Rewiring biology:Targeting dendritic cells to reset allergic disease

In this thesis we have investigated how to innovate allergen immunotherapy (AIT) strategies centered around dendritic cells (DCs) as orchestrators of adaptive immune responses. To that end, we characterized the immunological effects of allergens on DCs and investigated novel therapy candidates. Our data indicate that neither the major HDM allergens Der p 1 and Der p 2, nor the major cat allergen Fel d 1 activate DCs by them-selves. This emphasizes the need for immune-activating and -modulating adjuvants in AIT. One possibility to overcome this inertness it the concept of plant-produced enveloped bioparticles (eBPs) displaying recombinant allergen on their surface. We have shown that those eBPs lead to a more powerful DC maturation and cytokine response than soluble (or alum-conjugated) allergen. Based on our findings related to the HDM allergen Der p 2, the allergic background shows no major impact on the induced responses towards soluble and particulate allergen. Besides, we have shown that the eBPs reduce basophil degranulation, which suggests hypoallergenicity. Based on those intrinsic auto-adjuvant effects of eBPs, we conclude that allergen-displaying eBPs possibly contribute to safer and faster desensibilisation of patients. Furthermore, we have analyzed the immunomodulatory properties of subcutaneously administered vitamin D3 (VitD3) as a potential tolerance-inducing adjuvant in AIT in a human in vivo setting. While we detected peripheral immune modulations within innate and adaptive responses, those observations were not linked to tolerance-associated signatures. However, it remains important to explore whether VitD3 can trigger tolerogenic responses in an allergen-specific setting

Construction and characterization of a laser-driven proton beamline at GSI

The thesis includes the first experiments with the new 100 TW laser beamline of the PHELIX laser facility at GSI Darmstadt to drive a TNSA (Target Normal Sheath Acceleration) proton source at GSI's Z6 experimental area. At consecutive stages a pulsed solenoid has been applied for beam transport and energy selection via chromatic focusing, as well as a radiofrequency cavity for energy compression of the bunch. This novel laser-driven proton beamline, representing a central experiment of the German national LIGHT collaboration (Laser Ion Generation, Handling and Transport), has been used to create collimated, intense proton bunches at 10 MeV with 2.7% energy spread from the laser-driven source. Also, the feasibility of phase focusing experiments with this setup has been shown and simulations predict peak currents of 10^10 protons/ns at this energy level. Furthermore, first quantitative measurements on the spectral properties of the also present co-moving electrons from such a proton source could be performed and their influence on the protons within the solenoid observed. Finally, permanent magnetic quadrupoles as an alternative first ion collimation system have been investigated experimentally

Forward Secure Signatures on Smart Cards

We introduce the forward secure signature scheme XMSS$^{+}$ and present an implementation for smart cards. It is based on the hash-based signature scheme XMSS. In contrast to the only previous implementation of a hash-based signature scheme on smart cards by Rohde et al., we solve the problem of on-card key generation. Compared to XMSS, we reduce the key generation time from $\mathcal{O}(n)$ to $\mathcal{O}(\sqrt{n})$, where $n$ is the number of signatures that can be created with one key pair. To the best of our knowledge this is the first implementation of a forward secure signature scheme and the first full implementation of a hash-based signature scheme on smart cards. The resulting runtimes are comparable to those of RSA and ECDSA on the same device. This shows the practicality of forward secure signature schemes, even on constrained devices

IoTSan: Fortifying the Safety of IoT Systems

Today's IoT systems include event-driven smart applications (apps) that interact with sensors and actuators. A problem specific to IoT systems is that buggy apps, unforeseen bad app interactions, or device/communication failures, can cause unsafe and dangerous physical states. Detecting flaws that lead to such states, requires a holistic view of installed apps, component devices, their configurations, and more importantly, how they interact. In this paper, we design IoTSan, a novel practical system that uses model checking as a building block to reveal "interaction-level" flaws by identifying events that can lead the system to unsafe states. In building IoTSan, we design novel techniques tailored to IoT systems, to alleviate the state explosion associated with model checking. IoTSan also automatically translates IoT apps into a format amenable to model checking. Finally, to understand the root cause of a detected vulnerability, we design an attribution mechanism to identify problematic and potentially malicious apps. We evaluate IoTSan on the Samsung SmartThings platform. From 76 manually configured systems, IoTSan detects 147 vulnerabilities. We also evaluate IoTSan with malicious SmartThings apps from a previous effort. IoTSan detects the potential safety violations and also effectively attributes these apps as malicious.Comment: Proc. of the 14th ACM CoNEXT, 201

An integrated gene annotation and transcriptional profiling approach towards the full gene content of the Drosophila genome

BACKGROUND: While the genome sequences for a variety of organisms are now available, the precise number of the genes encoded is still a matter of debate. For the human genome several stringent annotation approaches have resulted in the same number of potential genes, but a careful comparison revealed only limited overlap. This indicates that only the combination of different computational prediction methods and experimental evaluation of such in silico data will provide more complete genome annotations. In order to get a more complete gene content of the Drosophila melanogaster genome, we based our new D. melanogaster whole-transcriptome microarray, the Heidelberg FlyArray, on the combination of the Berkeley Drosophila Genome Project (BDGP) annotation and a novel ab initio gene prediction of lower stringency using the Fgenesh software. RESULTS: Here we provide evidence for the transcription of approximately 2,600 additional genes predicted by Fgenesh. Validation of the developmental profiling data by RT-PCR and in situ hybridization indicates a lower limit of 2,000 novel annotations, thus substantially raising the number of genes that make a fly. CONCLUSIONS: The successful design and application of this novel Drosophila microarray on the basis of our integrated in silico/wet biology approach confirms our expectation that in silico approaches alone will always tend to be incomplete. The identification of at least 2,000 novel genes highlights the importance of gathering experimental evidence to discover all genes within a genome. Moreover, as such an approach is independent of homology criteria, it will allow the discovery of novel genes unrelated to known protein families or those that have not been strictly conserved between species