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Musso F.,Jülich Research Center | Musso F.,Heinrich Heine University Düsseldorf | Brinkmeyer J.,Jülich Research Center | Brinkmeyer J.,Heinrich Heine University Düsseldorf | And 10 more authors.
NeuroImage | Year: 2011

Background: Behavioral and electrophysiological human ketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology. Methods: We conducted a within-subject, randomized, placebo-controlled pharmacoimaging study in twenty-four male volunteers. Subjects were given low-dose S-ketamine (bolus prior to functional imaging: 0.1. mg/kg during 5. min, thereafter continuous infusion: 0.015625. mg/kg/min reduced by 10% every ten minutes) or placebo while performing a visual oddball task during simultaneous functional magnetic resonance imaging (fMRI) with continuous recording of event-related potentials (P300) and electrodermal activity (EDA). Before and after intervention, psychopathological status was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale. Results: P300 amplitude and corresponding BOLD responses were diminished in the ketamine condition in cortical regions being involved in sensory processing/selective attention. In both measurement modalities separation of drug conditions was achieved with area under the curve (AUC) values of up to 0.8-0.9. Ketamine effects were also observed in the clinical, behavioral and peripheral physiological domains (Positive and Negative Syndrome Scale, reaction hit and false alarm rate, electrodermal activity and heart rate) which were in part related to the P300/fMRI measures. Conclusion: The findings from our ketamine experiment are consistent across modalities and directly related to observations in schizophrenia supporting the validity of the model. Our investigation provides the first prototypic example of a pharmacoimaging study using simultaneously acquired fMRI/EEG. © 2011 Elsevier Inc.

The new version of the bioequivalence guidance offers for highly variable drug substances a new approach as an alternative to the standard 2-period cross-over design. Some vague phrases in the old guidance ("in certain cases . . . may be") were converted into fixed rules. The confidence intervals now are compared to acceptance ranges which depend directly on the intra-individual variability of the reference preparation. This requires that the bioequivalence study is performed according to a repetitive design, but this design nevertheless requires fewer concentration-time profiles than a comparable 2-period cross-over design. The widening of the acceptance limits stops at 50 % intra-individual variability, but the new alternative approach also is of advantage for drug substances of even higher variability. © ECV • Editio Cantor Verlag.

Heger-Mahn D.,Dinox GmbH Female Health Research | Pabst G.,FOCUS GmbH | Dienel A.,Willmar Schwabe GmbH & Co. KG | Schlafke S.,Willmar Schwabe GmbH & Co. KG | Klipping C.,Dinox B. V
Drugs in R and D | Year: 2014

Methods: A double-blind, randomised, 2-period crossover study was performed to investigate the effects of Silexan on the pharmacokinetics and pharmacodynamics of Microgynon®, a combination oral contraceptive containing ethinyl estradiol 0.03 mg (EE) and levonorgestrel 0.15 mg (LNG) in healthy, fertile, adult females. During 2 consecutive cycles of 28 days, oral contraception was given for 21 days combined with 1 × 160 mg/day Silexan or placebo. Plasma concentration–time profiles of EE and LNG were obtained on day 18 ± 1 up to 24 h after dosing. The primary outcome measure was the area under the concentration–time curve over a dosing interval of τ = 24 h (AUCτ) for EE and LNG plasma levels. An interaction with Silexan was formally excluded if the 90 % confidence interval for the AUCτ ratio during co-administration with Silexan or placebo was included within the range of 0.80–1.25. Secondary outcomes included EE and LNG peak concentration (Cmax) and time to Cmax (tmax), follicle size, endometrial thickness, the Hoogland score, and serum levels of estradiol, progesterone, and sex hormone-binding globulin.Results: A total of 24 women (mean age 27.3 years; mean body mass index 22.2 kg/m2) participated. The confidence intervals for the EE and LNG AUCτ and Cmax ratios fell within the pre-specified limits, indicating no interaction (point estimates [Silexan/placebo] AUCτ EE 0.97, LNG 0.94; Cmax EE 0.99, LNG 0.96). For LNG, tmax was slightly delayed. No secondary outcome indicated any impairment of contraceptive efficacy.Conclusions: Co-administration of Silexan did not affect the efficacy of a combination oral contraceptive containing EE and LNG and was well tolerated.Purpose: Silexan is an oral Lavender oil preparation with proven anxiolytic efficacy. Given the high prevalence of anxiety and restlessness in younger women, oral contraceptives and Silexan will likely be co-administered. © 2014, The Author(s).

Lavayssiere M.,CEA Grenoble | Escher M.,FOCUS GmbH | Renault O.,CEA Grenoble | Mariolle D.,CEA Grenoble | Barrett N.,CEA Saclay Nuclear Research Center
Journal of Electron Spectroscopy and Related Phenomena | Year: 2013

Photoelectron emission microscopy (PEEM) is a powerful non-destructive tool for spatially resolved, spectroscopic analysis of surfaces with sub-micron chemical heterogeneities. However, in the case of micron scale patterned semiconductors, band line-ups at pn junctions have a built-in lateral electric field which can significantly alter the PEEM image of the structure with respect to its physical dimensions. Furthermore, real surfaces may also have physical topography which can reinforce or counteract the electrically induced distortion at a pn junction. We have measured the experimental PEEM image distortion at such a junction and carried out numerical simulations of the PEEM images. The simulations include energy filtering and the use of a contrast aperture in the back focal plane in order to describe the changes in the PEEM image of the junction with respect to its real physical dimensions. Threshold imaging does not give a reliable measurement of micron sized p and n type patterns. At higher take-off energies, for example using Si 2p electrons, the pattern width is closer to the real physical size. Physical topography must also be quantitatively accounted for. The results can be generalized to PEEM imaging of any structure with a built-in lateral electric field. © 2013 Elsevier B.V. All rights reserved.

Escher M.,FOCUS GmbH | Winkler K.,Omicron Nanotechnology GmbH | Renault O.,CEA Grenoble | Barrett N.,French Atomic Energy Commission
Journal of Electron Spectroscopy and Related Phenomena | Year: 2010

The design and applications of an instrument for imaging X-ray photoelectron spectroscopy (XPS) are reviewed. The instrument is based on a photoelectron microscope and a double hemispherical analyser whose symmetric configuration avoids the spherical aberration (α2-term) inherent for standard analysers. The analyser allows high transmission imaging without sacrificing the lateral and energy resolution of the instrument. The importance of high transmission, especially for highest resolution imaging XPS with monochromated laboratory X-ray sources, is outlined and the close interrelation of energy resolution, lateral resolution and analyser transmission is illustrated. Chemical imaging applications using a monochromatic laboratory Al Kα-source are shown, with a lateral resolution of 610 nm. Examples of measurements made using synchrotron and laboratory ultra-violet light show the broad field of applications from imaging of core level electrons with chemical shift identification, high resolution threshold photoelectron emission microscopy (PEEM), work function imaging and band structure imaging. © 2009 Elsevier B.V. All rights reserved.

Wiemann C.,Jülich Research Center | Patt M.,Jülich Research Center | Cramm S.,Jülich Research Center | Escher M.,FOCUS GmbH | And 6 more authors.
Applied Physics Letters | Year: 2012

We report about a proof-of-principle experiment which explores the perspectives of performing hard x-ray photoemission spectromicroscopy with high lateral resolution. Our results obtained with an energy-filtered photoemission microscope at the PETRA III storage ring facility using hard x-ray excitation up to 6.5 keV photon energy demonstrate that it is possible to obtain selected-area x-ray photoemission spectra from regions less than 500 nm in diameter. © 2012 American Institute of Physics.

Rubio-Zuazo J.,European Synchrotron Radiation Facility | Rubio-Zuazo J.,CSIC - Institute of Materials Science | Escher M.,FOCUS GmbH | Merkel M.,FOCUS GmbH | And 2 more authors.
Review of Scientific Instruments | Year: 2010

We have developed an energy analyzer, High Voltage-Cylinder Sector Analyzer 300/15, for electron kinetic energies up to 15 keV. It is especially suited for hard x-ray photoelectron spectroscopy, but also for ultraviolet and soft x-ray photoelectron spectroscopy (ultraviolet photoemission spectroscopy, x-ray photoemission spectroscopy), Auger electron spectroscopy, and reflection high energy electron spectroscopy. The analyzer is based on a cylinder sector with 90° deflection, 300 mm slit-to-slit distance, and a four-element pre-retarding lens system with 50 mm sample-to-lens distance. The result is a very compact design of the analyzer that is easily integrated into a multipurpose experiment with different techniques. A low noise/low drift electronics is capable of continuous energy scans from 0 to 15 keV using nonlinear lens curves. The first analyzer is allocated at the Spanish CRG SpLine beamline at the ESRF at an end station where simultaneous surface x-ray diffraction is possible. The analyzer is operated routinely since 2006 up to 15 keV electron kinetic energy, expanding the achievable electron kinetic energy range compared to other commercial analyzers. In this work we present a detailed description of the developed electron analyzer. The analyzer capabilities, in terms of energy resolution and transmission, are shown by using an electron gun, an ultraviolet-discharge lamp, and hard x-ray synchrotron radiation as excitation sources. © 2010 American Institute of Physics.

Otten C.,FOCUS GmbH | Reisgen U.,RWTH Aachen | Schmachtenberg M.,RWTH Aachen
Welding in the World | Year: 2016

The electrification of the traffic sector increases the importance of the joining of aluminum with copper. During the fusion welding of this joint, brittle intermetallic phases which exert a great influence on the load-bearing capability are developing. Until today, systematic investigations of the different, developing phases neither have been carried out nor has a direct correlation with the mechanical properties been made. Within the scope of this paper, electron beam welding on Al-Cu plates is examined. The focus is put on the identification of the different phases and on their influence on the tensile strength. To this end, the mixture ratio and the energy-per-unit length are varied within the framework of test series. As a result, the microstructure of the welded joint can be characterized via electron backscatter diffraction (EBSD) tests. Further, a direct correlation of these tests with the failure of the welded joint will be made. The greatest weld joint strength of 104 MPa was achieved when the microstructure of the joint featured a lamellar structure, whereas formation of the Al2Cu phase resulted in brittle fracture of the welded joints along the Al2Cu/lamellar matrix interfaces. © 2015, International Institute of Welding.

Bretschneider R.A.,FOCUS GmbH
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2015

Over the past few years the interest in period tracking apps increased, which represent a sub-genre of quantified self apps in women health. They are available in a variety of complexity levels ranging from simple menstruation diaries up to applications with complex fertility calculation algorithms. The goal of this paper is to propose an approach for a period tracking app with an adaptive user interface that takes the users goal and context into account. Our research focusses on the motivations to use a period tracker, the questions that users have regarding their cycle data and how a quantified self app could help in answering these questions. © Springer International Publishing Switzerland 2015.

FOCUS GmbH | Date: 2011-01-25

Printed matter all in the field of television broadcasting and television entertainment, namely, leaflets, periodicals, newspapers, books, posters, stickers, calendars, photographs, stationery, printed instructional and teaching material pertaining to the field of television broadcasting and television entertainment. Telecommunication services for others in the field of television broadcasting and television entertainment, namely, transmission of information via wireless networks, cable networks, and radio and television broadcasting; on-line-services for others in the field of television broadcasting and television entertainment, namely, transmission of news, e-mail-data-services, and providing internet services. Providing services for others in the field of television broadcasting and television entertainment, namely, gathering and disseminating of news and publishing printed matter, in particular newspapers, periodicals and books, and teaching and instructional material, including sound and image information maintained and accessible in electronic format via intranets and the internet, and publications on the Internet including electronic books and periodicals; providing services of a television studio, namely, production of sound and image recordings on sound and image carriers; rental of sound and image recordings in the field of television broadcasting and television entertainment; production of TV and radio entertainment programs and programming; conducting entertainment events in the fields of education, sports, music, arts, culture and humanities via television broadcasting and television entertainment, providing entertainment services for other in the form of live-events in the fields education, sports, music, arts, culture and humanities via television broadcasting and television entertainment.

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