Effekte einer Langzeit-Therapie mit Pramipexol oder Levodopa auf die [123I]FP-CIT SPECT in einem Mausmodell der Parkinson-Krankheit

Die zuvor durchgeführte klinische Studie CALM-PD (ParkinsonStudyGroup, 2002) untersuchte den Effekt einer Langzeittherapie mit Levodopa oder Pramipexol auf das Fortschreiten der Parkinson-Krankheit mittels SPECT unter Verwendung des Dopamintransporter-Liganden [123I]β-CIT als Surrogat-Marker. Die [123I]β-CIT Bindung fiel in den Patienten, die Levodopa erhalten hatten, auf ein signifikant niedrigeres Niveau ab, als bei den Patienten, die Pramipexol erhalten hatten. Allerdings wurde dieses Ergebnis unterschiedlich interpretiert, zum einen als Ausdruck Levodopa-induzierter Neurotoxizität, zum anderen als Pramipexol-induzierte Neuroprotektion / -regeneration oder auch als lediglich medikamentös-induzierte Veränderung der Dopamintransporter-Verfügbarkeit. Um diese Fragestellung experimentell zu untersuchen, induzierten wir in Mäusen eine subtotale, bilaterale Läsion der Substantia nigra durch Injektion des Neurotoxins 6-Hydroxydopamin. Vier Wochen danach wurden die Mäuse über einen Zeitraum von 20 Wochen oral mit Levodopa (100mg/kg/Tag), Pramipexol (3mg/kg/Tag) oder lediglich Wasser (Placebo) behandelt. Die Integrität der nigrostriatalen Projektion wurde in vivo wiederholt mittels [123I]FP-CIT SPECT gemessen, sowie nach Tötung der Tiere durch immunhistologische Untersuchung des Dopamintransporter und der Dopamin-synthetisierenden Tyrosinehydroxylase. In scheinlädierten Tieren zeigte sich, dass Levodopa ebenso wie Pramipexol sowohl die striatale FP-CIT Bindung (LD: -21%; PPX: -14%), als auch die TH-Immunreaktivität (LD: -42%, PPX: -45%) signifikant senkten. Gleichzeitig wurde die DAT-Immunreaktivität im Vergleich zu den Kontrolltieren ohne Dopamin-Therapie signifikant erhöht (LD: +42%; PPX +33%). In operierten Tieren mit 6-OHDA-Läsion hingegen hatten weder Levodopa noch Pramipexol einen signifikanten Einfluss auf das stabil reduzierte Niveau der FP-CIT SPECT-Bindung (LD: -66%; PPX: -66%; Placebo: -66%), die striatale TH-Immunreaktivität (LD: -70%, PPX: -72%; Placebo: -77%), die striatale DAT-Immunreaktivität (LD: -70%, PPX: -75%; Placebo: -75%) oder die Anzahl TH-positiver Zellen in der Substantia nigra (LD: -88%, PPX: -88%; Placebo: -86%) im Vergleich zu den Tieren ohne Dopamin-Therapie. Zusammenfassend zeigte sich, dass eine chronische dopaminerge Stimulation mit Levodopa oder Pramipexol ähnliche präsynaptische Anpassungsphänomene in gesunden Mäusen verursacht, allerdings keine erkennbaren Veränderungen in Mäusen mit ausgeprägter Läsion der nigrostriatalen dopaminergen Projektion. Die hier erzielten Ergebnisse ermöglichen eine verlässlichere Interpretation klinischer Studien, die Verfahren zur Dopamintransporter-Bildgebung als Surrogat-Parameter verwenden

Diese Quatsche

Der Spielfilm Die Halbstarken (BRD 1956) gilt nicht nur als erster Kinobeitrag zum sogenannten Halbstarken-Phänomen der fünfziger Jahre, sondern auch als erste filmische Auseinandersetzung mit dem Thema amerikanisierte Jugendkultur in Deutschland (und Österreich) überhaupt. Dabei allerdings ist er von einer auffälligen Widersprüchlichkeit geprägt. Einerseits nämlich erzählt er eine kolportagehafte Geschichte, die in ihrem moralisierenden und didaktischen Impetus deutlich an die tendenziell negative Meinung der damaligen medialen Öffentlichkeit gegenüber der Halbstarken-Bewegung erinnert. Andererseits ist er spürbar um eine unaufgeregte, positive Beschreibung des neuen jugendlichen Selbstverständnisses bemüht. Ausgehend von subkulturtheoretischen und semiologischen Überlegungen, wird in dieser Arbeit nachgefragt, in welcher Weise zentrale jugendkulturelle Kategorien (Kleidungs-Stil, soziale Orte, Musik, Sprache) und deren Kontexte (Generation Gap, Geschlechter-Verhältnis) im Licht dieser Widersprüchlichkeit in Die Halbstarken verhandelt werden. Es wird also untersucht, inwieweit die authentische Darstellung von Jugendkultur an den ideologischen und moralischen Implikationen des Films gebrochen ist

Tunneling Time in Ultrafast Science is Real and Probabilistic

We compare the main competing theories of tunneling time against experimental measurements using the attoclock in strong laser field ionization of helium atoms. Refined attoclock measurements reveal a real and not instantaneous tunneling delay time over a large intensity regime, using two different experimental apparatus. Only two of the theoretical predictions are compatible within our experimental error: the Larmor time, and the probability distribution of tunneling times constructed using a Feynman Path Integral (FPI) formulation. The latter better matches the observed qualitative change in tunneling time over a wide intensity range, and predicts a broad tunneling time distribution with a long tail. The implication of such a probability distribution of tunneling times, as opposed to a distinct tunneling time, challenges how valence electron dynamics are currently reconstructed in attosecond science. It means that one must account for a significant uncertainty as to when the hole dynamics begin to evolve.Comment: 11 pages, 4 figure

Cavity-Based 3D Cooling of a Levitated Nanoparticle via Coherent Scattering

We experimentally realize cavity cooling of all three translational degrees of motion of a levitated nanoparticle in vacuum. The particle is trapped by a cavity-independent optical tweezer and coherently scatters tweezer light into the blue detuned cavity mode. For vacuum pressures around $10^{-5}\,{\rm mbar}$, minimal temperatures along the cavity axis in the mK regime are observed. Simultaneously, the center-of-mass (COM) motion along the other two spatial directions is cooled to minimal temperatures of a few hundred $\rm mK$. Measuring temperatures and damping rates as the pressure is varied, we find that the cooling efficiencies depend on the particle position within the intracavity standing wave. This data and the behaviour of the COM temperatures as functions of cavity detuning and tweezer power are consistent with a theoretical analysis of the experiment. Experimental limits and opportunities of our approach are outlined

Exhaled Aldehydes as Biomarkers for Lung Diseases : A Narrative Review

Breath analysis provides great potential as a fast and non-invasive diagnostic tool for several diseases. Straight-chain aliphatic aldehydes were repeatedly detected in the breath of patients suffering from lung diseases using a variety of methods, such as mass spectrometry, ion mobility spectrometry, or electro-chemical sensors. Several studies found increased concentrations of exhaled aldehydes in patients suffering from lung cancer, inflammatory and infectious lung diseases, and mechanical lung injury. This article reviews the origin of exhaled straight-chain aliphatic aldehydes, available detection methods, and studies that found increased aldehyde exhalation in lung diseases

Generation of macro- and microplastic databases by high-throughput FTIR analysis with microplate readers

FTIR spectral identification is today’s gold standard analytical procedure for plastic pollution material characterization. High-throughput FTIR techniques have been advanced for small microplastics (10–500 µm) but less so for large microplastics (500–5 mm) and macroplastics (> 5 mm). These larger plastics are typically analyzed using ATR, which is highly manual and can sometimes destroy particles of interest. Furthermore, spectral libraries are often inadequate due to the limited variety of reference materials and spectral collection modes, resulting from expensive spectral data collection. We advance a new high-throughput technique to remedy these problems using FTIR microplate readers for measuring large particles (> 500 µm). We created a new reference database of over 6000 spectra for transmission, ATR, and reflection spectral collection modes with over 600 plastic, organic, and mineral reference materials relevant to plastic pollution research. We also streamline future analysis in microplate readers by creating a new particle holder for transmission measurements using off-the-shelf parts and fabricating a nonplastic 96-well microplate for storing particles. We determined that particles should be presented to microplate readers as thin as possible due to thick particles causing poor-quality spectra and identifications. We validated the new database using Open Specy and demonstrated that additional transmission and reflection spectra reference data were needed in spectral libraries

First-principles calculations of hybrid inorganic–organic interfaces : from state-of-the-art to best practice

This work highlights the challenges and problems when modelling inorganic–organic interfaces and provides practical tips and suggestions for efficient calculations

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column–ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power—a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury

Commission des Communautes Europeennes: Groupe du Porte-Parole. Reunion de la Commission du mercredi 29 octobre 1980 = Commission of European Communities: Spokesman Group. Meeting of the Commission on Wednesday, 29 October 1980. Spokesman Service Note to National Offices Bio No. (80) 432, 30 October 1980

We study strong-field ionization and rescattering beyond the long-wavelength limit of the dipole approximation with elliptically polarized mid-IR laser pulses. Full three-dimensional photoelectron momentum distributions (PMDs) measured with velocity map imaging and tomographic reconstruction revealed an unexpected sharp ridge structure in the polarization plane (2018 Phys. Rev. A 97 013404). This thin line-shaped ridge structure for low-energy photoelectrons is correlated with the ellipticity-dependent asymmetry of the PMD along the beam propagation direction. The peak of the projection of the PMD onto the beam propagation axis is shifted from negative to positive values when the sharp ridge fades away with increasing ellipticity. With classical trajectory Monte Carlo simulations and analytical analysis, we study the underlying physics of this feature. The underlying physics is based on the interplay between the lateral drift of the ionized electron, the laser magnetic field induced drift in the laser propagation direction, and Coulomb focusing. To apply our observations to emerging techniques relying on strong-field ionization processes, including time-resolved holography and molecular imaging, we present a detailed classical trajectory-based analysis of our observations. The analysis leads to the explanation of the fine structure of the ridge and its non-dipole behavior upon rescattering while introducing restrictions on the ellipticity. These restrictions as well as the ionization and recollision phases provide additional observables to gain information on the timing of the ionization and recollision process and non-dipole properties of the ionization process.ISSN:1361-6455ISSN:0368-3508ISSN:0953-4075ISSN:0022-370