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Fault zones are the locations where motion of tectonic plates, often associated with earthquakes, is accommodated. Despite a rapid increase in the understanding of faults in the last decades, our knowledge of their geometry, petrophysical properties, and controlling processes remains incomplete. The central questions addressed here in our study of the Dead Sea Transform (DST) in the Middle East are as follows: (1) What are the structure and kinematics of a large fault zone? (2) What controls its structure and kinematics? (3) How does the DST compare to other plate boundary fault zones? The DST has accommodated a total of 105 km of left-lateral transform motion between the African and Arabian plates since early Miocene (similar to 20 Ma). The DST segment between the Dead Sea and the Red Sea, called the Arava/Araba Fault (AF), is studied here using a multidisciplinary and multiscale approach from the mu m to the plate tectonic scale. We observe that under the DST a narrow, subvertical zone cuts through crust and lithosphere. First, from west to east the crustal thickness increases smoothly from 26 to 39 km, and a subhorizontal lower crustal reflector is detected east of the AF. Second, several faults exist in the upper crust in a 40 km wide zone centered on the AF, but none have kilometer-size zones of decreased seismic velocities or zones of high electrical conductivities in the upper crust expected for large damage zones. Third, the AF is the main branch of the DST system, even though it has accommodated only a part (up to 60 km) of the overall 105 km of sinistral plate motion. Fourth, the AF acts as a barrier to fluids to a depth of 4 km, and the lithology changes abruptly across it. Fifth, in the top few hundred meters of the AF a locally transpressional regime is observed in a 100-300 m wide zone of deformed and displaced material, bordered by subparallel faults forming a positive flower structure. Other segments of the AF have a transtensional character with small pull-aparts along them. The damage zones of the individual faults are only 5-20 m wide at this depth range. Sixth, two areas on the AF show mesoscale to microscale faulting and veining in limestone sequences with faulting depths between 2 and 5 km. Seventh, fluids in the AF are carried downward into the fault zone. Only a minor fraction of fluids is derived from ascending hydrothermal fluids. However, we found that on the kilometer scale the AF does not act as an important fluid conduit. Most of these findings are corroborated using thermomechanical modeling where shear deformation in the upper crust is localized in one or two major faults; at larger depth, shear deformation occurs in a 20-40 km wide zone with a mechanically weak decoupling zone extending subvertically through the entire lithosphere.
Strassenfußball für Toleranz
(2005)
Inhibition of MAP kinase pathways by selective BRAF inhibitors, such as vemurafenib and dabrafenib, have evolved as key therapies of BRAF-mutated melanoma. However, tumor relapse and therapy resistance have remained as major problems, which may be addressed by combination with other pathway inhibitors. Here we identified the potassium channel inhibitor TRAM-34 as highly effective in combination with vemurafenib. Thus apoptosis was significantly enhanced and cell viability was decreased. The combination vemurafenib/TRAM-34 was also effective in vemurafenib-resistant cells, suggesting that acquired resistance may be overcome. Vemurafenib decreased ERK phosphorylation, suppressed antiapoptotic Mcl-1 and enhanced proapoptotic Puma and Bim. The combination resulted in enhancement of proapoptotic pathways as caspase-3 and loss of mitochondrial membrane potential. Indicating a special mechanism of vemurafenib-induced apoptosis, we found strong enhancement of intracellular ROS levels already at 1 h of treatment. The critical role of ROS was demonstrated by the antioxidant vitamin E (alpha-tocopherol), which decreased intracellular ROS as well as apoptosis. Also caspase activation and loss of mitochondrial membrane potential were suppressed, proving ROS as an upstream effect. Thus ROS represents an initial and independent apoptosis pathway in melanoma cells that is of particular importance for vemurafenib and its combination with TRAM-34.
Background:
The overall goal of the project ‘StiEL’ is to contribute to the professional development of teachers and other educational staff working at German secondary schools. The aim is to develop an evidence-based training concept for the inclusion of students with diverse abilities. The project is organized as a collaborative research effort of three partnering institutions and funded by the German Federal Ministry of Education and Research from 2018-2021.
Methods:
To support the on-going transition towards inclusive school practices, a multi-stage approach is envisaged. The first phase aims at a scoping review of existing literature and programmes on inclusion. The overview is supplemented by interviews with school staff members. Training modules are developed in the second project phase. The third phase of StiEL puts the newly developed training program into practice. The knowledge and skills acquired by the participants through the training as well as the teaching and management of inclusive classrooms after the training are evaluated through longitudinal and ethnographic approaches. The final project phase creates a best practice manual and makes the modules available via open access databases.
Results:
The presentation will focus on the first phase and try to explore the health-related consequences of the transition towards an inclusive school system in Germany for different participants. We will present preliminary results of expert interviews as well as some results from the literature screening. Due to our findings the current practice on German schools towards the road to inclusion is very stressful for all participants. We will explore recommendations for health promoting schools under conditions of inclusion.
Conclusions:
In terms of health-related consequences for all participants, the road to inclusion is very ambitious but also very stressful. Regarding the development of an inclusive school system, we need to focus much more on health and health promotion.
Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.