TheMPO: A knowledge-based system for therapy planning in pediatric oncology

This article describes the knowledge-based system THEMPO (Therapy Management in Pediatric Oncology), which supports protocol-directed therapy planning and configuration in pediatric oncology. THEMPO provides a semantic network controlled by graph grammars to cover the different types of knowledge relevant in the domain, and offers a suite of acquisition tools for knowledge base authoring. Medical problem solvers, operating on the oncological network, reason about adequate therapeutic and diagnostic timetables for a patient. Furthermore, a corresponding patient record, also based on semantic networks and graph grammars, has been implemented to represent the course of therapy of an oncological patient

Quantum Eavesdropping without Interception: An Attack Exploiting the Dead Time of Single Photon Detectors

The security of quantum key distribution (QKD) can easily be obscured if the eavesdropper can utilize technical imperfections of the actual implementation. Here we describe and experimentally demonstrate a very simple but highly effective attack which even does not need to intercept the quantum channel at all. Only by exploiting the dead time effect of single photon detectors the eavesdropper is able to gain (asymptotically) full information about the generated keys without being detected by state-of-the-art QKD protocols. In our experiment, the eavesdropper inferred up to 98.8% of the key correctly, without increasing the bit error rate between Alice and Bob significantly. Yet, we find an evenly simple and effective countermeasure to inhibit this and similar attacks

Field test of quantum key distribution in the Tokyo QKD Network

A novel secure communication network with quantum key distribution in a metropolitan area is reported. Different QKD schemes are integrated to demonstrate secure TV conferencing over a distance of 45km, stable long-term operation, and application to secure mobile phones.Comment: 21 pages, 19 figure

Fast optical source for quantum key distribution based on semiconductor optical amplifiers

A novel integrated optical source capable of emitting faint pulses with different polarization states and with different intensity levels at 100 MHz has been developed. The source relies on a single laser diode followed by four semiconductor optical amplifiers and thin film polarizers, connected through a fiber network. The use of a single laser ensures high level of indistinguishability in time and spectrum of the pulses for the four different polarizations and three different levels of intensity. The applicability of the source is demonstrated in the lab through a free space quantum key distribution experiment which makes use of the decoy state BB84 protocol. We achieved a lower bound secure key rate of the order of 3.64 Mbps and a quantum bit error ratio as low as $1.14\times 10^{-2}$ while the lower bound secure key rate became 187 bps for an equivalent attenuation of 35 dB. To our knowledge, this is the fastest polarization encoded QKD system which has been reported so far. The performance, reduced size, low power consumption and the fact that the components used can be space qualified make the source particularly suitable for secure satellite communication

Heterogeneity assessment of functional T cell avidity.

The potency of cellular immune responses strongly depends on T cell avidity to antigen. Yet, functional avidity measurements are rarely performed in patients, mainly due to the technical challenges of characterizing heterogeneous T cells. The mean functional T cell avidity can be determined by the IFN-γ Elispot assay, with titrated amounts of peptide. Using this assay, we developed a method revealing the heterogeneity of functional avidity, represented by the steepness/hillslope of the peptide titration curve, documented by proof of principle experiments and mathematical modeling. Our data show that not only natural polyclonal CD8 T cell populations from cancer patients, but also monoclonal T cells differ strongly in their heterogeneity of functional avidity. Interestingly, clones and polyclonal cells displayed comparable ranges of heterogeneity. We conclude that besides the mean functional avidity, it is feasible and useful to determine its heterogeneity (hillslope) for characterizing T cell responses in basic research and patient investigation

Development of a novel TCR avidity assay for human CD8⁺ T cells.

T cells with high avidity for their specific ligand are believed to be most effective in clearing viral infections and inducing tumor regression. Thereby, an important part of the avidity seems to be hard wired in the structure of the T cell receptor (TCR). Existing methods do not allow for the exact measurement of this structural avidity on living cells. We therefore developed a novel assay, where the dissociation of monomeric MHC-molecules bound to surface expressed TCRs can be observed by real-time microscopy and can be quantified as koff-rate. Experiments with preclinical mouse models showed a clear correlation between functional avidity, koff-rate and protectivity of the T cells. This led to the assumption that the koff-rate might be an important parameter for determination of the quality of T cells used e.g. for adoptive immunotherapy. Hence, the assay was adapted to the measurement of human T cells. To achieve this, fundamental changes of the setups turned out to be necessary. Validation of the method with CMV-specific T cells showed that the assay allows for precise and reproducible determination of the koff-rate. High variability of the koff-rate assed for different CMV-positive donors indicates that this parameter might be important for the selection of high quality T cells for adoptive T cell therapy

Adoptive immunotherapy: New assay for the identification of T cells with optimal avidity.

T cells expressing high avidity T-cell receptors (TCRs) have been shown to mediate superior therapeutic effects. A novel koff-rate assay allows for the quantitative and reproducible assessment of the avidity of TCRs for their ligands directly on living T cells, ex vivo. This assay might facilitate the selection of T cells with an optimal avidity for their target, hence favoring the development of adoptive immunotherapeutic regimens