Species conserved DNA damage response at the inactive human X chromosome.

Chromatin modifications are long known as an essential part of the orchestrated response resulting in the repair of radiation-induced DNA double-strand breaks (DSBs). Only recently, however, the influence of the chromatin architecture itself on the DNA damage response has been recognised. Thus for heterochromatic DSBs the sensing and early recruitment of repair factors to the lesion occurs within the heterochromatic compartments, but the damage sites are subsequently relocated from the inside to the outside of the heterochromatin. While previous studies were accomplished at the constitutive heterochromatin of centromeric regions in mouse and flies, here we examine the DSB repair at the facultative heterochromatin of the inactive X chromosome (Xi) in humans. Using heavy ion irradiation we show that at later times after irradiation the DSB damage streaks bend around the Xi verifying that the relocation process is conserved between species and not specialised to repetitive sequences only. In addition, to measure chromatin relaxation at rare positions within the genome, we established live cell microscopy at the GSI microbeam thus allowing the aimed irradiation of small nuclear structures like the Xi. Chromatin decondensation at DSBs within the Xi is clearly visible within minutes as a continuous decrease of the DNA staining over time, comparable to the DNA relaxation revealed at DSBs in mouse chromocenters. Furthermore, despite being conserved between species, slight differences in the underlying regulation of these processes in heterochromatic DSBs are apparent.

An infrastructure for accurate characterization of single-event transients in digital circuits.

We present the architecture and a detailed pre-fabrication analysis of a digital measurement ASIC facilitating long-term irradiation experiments of basic asynchronous circuits, which also demonstrates the suitability of the general approach for obtaining accurate radiation failure models developed in our FATAL project. Our ASIC design combines radiation targets like Muller C-elements and elastic pipelines as well as standard combinational gates and flip-flops with an elaborate on-chip measurement infrastructure. Major architectural challenges result from the fact that the latter must operate reliably under the same radiation conditions the target circuits are exposed to, without wasting precious die area for a rad-hard design. A measurement architecture based on multiple non-rad-hard counters is used, which we show to be resilient against double faults, as well as many triple and even higher-multiplicity faults. The design evaluation is done by means of comprehensive fault injection experiments, which are based on detailed Spice models of the target circuits in conjunction with a standard double-exponential current injection model for single-event transients (SET). To be as accurate as possible, the parameters of this current model have been aligned with results obtained from 3D device simulation models, which have in turn been validated and calibrated using micro-beam radiation experiments at the GSI in Darmstadt, Germany. For the latter, target circuits instrumented with high-speed sense amplifiers have been used for analog SET recording. Together with a probabilistic analysis of the sustainable particle flow rates, based on a detailed area analysis and experimental cross-section data, we can conclude that the proposed architecture will indeed sustain significant target hit rates, without exceeding the resilience bound of the measurement infrastructure.

A disruptive approach to eliminating weapon-grade plutonium - Pu burning in a molten salt fast reactor.

The successful implementation of disarmament treaties of the last centuries has led to significant amounts of weapon-grade Plutonium which are currently stored in high security storage facilities. Disposing this Plutonium should be seen as 'good housekeeping' avoiding unnecessary costs and the hazards of storing this material indefinitely. In addition, the disarmament is only brought to a successful end when the Plutonium isn't available for the production of new weapons anymore. We propose a disruptive approach for Plutonium disposition and demonstrate the feasibility in a neutronic study. Burning of weapon-grade Plutonium in a molten salt fast reactor is significantly more efficient than in the studied other reactors, while efficient process design has the potential to reduce the security concerns significantly. The proposed system could turn about 1.25 tons of weapon-grade Plutonium into electric energy worth £ 0.5 to 1 billion/year, depending on the electricity price while avoiding the hassle and eliminating the risk of high security Plutonium storage. In conclusion, burning of the weapon-grade Plutonium resulting from disarmament could be an economically very attractive approach to reduce the nuclear threat.

An innovative way of thinking nuclear waste management - Neutron physics of a reactor directly operating on SNF.

A solution for the nuclear waste problem is the key challenge for an extensive use of nuclear reactors as a major carbon free, sustainable, and applied highly reliable energy source. Partitioning and Transmutation (P&T) promises a solution for improved waste management. Current strategies rely on systems designed in the 60's for the massive production of plutonium. We propose an innovative strategic development plan based on invention and innovation described with the concept of developments in s-curves identifying the current boundary conditions, and the evolvable objectives. This leads to the ultimate, universal vision for energy production characterized by minimal use of resources and production of waste, while being economically affordable and safe, secure and reliable in operation. This vision is transformed into a mission for a disruptive development of the future nuclear energy system operated by burning of existing spent nuclear fuel (SNF) without prior reprocessing. This highly innovative approach fulfils the sustainability goals and creates new options for P&T. A proof on the feasibility from neutronic point of view is given demonstrating sufficient breeding of fissile material from the inserted SNF. The system does neither require new resources nor produce additional waste, thus it provides a highly sustainable option for a future nuclear system fulfilling the requests of P&T as side effect. In addition, this nuclear system provides enhanced resistance against misuse of Pu and a significantly reduced fuel cycle. However, the new system requires a demand driven rethinking of the separation process to be efficient.

Transmutation of All German Transuranium under Nuclear Phase Out Conditions - Is This Feasible from Neutronic Point of View?

The German government has decided for the nuclear phase out, but a decision on a strategy for the management of the highly radioactive waste is not defined yet. Partitioning and Transmutation (P&T) could be considered as a technological option for the management of highly radioactive waste, therefore a wide study has been conducted. In the study group objectives for P&T and the boundary conditions of the phase out have been discussed. The fulfillment of the given objectives is analyzed from neutronics point of view using simulations of a molten salt reactor with fast neutron spectrum. It is shown that the efficient transmutation of all existing transuranium isotopes would be possible from neutronic point of view in a time frame of about 60 years. For this task three reactors of a mostly new technology would have to be developed and a twofold life cycle consisting of a transmuter operation and a deep burn phase would be required. A basic insight for the optimization of the time duration of the deep burn phase is given. Further on, a detailed balance of different isotopic inventories is given to allow a deeper understanding of the processes during transmutation in the molten salt fast reactor. The effect of modeling and simulation is investigated based on three different modeling strategies and two different code versions.

On the use of a molten salt fast reactor to apply an idealized transmutation scenario for the nuclear phase out.

In the view of transmutation of transuranium (TRU) elements, molten salt fast reactors (MSFRs) offer certain advantages compared to solid fuelled reactor types like sodium cooled fast reactors (SFRs). In the first part these advantages are discussed in comparison with the SFR technology, and the research challenges are analyzed. In the second part cycle studies for the MSFR are given for different configurations--a core with U-238 fertile, a fertile free core, and a core with Th-232 as fertile material. For all cases, the transmutation potential is determined and efficient transmutation performance for the case with thorium as a fertile material as well as for the fertile free case is demonstrated and the individual advantages are discussed. The time evolution of different important isotopes is analyzed. In the third part a strategy for the optimization of the transmutation efficiency is developed. The final aim is dictated by the phase out decision of the German government, which requests to put the focus on the determination of the maximal transmutation efficiency and on an as much as possible reduced leftover of transuranium elements at the end of the reactor life. This minimal leftover is achieved by a two step procedure of a first transmuter operation phase followed by a second deep burning phase. There the U-233, which is bred in the blanket of the core consisting of thorium containing salt, is used as feed. It is demonstrated, that transmutation rates up to more than 90% can be achieved for all transuranium isotopes, while the production of undesired high elements like californium is very limited. Additionally, the adaptations needed for the simulation of a MSFR, and the used tool HELIOS 1.10 is described.

The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutations and evidence of a mutational hot spot.

Paroxysmal nocturnal hemoglobinuria (PNH) may arise during long-term follow- up of aplastic anemia (AA), and many AA patients have minor glycosylphosphatidylinositol (GPI) anchor-deficient clones, even at presentation. PIG-A gene mutations in AA/PNH and hemolytic PNH are thought to be similar, but studies on AA/PNH have been limited to individual cases and a few small series. We have studied a large series of AA patients with a GPI anchor-deficient clone (AA/PNH), including patients with minor clones, to determine whether their pattern of PIG-A mutations was identical to the reported spectrum in hemolytic PNH. AA patients with GPI anchor-deficient clones were identified by flow cytometry and minor clones were enriched by immunomagnetic selection. A variety of methods was used to analyze PIG-A mutations, and 57 mutations were identified in 40 patients. The majority were similar to those commonly reported, but insertions in the range of 30 to 88 bp, due to tandem duplication of PIG-A sequences, and deletions of more than 10 bp were also seen. In 3 patients we identified identical 5-bp deletions by conventional methods. This prompted the design of mutation-specific polymerase chain reaction (PCR) primers, which were used to demonstrate the presence of the same mutation in an additional 12 patients, identifying this as a mutational hot spot in the PIG-A gene. Multiple PIG-A mutations have been reported in 10% to 20% of PNH patients. Our results suggest that the large majority of AA/PNH patients have multiple mutations. These data may suggest a process of hypermutation in the PIG-A gene in AA stem cells.