Slow relaxation in weakly open vertex-splitting rational polygons

The problem of splitting effects by vertex angles is discussed for nonintegrable rational polygonal billiards. A statistical analysis of the decay dynamics in weakly open polygons is given through the orbit survival probability. Two distinct channels for the late-time relaxation of type 1/t^delta are established. The primary channel, associated with the universal relaxation of ''regular'' orbits, with delta = 1, is common for both the closed and open, chaotic and nonchaotic billiards. The secondary relaxation channel, with delta > 1, is originated from ''irregular'' orbits and is due to the rationality of vertices.Comment: Key words: Dynamics of systems of particles, control of chaos, channels of relaxation. 21 pages, 4 figure

Quasi-equilibria in one-dimensional self-gravitating many body systems

The microscopic dynamics of one-dimensional self-gravitating many-body systems is studied. We examine two courses of the evolution which has the isothermal and stationary water-bag distribution as initial conditions. We investigate the evolution of the systems toward thermal equilibrium. It is found that when the number of degrees of freedom of the system is increased, the water-bag distribution becomes a quasi-equilibrium, and also the stochasticity of the system reduces. This results suggest that the phase space of the system is effectively not ergodic and the system with large degreees of freedom approaches to the near-integrable one.Comment: 21pages + 7 figures (available upon request), revtex, submitted to Physical Review

Gene expression and immunohistochemical analyses identify SOX2 as major risk factor for overall survival and relapse in Ewing sarcoma patients

BACKGROUND: Up to 30-40% of Ewing sarcoma (EwS) patients with non-metastatic disease develop local or metastatic relapse within a time span of 2-10 years. This is in part caused by the absence of prognostic biomarkers that can identify high-risk patients and thus assign them to risk-adapted monitoring and treatment regimens. Since cancer stemness has been associated with tumour relapse and poor patient outcomes, we investigated in the current study the prognostic potential SOX2 (sex determining region Y box 2) - a major transcription factor involved in development and stemness - which was previously described to contribute to the undifferentiated phenotype of EwS. METHODS: Two independent patient cohorts, one consisting of 189 retrospectively collected EwS tumours with corresponding mRNA expression data (test-cohort) and the other consisting of 141 prospectively collected formalin-fixed and paraffin-embedded resected tumours (validation and cohort), were employed to analyse SOX2 expression levels through DNA microarrays or immunohistochemistry, respectively, and to compare them with clinical parameters and patient outcomes. Two methods were employed to test the validity of the results at both the mRNA and protein levels. FINDINGS: Both cohorts showed that only a subset of EwS patients (16-20%) expressed high SOX2 mRNA or protein levels, which significantly correlated with poor overall survival. Multivariate analyses of our validation-cohort revealed that high SOX2 expression represents a major risk-factor for poor survival (HR = 3·19; 95%CI 1·74-5·84; p < 0·01) that is independent from metastasis and other known clinical risk-factors at the time of diagnosis. Univariate analyses demonstrated that SOX2-high expression was correlated with tumour relapse (p = 0·002). The median first relapse was at 14·7 months (range: 3·5-180·7). INTERPRETATION: High SOX2 expression constitutes an independent prognostic biomarker for EwS patients with poor outcomes. This may help to identify patients with localised disease who are at high risk for tumour relapse within the first two years after diagnosis. FUNDING: The laboratory of T. G. P. Grünewald is supported by grants from the 'Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München (WiFoMed)', by LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the 'Mehr LEBEN für krebskranke Kinder - Bettina-Bräu-Stiftung', the Walter Schulz Foundation, the Wilhelm Sander-Foundation (2016.167.1), the Friedrich-Baur foundation, the Matthias-Lackas foundation, the Barbara & Hubertus Trettner foundation, the Dr. Leopold & Carmen Ellinger foundation, the Gert & Susanna Mayer foundation, the Deutsche Forschungsgemeinschaft (DFG 391665916), and by the German Cancer Aid (DKH-111886 and DKH-70112257). J. Li was supported by a scholarship of the China Scholarship Council (CSC), J. Musa was supported by a scholarship of the Kind-Philipp foundation, and T. L. B. Hölting by a scholarship of the German Cancer Aid. M. F. Orth and M. M. L. Knott were supported by scholarships of the German National Academic Foundation. G. Sannino was supported by a scholarship from the Fritz-Thyssen Foundation (FTF-40.15.0.030MN). The work of U. Dirksen is supported by grants from the German Cancer Aid (DKH-108128, DKH-70112018, and DKH-70113419), the ERA-Net-TRANSCAN consortium (project number 01KT1310), and Euro Ewing Consortium (EEC, project number EU-FP7 602,856), both funded under the European Commission Seventh Framework Program FP7-HEALTH (http://cordis.europa.eu/), the Barbara & Hubertus Trettner foundation, and the Gert & Susanna Mayer foundation. G. Hardiman was supported by grants from the National Science Foundation (SC EPSCoR) and National Institutes of Health (U01-DA045300). The laboratory of J. Alonso was supported by Instituto de Salud Carlos III (PI12/00816; PI16CIII/00026); Asociación Pablo Ugarte (TPY-M 1149/13; TRPV 205/18), ASION (TVP 141/17), Fundación Sonrisa de Alex & Todos somos Iván (TVP 1324/15).The laboratory of T. G. P. Grünewald is supported by grants from the ‘Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München (WiFoMed)’, by LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the ‘Mehr LEBEN für krebskranke Kinder – Bettina-Bräu-Stiftung’, the Walter Schulz Foundation, the Wilhelm Sander-Foundation (2016.167.1), the Friedrich-Baur foundation, the Matthias-Lackas foundation, the Barbara & Hubertus Trettner foundation, the Dr. Leopold und Carmen Ellinger foundation, the Gert & Susanna Mayer foundation, the Rolf M. Schwiete foundation, the Deutsche Forschungsgemeinschaft (DFG 391665916), and by the German Cancer Aid (DKH-111886 and DKH-70112257). J. Li was supported by a scholarship of the China Scholarship Council (CSC), J. Musa was supported by a scholarship of the Kind-Philipp foundation, and T. L. B. Hölting by a scholarship of the German Cancer Aid. M. F. Orth and M. M. L. Knott were supported by scholarships of the German National Academic Foundation. G. Sannino was supported from a scholarship from the Fritz-Thyssen Foundation (FTF-40.15.0.030MN). The work of U. Dirksen is supported by grants from the German Cancerr Aid (DKH-108128, DKH-70112018, and DKH-70113419), the ERA-Net-TRANSCAN consortium (project number 01KT1310), and Euro Ewing Consortium (EEC, project number EU-FP7 602856), both funded under the European Commission Seventh Framework Program FP7-HEALTH (http://cordis.europa.eu/), the Barbara & Hubertus Trettner foundation, and the Gert & Susanna Mayer foundation. G. Hardiman was supported by grants from the National Science Foundation (SC EPSCoR) and National Institutes of Health (U01-DA045300). The laboratory of J. Alonso was supported by Instituto de Salud Carlos III (PI12/00816; PI16CIII/00026); Asociación Pablo Ugarte (TPY-M 1149/13; TRPV 205/18), ASION (TVP 141/17), Fundación Sonrisa de Alex & Todos somos Iván (TVP 1324/15).S

Using statolith elemental signatures to confirm ontogenetic migrations of the squid Doryteuthis gahi around the Falkland Islands (Southwest Atlantic)

This work was supported by the Falkland Islands Government. We thank Dr. Simon Chenery and the British Geological Survey for assistance with the LA-ICP-MS analysis and training and use of their facilities. We are grateful to the scientific observers from the Falkland Islands Fisheries Department for sample collection. We thank the Director of Fisheries, John Barton, and the director of SAERI, Paul Brickle, for supporting this work. We thank Dr. Elena Ieno, Dr. Andreas Winter, Dr. Haseeb Randhawa and three anonymous reviewers for their helpful comments that greatly improved the manuscript.Peer reviewedPostprin

Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies

Habitat and Scale Shape the Demographic Fate of the Keystone Sea Urchin Paracentrotus lividus in Mediterranean Macrophyte Communities

Demographic processes exert different degrees of control as individuals grow, and in species that span several habitats and spatial scales, this can influence our ability to predict their population at a particular life-history stage given the previous life stage. In particular, when keystone species are involved, this relative coupling between demographic stages can have significant implications for the functioning of ecosystems. We examined benthic and pelagic abundances of the sea urchin Paracentrotus lividus in order to: 1) understand the main life-history bottlenecks by observing the degree of coupling between demographic stages; and 2) explore the processes driving these linkages. P. lividus is the dominant invertebrate herbivore in the Mediterranean Sea, and has been repeatedly observed to overgraze shallow beds of the seagrass Posidonia oceanica and rocky macroalgal communities. We used a hierarchical sampling design at different spatial scales (100 s, 10 s and <1 km) and habitats (seagrass and rocky macroalgae) to describe the spatial patterns in the abundance of different demographic stages (larvae, settlers, recruits and adults). Our results indicate that large-scale factors (potentially currents, nutrients, temperature, etc.) determine larval availability and settlement in the pelagic stages of urchin life history. In rocky macroalgal habitats, benthic processes (like predation) acting at large or medium scales drive adult abundances. In contrast, adult numbers in seagrass meadows are most likely influenced by factors like local migration (from adjoining rocky habitats) functioning at much smaller scales. The complexity of spatial and habitat-dependent processes shaping urchin populations demands a multiplicity of approaches when addressing habitat conservation actions, yet such actions are currently mostly aimed at managing predation processes and fish numbers. We argue that a more holistic ecosystem management also needs to incorporate the landscape and habitat-quality level processes (eutrophication, fragmentation, etc.) that together regulate the populations of this keystone herbivore

Trace element fingerprinting of cockle (Cerastoderma edule) shells can reveal harvesting location in adjacent areas

Determining seafood geographic origin is critical for controlling its quality and safeguarding the interest of consumers. Here, we use trace element fingerprinting (TEF) of bivalve shells to discriminate the geographic origin of specimens. Barium (Ba), manganese (Mn), magnesium (Mg), strontium (Sr) and lead (Pb) were quantified in cockle shells (Cerastoderma edule) captured with two fishing methods (by hand and by hand-raking) and from five adjacent fishing locations within an estuarine system (Ria de Aveiro, Portugal). Results suggest no differences in TEF of cockle shells captured by hand or by hand-raking, thus confirming that metal rakes do not act as a potential source of metal contamination that could somehow bias TEF results. In contrast, significant differences were recorded among locations for all trace elements analysed. A Canonical Analysis of Principal Coordinates (CAP) revealed that 92% of the samples could be successfully classified according to their fishing location using TEF. We show that TEF can be an accurate, fast and reliable method to determine the geographic origin of bivalves, even among locations separated less than 1 km apart within the same estuarine system. Nonetheless, follow up studies are needed to determine if TEF can reliably discriminate between bivalves originating from different ecosystems