312 research outputs found

    Strongly lensed SNe Ia in the era of LSST: observing cadence for lens discoveries and time-delay measurements

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    The upcoming Large Synoptic Survey Telescope (LSST) will detect many strongly lensed Type Ia supernovae (LSNe Ia) for time-delay cosmography. This will provide an independent and direct way for measuring the Hubble constant H0H_0, which is necessary to address the current 4.4σ4.4 \sigma tension in H0H_0 between the local distance ladder and the early Universe measurements. We present a detailed analysis of different observing strategies for the LSST, and quantify their impact on time-delay measurement between multiple images of LSNe Ia. For this, we produced microlensed mock-LSST light curves for which we estimated the time delay between different images. We find that using only LSST data for time-delay cosmography is not ideal. Instead, we advocate using LSST as a discovery machine for LSNe Ia, enabling time delay measurements from follow-up observations from other instruments in order to increase the number of systems by a factor of 2 to 16 depending on the observing strategy. Furthermore, we find that LSST observing strategies, which provide a good sampling frequency (the mean inter-night gap is around two days) and high cumulative season length (ten seasons with a season length of around 170 days per season), are favored. Rolling cadences subdivide the survey and focus on different parts in different years; these observing strategies trade the number of seasons for better sampling frequency. In our investigation, this leads to half the number of systems in comparison to the best observing strategy. Therefore rolling cadences are disfavored because the gain from the increased sampling frequency cannot compensate for the shortened cumulative season length. We anticipate that the sample of lensed SNe Ia from our preferred LSST cadence strategies with rapid follow-up observations would yield an independent percent-level constraint on H0H_0.Comment: 25 pages, 22 figures; accepted for publication in A&

    Political Contest and Oppositional Voices in Postconflict Democracy:The Impact of Institutional Design on Government–Media Relations

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    The media are considered to play a crucial democratic role in the public sphere through representing political issues to the public (Gelders et al. 2007); facilitating deliberation, public opinion formation and political participation (Habermas 1989); acting as the 'watchdog' of powerful societal institutions (Norris 2000); and in assisting in the development of civil society in politically fragile and divided contexts (Taylor 2000). Journalists are expected to perform their news reporting within the framework of public interest values, such as objectivity, impartiality, public service, autonomy, and a critical questioning of power (Street 2001). Yet, it is acknowledged that political, cultural, organisational, economic, and relational factors affect this journalistic ideal (Davis 2010). In deeply divided, post-conflict societies, ethno-political antagonisms are fundamental to almost all aspects of civic life, yet there is limited research into how government-media relations operate in such contexts. Most media-politics studies focus on Western majoritarian parliamentary or presidential systems - that is, any system that has clear ‘winners’ and ‘losers’ after elections - and where institutional factors are considered, the focus is largely on how party systems impact on journalism (e.g. Çarkoğlu et al. 2014; Hallin and Mancini 2004; Sheafer and Wolfsfeld 2009). This focus however, neglects important institutional variables, such as mandatory coalition, proportionality and special cross-community voting arrangements, which pertain in more constitutionally complex democracies and which may have a significant impact on media-politics relations

    The Diffusion of Inclusion: An Open Polity Model of Ethnic Power Sharing

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    While there is a growing consensus that ethnic inclusion produces peace, less is known about what causes transitions to power sharing between ethnic groups in central governments in multiethnic states. The few studies that have addressed this question have proposed explanations stressing exclusively domestic factors. Yet, power sharing is spatially clustered, which suggests that diffusion may be at play. Inspired by studies of democratic diffusion, we study the spread of inclusive policies with an “open polity model” that explicitly traces diffusion from inclusion in other states. Our findings indicate that the relevant diffusion processes operate primarily at the level of world regions rather than globally or between territorial neighbors. Thus, the more inclusive the region, the more likely a shift to power sharing becomes. Shifts away from inclusion to dominance are less common since World War II, but they are more likely in regional settings characterized by ethnic exclusion

    The effects of luteinizing hormone ablation/replacement versus steroid ablation/replacement on gene expression in the primate corpus luteum

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    This study was designed to provide a genome-wide analysis of the effects of luteinizing hormone (LH) versus steroid ablation/replacement on gene expression in the developed corpus luteum (CL) in primates during the menstrual cycle. On Days 9–11 of the luteal phase, female rhesus monkeys were left untreated (control) or received a GnRH antagonist Antide (A), A + LH, A + LH + the 3β-hydroxysteroid dehydrogenase inhibitor Trilostane (TRL) or A + LH + TRL + a progestin R5020. On Day 12 of the luteal phase, CL were removed and samples of RNA from individual CL were hybridized to Affymetrix™ rhesus macaque total genome microarrays. The greatest number of altered transcripts was associated with the ablation/replacement of LH, while steroid ablation/progestin replacement affected fewer transcripts. Replacement of LH during Antide treatment restored the expression of most transcripts to control levels. Validation of a subset of transcripts revealed that the expression patterns were similar between microarray and real-time PCR. Analyses of protein levels were subsequently determined for two transcripts. This is the first genome-wide analysis of LH and steroid regulation of gene transcription in the developed primate CL. Further analysis of novel transcripts identified in this data set can clarify the relative role for LH and steroids in CL maintenance and luteolysis

    Generating Sustainable Value from Open Data in a Sharing Society

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    Part 1: Creating ValueInternational audienceOur societies are in the midst of a paradigm shift that transforms hierarchal markets into an open and networked economy based on digital technology and information. In that context, open data is widely presumed to have a positive effect on social, environmental and economic value; however the evidence to that effect has remained scarce. Subsequently, we address the question how the use of open data can stimulate the generation of sustainable value. We argue that open data sharing and reuse can empower new ways of generating value in the sharing society. Moreover, we propose a model that describes how different mechanisms that take part within an open system generate sustainable value. These mechanisms are enabled by a number of contextual factors that provide individuals with the motivation, opportunity and ability to generate sustainable value

    Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection

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    The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.This work was supported by the Portuguese Foundation for Science and Technology individual fellowship (CNA) www.fct.pt, a National Institutes of Health Grant R01 AI106725 (SMB) www.nih.gov, and a Center for AIDS Research Grant P30 AI 060354 (SMB) www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    EspA Acts as a Critical Mediator of ESX1-Dependent Virulence in Mycobacterium tuberculosis by Affecting Bacterial Cell Wall Integrity

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    Mycobacterium tuberculosis (Mtb) requires the ESX1 specialized protein secretion system for virulence, for triggering cytosolic immune surveillance pathways, and for priming an optimal CD8+ T cell response. This suggests that ESX1 might act primarily by destabilizing the phagosomal membrane that surrounds the bacterium. However, identifying the primary function of the ESX1 system has been difficult because deletion of any substrate inhibits the secretion of all known substrates, thereby abolishing all ESX1 activity. Here we demonstrate that the ESX1 substrate EspA forms a disulfide bonded homodimer after secretion. By disrupting EspA disulfide bond formation, we have dissociated virulence from other known ESX1-mediated activities. Inhibition of EspA disulfide bond formation does not inhibit ESX1 secretion, ESX1-dependent stimulation of the cytosolic pattern receptors in the infected macrophage or the ability of Mtb to prime an adaptive immune response to ESX1 substrates. However, blocking EspA disulfide bond formation severely attenuates the ability of Mtb to survive and cause disease in mice. Strikingly, we show that inhibition of EspA disulfide bond formation also significantly compromises the stability of the mycobacterial cell wall, as does deletion of the ESX1 locus or individual components of the ESX1 system. Thus, we demonstrate that EspA is a major determinant of ESX1-mediated virulence independent of its function in ESX1 secretion. We propose that ESX1 and EspA play central roles in the virulence of Mtb in vivo because they alter the integrity of the mycobacterial cell wall
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