014 Macmillan Publishers Limited. All rights reserved.


PubMed | Austrian Drug Screening Institute ADSI and Innsbruck Medical University
Type: | Journal: Nature communications | Year: 2014

The receptor tyrosine kinase Flt3 and its ligand are crucial for dendritic cell (DC) homeostasis by activating downstream effectors including mammalian target of Rapamycin (mTOR) signalling. LAMTOR2 is a member of the Ragulator/LAMTOR complex known to regulate mTOR and extracellular signal-regulated kinase activation on the late endosome as well as endosomal biogenesis. Here we show in mice that conditional ablation of LAMTOR2 in DCs results in a severe disturbance of the DC compartment caused by accumulation of Flt3 on the cell surface. This results in an increased downstream activation of the AKT/mTOR signalling pathway and subsequently to a massive expansion of conventional DCs and plasmacytoid DCs in ageing mice. Finally, we can revert the symptoms in vivo by inhibiting the activation of Flt3 and its downstream target mTOR.

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