Electromagnetic Radiation Hardness of Diamond Detectors

The behavior of artificially grown CVD diamond films under intense electromagnetic radiation has been studied. The properties of irradiated diamond samples have been investigated using the method of thermally stimulated current and by studying their charge collection properties. Diamonds have been found to remain unaffected after doses of 6.8 MGy of 10 keV photons and 10 MGy of MeV-range photons. This observation makes diamond an attractive detector material for a calorimeter in the very forward region of the proposed TESLA detector.Comment: 19 pages, 9 figure

Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia

Several chemo-resistance mechanisms including the Bcl-2 protein family overexpression and constitutive activation of the PI3K/Akt/mTOR signaling have been documented in acute lymphoblastic leukemia (ALL), encouraging targeted approaches to circumvent this clinical problem. Here we analyzed the activity of the BH3 mimetic ABT-737 in ALL, exploring the synergistic effects with the mTOR inhibitor CCI-779 on ABT-737 resistant cells. We showed that a low Mcl-1/Bcl-2 plus Bcl-xL protein ratio determined ABT-737 responsiveness. ABT-737 exposure further decreased Mcl-1, inducing apoptosis on sensitive models and primary samples, while not affecting resistant cells. Co-inhibition of Bcl-2 and the mTOR pathway resulted cytotoxic on ABT-737 resistant models, by downregulating mTORC1 activity and Mcl-1 in a proteasome-independent manner. Although Mcl-1 seemed to be critical, ectopic modulation did not correlate with apoptosis changes. Importantly, dual targeting proved effective on ABT-737 resistant samples, showing additive/synergistic effects. Together, our results show the efficacy of BH3 mimetics as single agent in the majority of the ALL samples and demonstrate that resistance to ABT-737 mostly correlated with Mcl-1 overexpression. Co-targeting of the Bcl-2 protein family and mTOR pathway enhanced drug-induced cytotoxicity by suppressing Mcl-1, providing a novel therapeutic approach to overcome BH3 mimetics resistance in ALL

CD95/CD95L interactions and their role in autoimmunity

CD95 (Fas/Apo-1) is a broadly expressed death receptor involved in a variety of physiological and pathological apoptotic processes. Since its discovery, defects in CD95/CD95L system have been proposed as major pathogenic factors responsible for impaired immunological tolerance to self antigens and autoimmunity. Later, analysis of altered sensitivity to CD95-induced apoptosis in cells targeted by the immune response has revealed an unexpected role for CD95 and CD95L in organ-specific autoimmunity. CD95 has been shown to be expressed and functional in virtually all cell types that are target of the organ-specific autoimmune response. Here we review some of the major findings concerning the role of CD95 in autoimmunity, in dysfunctions due to increased or decreased CD95-induced apoptosis

Death in 2000 ways

N/

Studies of aging and HV break down problems during development and operation of MSGC and GEM detectors for the Inner Tracking System of HERA-B

The results of five years of development of the inner tracking system of the HERA-B experiment and first experience from the data taking period of the year 2000 are reported. The system contains 184 chambers, covering a sensitive area of about 20 * 20 cm2 each. The detector is based on microstrip gas counters (MSGCs) with diamond like coated (DLC) glass wafers and gas electron multipliers (GEMs). The main problems in the development phase were gas discharges in intense hadron beams and aging in a high radiation dose environment. The observation of gas discharges which damage the electrode structure of the MSGC led to the addition of the GEM as a first amplification step. Spurious sparking at the GEM cannot be avoided completely. It does not affect the GEM itself but can produce secondary damage of the MSGC if the electric field between the GEM and the MSGC is above a threshold depending on operation conditions. We observed that aging does not only depend on the dose but also on the spot size of the irradiated area. Ar-DME mixtures had to be abandoned whereas a mixture of 70% Ar and 30% CO2 showed no serious aging effects up to about 40 mC/cm deposited charge on the anodes. X-ray measurements indicate that the DLC of the MSGC is deteriorated by the gas amplification process. As a consequence, long term gain variations are expected. The Inner Tracker has successfully participated in the data taking at HERA-B during summer 2000.Comment: 29 pages, 22 figure

Probing topological invariants in the bulk of a non-Hermitian optical system

Topological insulators are insulating in the bulk but feature conducting states on their surfaces. Standard methods for probing their topological properties largely involve probing the surface, even though topological invariants are defined via the bulk band structure. Here, we utilize non-hermiticy to experimentally demonstrate a topological transition in an optical system, using bulk behavior only, without recourse to surface properties. This concept is relevant for a wide range of systems beyond optics, where the surface physics is difficult to probe

Influence of a Pronounced Pre-Deformation on the Attachment of Melt Droplets and the Fatigue Behavior of Laser-Cut AISI 304

Laser cutting is a suitable manufacturing method for generating complex geometries for sheet metal components. However, their cyclic load capacity is reduced compared to, for example, milled components. This is due to the influence of the laser-cut edge, whose characteristic features act as crack initiation sites, especially resolidified material in the form of burr and melt droplets. Since sheet metal components are often formed into their final geometry after cutting, another important factor influencing fatigue behavior is the effect of the forming process on the laser-cut edge. In particular, the effect of high degrees of deformation has not yet been researched in detail. Accordingly, sheets of AISI 304 were processed by laser cutting and pre-deformed. In the process, α’-martensite content was set to be comparable despite different degrees of deformation. It was found that deformation to high elongations caused a large part of the melt adhesions to fall off, but those still attaching were partially detached and thus formed an initial notch for crack initiation. This significantly lowered the fatigue strength