Differentiability of quadratic BSDEs generated by continuous martingales

In this paper we consider a class of BSDEs with drivers of quadratic growth, on a stochastic basis generated by continuous local martingales. We first derive the Markov property of a forward--backward system (FBSDE) if the generating martingale is a strong Markov process. Then we establish the differentiability of a FBSDE with respect to the initial value of its forward component. This enables us to obtain the main result of this article, namely a representation formula for the control component of its solution. The latter is relevant in the context of securitization of random liabilities arising from exogenous risk, which are optimally hedged by investment in a given financial market with respect to exponential preferences. In a purely stochastic formulation, the control process of the backward component of the FBSDE steers the system into the random liability and describes its optimal derivative hedge by investment in the capital market, the dynamics of which is given by the forward component.Comment: Published in at http://dx.doi.org/10.1214/11-AAP769 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

c-di-GMP-abhängige Signal-transduktion bei der Kontrolle der Cellulose-Synthese in Escherichia coli Biofilmen

c-di-GMP stellt einen wichtigen Regulator bei der Kontrolle von Motilität, Virulenz und der Biofilmbildung in Bakterien dar. Aufgrund der Vielfalt c-di-GMP-synthetisierender (Diguanylatzyklasen, DGC) bzw. abbauender (Phosphodiesterasen, PDE) Enzyme, c-di-GMP-bindender Effektoren und zellulärer Antworten etablierte sich die Theorie paralleler Regulationsmodule, die sich aus DGC, PDE, Effektor und Zielmolekül zusammensetzen und spezifische Prozesse wie die Cellulose-Synthese kontrollieren. Während die Aktivierung dieser durch c-di-GMP bereits verstanden und damit Effektor und Zielmolekül bekannt sind, konnten dem Modul bisher keine spezifisch wirkenden DGCs und PDEs zugeordnet werden. Im Rahmen dieser Arbeit konnte gezeigt werden, dass die Proteine DgcC und PdeK in E. coli spezifisch auf die Cellulose-Synthese in Makrokolonie-Biofilmen wirken und ein solches c-di-GMP-Modul bilden. Beide sind aktiv an der Umsetzung von c-di-GMP beteiligt und mittels Interaktionen Teil eines Multi-Protein-Komplexes, der auch die Cellulose-Synthase-Einheiten BcsA und BcsB umfasst. Aufgrund dieser Co-Lokalisation können DgcC und PdeK die c-di-GMP-Konzentration in unmittelbarer Umgebung zum c-di-GMP-bindenden Effektor BcsA kontrollieren. DgcC-PdeK somit stellen das erste Regulationsmodul dar, welches durch lokalisierte Synthese und Abbau von c-di-GMP wirkt und dessen Spezifität aufgrund multipler Protein-Interaktionen gewährleistet wird. 2011 kam es in Mitteleuropa zu einem schweren Ausbruch von Shiga-Toxin-produzierenden E. coli O104:H4, in dessen Verlauf fast 4000 Menschen erkrankten und etwa 20% ein Hämolytisch-urämisches Syndrom entwickelten. Die in dieser Arbeit erlangten Ergebnisse legen nahe, dass die einzigartige Kombination aus Toxin-Produktion und Biofilm-assoziierter Eigenschaften – das Potential zur c-di-GMP-Akkumulation (TL Povolotsky), verstärkte CsgD-Synthese und vor allem keine Cellulose-Produktion– möglicherweise zur erhöhten Virulenz dieses E. coli O104:H4 beitragen.c-di-GMP represents an important regulator in the control of motility, virulence and biofilm formation. Due to the multiplicity of c-di-GMP-forming (diguanylate cyclases, DGCc) and -degrading (phosphodiesterases, PDEs) enzymes, c-di-GMP-binding effectors and cellular outputs, the theory of parallel existing c-di-GMP-regulation modules was established. Such a module consists of a DGC, a PDE, an effector and a target controlling a specific cellular output such as cellulose synthesis. Whereas the activation of cellulose synthesis is well understood, and therefore effector and target molecule are known, so far no DGC or PDE has been associated with the cellulose-specific c-di-GMP-module. Within the framework of this work it was shown that DgcC and PdeK act specifically on the regulation of cellulose synthesis in macrocolony biofilms, thus forming a c-di-GMP module. Both proteins are enzymatically active concerning c-di-GMP metabolism and through protein-interactions part of a multi-protein-complex, which includes the cellulose synthase-subunits BcsA and BcsB, too. Due to this co-localisation DgcC and PdeK can control the c-di-GMP-concentration in close proximity to the c-di-GMP-binding cellulose-synthase BcsA. Therefore, DgcC-PdeK represents the first signalling module, which acts through local c-di-GMP-synthesis and -degradation and controls specifically cellulose because of multiple protein-interactions with the synthase-complex. In 2011 a serious outbreak of shiga toxin producing E. coli O104:H4 occurred in Middle Europe with nearly 4000 patients of whom approximately 20% developing haemolytic uraemic syndrome. The results obtained in this study suggest that a unique combination of shiga toxin production and biofilm-associated properties – the potential of c-di-GMP accumulation (see PhD Thesis T. L. Povolotsky), enhanced CsgD-synthesis at 37°C and especially no cellulose production – potentially contribute to the enhanced virulence of E. coli O104:H4

A Multi-perspective Analysis of Carrier-Grade NAT Deployment

As ISPs face IPv4 address scarcity they increasingly turn to network address translation (NAT) to accommodate the address needs of their customers. Recently, ISPs have moved beyond employing NATs only directly at individual customers and instead begun deploying Carrier-Grade NATs (CGNs) to apply address translation to many independent and disparate endpoints spanning physical locations, a phenomenon that so far has received little in the way of empirical assessment. In this work we present a broad and systematic study of the deployment and behavior of these middleboxes. We develop a methodology to detect the existence of hosts behind CGNs by extracting non-routable IP addresses from peer lists we obtain by crawling the BitTorrent DHT. We complement this approach with improvements to our Netalyzr troubleshooting service, enabling us to determine a range of indicators of CGN presence as well as detailed insights into key properties of CGNs. Combining the two data sources we illustrate the scope of CGN deployment on today's Internet, and report on characteristics of commonly deployed CGNs and their effect on end users

How has body weight changed since the beginning of the COVID-19 pandemic?

Background: Measures for containing the COVID-19 pandemic in 2020 and 2021 resulted in drastic changes in physical activity and dietary habits that also impacted body weight. Methods: The representative study German Health Update (GEDA 2021) includes self-reported information about body weight and body height for adults aged 18 years and older (n=2,985) from July to October 2021. In addition, the study asked about changes in body weight since the beginning of the COVID-19 pandemic. Results: For 59% of participants, body weight has not changed since the beginning of the COVID-19 pandemic, 26% report weight gain, and 15% report weight loss. Younger people indicate weight gain more often than older people, and individuals with obesity report weight gain more often than individuals without obesity. 1.5 years after the beginning of the COVID-19 pandemic, the average weight change within the population is approximately +0.34kg. Conclusions: The effects of restrictions in everyday life with regard to the possible negative impacts on body weight should be given greater consideration and should be monitored in the future

Recognising addiction: For addicts‘ relatives and friends

Someone close to you has problems due to drinking alcohol or taking drugs, medicines, etc. Or they are acting oddly when it comes to screen time, gaming, shopping or eating. And you are worried about it, but at the same time feel helpless, overwhelmed and afraid. You may know the feeling of calling for help inside, but without anyone hearing you. Or you might feel as if you cannot or should not talk about what you have noticed. The situation this puts you in is unpleasant to you, and you shy away from this topic. Redaktionsschluss: December 2019Eine Ihnen nahestehende Person hat Probleme wegen des Konsums von Alkohol, Drogen, Medikamenten oder anderem. Oder sie zeigt ein auffälliges Verhalten im Umgang mit Medien, beim Spielen, Kaufen oder Essen. Und Sie machen sich deswegen Sorgen, fühlen sich zugleich hilflos, überfordert und haben Angst. Wenn Sie merken, dass Sie an Ihre eigenen Grenzen gelangen oder bereits darüber hinaus gehen, bleiben Sie bitte nicht isoliert. Auch Sie haben das Recht und die Möglichkeit, Hilfe in Anspruch zu nehmen oder sich mit anderen Menschen in ähnlicher Lage auszutauschen. Sie sind nicht allein mit diesem Problem und dürfen darüber sprechen. Redaktionsschluss: Dezember 201

2D and 3D similarity landscape analysis identifies PARP as a novel off-target for the drug Vatalanib

Background Searching for two-dimensional (2D) structural similarities is a useful tool to identify new active compounds in drug-discovery programs. However, as 2D similarity measures neglect important structural and functional features, similarity by 2D might be underestimated. In the present study, we used combined 2D and three-dimensional (3D) similarity comparisons to reveal possible new functions and/or side-effects of known bioactive compounds. Results We utilised more than 10,000 compounds from the SuperTarget database with known inhibition values for twelve different anti-cancer targets. We performed all-against-all comparisons resulting in 2D similarity landscapes. Among the regions with low 2D similarity scores are inhibitors of vascular endothelial growth factor receptor (VEGFR) and inhibitors of poly ADP-ribose polymerase (PARP). To demonstrate that 3D landscape comparison can identify similarities, which are untraceable in 2D similarity comparisons, we analysed this region in more detail. This 3D analysis showed the unexpected structural similarity between inhibitors of VEGFR and inhibitors of PARP. Among the VEGFR inhibitors that show similarities to PARP inhibitors was Vatalanib, an oral “multi-targeted” small molecule protein kinase inhibitor being studied in phase-III clinical trials in cancer therapy. An in silico docking simulation and an in vitro HT universal colorimetric PARP assay confirmed that the VEGFR inhibitor Vatalanib exhibits off-target activity as a PARP inhibitor, broadening its mode of action. Conclusion In contrast to the 2D-similarity search, the 3D-similarity landscape comparison identifies new functions and side effects of the known VEGFR inhibitor Vatalanib