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We present the characterization and application of a new gas chromatography time-of-flight mass spectrometry instrument (GC-TOFMS) for the quantitative analysis of halocarbons in air samples. The setup comprises three fundamental enhancements compared to our earlier work (Hoker et al., 2015): (1) full automation, (2) a mass resolving power R = m/Δm of the TOFMS (Tofwerk AG, Switzerland) increased up to 4000 and (3) a fully accessible data format of the mass spectrometric data. Automation in combination with the accessible data allowed an in-depth characterization of the instrument. Mass accuracy was found to be approximately 5 ppm in mean after automatic recalibration of the mass axis in each measurement. A TOFMS configuration giving R = 3500 was chosen to provide an R-to-sensitivity ratio suitable for our purpose. Calculated detection limits are as low as a few femtograms by means of the accurate mass information. The precision for substance quantification was 0.15 % at the best for an individual measurement and in general mainly determined by the signal-to-noise ratio of the chromatographic peak. Detector non-linearity was found to be insignificant up to a mixing ratio of roughly 150 ppt at 0.5 L sampled volume. At higher concentrations, non-linearities of a few percent were observed (precision level: 0.2 %) but could be attributed to a potential source within the detection system. A straightforward correction for those non-linearities was applied in data processing, again by exploiting the accurate mass information. Based on the overall characterization results, the GC-TOFMS instrument was found to be very well suited for the task of quantitative halocarbon trace gas observation and a big step forward compared to scanning, quadrupole MS with low mass resolving power and a TOFMS technique reported to be non-linear and restricted by a small dynamical range.
We present the characterization and application of a new gas chromatography time-of-flight mass spectrometry instrument (GC-TOFMS) for the quantitative analysis of halocarbons in air samples. The setup comprises three fundamental enhancements compared to our earlier work (Hoker et al., 2015): (1) full automation, (2) a mass resolving power R = m/Δm of the TOFMS (Tofwerk AG, Switzerland) increased up to 4000 and (3) a fully accessible data format of the mass spectrometric data. Automation in combination with the accessible data allowed an in-depth characterization of the instrument. Mass accuracy was found to be approximately 5 ppm in mean after automatic recalibration of the mass axis in each measurement. A TOFMS configuration giving R = 3500 was chosen to provide an R-to-sensitivity ratio suitable for our purpose. Calculated detection limits are as low as a few femtograms by means of the accurate mass information. The precision for substance quantification was 0.15 % at the best for an individual measurement and in general mainly determined by the signal-to-noise ratio of the chromatographic peak. Detector non-linearity was found to be insignificant up to a mixing ratio of roughly 150 ppt at 0.5 L sampled volume. At higher concentrations, non-linearities of a few percent were observed (precision level: 0.2 %) but could be attributed to a potential source within the detection system. A straightforward correction for those non-linearities was applied in data processing, again by exploiting the accurate mass information. Based on the overall characterization results, the GC-TOFMS instrument was found to be very well suited for the task of quantitative halocarbon trace gas observation and a big step forward compared to scanning, quadrupole MS with low mass resolving power and a TOFMS technique reported to be non-linear and restricted by a small dynamical range.
Introduction
(2014)
Be it in the case of opening a website, sending an email, or high-frequency trading, bits and bytes of information have to cross numerous nodes at which micro-decisions are made. These decisions concern the most efficient path through the network, the processing speed, or the priority of incoming data packets.
Despite their multifaceted nature, micro-decisions are a dimension of control and surveillance in the twenty-first century that has received little critical attention. They represent the smallest unit and the technical precondition of a contemporary network politics – and of our potential opposition to it. The current debates regarding net neutrality and Edward Snowden’s revelation of NSA surveillance are only the tip of the iceberg. What is at stake is nothing less than the future of the Internet as we know it.
Angaben aus der Verlagsmeldung:
Ob beim Aufrufen einer Webseite, beim Versenden einer E-Mail oder beim Hochfrequenzhandel an der Börse: Auf ihrem Weg durch die Weiten digitaler Netze durchqueren Bits zahlreiche Knoten, an denen eine Reihe von Mikroentscheidungen getroffen werden. Diese Entscheidungen betreffen den besten Pfad zum Ziel, die Verarbeitungsgeschwindigkeit oder die Priorität zwischen den ankommenden Paketen.
In ihrer vielschichtigen Gestalt bilden solche Mikroentscheidungen eine bislang nur marginal beachtete Dimension von Kontrolle und Überwachung im 21. Jahrhundert. Sie sind sowohl die kleinste Einheit als auch die technische Voraussetzung einer gegenwärtigen Politik digitaler Netzwerke – und des Widerstands gegen sie. Die aktuellen Debatten um Netzneutralität und Edward Snowdens Enthüllung der NSA-Überwachung bilden dabei lediglich die Spitze des Eisbergs. Auf dem Spiel steht nicht weniger als die Zukunft des Internets, wie wir es kennen.
The brain is a highly dynamic and variable system: when the same stimulus is presented to the same animal on the same day multiple times, the neural responses show high trial-to-trial variability. In addition, even in the absence of sensory stimulation neural recordings spontaneously show seemingly random activity patterns. Evoked and spontaneous neural variability is not restricted to activity but is also found in structure: most synapses do not survive for longer than two weeks and even those that do show high fluctuations in their efficacy.
Both forms of variability are further affected by stochastic components of neural processing such as frequent transmission failure. At present it is unclear how these observations relate to each other and how they arise in cortical circuits.
Here, we will investigate how the self-organizational processes of neural circuits affect the high variability in two different directions: First, we will show that recurrent dynamics of self-organizing neural networks can account for key features of neural variability. This is achieved in the absence of any intrinsic noise sources by the neural network models learning a predictive model of their environment with sampling-like dynamics. Second, we will show that the same self-organizational processes can compensate for intrinsic noise sources. For this, an analytical model and more biologically plausible models are established to explain the alignment of parallel synapses in the presence of synaptic failure.
Both modeling studies predict properties of neural variability, of which two are subsequently tested on a synapse database from a dense electron microscopy reconstruction from mouse somatosensory cortex and on multi-unit recordings from the visual cortex of macaque monkeys during a passive viewing task. While both analyses yield interesting results, the predicted properties were not confirmed, guiding the next iteration of experiments and modeling studies.
kurz und kn@pp news : Nr. 38
(2016)
Amines are potentially important for atmospheric new particle formation, but their concentrations are usually low with typical mixing ratios in the pptv range or even smaller. Therefore, the demand for highly sensitive gas-phase amine measurements has emerged in the last several years. Nitrate chemical ionization mass spectrometry (CIMS) is routinely used for the measurement of gasphase sulfuric acid in the sub-pptv range. Furthermore, extremely low volatile organic compounds (ELVOCs) can be detected with a nitrate CIMS. In this study we demonstrate that a nitrate CIMS can also be used for the sensitive measurement of dimethylamine (DMA, (CH3/2NH) using the NO3−•(HNO3)1 − 2• (DMA) cluster ion signal. Calibration measurements were made at the CLOUD chamber during two different measurement campaigns. Good linearity between 0 and ~120 pptv of DMA as well as a sub-pptv detection limit of 0.7 pptv for a 10 min integration time are demonstrated at 278K and 38% RH.
We present a compact and versatile cryofocusing– thermodesorption unit, which we developed for quantitative analysis of halogenated trace gases in ambient air. Possible applications include aircraft-based in situ measurements, in situ monitoring and laboratory operation for the analysis of flask samples. Analytes are trapped on adsorptive material cooled by a Stirling cooler to low temperatures (e.g. -80°C) and subsequently desorbed by rapid heating of the adsorptive material (e.g. 200°C). The set-up involves neither the exchange of adsorption tubes nor any further condensation or refocusing steps. No moving parts are used that would require vacuum insulation. This allows for a simple and robust design. Reliable operation is ensured by the Stirling cooler, which neither contains a liquid refrigerant nor requires refilling a cryogen. At the same time, it allows for significantly lower adsorption temperatures compared to commonly used Peltier elements. We use gas chromatography – mass spectrometry (GC–MS) for separation and detection of the preconcentrated analytes after splitless injection. A substance boiling point range of approximately -80 to +150°C and a substance mixing ratio range of less than 1 ppt (pmol mol−1)to more than 500 ppt in preconcentrated sample volumes of 0.1 to 10 L of ambient air is covered, depending on the application and its analytical demands. We present the instrumental design of the preconcentration unit and demonstrate capabilities and performance through the examination of analyte breakthrough during adsorption, repeatability of desorption and analyte residues in blank tests. Examples of application are taken from the analysis of flask samples collected at Mace Head Atmospheric Research Station in Ireland using our laboratory GC–MS instruments and by data obtained during a research flight with our in situ aircraft instrument GhOSTMS (Gas chromatograph for the Observation of Tracers – coupled with a Mass Spectrometer).
We present a compact and versatile cryofocusing–thermodesorption unit, which we developed for quantitative analysis of halogenated trace gases in ambient air. Possible applications include aircraft-based in situ measurements, in situ monitoring and laboratory operation for the analysis of flask samples. Analytes are trapped on adsorptive material cooled by a Stirling cooler to low temperatures (e.g. −80 °C) and subsequently desorbed by rapid heating of the adsorptive material (e.g. +200 °C). The set-up involves neither the exchange of adsorption tubes nor any further condensation or refocusing steps. No moving parts are used that would require vacuum insulation. This allows for a simple and robust design. Reliable operation is ensured by the Stirling cooler, which neither contains a liquid refrigerant nor requires refilling a cryogen. At the same time, it allows for significantly lower adsorption temperatures compared to commonly used Peltier elements. We use gas chromatography – mass spectrometry (GC–MS) for separation and detection of the preconcentrated analytes after splitless injection. A substance boiling point range of approximately −80 to +150 °C and a substance mixing ratio range of less than 1 ppt (pmol mol−1) to more than 500 ppt in preconcentrated sample volumes of 0.1 to 10 L of ambient air is covered, depending on the application and its analytical demands. We present the instrumental design of the preconcentration unit and demonstrate capabilities and performance through the examination of analyte breakthrough during adsorption, repeatability of desorption and analyte residues in blank tests. Examples of application are taken from the analysis of flask samples collected at Mace Head Atmospheric Research Station in Ireland using our laboratory GC–MS instruments and by data obtained during a research flight with our in situ aircraft instrument GhOST-MS (Gas chromatograph for the Observation of Tracers – coupled with a Mass Spectrometer).
Knowledge about mass discrimination effects in a chemical ionization mass spectrometer (CIMS) is crucial for quantifying, e.g., the recently discovered extremely low volatile organic compounds (ELVOCs) and other compounds for which no calibration standard exists so far. Here, we present a simple way of estimating mass discrimination effects of a nitrate-based chemical ionization atmospheric pressure interface time-of-flight (CI-APi-TOF) mass spectrometer. Characterization of the mass discrimination is achieved by adding different perfluorinated acids to the mass spectrometer in amounts sufficient to deplete the primary ions significantly. The relative transmission efficiency can then be determined by comparing the decrease of signals from the primary ions and the increase of signals from the perfluorinated acids at higher masses. This method is in use already for PTR-MS; however, its application to a CI-APi-TOF brings additional difficulties, namely clustering and fragmentation of the measured compounds, which can be treated with statistical analysis of the measured data, leading to selfconsistent results. We also compare this method to a transmission estimation obtained with a setup using an electrospray ion source, a high-resolution differential mobility analyzer and an electrometer, which estimates the transmission of the instrument without the CI source. Both methods give different transmission curves, indicating non-negligible mass discrimination effects of the CI source. The absolute transmission of the instrument without the CI source was estimated with the HR-DMA method to plateau between the m=z range of 127 and 568 Th at around 1.5 %; however, for the CI source included, the depletion method showed a steady increase in relative transmission efficiency from the m=z range of the primary ion (mainly at 62 Th) to around 550 Th by a factor of around 5. The main advantages of the depletion method are that the instrument is used in the same operation mode as during standard measurements and no knowledge of the absolute amount of the measured substance is necessary, which results in a simple setup.
Knowledge about mass discrimination effects in a chemical ionization mass spectrometer (CIMS) is crucial for quantifying, e.g., the recently discovered extremely low volatile organic compounds (ELVOCs) and other compounds for which no calibration standard exists so far. Here, we present a simple way of estimating mass discrimination effects of a nitrate-based chemical ionization atmospheric pressure interface time-of-flight (CI-APi-TOF) mass spectrometer. Characterization of the mass discrimination is achieved by adding different perfluorinated acids to the mass spectrometer in amounts sufficient to deplete the primary ions significantly. The relative transmission efficiency can then be determined by comparing the decrease of signals from the primary ions and the increase of signals from the perfluorinated acids at higher masses. This method is in use already for PTR-MS; however, its application to a CI-APi-TOF brings additional difficulties, namely clustering and fragmentation of the measured compounds, which can be treated with statistical analysis of the measured data, leading to self-consistent results. We also compare this method to a transmission estimation obtained with a setup using an electrospray ion source, a high-resolution differential mobility analyzer and an electrometer, which estimates the transmission of the instrument without the CI source. Both methods give different transmission curves, indicating non-negligible mass discrimination effects of the CI source. The absolute transmission of the instrument without the CI source was estimated with the HR-DMA method to plateau between the m∕z range of 127 and 568 Th at around 1.5 %; however, for the CI source included, the depletion method showed a steady increase in relative transmission efficiency from the m∕z range of the primary ion (mainly at 62 Th) to around 550 Th by a factor of around 5. The main advantages of the depletion method are that the instrument is used in the same operation mode as during standard measurements and no knowledge of the absolute amount of the measured substance is necessary, which results in a simple setup.
AirCore-HR: a high resolution column sampling to enhance the vertical description of CH₄ and CO₂
(2016)
An original and innovative sampling system called AirCore was presented by NOAA in 2010 (Karion et al., 2010). It consists of a long (> 100 m) and narrow (< 1 cm) stainless steel tube that can retain a profile of atmospheric air. The captured air sample has then to be analyzed with a gas analyzer for trace mole fraction. In this study, we introduce a new AirCore aiming at improved resolution along the vertical with the objectives to: (i) better capture the vertical distribution of CO2 and CH4, (ii) provide a tool to compare AirCores and validate the estimated vertical resolution achieved by AirCores. This AirCore-HR (high resolution) consists of a 300 m tube, combining 200 m of 1/8 in. (3.175 mm) tube and a 100 m of 1/4 in. (6.35 mm) tube. This new configuration allows to achieve a vertical resolution of 300 m up to 15 km and better than 500 m up to 22 km (if analysis of the retained sample is performed within 3 hours). The AirCore-HR was flown for the first time during the annual StratoScience campaign from CNES in August 2014 from Timmins (Ontario, Canada). High-resolution vertical profiles of CO2 and CH4 up to 25 km were successfully retrieved. These profiles revealed well defined transport structures in the troposphere (also seen in CAMS-ECMWF high resolution forecasts of CO2 and CH4 profiles) and captured the decrease of CO2 and CH4 in the stratosphere. The multi-instruments gondola from the flight carried two other low-resolution AirCore-GUF that allowed to perform direct comparisons and study the underlying processing method used to convert the sample of air to greenhouse gases vertical profiles. In particular, degrading the AirCore-HR derived profiles to the low resolution of AirCore-GUF yields an excellent match between both sets of CH4 profiles, and shows a good consistency between vertical structures of CO2 and CH4. These results fully validate the theoretical vertical resolution achievable by AirCores. Finally, the uncertainties associated with the measurements are assessed, yielding an average uncertainty below 3 ppb for CH4 and 0.25 ppm for CO2 with the major source of uncertainty coming from the potential loss of air sample on the ground and the choice of the starting and ending point of the collected air sample inside the tube. In an ideal case where the sample would be fully retained, it would be possible to know precisely the pressure at which air was sampled last and thus to improve the overall uncertainty to about 0.1 ppm for CO2 and 2 ppb for CH4.
Die vielen Tode des Sokrates : zum Schicksal einer Figur der abrahamitischen Religionskulturen
(2011)
Einer der ersten islamischen Philosophen, der sich mit der griechischen Philosophie eingehend befasste, war der iranische Gelehrte Abu al-Hasan al-Amiri (gest. 992). In seiner auf Arabisch verfassten Abhandlung 'Al-Amad ala al-abad' ('Über das Leben nach dem Tod') wird die Thematik des Lebens nach dem Tod auf eine Reihe von Argumenten gestützt, welche die Unsterblichkeit der Seele zu beweisen suchen. Hierbei beruft sich al-Amiri nicht nur auf Aristoteles, sondern auch auf die Lehren von Empedokles, Pythagoras, Sokrates und Platon, die er in der Einleitung seiner Schrift namentlich erwähnt. Nur diese fünf Denker verdienten es, als die Weisen (al-hukama) bezeichnet zu werden. Auf andere griechische Denker träfe diese Bezeichnung nicht zu, da sich diese nur in einzelnen Wissensbereichen etabliert hätten, ohne grundlegende Kenntnis der Gotteslehre ('al-'ulum al-ilahiya', wörtlich: 'göttliche Wissenschaften'), besessen zu haben. Im al-Amad findet sich auch eine bemerkenswerte, wenn auch äußerst knappe biographische Skizze von Sokrates.
Recently significant advances have been made in the collection, detection, and characterization of ice nucleating particles (INP). Ice nuclei are particles that facilitate the heterogeneous formation of ice within the atmospheric aerosol by lowering the free energy barrier to spontaneous nucleation and growth of ice from atmospheric water and/or vapor. The Frankfurt isostatic diiffusion chamber (FRIDGE) is an INP collection and offline detection system that has become widely deployed and shows additional potential for ambient measurements. Since its initial development FRIDGE has gone through several iterations and improvements. Here we describe improvements that have been made in the collection and analysis techniques. We detail the uncertainties inherent in the measurement method, and suggest a systematic method of error analysis for FRIDGE measurements. Thus what is presented herein should serve as a foundation for the dissemination of all current and future measurements using FRIDGE instrumentation.
Jesus als Märtyrer
(2011)
Zu definieren, was einen Märtyrer ausmacht, ist für das Altertum ebenso wichtig wie für die Moderne. Was meinen wir mit dem Begriff 'Märtyrer', wenn wir Jesus von Nazareth so nennen? Liegt dabei der Schwerpunkt auf dem historischen Jesus und den Motiven für seinen gewaltsamen Tod, den er erwartet haben mag? Oder sollten nicht eher die frühen Textteile des Neuen Testaments, die die Reaktionen der Anhänger Jesu auf dessen gewaltsamen Tod und seine Rechtfertigung schildern, den Ausgangspunkt für unsere Analyse bilden? Natürlich verfügen wir im Falle Jesu über keine Internetquellen, kein Videomaterial, keine Interviews mit dem Märtyrer vor seiner Tat. Wir haben nur kanonische und apokryphe Texte. Deshalb beginne ich bei meiner Diskussion über Jesus als Märtyrer mit einer Definition des Martyriums, die sich auf die zweite oben angeführte Möglichkeit stützt. Sie fußt auf antiken jüdischen und christlichen Texten, von denen allgemein angenommen wird, dass ihre Rezipienten sie als Beschreibungen des Lebens und Leidens von Märtyrern verstanden; die Berichte, die solches erinnern sind schriftlich festgehalten (Abschnitt 1). Danach kehre ich zur ersten Definitionsmöglichkeit zurück und konzentriere mich kurz auf die Person des historischen Jesus, um mit Hilfe der antiken jüdischen und christlichen Märtyrerberichte herauszufinden, was wir möglicherweise über Jesu eigene Sicht auf seinen nahen Tod als den eines Märtyrers wissen können (Abschnitt 2). Im letzten Abschnitt widme ich mich den Passionsberichten des Neuen Testaments. In der Forschung wurden diese Narrative häufig mit den Erzählungen der antiken Märtyrer verglichen, diese wurden sogar als Modell herangezogen, um den Ursprung des Passionsberichts zu rekonstruieren. Sei dieser Ansatz plausibel oder nicht, auf jeden Fall spiegeln die Passionsberichte auf faszinierende Art und Weise die dialogische Gegenüberstellung von Märtyrer und Gegner wider, die so oft das Herzstück der Prozess- und Folterszenen antiker jüdischer und christlicher Märtyrererzählungen darstellt. So gibt es offensichtlich gute Gründe, diese beiden Textgruppen zu vergleichen (Abschnitt 3).
Recently significant advances have been made in the collection, detection and characterization of ice nucleating particles (INPs). Ice nuclei are particles that facilitate the heterogeneous formation of ice within the atmospheric aerosol by lowering the free energy barrier to spontaneous nucleation and growth of ice from atmospheric water and/or vapor. The Frankfurt isostatic diffusion chamber (FRankfurt Ice nucleation Deposition freezinG Experiment: FRIDGE) is an INP collection and offline detection system that has become widely deployed and shows additional potential for ambient measurements. Since its initial development FRIDGE has gone through several iterations and improvements. Here we describe improvements that have been made in the collection and analysis techniques. We detail the uncertainties inherent in the measurement method and suggest a systematic method of error analysis for FRIDGE measurements. Thus what is presented herein should serve as a foundation for the dissemination of all current and future measurements using FRIDGE instrumentation.
BACKGROUND: Micro-RNAs (miRNA) are attributed to the systems biological role of a regulatory mechanism of the expression of protein coding genes. Research has identified miRNAs dysregulations in several but distinct pathophysiological processes, which hints at distinct systems-biology functions of miRNAs. The present analysis approached the role of miRNAs from a genomics perspective and assessed the biological roles of 2954 genes and 788 human miRNAs, which can be considered to interact, based on empirical evidence and computational predictions of miRNA versus gene interactions.
RESULTS: From a genomics perspective, the biological processes in which the genes that are influenced by miRNAs are involved comprise of six major topics comprising biological regulation, cellular metabolism, information processing, development, gene expression and tissue homeostasis. The usage of this knowledge as a guidance for further research is sketched for two genetically defined functional areas: cell death and gene expression. Results suggest that the latter points to a fundamental role of miRNAs consisting of hyper-regulation of gene expression, i.e., the control of the expression of such genes which control specifically the expression of genes.
CONCLUSIONS: Laboratory research identified contributions of miRNA regulation to several distinct biological processes. The present analysis transferred this knowledge to a systems-biology level. A comprehensible and precise description of the biological processes in which the genes that are influenced by miRNAs are notably involved could be made. This knowledge can be employed to guide future research concerning the biological role of miRNA (dys-) regulations. The analysis also suggests that miRNAs especially control the expression of genes that control the expression of genes.
Background: In addition to controlled post-translational modifications proteins can be modified with highly reactive compounds. Usually this leads to a compromised functionality of the protein. Methylglyoxal is one of the most common agents that attack arginine residues. Methylglyoxal is also regarded as a pro-oxidant that affects cellular redox homeostasis by contributing to the formation of reactive oxygen species. Antioxidant enzymes like catalase are required to protect the cell from oxidative damage. These enzymes are also targets for methylglyoxal-mediated modification which could severely affect their catalytic activity in breaking down reactive oxygen species to less reactive or inert compounds.
Results: Here, bovine liver catalase was incubated with high levels of methylglyoxal to induce its glycation. This treatment did not lead to a pronounced reduction of enzymatic activity. Subsequently methylglyoxal-mediated arginine modifications (hydroimidazolone and dihydroxyimidazolidine) were quantitatively analysed by sensitive nano high performance liquid chromatography/electron spray ionisation/tandem mass spectrometry. Whereas several arginine residues displayed low to moderate levels of glycation (e.g., Arg93, Arg365, Arg444) Arg354 in the active centre of catalase was never found to be modified.
Conclusions: Bovine liver catalase is able to tolerate very high levels of the modifying α-oxoaldehyde methylglyoxal so that its essential enzymatic function is not impaired.
Electronic supplementary material: The online version of this article (doi:10.1186/s13104-015-1793-5) contains supplementary material, which is available to authorized users.
Mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a key enzyme in cellular energy metabolism and provides approximately 40% of the proton-motive force that is utilized during mitochondrial ATP production. The dysregulation of complex I function--either genetically, pharmacologically, or metabolically induced--has severe pathophysiological consequences that often involve an imbalance in the production of reactive oxygen species (ROS). Slow transition of the active (A) enzyme to the deactive, dormant (D) form takes place during ischemia in metabolically active organs such as the heart and brain. The reactivation of complex I occurs upon reoxygenation of ischemic tissue, a process that is usually accompanied by an increase in cellular ROS production. Complex I in the D-form serves as a protective mechanism preventing the oxidative burst upon reperfusion. Conversely, however, the D-form is more vulnerable to oxidative/nitrosative damage. Understanding the so-called active/deactive (A/D) transition may contribute to the development of new therapeutic interventions for conditions like stroke, cardiac infarction, and other ischemia-associated pathologies. In this review, we summarize current knowledge on the mechanism of A/D transition of mitochondrial complex I considering recently available structural data and site-specific labeling experiments. In addition, this review discusses in detail the impact of the A/D transition on ROS production by complex I and the S-nitrosation of a critical cysteine residue of subunit ND3 as a strategy to prevent oxidative damage and tissue damage during ischemia-reperfusion injury. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.
Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, either using well-founded empirical relationships or process-based models with good predictive skill. A large variety of models exist today and it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project - FireMIP, an international project to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we summarise the current state-of-the-art in fire regime modelling and model evaluation, and outline what lessons may be learned from FireMIP.
Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients' survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients' tumor samples may result.
Since Mobile Virtual Assistants are rising in popularity and come with most new smartphones out of the box and theoretical work in the field is hard to come by, a test is in order to establish the status quo of development. We did a manual test on six different Mobile Virtual Assistants in the categories Voice Recognition, Online Search, Phone Control and Natural Conversation and the results show that Siri is currently the best Mobile Virtual Assistant on the market with a success rate of 65.8% on average over all four categories.
Electronic states with non-trivial topology host a number of novel phenomena with potential for revolutionizing information technology. The quantum anomalous Hall effect provides spin-polarized dissipation-free transport of electrons, while the quantum spin Hall effect in combination with superconductivity has been proposed as the basis for realizing decoherence-free quantum computing. We introduce a new strategy for realizing these effects, namely by hole and electron doping kagome lattice Mott insulators through, for instance, chemical substitution. As an example, we apply this new approach to the natural mineral herbertsmithite. We prove the feasibility of the proposed modifications by performing ab-initio density functional theory calculations and demonstrate the occurrence of the predicted effects using realistic models. Our results herald a new family of quantum anomalous Hall and quantum spin Hall insulators at affordable energy/temperature scales based on kagome lattices of transition metal ions.
We discuss applications of a recently developed method for model reduction based on linear response theory of weakly coupled dynamical systems. We apply the weak coupling method to simple stochastic differential equations with slow and fast degrees of freedom. The weak coupling model reduction method results in general in a non-Markovian system; we therefore discuss the Markovianization of the system to allow for straightforward numerical integration. We compare the applied method to the equations obtained through homogenization in the limit of large timescale separation between slow and fast degrees of freedom. We numerically compare the ensemble spread from a fixed initial condition, correlation functions and exit times from a domain. The weak coupling method gives more accurate results in all test cases, albeit with a higher numerical cost.
The Central Nigerian Nok Culture has been well known for its elaborate terracotta sculptures and evidence of iron metallurgy since its discovery by British archaeologist Bernard Fagg in the 1940s. With a date in the first millennium BCE, both, sculptures and ironworking, belong to the earliest of their kind in sub-Saharan Africa. After a period of destruction of Nok sites by looting, scientific research resumed in 2006, when a team of archaeologists from Goethe University in Germany started to explore different Nok Culture aspects, one of which focused on chronology. Establishing a chronology for the Nok Culture employed two approaches: a comprehensive pottery analysis based on decoration and form elements and a wealth of radiocarbon dates from a large number of excavated sites. This volume presents the radiocarbon dates and the methods, data and results of the chronological pottery analysis, conducted within the scope of a dissertation project completed in 2015. Combining the two strands of information, a chronology emerges, dividing the Nok Culture into three phases from the middle of the second millennium BCE to the last centuries BCE and defining seven pottery groups that can be arranged to some extent in a chronological order.
The degradation of cytosol-invading pathogens by autophagy, a process known as xenophagy, is an important mechanism of the innate immune system. Inside the host, Salmonella Typhimurium invades epithelial cells and resides within a specialized intracellular compartment, the Salmonella-containing vacuole. A fraction of these bacteria does not persist inside the vacuole and enters the host cytosol. Salmonella Typhimurium that invades the host cytosol becomes a target of the autophagy machinery for degradation. The xenophagy pathway has recently been discovered, and the exact molecular processes are not entirely characterized. Complete kinetic data for each molecular process is not available, so far. We developed a mathematical model of the xenophagy pathway to investigate this key defense mechanism. In this paper, we present a Petri net model of Salmonella xenophagy in epithelial cells. The model is based on functional information derived from literature data. It comprises the molecular mechanism of galectin-8-dependent and ubiquitin-dependent autophagy, including regulatory processes, like nutrient-dependent regulation of autophagy and TBK1-dependent activation of the autophagy receptor, OPTN. To model the activation of TBK1, we proposed a new mechanism of TBK1 activation, suggesting a spatial and temporal regulation of this process. Using standard Petri net analysis techniques, we found basic functional modules, which describe different pathways of the autophagic capture of Salmonella and reflect the basic dynamics of the system. To verify the model, we performed in silico knockout experiments. We introduced a new concept of knockout analysis to systematically compute and visualize the results, using an in silico knockout matrix. The results of the in silico knockout analyses were consistent with published experimental results and provide a basis for future investigations of the Salmonella xenophagy pathway.
Author Summary
Salmonellae are Gram-negative bacteria, which cause the majority of foodborne diseases worldwide. Serovars of Salmonella cause a broad range of diseases, ranging from diarrhea to typhoid fever in a variety of hosts. In the year 2010, Salmonella Typhi caused 7.6 million foodborne diseases and 52 000 deaths, and Salmonella enterica was responsible for 78.7 million diseases and 59 000 deaths. After invasion of Salmonella into host epithelial cells, a small fraction of Salmonella escapes from a specialized intracellular compartment and replicates inside the host cytosol. Xenophagy is a host defense mechanism to protect the host cell from cytosolic pathogens. Understanding how Salmonella is recognized and targeted for xenophagy is an important subject of current research. To the best of our knowledge, no mathematical model has been presented so far, describing the process of Salmonella Typhimurium xenophagy. Here, we present a manually curated and mathematically verified theoretical model of Salmonella Typhimurium xenophagy in epithelial cells, which is consistent with the current state of knowledge. Our model reproduces literature data and postulates new hypotheses for future investigations.
Recently a considerable amount of effort has been put into quantifying how interactions of the carbon and nitrogen cycle affect future terrestrial carbon sinks. Dynamic vegetation models, representing the nitrogen cycle with varying degree of complexity, have shown diverging constraints of nitrogen dynamics on future carbon sequestration. In this study, we use LPJ-GUESS, a dynamic vegetation model employing a detailed individual- and patch-based representation of vegetation dynamics, to evaluate how population dynamics and resource competition between plant functional types, combined with nitrogen dynamics, have influenced the terrestrial carbon storage in the past and to investigate how terrestrial carbon and nitrogen dynamics might change in the future (1850 to 2100; one representative "business-as-usual" climate scenario). Single-factor model experiments of CO2 fertilisation and climate change show generally similar directions of the responses of C–N interactions, compared to the C-only version of the model as documented in previous studies using other global models. Under an RCP 8.5 scenario, nitrogen limitation suppresses potential CO2 fertilisation, reducing the cumulative net ecosystem carbon uptake between 1850 and 2100 by 61%, and soil warming-induced increase in nitrogen mineralisation reduces terrestrial carbon loss by 31%. When environmental changes are considered conjointly, carbon sequestration is limited by nitrogen dynamics up to the present. However, during the 21st century, nitrogen dynamics induce a net increase in carbon sequestration, resulting in an overall larger carbon uptake of 17% over the full period. This contrasts with previous results with other global models that have shown an 8 to 37% decrease in carbon uptake relative to modern baseline conditions. Implications for the plausibility of earlier projections of future terrestrial C dynamics based on C-only models are discussed.
An Versuchen, Walter Benjamins 'Einbahnstraße' in die literarhistorischen Traditionen einzuordnen, fehlt es nicht. Vorzugsweise hat man dabei auf den Feldern gesucht, die sich von Benjamins eigenen frühen literarhistorischen Schwerpunkten aus anbieten, dem Barock mit dem Emblem und der Romantik mit dem Fragment, beides mit ebenso vielen Erträgen wie Problemen. Von anderen Aspekten in seinem Werk gehen die Erörterungen zu Traktat und Denkbild aus. Zum Traktat setzen sie bei Benjamins "Innenarchitektur" (WuN VIII, 38) an und nehmen Bezug auf den Konstruktivismus; zum Denkbild gehen sie von seinen "Denkbildern " aus, die unter dem Pseudonym Detlev Holz in der 'Frankfurter Zeitung' vom 15. November 1933 erschienen, wesentlich gestützt durch die Autorität Adornos etwa von Schlaffer und Jäger. Fernerliegendes, wie Anekdote und Mosaik, ist (von Bertrams Nietzsche-Bild her) gleichfalls erprobt worden, und Schöttker hat aus dem jeweiligen Ungenügen heraus auch integrierende Versuche unternommen. Benjamin habe versucht, "den frühromantischen Fragmentarismus, den er im barocken Drama vorbereitet sah, mit den Ideen der konstruktivistischen Avantgarde zu verbinden". Miniatur oder Minimalprosa sind daneben eher unverbindliche Verlegenheitslösungen geblieben. Am nachhaltigsten ist wohl der Aphorismus zur zentralen Kategorie erklärt worden, mit sehr viel Berechtigung und wiederum nicht ohne erhebliche einschränkende Bemerkungen.
Raytracing und Szenegraphen
(2006)
Raytracing ist ein bekanntes Verfahren zur Erzeugung fotorealistischer Bilder. Globale Beleuchtungseffekte einer 3D-Szene werden durch das Raytracing-Verfahren physikalisch korrekt dargestellt. Erst aktuelle Forschungsarbeiten erm¨oglichen es, das sehr rechenintensive Verfahren bei interaktiven Bildraten in Echtzeit zu berechnen.
Komplexe 3D-Szenen, wie sie beispielsweise in 3D-Spielen oder Simulationen vorkommen, können durch einen Szenengraphen modelliert und animiert werden. Damit die Rendering-Ergebnisse eines Szenengraphen n¨aher an einem realen Bild liegen, ist es erforderlich das Raytracing-Verfahren in einen Szenengraphen einzugliedern.
In dieser Arbeit werden die Möglichkeiten zur Integration eines Echtzeit-Raytracers in eine Szenengraph-API untersucht. Ziel dieser Diplomarbeit ist die Darstellung dynamischer Szenen bei interaktiven Bildraten unter Verwendung des Raytracing-Verfahrens auf einem herk¨ommlichen PC. Zun¨achst m¨ussen bestehende Open Source Szenengraph-APIs und aktuelle Echtzeit-Raytracer auf ihre Eignung zur Integration hin überprüft werden.
Bei der Verarbeitung dynamischer Szenen spielt die verwendete Beschleunigungsdatenstruktur des Raytracers eine entscheidende Rolle. Da eine komplette Neuerstellung der Datenstruktur in jedem Bild zuviel Zeit in Anspruch nimmt, ist eine schnelle und kostengünstige Aktualisierung erforderlich. Die in [LAM01] vorgestellte Lösung, eine Hüllkörperhierarchie (BVH) als Beschleunigungsdatenstruktur zu verwenden, fügt sich sehr gut in das Konzept eines Szenengraphen ein. Dadurch wird eine einfache Aktualisierung ermöglicht.
Um das Ziel dieser Arbeit zu erreichen, ist es notwendig, die Parallelisierbarkeit des Raytracing-Verfahrens auszunutzen. Purcell zeigt in [Pur04], dass Grafikprozessoren (GPUs) neben ihrer eigentlichen Aufgabe auch für allgemeine, parallele Berechnungen wie das Raytracing verwendet werden können.
Die in bisherigen Arbeiten über GPU-basiertes Raytracing entwickelten Systeme können dynamische Szenen nicht bei interaktiven Bildraten darstellen. Aus diesem Grund wird in dieser Diplomarbeit ein neues System konzipiert und implementiert, das den in [TS05] entwickelten Raytracer erweitert und in die Open Source Szenengraph-API OGRE 3D integriert.
Das implementierte System ermöglicht die Darstellung statischer und dynamischer Szenen unter Verwendung einer Consumer-Grafikkarte bei interaktiven Bildraten. Durch seine Erweiterbarkeit bildet das System das Grundger¨ust für ein Realtime-High-Quality-Rendering-System.
We study the impact of higher capital requirements on banks’ balance sheets and its transmission to the real economy. The 2011 EBA capital exercise provides an almost ideal quasi-natural experiment, which allows us to identify the effect of higher capital requirements using a difference-in-differences matching estimator. We find that treated banks increase their capital ratios not by raising their levels of equity, but by reducing their credit supply. We also show that this reduction in credit supply results in lower firm-, investment-, and sales growth for firms which obtain a larger share of their bank credit from the treated banks.
This paper studies the role of the Community Reinvestment Act (CRA) in the recent US housing boom-bust cycle. Using a difference-in-differences matching estimation, I find that the enhancement of CRA enforcement in 1998 caused a 7.7 percentage points increase in annual growth rate of mortgage lending by CRA-regulated banks to CRA-eligible census tracts relative to a group of similar-income CRA-ineligible census tracts within the same state. Financial institutions which are not subject to the CRA, however, do not show any change in their mortgage supply between these two types of census tracts after 1998. I take advantage of this exogenous shift in mortgage supply within an instrumental variable framework to identify the causal effect of mortgage supply on housing prices. I find that every 1 percentage point higher annual growth rate of mortgage supply leads to 0.3 percentage points higher annual growth rate of housing prices. Reduced form regressions show that CRA-eligible neighborhoods experienced higher house price growth during the boom and sharper decline during the bust period. I use placebo tests to confirm that this effect is in fact channeled through the shift in mortgage supply by CRA-regulated banks and not by unobserved demand factors. Furthermore, my results indicate that CRA-induced mortgages went to borrowers with lower FICO scores, carried higher interest rates, and encountered more frequent delinquencies.
In order to better differentiate the drivers of corporations’ actions, in particular shareholder wealth and stakeholder interests, the paper explores the significance of the comply or explain-principle and its underlying enforcement mechanisms more generally. Against this background, compliance rates with specific provisions may shed a light on companies’ reasons for following the code. An analysis of these rates at the example of distinct provisions of the German Corporate Governance Code is therefore entered into. In light of the current corporate governance debate and the legitimacy problems that are raised, among the code provisions that exemplify these questions very well are those regulating incentive pay, severance pay caps, and age limits for supervisory board members. Their analysis will lay a basis for an answer to the question about what motivates companies to comply with the code. The motivation then paves the way to arrive at a further specification of the determinants of the regulatory evolution of the Code and the range of stakeholders and their concerns that enter into it.
owards their best performing products; and also extend the range of products sold to that market. We develop a theoretical model of multiproduct firms and derive the specific demand and cost conditions needed to generate these product-mix reallocations. Our theoretical model highlights how the increased competition from demand shocks in export markets - and the induced product mix reallocations - induce productivity changes within the firm. We then empirically test for this connection between the demand shocks and the productivity of multi-product firms exporting to those destinations. We find that the effect of those demand shocks on productivity are substantial - and explain an important share of aggregate productivity fluctuations for French manufacturing.
We use detailed data on exporters from Costa Rica, Ecuador and Uruguay as well as on their buyers to show that: aggregate exports are disproportionally driven by few multi-buyers exporters; and each multi-buyer exporter's foreign sales of any product are in turn accounted for by few dominant buyers. We propose an analytically solvable multi-country model of endogenous selection in which dominant exporters, dominant products and dominant buyers emerge in parallel as multi-product sellers with heterogeneous technologies compete for buyers with heterogeneous needs. The model not only provides an explanation of the existence of dominant buyers but also makes specific predictions on how the relative importance of dominant buyers should vary across export destinations depending on their market size and accessibility. We show that these predictions are borne out by our data and discuss their welfare implications in terms of gains from trade.
For the transport of high-intensity hadron beams in low-energy beam lines of linear accelerators, the compensation of space charge forces by the accumulation of particles of opposite charge is an important effect, reducing the required focusing strength and potentially the emittance growth due to space charge forces. In this thesis, space charge compensation was studied by including the secondary particles in particle-in-cell simulations.
For this purpose, a new electrostatic particle-in-cell code named bender was developed. The software was tested using known self-consistent solutions for an electron plasma confined in an external potential as well as for a KV distributed beam in a periodic focusing lattice. For the simulation of compensation, models for residual gas ionisation by proton and electron impact were implemented.
The compensation process was studied for a 120 keV, 100 mA proton beam transported through a short drift section. Various features in the particle distributions were identified, which can not explained by a uniform reduction in the electric field of the beam. These were tied to the presence of thermal electrons confined within the beam potential. Using the Poisson-Boltzmann equation, their distribution could be reproduced and their influence on the beam for a wider range of parameters studied. However, the observed temperatures show a significant numerical influence. The hypothesis was formed, that stochastical heating present in particle-in-cell simulations is the mechanism leading to the formation of the observed (partial) thermal equilibrium.
For the low-energy beam transport line of the Frankfurt neutron source FRANZ, bender was used to predict the pulse shaping in the novel ExB chopper system. The code was also used for the design and the study of an electron lens for the Integrable Optics Test Accelerator at Fermi National Accelerator Laboratory. Aberrations due to guiding center drifts and the strong electric field of the electron beam as well as the current limits in such a system were investigated.