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We analyze global data about electricity generation and document that the risk exposure of a firm’s owners and its workers depends on competitors’ ability or willingness to change their output in response to productivity shocks. Competitor inflexibility appears to be a risk factor: the sales of firms with more inflexible competitors respond more strongly to aggregate sales shocks. As a consequence, competitor inflexibility also affects the stability of firms’ total wage- and dividend-payments. Firms with relatively flexible competitors appear to smoothen both wages and dividends, but an increase in competitor inflexibility is associated with less dividend-smoothing and more wage-smoothing. Our evidence supports the idea that labor productivity risk associated with competitor inflexibility should be borne by firms’ shareholders, rather than by their workers.
Low risk anomalies?
(2016)
This paper shows theoretically and empirically that beta- and volatility-based low risk anomalies are driven by return skewness. The empirical patterns concisely match the predictions of our model which generates skewness of stock returns via default risk. With increasing downside risk, the standard capital asset pricing model increasingly overestimates required equity returns relative to firms' true (skew-adjusted) market risk. Empirically, the profitability of betting against beta/volatility increases with firms' downside risk. Our results suggest that the returns to betting against beta/volatility do not necessarily pose asset pricing puzzles but rather that such strategies collect premia that compensate for skew risk.
Using merger announcements and applying methods from computational linguistics we find strong evidence that stock prices under-react to information in financial media. A one standard deviation increase in the media-implied probability of merger completion increases the subsequent 12-day return of a long-short merger strategy by 1.2 percentage points. Filtering out the 28% of announced deals with the lowest media-implied completion probability increases the annualized alpha from merger arbitrage by 9.3 percentage points. Our results are particularly pronounced when high-yield spreads are large and on days when only few merger deals are announced. We also document that financial media information is orthogonal to announcement day returns.
The ECB’s Outright Monetary Transactions (OMT) program, launched in summer 2012, indirectly recapitalized periphery country banks through its positive impact on the value of sovereign bonds. However, the regained stability of the European banking sector has not fully transferred into economic growth. We show that zombie lending behavior of banks that still remained undercapitalized after the OMT announcement is an important reason for this development. As a result, there was no positive impact on real economic activity like employment or investment. Instead, firms mainly used the newly acquired funds to build up cash reserves. Finally, we document that creditworthy firms in industries with a high prevalence of zombie firms suffered significantly from the credit misallocation, which slowed down the economic recovery.
SAFE Newsletter : 2016, Q3
(2016)
SAFE Newsletter : 2016, Q4
(2016)
The grammar of global law
(2016)
Legal grammar is understood as the conceptual and linguistic foundation on which legal decisions rest – law’s meta-structure, its argumentative techniques and its systematicity. The essay distinguishes between two ways of thinking about this grammar. The first way of thinking appeals to a grammar as a stabilizing factor, maintaining the coherence of the law. The second way of thinking highlights the asymmetries of power within this structure and perceives legal grammar as the medium carrying the ideological commitments of the law. As the essay ultimately argues, both perspectives react differently to the challenges of globalization that the law is confronted with. While the debate on the grammar(s) of global law is one place where future political order is negotiated, the outcome of the debate is largely open.
Background: Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types.
Methods: Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition.
Results: VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5.
Conclusions: Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.
Objective: Gestational diabetes mellitus (GDM) is associated with substantial morbidity for mothers and their offspring. While clinical and basic research activities on this important disease grow constantly, there is no concise analysis of global architecture of GDM research. Hence, it was the objective of this study to assess the global scientific performance chronologically, geographically and in relation to existing research networks and gender distribution of publishing authors.
Study design: On the basis of the New Quality and Quantity Indices in Science (NewQIS) platform, scientometric methods were combined with modern visualizing techniques such as density equalizing mapping, and the Web of Science database was used to assess GDM-related entries from 1900 to 2012.
Results: Twelve thousand five hundred four GDM-related publications were identified and analyzed. The USA (4295 publications) and the UK (1354 publications) dominated the field concerning research activity, overall citations and country-specific Hirsch-Index, which quantified the impact of a country’s published research on the scientific community. Semi-qualitative indices such as country-specific citation rates ranked New Zealand and the UK at top positions. Annual collaborative publications increased steeply between the years 1990 and 2012 (71 to 1157 respectively). Subject category analysis pointed to a minor interest of public health issues in GDM research. Gender analysis in terms of publication authorship revealed a clear dominance of the male gender until 2005; then a trend towards gender equity started and the activity of female scientists grew visibly in many countries. The country-specific gender analysis revealed large differences, i.e. female scientists dominated the scientific output in the USA, whereas the majority of research was published by male authors in countries such as Japan.
Conclusion: This study provides the first global sketch of GDM research architecture. While North-American and Western-European countries were dominating the GDM-related scientific landscape, a disparity exists in terms of research output between developed and low-resource countries. Since GDM is linked to considerable mortality and morbidity of mothers and their offspring and constitutes a tremendous burden for the healthcare systems in underserved countries, our findings emphasize the need to address disparities by fostering research endeavors, public health programs and collaborative efforts in these nations.
Mitochondrial complex I is a 1MDa membrane protein complex with a central role in aerobic energy metabolism. The bioenergetic core functions are executed by 14 central subunits that are conserved from bacteria to man. Despite recent progress in structure determination, our understanding of the function of the ~30 accessory subunits associated with the mitochondrial complex is still limited. We have investigated the structure of complex I from the aerobic yeast Yarrowia lipolytica by cryo-electron microscopy. Our density map at 7.9Å resolution closely matches the 3.6-3.9Å X-ray structure of the Yarrowia lipolytica complex. However, the cryo-EM map indicated an additional subunit on the side of the matrix arm above the membrane surface, pointing away from the membrane arm. The density, which is not present in any previously described complex I structure and occurs in about 20 % of the particles, was identified as the accessory sulfur transferase subunit ST1. The Yarrowia lipolytica complex I preparation is active in generating H2S from the cysteine derivative 3-mercaptopyruvate, catalyzed by ST1. We thus provide evidence for a link between respiratory complex I and mitochondrial sulfur metabolism.
As part of her tour of Africa, German chancellor Angela Merkel recently (Tuesday, 11 October 2016) visited the Ethiopian capital Addis Ababa, which is also home to the headquarters of the African Union. During a joint press conference with Prime Minister Hailemariam Desalegn, Merkel urged the Ethiopian government to open up politics and halt violent behaviour by police in response to peaceful demonstrations...
Ein historischer Moment? Die UN beschließen erstmals Verhandlungen zu einem Nuklearwaffenverbot
(2016)
Um Mitternacht deutscher Zeit beschloss der Erste Hauptausschuss (Ausschuss für Abrüstung und Internationale Sicherheit) der UN-Generalversammlung mit großer Mehrheit, dass im nächsten Jahr Verhandlungen über ein Verbot von Kernwaffen aufgenommen werden sollen. Damit gipfelte die sogenannte Humanitäre Initiative, die sich in den vergangenen Jahren formierte und zunehmend an Momentum gewann, in einer historischen Resolution. Mit 123 zu 38 Stimmen, bei 16 Enthaltungen, stimmten knapp Zweidrittel der Staaten für Resolution L.41 („Taking forward multilateral nuclear disarmament negotiations“). Die USA und Russland, deren Arsenale zusammen über 95% der weltweiten Kernwaffen ausmachen, stimmten ebenso dagegen, wie (mit Ausnahme der Niederlande) sämtliche NATO-Mitglieder, darunter auch Deutschland. Wir rufen an dieser Stelle in Erinnerung, was sich hinter der Humanitären Initiative verbirgt, was es mit dem nun zu verhandelnden Kernwaffenverbot auf sich hat und werfen einen Blick auf das Abstimmungsergebnis....
Im Rahmen dieser Arbeit wurde die humane Leukotrien A4-Hydrolase untersucht.
Die hLTA4H ist ein bifunktionelles Enzym, welches neben der Hydrolaseaktivität, welche für die Umwandlung des instabilen LTA4 zu LTB4 verantwortlich ist, auch eine Peptidaseaktivität aufweist. Beide Enzymaktivitäten spielen bei Entzündungsprozessen eine wichtige Rolle, weshalb die LTA4H ein interessantes pharmakologisches Target darstellt. Aufgrund der gegensätzlichen Eigenschaften der beiden Aktivitäten der LTA4H (Produktion des proinflammatorischen LTB4 durch die Hydrolase-Aktivität, sowie der Abbau des PGP-Tripeptids durch die Peptidase-Aktivität) wird deutlich, dass die Entwicklung selektiver Hydrolase-Inhibitoren von Vorteil ist.
Das Protein der humanen LTA4H konnte erfolgreich kloniert werden und in E. coli-Zellen exprimiert werden. Zur Gewinnung des reinen rekombinanten Proteins konnte ein Aufreinigungsprotokoll mittels Nickel-Affinitätschromatographie sowie anschließender Größenausschlusschromatographie etabliert werden. Durch die Testung unterschiedlicher Lysemethoden konnte die Ausbeute deutlich erhöht werden.
Um herauszufinden, ob es durch den potentiellen Inhibitor zu einer Hemmung der Enzymaktivität kommt, muss diese detektiert werden können. Hierfür wurde ein geeignetes fluoreszenzbasiertes Testsystem zur Detektion der Enzymaktivität der hLTA4H entwickelt. Dies lässt auch die Quantifizierung der Wirksamkeit der möglichen Inhibitoren zu. Mit Hilfe eines pharmakophorbasierten Ansatzes wurden 22 Testsubstanzen für die in vitro Testung ausgewählt. Nach der Evaluierung dieser Substanzen wurden weitere 14 Derivate der besten Verbindung ausgewählt und ihre inhibitorischen Eigenschaften an rekombinanter LTA4H getestet. Die Ergebnisse wurden mittels Differential Scanning Fluorimetrie validiert, wofür ein einfaches Protokoll etabliert werden konnte.
Im Rahmen dieser Arbeit wurden weiterhin 5 bereits bekannte Inhibitoren der LTA4H ausgewählt, um sie hinsichtlich ihres thermodynamischen Profils zu untersuchen. Hierzu wurden die ausgewählten Inhibitoren mittels Isothermer Titrationskalorimetrie vermessen. Die Dissoziationskonstanten der untersuchten Inhibitoren wurden ebenfalls mittels Differential Scanning Fluorimetrie bestimmt, wobei sich zeigte, dass diese Methode nicht zur präzisen Messung von Protein/Ligand Interaktionen herangezogen werden kann. Mittels eines in silico Ansatzes zur Vorhersage von stabilisierten und destabilisierten Wassermolekülen in der Bindetasche konnten die thermodynamischen Daten im strukturellen Kontext interpretiert werden. Durch diese Kombination konnten neue Erkenntnisse zum Design neuer Inhibitoren der LTA4H gewonnen werden.
Amid increasing regulation, structural changes of the market and Quantitative Easing as well as extremely low yields, concerns about the market liquidity of the Eurozone sovereign debt markets have been raised. We aim to quantify illiquidity risks, especially such related to liquidity dry-ups, and illiquidity spillover across maturities by examining the reaction to illiquidity shocks at high frequencies in two ways:
a) the regular response to shocks using a variance decomposition and,
b) the response to shocks in the extremes by detecting illiquidity shocks and modeling those as ultivariate Hawkes processes.
We find that:
a) market liquidity is more fragile and less predictable when an asset is very illiquid and,
b) the response to shocks in the extremes is structurally different from the regular response.
In 2015 long-term bonds are less liquid and the medium-term bonds are liquid, although we observe that in the extremes the medium-term bonds are increasingly driven by illiquidity spillover from the long-term titles.
Die NADPH-Oxidasen stellen eine wichtige Quelle für reaktive Sauerstoffspezies (Reactive oxygen species; ROS) im Organismus dar. Hierbei dienen die NADPH-Oxidasen nicht nur der Pathogenabwehr, sondern haben einen Einfluss auf eine Vielzahl an oxidativen, physiologischen Prozessen. Unter den NADPH-Oxidasen ist NOX4 einzigartig, da es hauptsächlich im endoplasmatischen Retikulum (ER) lokalisiert ist, konstitutiv aktiv ist und Wasserstoffperoxid (H2O2) produziert. Wir vermuten, dass diese besonderen Eigenschaften eine Konsequenz aus der Interaktion mit bislang unentdeckten NOX4-interagiereden Proteinen ist.
Zweidimensionale blau-native Polyacrylamid-Gelelektrophorese (BN-PAGE) kombiniert mit SDS-PAGE zeigte NOX4 in makromolekularen Komplexen. Interagierende Proteine wurden durch eine quantitative SILAC (stable isotope labeling of amino acids in cell culture)-Co-immunopräzipitation (Co-IP) in NOX4-überexprimierenden HEK293-Zellen gescreent. Hierdurch konnten verschiedene interagierende Proteine identifiziert werden, wobei Calnexin die robusteste Interaktion aufwies. Calnexin konnte zudem in NOX4-haltigen Komplexen durch Complexome Profiling der BN-PAGE oder gleichzeitiger Antikörperfärbung nachgewiesen werden. Die Calnexin-NOX4-Interaktion konnte mittels reverser Co-IP und Proximity ligation assay bestätigt werden, während NOX1, NOX2 und NOX5 nicht mit Calnexin interagierten. Calnexin-Defizienz, untersucht in embryonalen Mausfibroblasten oder durch shRNA gegen Calnexin, reduzierte die NOX4-Proteinexpression und ROS-Bildung, wobei die mRNA-Expression unverändert blieb. Des Weiteren wurde untersucht, ob der bekannte Interaktionspartner von NADPH-Oxidasen, p22phox, wirklich essentiell für die Expression oder Aktivität von NOX4 ist, da es nur in manchen der NOX4-Co-IPs nachgewiesen wurde. Um den Einfluss von p22phox für NOX4 aufzuklären wurde ein CRISPR/Cas9 Knockdown in NOX4-überexprimierenden HEK293 Zellen etabliert. p22phox zeigte keinen Einfluss auf die NOX4-Expression, jedoch war die NOX4-abhängige ROS-Produktion in p22phox-Knockout Zellen verschwunden.
Unsere Ergebnisse deuten darauf hin, dass endogenes NOX4 makromolekulare Komplexe mit Calnexin ausbildet, welches für die korrekte Reifung, Prozessierung und Funktion von NOX4 im ER nötig ist. Darüber hinaus ist p22phox nicht für die Reifung von NOX4, aber für dessen Aktivität nötig. Diese Ergebnisse zeigen eine vielfältige Regulation von NOX4 auf Proteinebene.
How do insiders trade?
(2016)
We characterize how informed investors trade in the options market ahead of corporate news when they receive private, but noisy, information about (i) the timing of the announcement and (ii) its impact on stock prices. Our theoretical framework generates a rich set of predictions about the insiders’ behavior and their maximum expected returns. Three different analyses offer empirical support for our approach. First, predicted trades resemble illegal insider trades documented in SEC litigation cases with insiders being more likely to trade in options that offer higher expected returns. Second, pre-announcement patterns in unusual activity in the options market ahead of significant corporate news are consistent with the predictions of our framework. We employ our approach to characterize informed trading ahead of twelve different types of news including the announcement of earnings, corporate guidance, M&As, product innovations, management changes, and analyst recommendations. Third, to address concerns that pre-announcement patterns are driven by speculation, we show that measures capturing trading activity in call (put) options with high expected returns predict significant positive (negative) corporate news in the aggregate cross-section.
Data show that sovereign risk reduces liquidity, increases funding cost and risk of banks highly exposed to it. I build a model that rationalizes this fact. Banks act as delegated monitors and invest in risky projects and in risky sovereign bonds. As investors hear rumors of increased sovereign risk, they run the bank (via global games). Banks could rollover liquidity in repo market using government bonds as collateral, but as sovereign risk raises collateral values shrink. Overall banks’ liquidity falls (its cost increases) and so does banks’ credit. In this context noisy news (announcements with signal extraction) of consolidation policies are recessionary in the short run, as they contribute to investors and banks pessimism, and mildly expansionary in the medium run. The banks liquidity channel plays a major role in the fiscal transmission.
n traditional portfolio theory, risk management is limited to the choice of the relative weights of the riskless asset and a diversified basket of risky securities, respectively. Yet in industry, risk management represents a central aspect of asset management, with distinct responsibilities and organizational structures. We identify frictions that lead to increased importance of risk management and describe three major challenges to be met by the risk manager. First, we derive a framework to determine a portfolio position's marginal risk contribution and to decide on optimal portfolio weights of active managers. Second, we survey methods to control downside risk and unwanted risks since investors frequently have non-standard preferences which make them seek protection against excessive losses. Third, we point out that quantitative portfolio management usually requires the selection and parametrization of stylized models of financial markets. We therefore discuss risk management approaches to deal with parameter uncertainty, such as shrinkage procedures or re- sampling procedures, and techniques of dealing with model uncertainty via methods of Bayesian model averaging.
Am 27. Dezember 2015 verabschiedete der Ständige Ausschuss des Nationalen Volkskongresses das erste Antiterrorgesetz in der Geschichte der Volksrepublik China (VRC). Damit wurde eine über 25 Jahre erarbeitete umfangreiche Antiterrorstrategie zu Papier gebracht und mit ihr endlich eine verbindliche rechtliche Definition von „Terrorismus.“ Bereits gängige Praktiken wie öffentliche Medienzensur oder die Verpflichtung von Telekommunikationsunternehmen und Internetprovidern zur Bereitstellung von Inhaltsdaten wurden formalisiert und verschärft, sowie auch die Mobilisierung zivilgesellschaftlicher Organisationen auf eine rechtliche Grundlage gestellt. Allerdings stellt das Gesetz nur den finalen, formalen Schritt einer fünfundzwanzigjährigen Entwicklung dar. Tatsächlich kämpft Beijing seit Anfang der 1990er Jahre in der Provinz Xinjiang mit einer Mischung aus separatistisch und islamistisch motivierter politischer Gewalt, an deren Spitze seit spätestens 2008 das East Turkestan Independence Movement (ETIM) steht. ETIM weist ideell und organisatorisch eine Nähe zu Al Qaeda auf, und arbeitet transnational mit der Islamischen Bewegung Usbekistans, Tehrik-i-Taliban (Pakistan) und der al-Nusra Front (Syrien) zusammen...
This is the ninth post in the blog series „Movements and Institutions“.
This article disputes the conceptualization of institutionalization as a one-way process. Instead, it argues that social movement organizations can make use of contentious tactics while being institutionalized. The environmental NGO Birdlife Malta provides an example to illustrate this argument
This paper is the outcome of a related broader project, exploring the explanatory power of the Legal Theory of Finance, which proposes a new institution-based analytical framework for the analysis of phenomena of financial markets. One of its most important theoretical assumptions, the legal construction of financial markets, is highlighted by the example of the private creation of money by structured finance products in this paper. Further implications can then be shown referring to pari passu clauses and collective action clauses, which are both exhibit a differential application of these legal rules according to the hierarchical status of the respective market participant, and can therefore endanger sovereign debt restructurings. Legal instruments to avoid this are briefly explored. An example of another key role of the law in crisis that is the task to resolve the tension between market discipline and financial stability is exemplified by the regulation of the OTC derivatives market and proposals of effective loss-sharing among CCPs. Related questions about the significance of legal rules to ensure financial stability are raised in the analysis of minimum capital requirements under Basel III.
Using two datasets containing demographically representative samples of the Dutch population, I study how lifetime experiences of aggregate labor market conditions affect personality. Three sets of findings are reported. First, experienced aggregate unemployment is negatively correlated with the levels of all Big Five personality traits, except for conscientiousness (no significant correlation). Second, in panel data models with individual fixed effects I find that changes in experienced aggregate unemployment cause changes in emotional stability and agreeableness for men, and conscientiousness for women. The correlation is positive, and effects are economically large. Thirdly, I report suggestive evidence that the main driver is experienced aggregate unemployment, instead of other macroeconomic variables as experienced GDP, stock market returns or inflation. Taken together, these findings suggest that changes in Big Five personality traits are systematically related to experienced aggregate labor market conditions.
The global financial crisis and the ensuing criticism of macroeconomics have inspired researchers to explore new modeling approaches. There are many new models that deliver improved estimates of the transmission of macroeconomic policies and aim to better integrate the financial sector in business cycle analysis. Policy making institutions need to compare available models of policy transmission and evaluate the impact and interaction of policy instruments in order to design effective policy strategies. This paper reviews the literature on model comparison and presents a new approach for comparative analysis. Its computational implementation enables individual researchers to conduct systematic model comparisons and policy evaluations easily and at low cost. This approach also contributes to improving reproducibility of computational research in macroeconomic modeling. Several applications serve to illustrate the usefulness of model comparison and the new tools in the area of monetary and fiscal policy. They include an analysis of the impact of parameter shifts on the effects of fiscal policy, a comparison of monetary policy transmission across model generations and a cross-country comparison of the impact of changes in central bank rates in the United States and the euro area. Furthermore, the paper includes a large-scale comparison of the dynamics and policy implications of different macro-financial models. The models considered account for financial accelerator effects in investment financing, credit and house price booms and a role for bank capital. A final exercise illustrates how these models can be used to assess the benefits of leaning against credit growth in monetary policy.
Correlated activity of cortical neurons survives extensive removal of feedforward sensory input
(2016)
A fundamental property of brain function is that the spiking activity of cortical neurons is variable and that some of this variability is correlated between neurons. Correlated activity not due to the stimulus arises from shared input but the neuronal circuit mechanisms that result in these noise correlations are not fully understood. Here we tested in the visual system if correlated variability in mid-level area V4 of visual cortex is altered following extensive lesions of primary visual cortex (V1). To this end we recorded longitudinally the neuronal correlations in area V4 of two behaving macaque monkeys before and after a V1 lesion while the monkeys fixated a grey screen. We found that the correlations of neuronal activity survived the lesions in both monkeys. In one monkey, the correlation of multi-unit spiking signals was strongly increased in the first week post-lesion, while in the second monkey, correlated activity was slightly increased, but not greater than some week-by-week fluctuations observed. The typical drop-off of inter-neuronal correlations with cortical distance was preserved after the lesion. Therefore, as V4 noise correlations remain without feedforward input from V1, these results suggest instead that local and/or feedback input seem to be necessary for correlated activity.
Infections are an important cause for morbidity and mortality in pediatric acute myeloid leukemia (AML). We therefore characterized infectious complications in children treated according to the trial AML-BFM 2004. Patients with Down syndrome were excluded from the analysis. Data were gathered from the medical records in the hospital where the patients were treated. A total of 405 patients (203 girls; median age 8.4 years) experienced 1326 infections. Fever without identifiable source occurred in 56.1% of the patients and clinically and microbiologically documented infections in 17.5% and 32.4% of the patients, respectively. In all, 240 Gram-positive (112 viridans group streptococci) and 90 Gram-negative isolates were recovered from the bloodstream. Invasive fungal infection was diagnosed in 3% of the patients. Three children each died of Gram-negative bacteremia and invasive aspergillosis, respectively. As compared with the results of AML-BFM 93 with lower dose intensity, infection-related morbidity was slightly higher in AML-BFM 2004 (3.3. versus 2.8 infections per patient), whereas infection-related mortality significantly decreased (1.5% versus 5.4%; P=0.003). Specific anti-infective recommendations included in the treatment protocol, regular training courses for pediatric hematologists and increasing experience may be the reason for reduced infection-related mortality in children with AML. Further studies are needed to decrease infection-related morbidity.
We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20–27%) and a median OS of 3.3 months (95% CI: 2.8–3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36–50%) and a median OS of 6.1 months (95% CI: 4.2–7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67–4.31) and improved OS (HR=0.536, 95% CI: 0.394–0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.
Background: Despite a recent statutory ruling stating the binding nature of advance directives (ADs), only a minority of the population has signed one. Yet, a majority deem it of utmost importance to ensure their wishes are followed through in case they are no longer able to decide. The reasons for this discrepancy have not yet been investigated sufficiently.
Patients and methods: This article is based on a survey of patients using a well-established structured questionnaire. First, patients were asked about their attitudes with respect to six therapeutic options at the end of life: intravenous fluids, artificial feeding, antibiotics, analgesia, chemotherapy/dialysis, and artificial ventilation; and second, they were asked about the negative effects related to the idea of ADs surveying their apprehensions: coercion to fulfill an AD, dictatorial reading of what had been laid down, and abuse of ADs.
Results: A total of 1,260 interviewees completed the questionnaires. A significant percentage of interviewees were indecisive with respect to therapeutic options, ranging from 25% (analgesia) to 45% (artificial feeding). There was no connection to health status. Apprehensions about unwanted effects of ADs were widespread, at 51%, 35%, and 43% for coercion, dictatorial reading, and abuse, respectively.
Conclusion: A significant percentage of interviewees were unable to anticipate decisions about treatment options at the end of life. Apprehensions about negative adverse effects of ADs are widespread.
"Toleranz kommt vor Glückseligkeit" : eine Zeitreise mit der Tugend des gegenseitigen Respekts
(2016)
Toleranz ist gerade da nötig, wo sie besonders schwerfällt. Das war schon vor gut 300 Jahren so, als Denker wie der französische Philosoph Pierre Bayle in Zeiten religiöser Auseinandersetzungen den Grundstein für ein fortschrittliches Toleranz-Verständnis legten. Warum der Begriff gerade heute wieder Konjunktur hat und wie umstritten er noch immer ist, erläutert der politische Philosoph Rainer Forst im Gespräch mit Bernd Frye.
Religion und Gesellschaft
(2016)
Sehnsucht nach absoluter Wissenschaft : die moderne Esoterik will nicht glauben, sondern wissen
(2016)
Esoterische Weltanschauungen versprechen "höhere", "ganzheitliche" Einsichten statt kalter, "materialistischer" Erkenntnis. Damit stellen sie sich in ein bewusstes, wenn auch aussichtsloses Konkurrenzverhältnis zu den akademischen Wissenschaften. Dennoch hat sich der esoterische Diskurs immer wieder gerade im Umfeld und im Schatten der gesellschaftlich anerkannten universitären Wissenschaften konstituiert, zumindest in reflexiver Abhängigkeit von ihren normativen Ansprüchen.
Gehört Religionsunterricht in den Fächerkanon einer staatlichen Schule? In Deutschland wird dies sogar im Grundgesetz bejaht. Während atheistische Kreise die Abschaffung dieses Grundrechts fordern, sehen Politik und Wissenschaft darin eine Chance, auch Kindern aus muslimischen Familien religiöses Wissen näherzubringen, sie auf diese Weise besser zu integrieren und vielleicht sogar gegen fundamentalistische Hasslehren zu wappnen. In Hessen erhalten Grundschüler seit dem Schuljahr 2013 / 2014 bekenntnisorientierten islamischen Religionsunterricht; die Justus-Liebig-Universität Gießen und künftig auch die Goethe-Universität bilden Lehrer aus.
Der Islam befindet sich in einer Phase fundamentaler Veränderungen, die neue progressive Spielarten, aber auch beunruhigende Formen religiösen Extremismus hervorbringt. In Deutschland diskutieren Muslime, ob es sinnvoll sei, einen spezifisch deutschen oder europäischen Islam zu entwickeln oder ob die herkunftsorientierte Religion der Moschee-Gemeinschaften beibehalten werden sollte.
Als Reaktion auf die von islamischen Extremisten begangenen Terroranschläge sowie auf das Wüten des IS in Syrien und im Irak werden diese Forderungen immer lauter: Muslime müssen selbstkritisch nach dem Zusammenhang von islamischer Religion und Gewalt fragen. Bloße Distanzierungen seien nicht ausreichend, so die Kritik von außen, aber zunehmend auch innerhalb der muslimischen Gemeinschaften. Wie setzt sich die islamische Theologie, wie sie u. a. in Frankfurt betrieben wird, damit auseinander?
In ihrem Gespräch beschäftigen sich Prof. Dr. Bekim Agai, geschäftsführender Direktor des Instituts für Studien der Kultur und Religion des Islam, und Ulrike Jaspers, Redakteurin von "Forschung Frankfurt", mit dem Wahrheitsanspruch der Religionen, der Debattenkultur in Deutschland, der jungen islamischen Theologie, den fundamentalistischen Strömungen und anderem mehr.
Die Geschichte der frühen Christenverfolgung wird in Hollywoodstreifen wesentlich dramatischer dargestellt, als sie in der jüngeren Forschung beurteilt wird. Auch andere Kulte wurden unterdrückt, denn es bestand kein Recht auf Religionsfreiheit. Die Gründe für solche Maßnahmen lagen nicht in Glaubensvorstellungen, sondern in Handlungen, die als gefährlich für das Gemeinwesen galten. So fürchtete man, dass die Weigerung der Christen, Opfer darzubringen, den Zorn der Götter heraufbeschwören könne oder ein Zeichen mangelnder Loyalität sei. Vor diesem Hintergrund forderten Christen Religionsfreiheit von den Heiden, doch wurde diese auch im später christlichen spätantiken Reich nicht praktiziert.
Seit seinen Anfängen ist das Christentum alles andere als einheitlich oder homogen. Mit dem Aufstieg zur Staatsreligion im Römischen Reich und dem Wunsch des Kaisertums, seine Herrschaft zu legitimieren, wuchs der Druck zur Vereinheitlichung. Diese Bemühungen ziehen sich wie ein roter Faden durch die mittelalterliche Geschichte. Doch die Alltags-, Gesellschafts- und Kulturgeschichte verweist in der mittelalterlichen Gesellschaft auf eine große Vielfalt der Ausprägungen des Christentums.
Rezension zu: Mathias Rohe (Hrsg.), Mouhanad Khorchide (Hrsg.), Havva Engin (Hrsg.), Hansjörg Schmid (Hrsg.), Ömer Özsoy (Hrsg.), Eugen-Biser-Stiftung (Hrsg.): Handbuch Christentum und Islam in Deutschland. Grundlagen, Erfahrungen und Perspektiven des Zusammenlebens, Freiburg 2015, Verlag Herder, ISBN: 978-3-451-31188-8, zwei Bände, 1297 Seiten, 48 Euro.
It is estimated that a number between 27,000 and 31,000 foreign fighters have been flocking to Iraq and Syria since the breakout of the war in 2011.
An updated assessment of the flow of foreign fighters into Syria and Iraq shows that there is a significant increase in the number of foreign fighters travelling to Syria. Data provided by the Soufan Group in 2014 estimated that the identifiable number of foreign fighters is approximately 12,000 from 81 countries. It was also believed that the number of foreign Jihadists coming form Western countries does not exceed 3000: “Around 2,500 are from Western countries, including most members of the European Union, the United States, Canada, Australia, and New Zealand”, according to Soufan’s initial report on Foreign Fighters in Syria. Now the number exceeds 27,000 foreign fighters from at least 86 countries...
The CARIBIC (Civil Aircraft for the Regular Investigation of the Atmosphere Based on an Instrument Container) passenger aircraft observatory performed in situ measurements at 10–12 km altitude in the South Asian summer monsoon anticyclone between June and September 2008. These measurements enable us to investigate this atmospheric region (which so far has mostly been observed from satellites) using the broad suite of trace gases and aerosol particles measured by CARIBIC. Elevated levels of a variety of atmospheric pollutants (e.g. carbon monoxide, total reactive nitrogen oxides, aerosol particles, and several volatile organic compounds) were recorded. The measurements provide detailed information about the chemical composition of air in different parts of the monsoon anticyclone, particularly of ozone precursors. While covering a range of 3500 km inside the monsoon anticyclone, CARIBIC observations show remarkable consistency, i.e. with distinct latitudinal patterns of trace gases during the entire monsoon period.
Using the CARIBIC trace gas and aerosol particle measurements in combination with the Lagrangian particle dispersion model FLEXPART, we investigated the characteristics of monsoon outflow and the chemical evolution of air masses during transport. The trajectory calculations indicate that these air masses originated mainly from South Asia and mainland Southeast Asia. Estimated photochemical ages of the air were found to agree well with transport times from a source region east of 90–95° E. The photochemical ages of the air in the southern part of the monsoon anticyclone were systematically younger (less than 7 days) and the air masses were mostly in an ozone-forming chemical mode. In its northern part the air masses were older (up to 13 days) and had unclear ozone formation or destruction potential. Based on analysis of forward trajectories, several receptor regions were identified. In addition to predominantly westward transport, we found evidence for efficient transport (within 10 days) to the Pacific and North America, particularly during June and September, and also of cross-tropopause exchange, which was strongest during June and July. Westward transport to Africa and further to the Mediterranean was the main pathway during July.
We present an estimation of the uptake coefficient (γ) and yield of nitryl chloride (ClNO2) (f) for the heterogeneous processing of dinitrogen pentoxide (N2O5) using simultaneous measurements of particle and trace gas composition at a semi-rural, non-coastal, mountain site in the summer of 2011. The yield of ClNO2 varied between (0.035 ± 0.027) and (1.38 ± 0.60) with a campaign average of (0.49 ± 0.35). The large variability in f reflects the highly variable chloride content of particles at the site. Uptake coefficients were also highly variable with minimum, maximum and average γ values of 0.004, 0.11 and 0.028 ± 0.029, respectively, with no significant correlation with particle composition, but a weak dependence on relative humidity. The uptake coefficients obtained are compared to existing parameterisations based on laboratory datasets and with other values obtained by analysis of field data.
We present an estimation of the uptake coefficient (γ) and yield of nitryl chloride (ClNO2) (f) for the heterogeneous processing of dinitrogen pentoxide (N2O5) using simultaneous measurements of particle and trace gas composition at a semi-rural, non-coastal, mountain site in the summer of 2011. The yield of ClNO2 varied between (0.035 ± 0.027) and (1.38 ± 0.60) with a campaign average of (0.49 ± 0.35). The large variability in f reflects the highly variable chloride content of particles at the site. Uptake coefficients were also highly variable with minimum, maximum and average γ values of 0.004, 0.11 and 0.028 ± 0.029, respectively, with no significant correlation with particle composition, but a weak dependence on relative humidity. The uptake coefficients obtained are compared to existing parameterizations based on laboratory datasets and with other values obtained by analysis of field data.
Directors have traditionally been elected by a plurality of the votes cast. This means that in uncontested elections, a candidate who receives even a single vote is elected. Proponents of “shareholder democracy” have advocated a shift to a majority voting rule in which a candidate must receive a majority of the votes cast to be elected. Over the past decade, they have been successful, and the shift to majority voting has been one of the most popular and successful governance reforms.
Yet critics are skeptical as to whether majority voting improves board accountability. Tellingly, directors of companies with majority voting rarely fail to receive majority approval – even more rarely than directors of companies with plurality voting. Even when such directors fail to receive majority approval, they are unlikely to be forced to leave the board. This poses a puzzle: why do firms switch to majority voting and what effect does the switch have, if any, on director behavior?
We empirically examine the adoption and impact of a majority voting rule using a sample of uncontested director elections from 2007 to 2013. We test and find partial support for four hypotheses that could explain why directors of majority voting firms so rarely fail to receive majority support: selection; deterrence/accountability; electioneering by firms; and restraint by shareholders.
Our results further suggest that the reasons for and effects of adopting majority voting may differ between early and later adopters. We find that early adopters of majority voting were more shareholder-responsive than other firms even before they adopted majority voting. These firms seem to have adopted majority voting voluntarily, and the adoption of majority voting has made little difference in their responsiveness to shareholders responsiveness going forward. By contrast, for late adopters, we find no evidence that they were more shareholder-responsive than other firms before they adopted majority voting, but strong evidence that they became more responsive after adopting majority voting.
Differences between early and late adopters can have important implications for understanding the spread of corporate governance reforms and evaluating their effects on firms. Reform advocates, rather than targeting the firms that, by their measures, are most in need of reform, instead seem to have targeted the firms that are already most responsive. They may then have used the widespread adoption of majority voting to create pressure on the nonadopting firms. Empirical studies of the effects of governance changes thus need to be sensitive to the possibility that early adopters and late adopters of reforms differ from each other and that the reforms may have different effects on these two groups of firms.
We examine the impact of house prices on labour supply decisions using UK micro data. We combine household survey data with local level house price measures and controls for local labour demand. Our micro data also allows us to control for individual level income expectations. We find significant house price effects on labour supply, consistent with leisure being a normal good. Labour supply responses to house prices are concentrated among young married female owners and older owners. This finding suggests house prices affect the decisions of marginal workers in the economy. Our estimates imply house prices are economically important for the participation decisions for these workers.
We reconsider the role for human capital in accounting for cross-country income differences. Our contribution is to bring to bear new data on the pre- and post- migration labor market experiences of immigrants to the U.S. Immigrants from poor countries experience wage gains that are only 40 percent of the GDP per worker gap, which implies that “country" accounts for 40 percent of income differences, while human capital accounts for 60 percent. Our approach handles selection by comparing the wage of the same individual in two different countries. We also provide evidence on and a correction for skill transfer.
Returns to experience for U.S. workers have changed over the post-war period. This paper argues that a simple model goes a long way towards replicating these changes. The model features three well-known ingredients: (i) an aggregate production function with constant skill-biased technical change; (ii) cohort qualities that vary with average years of schooling; and crucially (iii) time-invariant age-efficiency profiles. The model quantitatively accounts for changes in longitudinal and cross-sectional returns to experience, as well as the differential evolution of the college wage premium for young and old workers.
BACKGROUND: Microvascular ischemia is one of the hallmarks of hypertrophic cardiomyopathy (HCM) and has been associated with poor outcome. However, myocardial fibrosis, seen on cardiovascular magnetic resonance (CMR) as late gadolinium enhancement (LGE), can be responsible for rest perfusion defects in up to 30% of patients with HCM, potentially leading to an overestimation of the ischemic burden. We investigated the effect of left ventricle (LV) scar on the total LV ischemic burden using novel high-resolution perfusion analysis techniques in conjunction with LGE quantification.
METHODS: 30 patients with HCM and unobstructed epicardial coronary arteries underwent CMR with Fermi constrained quantitative perfusion analysis on segmental and high-resolution data. The latter were corrected for the presence of fibrosis on a pixel-by-pixel basis.
RESULTS: High-resolution quantification proved more sensitive for the detection of microvascular ischemia in comparison to segmental analysis. Areas of LGE were associated with significant reduction of myocardial perfusion reserve (MPR) leading to an overestimation of the total ischemic burden on non-corrected perfusion maps. Using a threshold MPR of 1.5, the presence of LGE caused an overestimation of the ischemic burden of 28%. The ischemic burden was more severe in patients with fibrosis, also after correction of the perfusion maps, in keeping with more severe disease in this subgroup.
CONCLUSIONS: LGE is an important confounder in the assessment of the ischemic burden in patients with HCM. High-resolution quantitative analysis with LGE correction enables the independent evaluation of microvascular ischemia and fibrosis and should be used when evaluating patients with HCM.
We examine the dynamics of assets under management (AUM) and management fees at the portfolio manager level in the closed-end fund industry. We find that managers capitalize on good past performance and favorable investor perception about future performance, as reflected in fund premiums, through AUM expansions and fee increases. However, the penalties for poor performance or unfavorable investor perception are either insignificant, or substantially mitigated by manager tenure. Long tenure is generally associated with poor performance and high discounts. Our findings suggest substantial managerial power in capturing CEF rents. We also document significant diseconomies of scale at the manager level.
Design typicality plays a major role in consumers’ reactions towards a product. Hence, assessing a product design’s typicality is vital to predicting consumers’ responses to a design. However, directly asking people for their subjective typicality experience may yield a biased measure as the rating arguably contains the overall aesthetic impression of the product. Against this background, we introduce four unbiased objective measures of design typicality (two based on feature points and two based on grids) and demonstrate their capability of capturing the subjective typicality experience. We validate the proposed measures in the context of automobile designs with ratings of aesthetic liking, processing fluency, and cumulative sales data by analysing 77 car models from four segments ranging from subcompact cars to SUVs. Our findings endorse the general notion that objective measures should be included in product design research; and the proposed objective approaches provide convenient means to easily assess design typicality.
Cells perform a wide range of functions such as signalling, transportation, immunoprotection and metabolism. Unravelling the molecular mechanism behind those processes will provide a platform for more targeted and rational drug design. This is achieved by discerning the structural and functional aspects of the biological macromolecules involved. This thesis discusses about the biophysical characterization of protein structures and the biological importance of protein dynamics. Membrane receptors and enzymes which are ubiquitously present in our biological systems and regulate wide variety of functions are excellent choice for such study. From a pharmaceutical point of view, receptor and enzymes are exceptionally important drug targets as they represent the major share (receptor, 30% and enzymes, 47%) of all marketed drugs. Therefore, apart from biological insights, the detailed study of receptors and enzymes will provide the basis for new pharmaceutical applications. Most information about receptor activation and enzyme activity come from the structural and functional analysis of target members of the above mentioned systems.
In “Chapter 1 – General Introduction” the readers are introduced to the world of proteins with special focus on G-protein coupled receptors (GPCRs) and methyltransferases. The first part of this chapter discusses about GPCRs with emphasis on their classification, structural features and functions. GPCRs are the most abundant membrane receptors present in mammalian cells, accounting for almost 15% of all membrane proteins. The GPCR superfamily consists of ~800 members and can be subdivided into six classes (A-F). Class A containing rhodopsin, peptide hormones, olfactory GPCRs, is the most abundant with a large share of 85% of GPCR protein family. GPCRs share a common architecture of 7 transmembrane a-helices, with different ligand binding sites. Although a variety of ligands ranging from subatomic particles (a photon) to large proteins can activate a GPCR, their mechanism of signal transduction is almost similar. There are two major signal transduction pathways identified for GPCRs: the cAMP pathway and the phosphatidylinositol pathway. The therapeutic relevance of GPCRs has also been pointed out here since a large share (30%) of modern marketed drugs target GPCRs.
In the second part of this chapter, the structural and functional characterizations of methyltransferases (MTs) are discussed in detail. Several important biological processes in cells e.g. drug metabolism, gene transcription, epigenetic regulations are modulated by methylation of targets ranging from small biomolecules to large proteins. MTs are the proteins which catalyze this methylation reaction and transfer the methyl group to an acceptor molecule through SN2 like nucleophilic substitution reaction. The MTs can be classified on the basis of the substrate atoms they methylate: O (54% of all MTs), N (23%), C (18%), S (3%) and other acceptors (such as halides; 2%). They can also be categorized into five different classes (Class I-V) depending upon distinctive structural features facilitating substrate binding or catalytic activity. Rossmann fold and SET (acronym acquired from the Drosophila Su(var)3-9 and 'Enhancer of zeste' proteins) domain are the two characteristic structural motifs commonly found in MTs. Similar to GPCRs, MTs dysfunction has been shown to be involved in various diseases including neuropsychiatric diseases and cancer. Therefore they are also interesting targets for drug development. The final part of this chapter discusses the importance of structural biology in gathering information related to structure and conformational dynamics of proteins. The two prominent biophysical techniques used in structural biology, X-ray crystallography and NMR, are discussed with focus on their advantages and limitation. The importance of NMR spectroscopic techniques to investigate different dynamic processes of protein at atomic resolution under physiological conditions is also discussed. Real time NMR spectroscopy required for the analysis of slow protein dynamic processes (protein folding, enzyme catalysis, domain rearrangement) has been explained in detail.
The second part of the thesis (Chapters 3-4), which is the cumulative part, comprises the original publications grouped into 2 chapters according to their topic:
• NMR-spectroscopic characterization of the transiently populated photointermediates of bovine rhodopsin and it’s interaction with arrestin (Chapter 3)
• Structural and biophysical characterization of PaMTH1, a putative SAM dependent O-methyltransferase from filamentous fungi Podospora anserina (Chapter 4)
Each chapter is initiated by a detailed introduction to the topic, providing the framework for the following papers. The personal contribution of this thesis’ author to each publication is stated in the introduction to the respective article.
The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.
Mumien im Film
(2016)
Inhalt:
Hans J. Wulff: Von lebenden Toten, der Verfluchung der Lebenden und später Rache: Die Mumien der Filmgeschichte.
Hans J. Wulff: Mumien im Film. Filmographie.
Fiktionale Filme, Serien und Serienfolgen.
Dokumentationen, Dokumentarfilme, Reality-TV-Sendungen.
Eismumien im Film.
Prähistorische Moorleichen.
Die Mumienfilme der Universal Pictures (1940–1955).
Die Mumienfilme der Hammer Film Productions.
Die mexikanischen Mumienfilme.
Adaptionen von Bram Stokers Roman Jewel of Seven Stars.
Hans J. Wulff: Mumien im Film. Bibliographie.