Steiner t-designs for large t

One of the most central and long-standing open questions in combinatorial design theory concerns the existence of Steiner t-designs for large values of t. Although in his classical 1987 paper, L. Teirlinck has shown that non-trivial t-designs exist for all values of t, no non-trivial Steiner t-design with t > 5 has been constructed until now. Understandingly, the case t = 6 has received considerable attention. There has been recent progress concerning the existence of highly symmetric Steiner 6-designs: It is shown in [M. Huber, J. Algebr. Comb. 26 (2007), pp. 453-476] that no non-trivial flag-transitive Steiner 6-design can exist. In this paper, we announce that essentially also no block-transitive Steiner 6-design can exist.Comment: 9 pages; to appear in: Mathematical Methods in Computer Science 2008, ed. by J.Calmet, W.Geiselmann, J.Mueller-Quade, Springer Lecture Notes in Computer Scienc

Sequential bottlenecks drive viral evolution in early acute Hepatitis C virus infection

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection

Curved Tails in Polymerization-Based Bacterial Motility

The curved actin ``comet-tail'' of the bacterium Listeria monocytogenes is a visually striking signature of actin polymerization-based motility. Similar actin tails are associated with Shigella flexneri, spotted-fever Rickettsiae, the Vaccinia virus, and vesicles and microspheres in related in vitro systems. We show that the torque required to produce the curvature in the tail can arise from randomly placed actin filaments pushing the bacterium or particle. We find that the curvature magnitude determines the number of actively pushing filaments, independent of viscosity and of the molecular details of force generation. The variation of the curvature with time can be used to infer the dynamics of actin filaments at the bacterial surface.Comment: 8 pages, 2 figures, Latex2

The clean conscience at work: Emotions, intuitions and morality

How do people decide what is right and wrong, and to what extent are their actions guided by such moral considerations? Inspired by philosophical traditions, early approaches to morality focused on rationality, and assumed that people arrive at moral standards by logical thought. More recently, however, psychologists have explored the influence of emotions and intuitions on morality, and evidence has been accumulating that moral decisions and behaviors are far from rational, but instead, are guided by intuitions and situational considerations. For example, seemingly irrelevant concerns such as keeping one’s mind and spirit clean and pure can change people’s moral judgment. Emotions can also influence behavior, and positive, uplifting emotions such as elevation and gratitude can be harnessed to produce beneficial outcomes for individuals and organizations alike. Furthermore, people appear to aspire to an equilibrium of moral self-worth, and engage in more or less ethical behavior depending on their currently perceived moral integrity. Thus, morality and ethical behavior is less likely to reside in the person than in the context, and thus, for the study of spirituality, it might be beneficial to focus on people’s situational constraints in the workplace rather than their stable dispositions. Further, because of their potential to inspire positive action, organizations might aim to make positive moral emotions, such as gratitude, elevation, and awe part of everyday work contexts. Overall, in organizations and the workplace, the goal shifts from trying to identify the moral individual to providing the contextual conditions that appeal to spiritual concerns in order to foster moral behavior.</jats:p

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2(IP-4T)](PF6)2 with bpy=2,2′-bipyridine and IP-4T=2-{5′-[3′,4′-diethyl-(2,2′-bithien-5-yl)]-3,4-diethyl-2,2′-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug. © 2020 The Authors. Published by Wiley-VCH Gmb

The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function

Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis

Addressing marine and coastal governance conflicts at the interface of multiple sectors and jurisdictions

Marine and coastal activities are closely interrelated, and conflicts among different sectors can undermine management and conservation objectives. Governance systems for fisheries, power generation, irrigation, aquaculture, marine biodiversity conservation, and other coastal and maritime activities are typically organized to manage conflicts within sectors, rather than across them. Based on the discussions around eight case studies presented at a workshop held in Brest in June 2019, this paper explores institutional approaches to move beyond managing conflicts within a sector. We primarily focus on cases where the groups and sectors involved are heterogeneous in terms of: the jurisdiction they fall under; their objectives; and the way they value ecosystem services. The paper first presents a synthesis of frameworks for understanding and managing cross-sectoral governance conflicts, drawing from social and natural sciences. We highlight commonalities but also conceptual differences across disciplines to address these issues. We then propose a novel analytical framework which we used to evaluate the eight case studies. Based on the main lessons learned from case studies, we then discuss the feasibility and key determinants of stakeholder collaboration as well as compensation and incentive schemes. The discussion concludes with future research needs to support policy development and inform integrated institutional regimes that consider the diversity of stakeholder interests and the potential benefits of cross-sectoral coordination

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

Fermi Large Area Telescope Third Source Catalog

101 pages, 26 figures, accepted for publication in Astrophysical Journal Supplement Series. The ancillary files are PDFs of the full versions of Tables 4 and 8 and a FITS version of Table 11. v3 has corrected Table 6 and minor edits. The 3FGL catalog is available at http://fermi.gsfc.nasa.gov/ssc/data/access/lat/4yr_catalogInternational audienceWe present the third Fermi Large Area Telescope source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first four years of science data from the Fermi Gamma-ray Space Telescope mission, it is the deepest yet in this energy range. Relative to the 2FGL catalog, the 3FGL catalog incorporates twice as much data as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse gamma-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above 4 sigma significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 232 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1009 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate the contribution of unresolved sources to the Galactic diffuse emission is ~3% at 1 GeV

Modelling spectral and timing properties of accreting black holes: the hybrid hot flow paradigm

The general picture that emerged by the end of 1990s from a large set of optical and X-ray, spectral and timing data was that the X-rays are produced in the innermost hot part of the accretion flow, while the optical/infrared (OIR) emission is mainly produced by the irradiated outer thin accretion disc. Recent multiwavelength observations of Galactic black hole transients show that the situation is not so simple. Fast variability in the OIR band, OIR excesses above the thermal emission and a complicated interplay between the X-ray and the OIR light curves imply that the OIR emitting region is much more compact. One of the popular hypotheses is that the jet contributes to the OIR emission and even is responsible for the bulk of the X-rays. However, this scenario is largely ad hoc and is in contradiction with many previously established facts. Alternatively, the hot accretion flow, known to be consistent with the X-ray spectral and timing data, is also a viable candidate to produce the OIR radiation. The hot-flow scenario naturally explains the power-law like OIR spectra, fast OIR variability and its complex relation to the X-rays if the hot flow contains non-thermal electrons (even in energetically negligible quantities), which are required by the presence of the MeV tail in Cyg X-1. The presence of non-thermal electrons also lowers the equilibrium electron temperature in the hot flow model to <100 keV, making it more consistent with observations. Here we argue that any viable model should simultaneously explain a large set of spectral and timing data and show that the hybrid (thermal/non-thermal) hot flow model satisfies most of the constraints.Comment: 26 pages, 13 figures. To be published in the Space Science Reviews and as hard cover in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher