A new double laser pulse pumping scheme for transient collisionally excited plasma soft X-ray lasers

Within this thesis a new double laser pulse pumping scheme for plasma-based, transient collisionally excited soft x-ray lasers (SXRL) was developed, characterized and utilized for applications. SXRL operations from ~50 up to ~200 electron volt were demonstrated applying this concept. As a central technical tool, a special Mach-Zehnder interferometer in the chirped pulse amplification (CPA) laser front-end was developed for the generation of fully controllable double-pulses to optimally pump SXRLs.rnThis Mach-Zehnder device is fully controllable and enables the creation of two CPA pulses of different pulse duration and variable energy balance with an adjustable time delay. Besides the SXRL pumping, the double-pulse configuration was applied to determine the B-integral in the CPA laser system by amplifying short pulse replica in the system, followed by an analysis in the time domain. The measurement of B-integral values in the 0.1 to 1.5 radian range, only limited by the reachable laser parameters, proved to be a promising tool to characterize nonlinear effects in the CPA laser systems.rnContributing to the issue of SXRL pumping, the double-pulse was configured to optimally produce the gain medium of the SXRL amplification. The focusing geometry of the two collinear pulses under the same grazing incidence angle on the target, significantly improved the generation of the active plasma medium. On one hand the effect was induced by the intrinsically guaranteed exact overlap of the two pulses on the target, and on the other hand by the grazing incidence pre-pulse plasma generation, which allows for a SXRL operation at higher electron densities, enabling higher gain in longer wavelength SXRLs and higher efficiency at shorter wavelength SXRLs. The observation of gain enhancement was confirmed by plasma hydrodynamic simulations.rnThe first introduction of double short-pulse single-beam grazing incidence pumping for SXRL pumping below 20 nanometer at the laser facility PHELIX in Darmstadt (Germany), resulted in a reliable operation of a nickel-like palladium SXRL at 14.7 nanometer with a pump energy threshold strongly reduced to less than 500 millijoule. With the adaptation of the concept, namely double-pulse single-beam grazing incidence pumping (DGRIP) and the transfer of this technology to the laser facility LASERIX in Palaiseau (France), improved efficiency and stability of table-top high-repetition soft x-ray lasers in the wavelength region below 20 nanometer was demonstrated. With a total pump laser energy below 1 joule the target, 2 mircojoule of nickel-like molybdenum soft x-ray laser emission at 18.9 nanometer was obtained at 10 hertz repetition rate, proving the attractiveness for high average power operation. An easy and rapid alignment procedure fulfilled the requirements for a sophisticated installation, and the highly stable output satisfied the need for a reliable strong SXRL source. The qualities of the DGRIP scheme were confirmed in an irradiation operation on user samples with over 50.000 shots corresponding to a deposited energy of ~ 50 millijoule.rnThe generation of double-pulses with high energies up to ~120 joule enabled the transfer to shorter wavelength SXRL operation at the laser facility PHELIX. The application of DGRIP proved to be a simple and efficient method for the generation of soft x-ray lasers below 10 nanometer. Nickel-like samarium soft x-ray lasing at 7.3 nanometer was achieved at a low total pump energy threshold of 36 joule, which confirmed the suitability of the applied pumping scheme. A reliable and stable SXRL operation was demonstrated, due to the single-beam pumping geometry despite the large optical apertures. The soft x-ray lasing of nickel-like samarium was an important milestone for the feasibility of applying the pumping scheme also for higher pumping pulse energies, which are necessary to obtain soft x-ray laser wavelengths in the water window. The reduction of the total pump energy below 40 joule for 7.3 nanometer short wavelength lasing now fulfilled the requirement for the installation at the high-repetition rate operation laser facility LASERIX.rn

The scintillating fiber focal plane detector for the use of Kaos as a double arm spectrometer

The upgrade of the Mainz Mikrotron (MAMI) electron accelerator facility in 2007 which raised the beam energy up to 1.5,GeV, gives the opportunity to study strangeness production channels through electromagnetic process. The Kaon Spectrometer (KAOS) managed by the A1 Collaboration, enables the efficient detection of the kaons associated with strangeness electroproduction. Used as a single arm spectrometer, it can be combined with the existing high-resolution spectrometers for exclusive measurements in the kinematic domain accessible to them.rnrnFor studying hypernuclear production in the ^A Z(e,e'K^+) _Lambda ^A(Z-1) reaction, the detection of electrons at very forward angles is needed. Therefore, the use of KAOS as a double-arm spectrometer for detection of kaons and the electrons at the same time is mandatory. Thus, the electron arm should be provided with a new detector package, with high counting rate capability and high granularity for a good spatial resolution. To this end, a new state-of-the-art scintillating fiber hodoscope has been developed as an electron detector.rnrnThe hodoscope is made of two planes with a total of 18432 scintillating double-clad fibers of 0.83 mm diameter. Each plane is formed by 72 modules. Each module is formed from a 60deg slanted multi-layer bundle, where 4 fibers of a tilted column are connected to a common read out. The read-out is made with 32 channels of linear array multianode photomultipliers. Signal processing makes use of newly developed double-threshold discriminators. The discriminated signal is sent in parallel to dead-time free time-to-digital modules and to logic modules for triggering purposes.rnrnTwo fiber modules were tested with a carbon beam at GSI, showing a time resolution of 220 ps (FWHM) and a position residual of 270 microm m (FWHM) with a detection efficiency epsilon>99%.rnrnThe characterization of the spectrometer arm has been achieved through simulations calculating the transfer matrix of track parameters from the fiber detector focal plane to the primary vertex. This transfer matrix has been calculated to first order using beam transport optics and has been checked by quasielastic scattering off a carbon target, where the full kinematics is determined by measuring the recoil proton momentum. The reconstruction accuracy for the emission parameters at the quasielastic vertex was found to be on the order of 0.3 % in first test realized.rnrnThe design, construction process, commissioning, testing and characterization of the fiber hodoscope are presented in this work which has been developed at the Institut für Kernphysik of the Johannes Gutenberg - Universität Mainz.

Production of antihydrogen via double charge exchange

Spectroscopy of the 1S-2S transition of antihydrogen confined in a neutral atom trap and comparison with the equivalent spectral line in hydrogen will provide an accurate test of CPT symmetry and the first one in a mixed baryon-lepton system. Also, with neutral antihydrogen atoms, the gravitational interaction between matter and antimatter can be tested unperturbed by the much stronger Coulomb forces.rnAntihydrogen is regularly produced at CERN's Antiproton Decelerator by three-body-recombination (TBR) of one antiproton and two positrons. The method requires injecting antiprotons into a cloud of positrons, which raises the average temperature of the antihydrogen atoms produced way above the typical 0.5 K trap depths of neutral atom traps. Therefore only very few antihydrogen atoms can be confined at a time. Precision measurements, like laser spectroscopy, will greatly benefit from larger numbers of simultaneously trapped antihydrogen atoms.rnTherefore, the ATRAP collaboration developed a different production method that has the potential to create much larger numbers of cold, trappable antihydrogen atoms. Positrons and antiprotons are stored and cooled in a Penning trap in close proximity. Laser excited cesium atoms collide with the positrons, forming Rydberg positronium, a bound state of an electron and a positron. The positronium atoms are no longer confined by the electric potentials of the Penning trap and some drift into the neighboring cloud of antiprotons where, in a second charge exchange collision, they form antihydrogen. The antiprotons remain at rest during the entire process, so much larger numbers of trappable antihydrogen atoms can be produced. Laser excitation is necessary to increase the efficiency of the process since the cross sections for charge-exchange collisions scale with the fourth power of the principal quantum number n.rnThis method, named double charge-exchange, was demonstrated by ATRAP in 2004. Since then, ATRAP constructed a new combined Penning Ioffe trap and a new laser system. The goal of this thesis was to implement the double charge-exchange method in this new apparatus and increase the number of antihydrogen atoms produced.rnCompared to our previous experiment, we could raise the numbers of positronium and antihydrogen atoms produced by two orders of magnitude. Most of this gain is due to the larger positron and antiproton plasmas available by now, but we could also achieve significant improvements in the efficiencies of the individual steps. We therefore showed that the double charge-exchange can produce comparable numbers of antihydrogen as the TBR method, but the fraction of cold, trappable atoms is expected to be much higher. Therefore this work is an important step towards precision measurements with trapped antihydrogen atoms.

NCX-1000, a nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study

NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), which showed selective vasodilatory effect on intrahepatic circulation in animal models of cirrhosis. This study was aimed at testing the efficacy and tolerability of this compound in patients with cirrhosis and portal hypertension.

Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.

Diffuse swelling of the buccal mucosa and palate as first and only manifestation of an extranodal non-Hodgkin 'double-hit' lymphoma: report of a case

Most of the lymphomas arising in the oral cavity are of B-cell origin. Among these, diffuse large B-cell lymphomas are the most common. Diffuse large B-cell lymphomas may exhibit more than one chromosomal rearrangement and are then referred to as 'double-hit' or 'triple-hit' lymphomas.

Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial

Eosinophilic oesophagitis (EoO) is a clinicopathological condition defined by proton pump inhibitor-refractory oesophageal symptoms combined with oesophageal eosinophilia. The pharmacodynamic effect of mepolizumab (a humanised anti-interleukin-5 monoclonal antibody) in EoO was evaluated.

MET inhibition in tumor cells by PHA665752 impairs homologous recombination repair of DNA double strand breaks

Abnormal activation of cellular DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems has broad implications for both cancer biology and treatment. Recent studies suggest a potential link between DNA repair and aberrant activation of the hepatocyte growth factor receptor Mesenchymal-Epithelial Transition (MET), an oncogene that is overexpressed in numerous types of human tumors and considered a prime target in clinical oncology. Using the homologous recombination (HR) direct-repeat direct-repeat green fluorescent protein ((DR)-GFP) system, we show that MET inhibition in tumor cells with deregulated MET activity by the small molecule PHA665752 significantly impairs in a dose-dependent manner HR. Using cells that express MET-mutated variants that respond differentially to PHA665752, we confirm that the observed HR inhibition is indeed MET-dependent. Furthermore, our data also suggest that decline in HR-dependent DNA repair activity is not a secondary effect due to cell cycle alterations caused by PHA665752. Mechanistically, we show that MET inhibition affects the formation of the RAD51-BRCA2 complex, which is crucial for error-free HR repair of double strand DNA lesions, presumably via downregulation and impaired translocation of RAD51 into the nucleus. Taken together, these findings assist to further support the role of MET in the cellular DNA damage response and highlight the potential future benefit of MET inhibitors for the sensitization of tumor cells to DNA damaging agents.

A double role of sperm in scorpions: the mating plug of Euscorpius italicus (Scorpiones: Euscorpiidae) consists of sperm

Mating plugs occluding the female gonopore after mating are a widespread phenomenon. In scorpions, two main types of mating plugs are found: sclerotized mating plugs being parts of the spermatophore that break off during mating, and gel-like mating plugs being gelatinous fluids that harden in the female genital tract. In this study, the gel-like mating plug of Euscorpius italicus was investigated with respect to its composition, fine structure, and changes over time. Sperm forms the major component of the mating plug, a phenomenon previously unknown in arachnids. Three parts of the mating plug can be distinguished. The part facing the outside of the female (outer part) contains sperm packages containing inactive spermatozoa. In this state, sperm is transferred. In the median part, the sperm packages get uncoiled to single spermatozoa. In the inner part, free sperm is embedded in a large amount of secretions. Fresh mating plugs are soft gelatinous, later they harden from outside toward inside. This process is completed after 3-5 days. Sperm from artificially triggered spermatophores could be activated by immersion in insect Ringer's solution indicating that the fluid condition in the females' genital tract or females' secretions causes sperm activation. Because of the male origin of the mating plug, it has likely evolved under sperm competition or sexual conflict. As females refused to remate irrespective of the presence or absence of a mating plug, females may have changed their mating behavior in the course of evolution from polyandry to monandry.

Histological evidence of delayed ischemic brain tissue damage in the rat double-hemorrhage model

The rat double-SAH model is one of the standard models to simulate delayed cerebral vasospasm (CVS) in humans. However, the proof of delayed ischemic brain damage is missing so far. Our objective was, therefore, to determine histological changes in correlation with the development of symptomatic and perfusion weighted imaging (PWI) proven CVS in this animal model. CVS was induced by injection of autologous blood in the cisterna magna of 22 Sprague-Dawley rats. Histological changes were analyzed on day 3 and day 5. Cerebral blood flow (CBF) was assessed by PWI at 3 tesla magnetic resonance (MR) tomography. Neuronal cell count did not differ between sham operated and SAH rats in the hippocampus and the cerebral cortex on day 3. In contrast, on day 5 after SAH the neuronal cell count was significantly reduced in the hippocampus (p<0.001) and the inner cortical layer (p=0.03). The present investigation provides quantitative data on brain tissue damage in association with delayed CVS for the first time in a rat SAH model. Accordingly, our data suggest that the rat double-SAH model may be suitable to mimic delayed ischemic brain damage due to CVS and to investigate the neuroprotective effects of drugs.

Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial

Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event.