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Heterologous mammalian gene regulation systems for adjustable expression of multiple transgenes are necessary for advanced human gene therapy and tissue engineering, and for sophisticated in vivo gene-function analyses, drug discovery, and biopharmaceutical manufacturing. The antibiotic-dependent interaction between the repressor (E) and operator (ETR)(More)
In multicellular systems cell identity is imprinted by epigenetic regulation circuits, which determine the global transcriptome of adult cells in a cell phenotype-specific manner. By combining two repressors, which control each other's expression, we have developed a mammalian epigenetic circuitry able to switch between two stable transgene expression(More)
Bistable and hysteretic switches, enabling cells to adopt multiple internal expression states in response to a single external input signal, have a pivotal impact on biological systems, ranging from cell-fate decisions to cell-cycle control. We have designed a synthetic hysteretic mammalian transcription network. A positive feedback loop, consisting of a(More)
The architecture of gene regulatory networks is reminiscent of electronic circuits. Modular building blocks that respond in a logical way to one or several inputs are connected to perform a variety of complex tasks. Gene circuit engineers have pioneered the construction of artificial gene regulatory networks with the intention to pave the way for the(More)
BACKGROUND AND OBJECTIVE To evaluate the capability of first responders to achieve and maintain normal ventilation of the lungs of victims employing a bag-valve device and two oxygen-driven resuscitators. METHODS Prospective, controlled, blinded, single-centre clinical trial using a bag-valve device and one of two FR-300 devices, with 20 cmH2O working(More)
CCAAT/enhancer-binding proteins (C/EBPs) as well as bone morphogenic proteins (BMPs) play essential roles in mammalian cell differentiation in shaping adipogenic and osteoblastic lineages in particular. Recent evidence suggested that adipocytes and osteoblasts share a common mesenchymal precursor cell phenotype. Yet, the molecular details underlying the(More)
In recent years gene network engineers have celebrated spectacular success: Genetic devices such as epigenetic toggle switches and oscillating networks have been engineered and pioneered a new ever-increasing scientific community known as synthetic biology. While synthetic biology was until recently restricted to network assembly and testing in prokaryotes,(More)
BACKGROUND The recently developed heterologous macrolide- (E.REX system) and streptogramin- (PIP system) responsive gene regulation systems show significant differences in their regulation performance in diverse cell lines. METHODS In order to provide optimal regulation modalities for a wide variety of mammalian cell lines, we have performed a detailed(More)
Prototype drug-adjustable heterologous transcription control systems designed for gene therapy applications typically show sigmoid dose-response characteristics and enable fine-tuning of therapeutic transgenes only within a narrow inducer concentration range of a few nanograms. However, the design of clinical dosing regimes which achieve tissue-specific(More)
Gene expression circuitries with time-delayed expression profiles regulate key events, such as oscillating systems, noise elimination, and coordinated multi-step processes, in all organisms from bacteria to mammalian cells. We present the rational synthesis of a genetic circuit displaying time-delayed expression in silico and in mammalian cells. The network(More)