Viral evolution under the pressure of an adaptive immune system - optimal mutation rates for viral escape

Based on a recent model of evolving viruses competing with an adapting immune system [1], we study the conditions under which a viral quasispecies can maximize its growth rate. The range of mutation rates that allows viruses to thrive is limited from above due to genomic information deterioration, and from below by insufficient sequence diversity, which leads to a quick eradication of the virus by the immune system. The mutation rate that optimally balances these two requirements depends to first order on the ratio of the inverse of the virus' growth rate and the time the immune system needs to develop a specific answer to an antigen. We find that a virus is most viable if it generates exactly one mutation within the time it takes for the immune system to adapt to a new viral epitope. Experimental viral mutation rates, in particular for HIV (human immunodeficiency virus), seem to suggest that many viruses have achieved their optimal mutation rate. [1] C.Kamp and S. Bornholdt, Phys. Rev. Lett., 88, 068104 (2002)Comment: 5 pages RevTeX including 3 figure

Early experience with the NexGen® CR-Flex Mobile knee arthroplasty system: results of 2-year follow-up

We evaluated our initial results in 57 patients who received the NexGen® CR-Flex Mobile knee system using the standard anterior approach in a prospective study. The bicondylar surface implant was cemented in position (Palacos®) without posterior patellar resurfacing. The clinical outcome and perioperative and post-operative complications were documented over 24 months of its use. Overall, after two years, good results were obtained for the categories of pain and ROM (range of motion), and for the HSS (knee society score) (pre-operative: 42/57; post-operative: 87/80). No pathological radiological findings were made during this period. Two patients, however, felt that the primary operation had not been successful because of lateral patellar tilt. This was corrected with revision surgery. It was remarkable that our patients achieved greater than 100° flexion within the first 14 days of the immediate post-operative period. Evaluation and comparison of the scores with those of conventional bicondylar surface replacement systems showed no relevant differences

Exploring nonlocal observables in shock wave collisions

We study the time evolution of 2-point functions and entanglement entropy in strongly anisotropic, inhomogeneous and time-dependent N=4 super Yang-Mills theory in the large N and large 't Hooft coupling limit using AdS/CFT. On the gravity side this amounts to calculating the length of geodesics and area of extremal surfaces in the dynamical background of two colliding gravitational shockwaves, which we do numerically. We discriminate between three classes of initial conditions corresponding to wide, intermediate and narrow shocks, and show that they exhibit different phenomenology with respect to the nonlocal observables that we determine. Our results permit to use (holographic) entanglement entropy as an order parameter to distinguish between the two phases of the cross-over from the transparency to the full-stopping scenario in dynamical Yang-Mills plasma formation, which is frequently used as a toy model for heavy ion collisions. The time evolution of entanglement entropy allows to discern four regimes: highly efficient initial growth of entanglement, linear growth, (post) collisional drama and late time (polynomial) fall off. Surprisingly, we found that 2-point functions can be sensitive to the geometry inside the black hole apparent horizon, while we did not find such cases for the entanglement entropy.Comment: 28 pp, 9 figs; v2: updated references, changed color bars in Figure 2 and Figure

Chancen und Risiken finanzieller Mitarbeiterbeteiligung: Ergebnisse einer repräsentativen Betriebsrätebefragung

In der öffentlichen Diskussion der letzten Jahre wurde die Idee der finanziellen Mitarbeiterbeteiligung wieder verstärkt diskutiert. Ihren vorläufigen Höhepunkt erreichte die Diskussion in der Verabschiedung des 'Mitarbeiterkapitalbeteiligungsgesetzes' im Jahr 2009. Auch in gewerkschaftlichen Kreisen kam es zu einer breiteren inhaltlichen Diskussion und stärkeren Anerkennung finanzieller Mitarbeiterbeteiligung. Wird die gewerkschaftliche Öffnung für das Thema Mitarbeiterbeteiligung von Betriebsräten mitgetragen? Um diese Frage zu beantworten, wurde von der Universität Rostock eine repräsentative Befragung von Betriebsräten in Deutschland durchgeführt. Befragt wurden 1.321 betriebliche Interessenvertreter in Unternehmen mit 50 und mehr Beschäftigten.Die Untersuchung zeigt, dass die Instrumente einer Erfolgs- und Kapitalbeteiligung von den befragten Betriebsräten überwiegend als modern und gerecht beurteilt werden. Es werden aber auch die Risiken gesehen, die eine finanzielle Beteiligung der Beschäftigten mit sich führen kann. Es ist davon auszugehen, dass Beteiligungsmodelle auch weiterhin lediglich für bestimmte (Teil-)Branchen und Betriebe attraktiv sind. Auf Basis der Untersuchung lassen sich keine Aussagen über die zukünftige Verbreitung von Beteiligungsmodellen machen. Insgesamt ist aber zu vermuten, dass die Zahl der Unternehmen mit finanziellen Beteiligungsangeboten wohl eher langsam zunehmen wird. Betriebsräte sind hier zumindest nach den Kernergebnissen der Studie nicht die hemmenden Akteure. Vor dem Hintergrund des zurzeit auf die Wirtschafts- und Finanzkrise folgenden wirtschaftlichen Aufschwungs ist ein Ergebnis von besonderer Bedeutung: Die in der Hochphase der Krise befragten Betriebsräte sind nicht davonüberzeugt, dass eine Beteiligung der Beschäftigten am Unternehmenskapital ein Instrument zur Sanierung eines Betriebes ist

Induced pluripotent stem cells (iPSCs) derived from cerebrotendinous xanthomatosis (CTX) patient's fibroblasts carrying a R395S mutation

AbstractInduced pluripotent stem cells (iPSCs) were generated from dermal fibroblasts from a 60-year-old cerebrotendinous xanthomatosis (CTX) patient, carrying a homozygous mutation c. [1183C>A]; p. R395S in CYP27A1. Episomal plasmids encoding the pluripotency genes OCT4, SOX2, KLF4, L-MYC and LIN28 were introduced via electroporation. The generated line iPS-CTX-R395S has no sign of plasmid integration or chromosomal aberration and retained the mutation site in CYP27A1. Furthermore, iPSCs express pluripotency markers and are able to differentiate in all germ layers in vitro. The generated line may be a useful tool for disease modelling of CTX

Targeting oxidative stress: Novel coumarin-based inverse agonists of GPR55

Oxidative stress is associated with different neurological and psychiatric diseases. Therefore, development of new pharmaceuticals targeting oxidative dysregulation might be a promising approach to treat these diseases. The G-protein coupled receptor 55 (GPR55) is broadly expressed in central nervous tissues and cells and is involved in the regulation of inflammatory and oxidative cell homeostasis. We have recently shown that coumarin-based compounds enfold inverse agonistic activities at GPR55 resulting in the inhibition of prostaglandin E2. However, the antioxidative effects mediated by GPR55 were not evaluated yet. Therefore, we investigated the antioxidative effects of two novel synthesized coumarin-based compounds, KIT C and KIT H, in primary mouse microglial and human neuronal SK-N-SK cells. KIT C and KIT H show antioxidative properties in SK-N-SH cells as well as in primary microglia. In GPR55-knockout SK-N-SH cells, the antioxidative effects are abolished, suggesting a GPR55-dependent antioxidative mechanism. Since inverse agonistic GPR55 activation in the brain seems to be associated with decreased oxidative stress, KIT C and KIT H possibly act as inverse agonists of GPR55 eliciting promising therapeutic options for oxidative stress related diseases

Fast approximation methods for credit portfolio risk calculations

Credit risk is one of the main risks financial institutions are exposed to. Within the last two decades, simulation-based credit portfolio models became extremely popular and replaced closed-form analytical ones as computers became more powerful. However, especially for non-homogenous and non-granular portfolios, a full simulation of a credit portfolio model is still time consuming, which can be disadvantageous within some use cases like credit pricing or within stress testing situations where results must be available very quickly. For this purpose, we investigate if methods based on artificial intelligence (AI) can be helpful to approximate a credit portfolio model. We compare the performance of AI-based methods within three different use cases with suitable non AI-based regression methods. As a result, we see that AI-based methods can generally capture portfolio characteristics and speed-up calculations but - depending on the specific use case and the availability of training data - they are not necessarily always the best choice. Particularly, considering the time and costs for collecting data and training of the complex algorithms, non-AI-based methods can be as good as or even better than AI-based ones, while requiring less computational effort