Electronic petitioning and modernization of petitioning systems in Europe

With the pilot project "Public Petitions", which started in September 2005, the German Bundestag included the internet in the petition procedure and thus achieved greater transparency of the petition process. Since then, petitions can be submitted electronically, signed on the internet and discussed. The Office of Technology Assessment at the German Bundestag (TAB) has accompanied this process scientifically and asked about the yields and consequences of the pilot project. Were more petitions submitted? Who participated in the electronic petitions? How were the petitions discussed in the online forums and how were the results of the discussions introduced into the political process of deliberation on petitions? This study provides answers to these and other questions for the first time on the basis of a comprehensive empirical study. The analyses of the pilot project of the German Bundestag are placed in the context of the development of petitioning and e-democracy as a whole. Case studies on the introduction of electronic petition systems in the Scottish Parliament, the British Prime Minister, South Korea, Australia (Queensland) and Norway complete the picture. This book is based on TAB report Nr. 146 "Elektronisches Petitionswesen und Modernisierung des Petitionswesens in Europa. Endbericht zum TA-Projekt"

Mathematical modelling of stress signalling and cell fate during genotoxic stress

Apoptosis is an intracellular signalling pathway that initiates cell suicide upon diverse stress signals, such as genotoxic stress caused by DNA damaging agents. Its deregulation is often associated with carcinogenesis and failure of chemotherapy. In human cells, mitochondrial outer membrane permeabilisation (MOMP) is a key event in linking intrinsic stress signals to the induction of apoptosis, and hence a major decision point that determines the cell’s fate. MOMP is caused and regulated by pro- and anti-apoptotic proteins of the BCL-2 family. Besides their various compositions and concentrations among different tissues, these proteins exhibit a high diversity in their molecular interactions. This diversity and the different binding affinities between proteins of this group aggravate reliable predictions of cell fates or patient responses to chemotherapy, based solely on protein expression levels. In this thesis, we designed a computational model that includes the topology of interaction of key members of the pro- and anti-apoptotic BCL-2 family and considered the distinct binding affinities of these proteins. Using the model, we were able to support the hypothesis of mode I and mode II inhibition of MOMP whereby the anti-apoptotic BCL-2 proteins are more effective in inhibiting the pro-apoptotic proteins BAK and BAX than the pro-apoptotic BH3-only proteins. Based on quantification of the BCL-2 proteins, we studied the concept of direct and indirect activation and found that the direct activation model successfully described cancer cell responses to the DNA damaging agents 5-fluorouracil and oxaliplatin. Applied to colorectal cancer patients, the designed model predicted patients’ clinical outcome to adjuvant and neo-adjuvant therapy based on patient-specific protein profiles. We investigated the model’s ability to determine whether, and to which extent, cancer cells can be re-sensitised to novel therapeutic agents that inhibit anti-apoptotic BCL-2 proteins. In conclusion, we provided a predictive and prognostic tool that may help to optimise chemotherapeutic treatment of colorectal cancer patients

Reconstruction of {\AA}ngstr{\o}m resolution exit-waves by the application of drift-corrected phase-shifting off-axis electron holography

Phase-shifting electron holography is an excellent method to reveal electron wave phase information with very high phase sensitivity over a large range of spatial frequencies. It circumvents the limiting trade-off between fringe spacing and visibility of standard off-axis holography. Previous implementations have been limited by the independent drift of biprism and sample. We demonstrate here an advanced drift correction scheme for the hologram series that allow to obtain reliable phase information at the 1 {\AA} information limit of the used Titan 80-300 kV environmental transmission electron microscope using a single biprism at moderate voltage of 250 V. The obtained phase and amplitude information is validated at a thin Pt sample by use of multislice image simulation with the frozen lattice approximation and shows excellent agreement. The presented method drastically reduces the hardware requirements and thus allows to achieve high resolution in off-axis holography in various instruments including those for in-situ applications. A software implementation for the acquisition, calibration and reconstruction is provided