Proton induced thermal stress-wave measurements using a Laser Doppler Vibrometer

Abstract.: Thermal stress-waves are generated in the solid target material when the proton beam interacts. These stress waves excite natural oscillations of the target or cause plastic deformations. Hence, an experimental setup with a laser Doppler vibrometer [CITE] was developed to investigate free surface vibrations of cylindrical targets. The target configurations for RIB and conventional neutrino beams (CNGS project) were investigated to analyze proton induced thermal stress-wave generation and propagatio

Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells

Receptor-PI3K-mTORC1 signaling and fatty acid synthase (FASN)-regulated lipid biosynthesis harbor numerous drug targets and are molecularly connected. We hypothesize that unraveling the mechanisms of pathway cross-talk will be useful for designing novel co-targeting strategies for ovarian cancer (OC). The impact of receptor-PI3K-mTORC1 onto FASN is already well-characterized. However, reverse actions–from FASN towards receptor-PI3K-mTORC1–are still elusive. We show that FASN-blockade impairs receptor-PI3K-mTORC1 signaling at multiple levels. Thin-layer chromatography and MALDI-MS/MS reveals that FASN-inhibitors (C75, G28UCM) augment polyunsaturated fatty acids and diminish signaling lipids diacylglycerol (DAG) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) in OC cells (SKOV3, OVCAR-3, A2780, HOC-7). Western blotting and micropatterning demonstrate that FASN-blockers impair phosphorylation/expression of EGF-receptor/ERBB/HER and decrease GRB2–EGF-receptor recruitment leading to PI3K-AKT suppression. FASN-inhibitors activate stress response-genes HIF-1α-REDD1 (RTP801/DIG2/DDIT4) and AMPKα causing mTORC1- and S6-repression. We conclude that FASN-inhibitor-mediated blockade of receptor-PI3K-mTORC1 occurs due to a number of distinct but cooperating processes. Moreover, decrease of PI3K-mTORC1 abolishes cross-repression of MEK-ERK causing ERK activation. Consequently, the MEK-inhibitor selumetinib/AZD6244, in contrast to the PI3K/mTOR-inhibitor dactolisib/NVP-BEZ235, increases growth inhibition when given together with a FASN-blocker. We are the first to provide deep insight on how FASN-inhibition blocks ERBB-PI3K-mTORC1 activity at multiple molecular levels. Moreover, our data encourage therapeutic approaches using FASN-antagonists together with MEK-ERK-inhibitors

State-of-the-art microscopy to understand islets of Langerhans:what to expect next?

The discovery of Langerhans and microscopic description of islets in the pancreas were crucial steps in the discovery of insulin. Over the past 150 years, many discoveries in islet biology and type 1 diabetes have been made using powerful microscopic techniques. In the past decade, combination of new probes, animal and tissue models, application of new biosensors and automation of light and electron microscopic methods and other (sub)cellular imaging modalities have proven their potential in understanding the beta cell under (patho)physiological conditions. The imaging evolution, from fluorescent jellyfish to real-time intravital functional imaging, the revolution in automation and data handling and the increased resolving power of analytical imaging techniques are now converging. Here, we review innovative approaches that address islet biology from new angles by studying cells and molecules at high spatiotemporal resolution and in live models. Broad implementation of these cellular imaging techniques will shed new light on cause/consequence of (mal)function in islets of Langerhans in the years to come

Considerations on the proton beam shape for Refractory Metal Foil Targets

Document illustrating different proton beam steering characteristics onto the refractory foil targe

Feasibility of High Power Refractory Metal-Foil Targets for EURISOL

Manuscript on the feasibility and design of the 100kW refractory metal targe

Ceramic materials testing and modeling

Certain refractory ceramics (notably oxides) have desirable properties suitable for the construction of ceramic waste containers for long term use in nuclear waste disposal applications. In particular, they are far less prone to environmental corrosion than metals under realistic repository conditions. The aqueous corrosion rates of oxides such as magnesium aluminate spinel (MgAl{sub 2}0{sub 4}) and alumina (Al{sub 2}0{sub 4}) fall in the range of a few millimeters per million years. Oxide ceramics are also not likely to be subject to microbiologically influenced corrosion, which apparently can attack most, if not all, of the available engineering metals. Ceramics have a reputation for poor mechanical performance and large, impermeable objects are not easily fabricated by most current fabrication methods. As a result, the most promising approach for incorporating ceramics in large waste packages appears to be to apply a high density ceramic coating to a supporting metallic structure. Ceramic coatings 2048 applied by a thermal spray technique can be made effectively seamless and provide a method for final closure of the waste package while maintaining low average temperatures for the entire assembly. The corrosion resistance of the ceramic should prevent or delay water penetration to the underlying metal, which will in turn provide most of the mechanical strength and toughness required by the application. In this way, the major concerns regarding the ceramic coating become ensuring it is impervious to moisture, its adherence and its resistance to mechanical stresses during handling or resulting from rock fall in the repository. Without water, electrochemical corrosion and microbiologically influenced corrosion processes are considered impossible, so a complete coating should protect the metal vessels for far longer than the current design requirements. Even an imperfect coating should extend the life of the package, delaying the onset and reducing the severity of corrosion by limiting the transport of water and oxygen to the ceramic-metal interface. Thermal spray techniques for ceramic coating metallic structures are currently being explored. The mechanics of thermal spray resembles spray painting in many respects, allowing large surfaces and contours to be covered smoothly. All of the relevant thermal spray processes use a high energy input to melt or partially melt a powdered oxide material, along with a high velocity gas to impinge the molten droplets onto a substrate where they conform, quench, solidify and adhere mechanically. The energy input can be an arc generated plasma, an oxy-fuel flame or an explosion. The appropriate feed material and the resulting coating morphologies vary with technique as well as with application parameters. To date on this project, several versions of arc plasma systems, a detonation coating system and two variations of high velocity oxy-fuel (HVOF) fired processes have been investigated, operating on several different ceramic materials

Feasibility of high power refractory metal-foil targets for EURISOL

EURISOL foil-targets have to withstand a primary proton beam of 1 GeV kinetic energy and up to 100 μA beam current. These foil targets will be based on previous high-power target concepts, i.e. the RIST target [J.R.J. Bennett et al., Nucl. Instrum. Meth. Phys. Res. B 126, 117 (1997)] or high power targets used at TRIUMF [P. Bricault et al., Nucl. Instrum. Meth. Phys. Res. B 204, 319 (2003), M. Dombsky et al., Nucl. Instrum. Meth. Phys. Res. B 204, 191 (2003)]. A single target unit is capable of dissipating up to 25 kW, hence, several target units can be merged together by individual transfer lines to one common ion source. The single target units will be irradiated by a proton beam in a time sharing mode to distribute the primary proton beam current to the individual target units. In this feasibility study the necessary properties of high-power foil targets are discussed and the requirements to design a foil target according to the proton beam parameters [CITE] for the future EURISOL facility are given