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Nocon, Justyna,Steiger, Matthias G.,Pfeffer, Martin,Sohn, Seung Bum,Kim, Tae Yong,Maurer, Michael,Rußmayer, Hannes,Pflü,gl, Stefan,Ask, Magnus,Haberhauer-Troyer, Christina,Ortmayr, Karin,Hann, Ste Academic Press 2014 Metabolic engineering Vol.24 No.-
<▼1><P>The production of recombinant proteins is frequently enhanced at the levels of transcription, codon usage, protein folding and secretion. Overproduction of heterologous proteins, however, also directly affects the primary metabolism of the producing cells. By incorporation of the production of a heterologous protein into a genome scale metabolic model of the yeast <I>Pichia pastoris</I>, the effects of overproduction were simulated and gene targets for deletion or overexpression for enhanced productivity were predicted. Overexpression targets were localized in the pentose phosphate pathway and the TCA cycle, while knockout targets were found in several branch points of glycolysis. Five out of 9 tested targets led to an enhanced production of cytosolic human superoxide dismutase (hSOD). Expression of bacterial β-glucuronidase could be enhanced as well by most of the same genetic modifications. Beneficial mutations were mainly related to reduction of the NADP/H pool and the deletion of fermentative pathways. Overexpression of the hSOD gene itself had a strong impact on intracellular fluxes, most of which changed in the same direction as predicted by the model. <I>In vivo</I> fluxes changed in the same direction as predicted to improve hSOD production. Genome scale metabolic modeling is shown to predict overexpression and deletion mutants which enhance recombinant protein production with high accuracy.</P></▼1><▼2><P><B>Highlights</B></P><P>•<P>Recombinant protein production in <I>P. pastoris</I> affects the central metabolism.</P>•<P>A genome scale metabolic model can predict these metabolic flux changes.</P>•<P>Mutations in central metabolic genes enhanced recombinant protein yield up to 40%.</P>•<P>These beneficial mutations were predicted by the metabolic model with high accuracy.</P></P></▼2>
On an Analytical Quick Game to Investigate the Battle Effectiveness of Forward Depense Concepts
Huber, Reiner K.,Steiger, Karl,Wobith, Bernt 한국경영과학회 1981 韓國經營科學會誌 Vol.6 No.1
The so-called "Quick Game" -models resemble a central element within the Compound Gaming approach of military systems analysis proposed by Huber [1, 2]. This paper introduces such an analytical model designed to investigate the battle-effectiveness of alternative army structures. The nature of its results is discussed from numerical experiments covering the (German) Army Structure 4, Loser's Area Coverage Defence Concept, and Afheldt's Area Defence Concept. It turns out that Lo¨ser's concept promises to have a comparatively high potential to stabilize the early conventional forward defence, hence being an interesting alternative for further analysis in depth.
Sputter-Redeposition Method for the Fabrication of Automatically Sealed Micro/Nanochannel using FIBs
김흥배,Gerhard Hobler,Andreas Steiger,Alois Lugstein,Emmerich Bertagnolli,Elmar Platzgummer,Hans Loeschner 한국정밀공학회 2011 International Journal of Precision Engineering and Vol. No.
In this article, we report a new method for micro/nano fluidic channel fabrication by focused ion beams (FIB) utilizing the redeposition flux, or what we will refer to in this paper as SRM (sputter-redeposition method). Sputtered particles are byproduct of sputter process whereas it limits the focused ion beam (FIB) process. However, the sputtered particles can be useful in the fabrication of certain shapes of structures. The objective of this article is the demonstration of active utilization of the sputtered particles. A micro/nano-fluidic channel fabrication is demonstrated for the topic. As an application, in the fluidic channel fabrication we demonstrate two-step process; trench formation and automatic sealing in the micro-/nanometer range. This method channels from hundreds to tens of nanometers wide can be fabricated by using silicon as a channel substrate. The shape and dimensions of the channel cross-section are readily changed by varying the process parameters. This control of redeposition technique is advantageous because of the accuracy and simplicity of the process compare to other fluidic channel fabrication process.
Sputter-Redeposition Method for the Fabrication of Automatically Sealed Micro/Nanochannel using FIBs
Kim, Heung-Bae,Hobler, Gerhard,Steiger, Andreas,Lugstein, Alois,Bertagnolli, Emmerich,Platzgummer, Elmar,Loeschner, Hans 한국정밀공학회 2011 International Journal of Precision Engineering and Vol.12 No.5
In this article. we report a new method for micro/nano fluidic channel fabrication by focused ion beams (FIB) utilizing the redeposition flux. or what we will refer to in this paper as SRM (sputter-redeposition method). Sputtered particles are byproduct of sputter process whereas it limits the focused ion beam (FIB) process. However, the sputtered particles can be useful in the fabrication of certain shapes of structures. The objective of this article is the demonstration of active utilization of the sputtered particles. A micro/nano-fluidic channel fabrication is demonstrated for the topic. As an application, in the fluidic channel fabrication we demonstrate two-step process; trench formation and automatic sealing in the micro-/nanometer range. This method channels from hundreds to tens of nanometers wide can be fabricated by using silicon as a channel substrate. The shape and dimensions of the channel cross-section are readily changed by varying the process parameters. This control of redeposition technique is advantageous because of the accuracy and simplicity of the process compare to other fluidic channel fabrication process.
Antonia Richter,Karina Knorr,Martin Schlapschy,Stephanie Robu,Volker Morath,Claudia Mendler,Hsi-Yu Yen,Katja Steiger,Marion Kiechle,Wolfgang Weber,Arne Skerra,Markus Schwaiger 대한핵의학회 2020 핵의학 분자영상 Vol.54 No.2
Purpose PASylation® offers the ability to systematically tune and optimize the pharmacokinetics of protein tracers for molecular imaging. Here we report the first clinical translation of a PASylated Fab fragment (89Zr∙Df-HER2-Fab-PAS200) for the molecular imaging of tumor-related HER2 expression. Methods A patient with HER2-positive metastatic breast cancer received 37 MBq of 89Zr∙Df-HER2-Fab-PAS200 at a total mass dose of 70 μg. PET/CT was carried out 6, 24, and 45 h after injection, followed by image analysis of biodistribution, normal organ uptake, and lesion targeting. Results Images show a biodistribution typical for protein tracers, characterized by a prominent blood pool 6 h p.i., which decreased over time. Lesions were detectable as early as 24 h p.i. 89Zr∙Df-HER2-Fab-PAS200 was tolerated well. Conclusion This study demonstrates that a PASylated Fab tracer shows appropriate blood clearance to allow sensitive visualization of small tumor lesions in a clinical setting.