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Capturing the zero: a new class of zero-augmented distributions and multiplicative error processes
(2010)
We propose a novel approach to model serially dependent positive-valued variables which realize a non-trivial proportion of zero outcomes. This is a typical phenomenon in financial time series observed on high frequencies, such as cumulated trading volumes or the time between potentially simultaneously occurring market events. We introduce a flexible pointmass mixture distribution and develop a semiparametric specification test explicitly tailored for such distributions. Moreover, we propose a new type of multiplicative error model (MEM) based on a zero-augmented distribution, which incorporates an autoregressive binary choice component and thus captures the (potentially different) dynamics of both zero occurrences and of strictly positive realizations. Applying the proposed model to high-frequency cumulated trading volumes of liquid NYSE stocks, we show that the model captures both the dynamic and distribution properties of the data very well and is able to correctly predict future distributions. Keywords: High-frequency Data , Point-mass Mixture , Multiplicative Error Model , Excess Zeros , Semiparametric Specification Test , Market Microstructure JEL Classification: C22, C25, C14, C16, C51
Despite sensible guidelines for the use of opioid analgesics, respiratory depression remains a significant risk with a possibility of fatal outcomes. Clinicians need to find a balance of analgesia with manageable respiratory effects. The ampakine CX717 (Cortex Pharmaceuticals, Irvine, CA, USA), an allosteric enhancer of glutamate-stimulated AMPA receptor activation, has been shown to counteract opioid-induced respiratory depression in rats while preserving opioid-induced analgesia. Adopting a translational approach, we orally administered 1500 mg of CX717 to 16 male healthy volunteers in a placebo controlled double-blind study. Starting 100 min after CX717 or placebo intake, alfentanil was administered by computerized intravenous infusion targeting a plateau of effective alfentanil plasma concentrations of 100 ng/ml. One hour after start of opioid infusion, its effects were antagonized by intravenous injection of 1.6 mg of the classical opioid antidote naloxone. Respiration was quantified prior to drug administration (baseline), during alfentanil infusion and after naloxone administration by (i) counting the spontaneous respiratory frequency at rest and (ii) by employing hypercapnic challenge with CO2 rebreathing that assessed the expiratory volume at a carbon dioxide concentration in the breathable air of 55% (VE55). Pain was quantified at the same time points, immediately after assessment of respiratory parameters, by (i) measuring the tolerance to electrical stimuli (5 Hz sine increased by 0.2 mA/s from 0 to 20 mA and applied via two gold electrodes placed on the medial and lateral side of the mid-phalanx of the right middle finger) and (ii) by measuring the tolerance to heat (increased by 0.3°C/s from 32 to 52.5°C applied to a 3 x 3 cm2 skin area of the left volar forearm, after sensitization with 0.15 g capsaicin cream 0.1%). CX717 was tolerated by all subjects without side effects that would have required medical intervention. We observed that CX717 was approximately as effective as naloxone in reversing the opioid induced reduction of the respiratory frequency. Despite the presence of high plasma alfentanil concentrations, the respiratory frequency decreased only by 8.9 ± 22.4% when CX717 was pre-administered, which was comparable to the 7.0 ± 19.3% decrease observed after administration of naloxone. In contrast, after placebo pre-administration the respiratory rate decreased by 30.0 ± 21.3% (p=0.0054 for CX717 versus placebo). In agreement with this, periods of a very low respiratory frequency of <= 4 min-1 under alfentanil alone were shortened by ampakine pre-dosing by 52.9% (p=0.0182 for CX717 versus placebo). Furthermore, VE55 was decreased during alfentanil infusion by 55.9 ± 16.7% under placebo preadministration but only by 46.0 ± 18.1% under CX717 pre-administration (p=0.017 for CX717 versus placebo). Most importantly, in contrast to naloxone, CX717 had no effect on opioid induced analgesia. Alfentanil increased the pain tolerance to electrical stimuli by 68.7 ± 59.5% with placebo pre-administration. With CX717 pre-administration, the increase of the electrical pain tolerance was similar (54.6 ± 56.7%, p=0.1 for CX717 versus placebo). Similarly, alfentanil increased the heat pain tolerance threshold by 24.6 ± 10.0% with placebo pre-administration. Ampakine co-administration had also no effect on the increase of the heat pain tolerance of the capsaicin-sensitized skin (23.1 ± 8.3%, p=0.46 for CX717 versus placebo). The results of this study allow us to draw the conclusion, that opioid induced ventilatory depression can be selectively antagonized in humans by co-administering an ampakine. This is the first successful translation of a selective antagonism of opioidinduced respiratory depression from animal research into application in humans. Ampakines, namely CX717, thus are the first selective antidote for opioid-induced respiratory depression without loss of analgesia, available for the use in humans.
Within this thesis, an experimental study of the photo double ionization (PDI) and the simultaneous ionization-excitation is performed for lithium in different initial states Li (1s22l) (l = s, p). The excess energy of the linearly polarized VUV-light is between 4 and 12 eV above the PDI-threshold. Three forefront technologies are combined: a magneto-optical trap (MOT) for lithium generating an ultra-cold and, by means of optical pumping, a state-prepared target; a reaction microscope (ReMi), enabling the momentum resolved detection of all reaction fragments with high-resolution and the free-electron laser in Hamburg (FLASH), providing an unprecedented brilliant photon beam at favourable time structure to access small cross sections. Close to threshold the total as well as differential PDI cross sections are observed to critically depend on the excitation level and the symmetry of the initial state. For the excited state Li (1s22p) the PDI dynamics strongly depends on the alignment of the 2p-orbital with respect to the VUV-light polarization and, thus, from the population of the magnetic substates (mp = 0, ±1). This alignment sensitivity decreases for increasing excess energy and is completely absent for ionization-excitation. Time-dependent close-coupling calculations are able to reproduce the experimental total cross sections with deviations of at most 30%. All the experimental observations can be consistently understood in terms of the long range electron correlation among the continuum electrons which gives rise to their preferential back-to-back emission. This alignment effect, which is observed here for the first time, allows controlling the PDI dynamics through a purely geometrical modification of the target initial state without changing its internal energy.
Synthese und Optimierung von Nitroxyl-Spin-Labeln zur Analyse von Nukleinsäuren mittels EPR und NMR
(2010)
Im Rahmen dieser Doktorarbeit wurde der Einsatz der Nitroxyl-Spin-Markierung für die Strukturaufklärung von Oligonukleotiden getestet. Dafür wurden im Vorfeld verschiedene Spin-Label synthetisiert und charakterisiert. Bei den Nitroxiden handelt es sich hierbei um das Spin-Label TPA (2,2,5,5-Tetramethyl-pyrrolin-1-oxyl-3-acetylene) und TEMPA (2,2,6,6-Tetramethyl-3,4-dehydro-piperidin-N-oxyl-4-acetylene). Beide Spin-Label wurden auch als deuteriert und 15N-markiert synthetisiert. Basierend auf den erhaltenen Ergebnissen auf dem Gebiet der Modell-Systeme und Modell-RNAs wurden biologisch relevante und strukturell anspruchsvolle Oligonukleinsäuren untersucht. Dabei konnten DNA-RNA-Hybride, die HCV-IRES Domain II, ein Tetra-Loop, das Neomycin-B Aptamer, das Diels-Alder Ribozym und ein Nep1-RNA-Komplex charakterisiert werden. Die Einführung des Spin-Labels erfolgte noch auf der Festphase mittels der Sonogashira-Kreuz-Kupplungs Reaktion.
Transmissible spongiform encephalopathies (TSEs) are rare but fatal neurodegenerative diseases affecting human and animals. The prion protein which is the causative agent, according to “protein-only” hypothesis misfold in to rogue amyloid conformer. Despite several years of studies, the atomic structural details of the rogue conformers have not been clearly understood. This study focused on developing an in-vitro conversion method, which allows us to monitor the transition from unfolded state of prion protein to fibril state. In order to reach maximal unfolded state, we have used 8 M urea as chemical denaturant, pH 2 and prion fragment 90-230 as the model. It has been demonstrated earlier that acidic pH and mild denaturant induce the fibril formation. The mechanism underlying the structural transition from monomeric state to polymeric form is largely unknown. We have confirmed by EM and AFM that fibrils are formed in our conditions, which resemble to naturally occurring fibrils in morphologies observed. The agitation accelerates the rate of fibril formation and, which allow us to do time-resolved NMR on these preparations. The conformational flexibility is inherent to amyloid fibrils and has been observed in our preparations. We aimed to map the important segment of prion protein, which forms the rigid core in its fibrillar structured form. Our time-resolved NMR studies allowed us to monitor the changes happening from unfolded state to fibrillar state. Analysis of data identified the segment between residues 145 to 223 forming the rigid core in these fibrils, which correspond to β strand 2, helix 2 and major part of helix 3 of native prion monomeric structure. Most of the point mutations which are associated with hereditary prion disease are part of rigid core, which undergo a refolding on fibril formation. The C-terminal residues from 224 to 230 displayed peak shifting and therefore, indicate the adaptation to a fibril specific conformation. The major part of N-terminal 90-144 segment, remains dynamic, which can be understood by their accessibility to amyloid specific antibodies. This provides novel structural insight to the amyloid formation from unfolded state of prion protein fragment 90-230, which represents the proteinase-K resistant part naturally occurring prions. Earlier studies have established the core to 160-220 where hydrogen-deuterium exchange mass spectrometry or site-directed spin labeling EPR spectroscopy was used for analysis. Those studies have been initiated from either native-like or partially unfolded state of recombinant prion protein, and therefore, it is quite striking to find out that fibrils initiated from unfolded monomeric state share the same “amyloid core”. This structural insight has important implications for understanding the molecular basis of prion propagation.
The first part of the following paper deals with varying points of criticism forwarded against Ordoliberalism. Here, it is not the aim to directly falsify each argument on its own; rather, the author tries to give a precise overview of the spectrum of critique. The second section picks out one argument of critical review – namely that the ordoliberal concept of the state is somewhat elitist and grounded on intellectual experts. Based on the previous sections, the final part differentiates two kinds of genesis of norms: an evolutionary and an elitist one – both (latently) present within Ordoliberalism. In combination with the two-level differentiation between individual and regulatory ethics, the essay allows for a distinction between individual-ethical norms based on an evolutionary genesis of norms and regulatory-ethical norms based on an elitist understanding of norms. A by-product of the author’s argument is a (further) demarcation within neoliberalism.
Mit Mount St. Elias. Die längste Skiabfahrt der Welt. ist Mitte November ein Ski- und Bergfilm in den deutschen Kinos angelaufen, der schon jetzt als einer der meistgesehenen Dokumentarfilme der österreichischen Kinogeschichte gilt. Auch in Deutschland wurde der Film als Bergfilm angekündigt, der neue Maßstäbe setze. Dieser Kommentar beschäftigt sich mit den dramaturgischen Bausteinen des Erfolgs von Mount St. Elias und legt besonderes Augenmerk auf die Inszenierungsstrategien des ,Dokumentarischen‘ im Kontext des alpinen Diskurses.
Um 1795, unter der Regentschaft des aufgeklärten Fürsten Friedrich und wenige Jahre nach dem Ausbruch der Französischen Revolution, wird in der Hofbibliothek der Fürsten zu Waldeck und Pyrmont „jedermann zu lesen gnädigst erlaubet“ (StA MR Best. 118d, Generalia I,1). Damit wird diese Fürstenbibliothek, deren Ursprünge bis ins Mittelalter zurückreichen und die in der Frühen Neuzeit zu einer prachtvollen Sammlung von Büchern und Kunstobjekten zusammenwächst, für eine breite Öffentlichkeit zugänglich. Dies legen alte Ausleihlisten und Kataloge unmissverständlich dar. Wer waren aber die Nutzer dieser und anderer Bibliotheken im Aufklärungsjahrhundert? Welche Bücher und Archivalien wurden gesammelt, gelesen oder erforscht? In welchem Maße und auf welche Art fanden das „Schöne“ und das „Nützliche“ in Bibliotheken dieser Zeit zueinander? Ausgehend von diesen Themenkomplexen fokussierte der Workshop das Spannungsverhältnis von Repräsentation, Wissen und Öffentlichkeit in (Hof)bibliotheken der Zeit zwischen Barock und Aufklärung und ging der Frage nach, wie diese drei Aspekte in der Entwicklung von der Raritätenkammer zur „modernen“ Bibliothek sich zueinander verhalten und gegenseitig beeinflussen.
Dieser Artikel widmet sich der Erstrezeption des Romans „Gilgi – eine von uns“, geschrieben von Irmgard Keun, erschienen 1931. Die Rezeption wird mithilfe von Rezensionen betrachtet, welche als öffentliche Rezeptionszeugnisse gewertet werden, und Leserinnenzuschriften, die als private Rezeptionszeugnisse gelten. Um den Roman und die Diskussion um den Roman zu verstehen und zeitgeschichtlich einordnen zu können, wird zunächst in einem Exkurs auf die Debatte über die Neue Frau zur Zeit der Weimarer Republik eingegangen. Dabei soll die Betrachtung des Frauenbildes in den Zeitschriften „Die Frau“ und „Der Querschnitt“ helfen, stellvertretend für die Repräsentation des Frauenbildes innerhalb der medialen Öffentlichkeit. Danach wird der Roman kurz vorgestellt, um schließlich die Rezeption auszuwerten.
Im Mittelpunkt der Untersuchung steht die Rolle der Frau bei der Verbreitung, Förderung, öffentlichen Etablierung und Produktion von Kunst und Literatur des Expressionismus. Unter der Schirmherrschaft der engagierten Frauenrechtlerin und Schriftstellerin Ida Dehmel (1870–1940) sowie der ersten promovierten Kunsthistorikerin Deutschlands Rosa Schapire (1874–1954) gelang 1916 in Hamburg die Gründung des „Frauenbundes zur Förderung deutscher bildender Kunst“. Dieser leistete Pionierarbeit auf dem Gebiet der professionell geführten Kunstförderung durch Frauen – in diesem Fall bei der Kunst des Expressionismus. Er steht in der Tradition von Vereinen, die sich im Umfeld der Aktivitäten der deutschen Frauenbewegung herausbildeten, beerbt also letztlich ein politisches Engagement zugunsten eines gesellschaftlichen Status der Frau im Deutschen Kaiserreich und festigt ein neues weibliches Selbstverständnis. Die Bedeutung der Frau in Wirkungsbereichen des Expressionismus beweisen des Weiteren diverse Publikationen in der vielfältigen Zeitungslandschaft des Expressionismus. Es lassen sich zahlreiche literarische Texte von Schriftstellerinnen sowie politische Stellungnahmen von Frauenrechtlerinnen sichten, die eine individuelle, kritischreflexive Sichtweise der wirtschaftlichen und sozialen Stellung der Frau offenbaren.