Spectral flow, crossing forms and homoclinics of Hamiltonian systems

We prove a spectral flow formula for one-parameter families of Hamiltonian systems under homoclinic boundary conditions, which relates the spectral flow to the relative Maslov index of a pair of curves of Lagrangians induced by the stable and unstable subspaces, respectively. Finally, we deduce sufficient conditions for bifurcation of homoclinic trajectories of one-parameter families of nonautonomous amiltonian vector fields

"Last-Mile" preparation for a potential disaster - Interdisciplinary approach towards tsunami early warning and an evacuation information system for the coastal city of Padang, Indonesia

Extreme natural events, like e.g. tsunamis or earthquakes, regularly lead to catastrophes with dramatic consequences. In recent years natural disasters caused hundreds of thousands of deaths, destruction of infrastructure, disruption of economic activity and loss of billions of dollars worth of property and thus revealed considerable deficits hindering their effective management: Needs for stakeholders, decision-makers as well as for persons concerned include systematic risk identification and evaluation, a way to assess countermeasures, awareness raising and decision support systems to be employed before, during and after crisis situations. The overall goal of this study focuses on interdisciplinary integration of various scientific disciplines to contribute to a tsunami early warning information system. In comparison to most studies our focus is on high-end geometric and thematic analysis to meet the requirements of smallscale, heterogeneous and complex coastal urban systems. Data, methods and results from engineering, remote sensing and social sciences are interlinked and provide comprehensive information for disaster risk assessment, management and reduction. In detail, we combine inundation modeling, urban morphology analysis, population assessment, socioeconomic analysis of the population and evacuation modeling. The interdisciplinary results eventually lead to recommendations for mitigation strategies in the fields of spatial planning or coping capacity.DFG/03G0666A-

Invasion of a Legume Ecosystem Engineer in a Cold Biome Alters Plant Biodiversity

Plant ecosystem engineers are widely used to combat land degradation. However, the ability of those plants to modulate limiting abiotic and biotic resources of other species can cause damage to ecosystems in which they become invasive. Here, we use Lupinus nootkatensis as example to estimate and project the hazardous potential of nitrogen fixing herbaceous plants in a sub-polar oceanic climate. L. nootkatensis was introduced to Iceland in the 1940s to address erosion problems and foster reforestation, but subsequently became a high-latitude invader. In a local field survey, we quantified the impact of L. nootkatensis invasion at three different cover levels (0, 10–50, and 51–100%) upon native plant diversity, richness, and community composition of heath-, wood-, and grasslands using a pairwise comparison design and comparisons of means. Afterward, we scaled impacts up to the ecosystem and landscape level by relating occurrences of L. nootkatensis to environmental and human-mediated variables across Iceland using a species distribution model. Plant diversity was significantly deteriorated under high lupine cover levels of the heath- and woodland, but not in the grassland. Plant species richness of the most diverse habitat, the heathland, linearly decreased with lupine cover level. The abundance of small rosettes, cushion plants, orchids, and small woody long-lived plants of the heath declined with invader presence, while the abundance of late successional species and widespread nitrophilous ruderals in wood- and grasslands increased. Distribution modeling revealed 13.3% of Iceland’s land surface area to be suitable lupine habitat. Until 2061–2080, this area will more than double and expand significantly into the Central Highlands due to human mediation and increasingly favorable climatic conditions. Species-rich habitats showed a loss of plant species diversity and richness as well as a change in community composition even in low lupine cover classes. The future increase of suitable lupine habitat might lead to the displacement of cold-adapted native plant species and will certainly challenge conservation as well as restoration of ecosystems in the cold climate of Iceland, but also elsewhere. Lupine invasion speeds up succession, which may be additive with climate change effects, and accelerates ecological change in cold biomes

Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-kappa B-driven inflammation and cardiovascular risk

Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-kappa B-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-kappa B regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-kappa B. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-kappa B through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-kappa B signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.Peer reviewe

Conformational Dynamics of Single pre-mRNA Molecules During \u3cem\u3eIn Vitro\u3c/em\u3e Splicing

The spliceosome is a complex small nuclear RNA (snRNA)-protein machine that removes introns from pre-mRNAs via two successive phosphoryl transfer reactions. The chemical steps are isoenergetic, yet splicing requires at least eight RNA-dependent ATPases responsible for substantial conformational rearrangements. To comprehensively monitor pre-mRNA conformational dynamics, we developed a strategy for single-molecule FRET (smFRET) that uses a small, efficiently spliced yeast pre-mRNA, Ubc4, in which donor and acceptor fluorophores are placed in the exons adjacent to the 5′ and 3′ splice sites. During splicing in vitro, we observed a multitude of generally reversible time-and ATP-dependent conformational transitions of individual pre-mRNAs. The conformational dynamics of branchpoint and 3′-splice site mutants differ from one another and from wild type. Because all transitions are reversible, spliceosome assembly appears to be occurring close to thermal equilibrium

Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo

Long-lasting, latently infected resting CD4+ T cells are the greatest obstacle to obtaining a cure for HIV infection, as these cells can persist despite decades of treatment with antiretroviral therapy (ART). Estimates indicate that more than 70 years of continuous, fully suppressive ART are needed to eliminate the HIV reservoir1. Alternatively, induction of HIV from its latent state could accelerate the decrease in the reservoir, thus reducing the time to eradication. Previous attempts to reactivate latent HIV in preclinical animal models and in clinical trials have measured HIV induction in the peripheral blood with minimal focus on tissue reservoirs and have had limited effect2–9. Here we show that activation of the non-canonical NF-κB signalling pathway by AZD5582 results in the induction of HIV and SIV RNA expression in the blood and tissues of ART-suppressed bone-marrow–liver–thymus (BLT) humanized mice and rhesus macaques infected with HIV and SIV, respectively. Analysis of resting CD4+ T cells from tissues after AZD5582 treatment revealed increased SIV RNA expression in the lymph nodes of macaques and robust induction of HIV in almost all tissues analysed in humanized mice, including the lymph nodes, thymus, bone marrow, liver and lung. This promising approach to latency reversal—in combination with appropriate tools for systemic clearance of persistent HIV infection—greatly increases opportunities for HIV eradication

Blowin’ against the Wind: the Future of EU trade Policy

U.S. President-elect Trump has announced his intention to stop the Trans Pacific Partnership (TPP) trade agreement. In the EU too the wind seems to be blowing in a similar direction. There appears to be a widespread and growing anti-free-trade sentiment in some parts of the population. Should the EU, at this moment in time, continue to pursue a free trade agenda? If so, does the EU have the means to do that effectively? </p