668 research outputs found

    Electoral Control when Policies are for Sale

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    This article analyses the dynamics of electoral promises, building on an electoral competition model with endogenous policies. It extends the Grossman-Helpman (1994) model [Grossman G., Helpman E. [1994], "Protection for sale", American Economic Review, 84, 4, 833-850] to include sanctions from the electorate and lobbies when the incumbent does not satisfy the expected performance she promised to deliver. This framework allows to deal with the intertemporal dimension needed to understand the prevalent cycle of promises, disappointment, new promises, new disappointment 
.lobbies, promises, elections, electoral competition, lies

    Studies on the release of neutrophil extracellular traps and IFN-Îł as part of the innate immune response to Aspergillus fumigatus and on the fungal stress response via the hybrid sensor kinase TcsC

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    Aspergillus fumigatus is a saprophytic mold that naturally inhabits the soil. Asexual reproduction yields hardy conidia that circulate in the air and are inhaled daily by humans. The fungus seems not to have evolved distinct mechanisms of pathogenicity, but is capable of responding to many stressful environmental cues present in its naturally harsh niche. The robust conidia present no problem to a fully functioning immune system, but if the innate immune system is compromised, the conidia can become activated and differentiate within the lung tissue to form invasive and disseminating hyphae. The resulting disease is called aspergillosis and is difficult to detect and to treat. To date, scientists have yet to find the factor(s) missing during immunosuppression that allow a healthy patient to easily dispose of A. fumigatus. We explored two possibilities: the production of neutrophil extracellular traps (NETs) and the release of IFN-γ by natural killer (NK) cells. We report here that NETs alone cannot kill the fungus, but do inhibit polar growth. Elongation of hyphal tips is abrogated due to zinc starvation, likely a consequence of the zinc-chelating, NETs-associated protein calprotectin. NK cells alone are also incapable of fungicidal activity, but their release of IFN-γ upon contact with A. fumigatus abrogates hyphal growth by a yet unknown mechanism. In vitro studies of the innate immune response, though helpful, are far from representative of the in vivo response. Neither NETs nor IFN-γ alone can manage Aspergillus infection, but in combination, these and other immune assaults certainly can. The difficulty lies in identifying the precise combination of immune cells and cytokine milieu that in a healthy individual prevent infection. Additionally, we explored mechanisms by which the fungus responds to stress, namely the HOG MAPK pathway, historically involved in osmotic stress response. In filamentous fungi, certain stress signals are sensed by a cytoplasmic hybrid histidine kinase sensor and then passed through the HOG system via phosphorylation. We identified the putative hybrid sensor kinase in A. fumigatus, and generated a corresponding knockout mutant. The ΔtcsC mutant was indeed sensitive to osmotic stress, and resistant to the phenolpyrrole fungicide fludioxonil. In the wild type the addition of either osmotic stress or fludioxonil resulted in SakA phosphorylation and translocation to the nucleus. SakA, the Hog1 homolog in A. fumigatus, is located at the end of the HOG pathway, confirming the role of TcsC as the cytoplasmic sensor upstream of SakA. In hypoxia, on farnesol, and in high concentrations of divalent cations the ΔtcsC mutant exhibited a striking “fluffy” phenotype characterized by the production of tremendous aerial hyphae and little or no differentiation, i.e., no conidiation. Though the ΔtcsC mutant showed no change in virulence compared to wild type, components of the TcsC signalling pathway remain promising targets for antifungal agents

    International actors and traditional justice in Sub-Saharan Africa :policies and interventions in transitional justice and justice sector aid

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    Due to a number of important differences between transitional justice and justice sector aid, this book explored how international actors address ‘traditional justice’ in these fields in two distinct parts, which has led to separate analyses. Justice sector aid is often part of broader development cooperation programmes, which may or may not take place in a ost-conflict country. Transitional justice processes are part of conflict-related international interventions, such as peacebuilding programmes, which are often implemented before the wheels of more longterm development cooperation programmes are set in motion. Chronologically speaking, both kinds of programmes – support for transitional justice and justice sector aid – often do not run parallel, although there can be overlaps. It also turns out that the international actors are not necessarily the same. Although in principle the same donor countries are involved, justice sector aid is often provided by bilateral or multilateral development organisations, while transitional justice interventions are more often – but certainly not exclusively – initiatives of specific agencies aimed at post-conflict reconstruction, which are established by several donor countries. Although respect for human rights is heavily emphasised in both domains, policy and interventions regarding transitional justice also need to take international norms regarding the criminal prosecution of international crimes into account. In spite of these differences, this concluding chapter formulates a number of mutual findings and recommendations. First, it discusses common elements at the level of policies, then it identifies a number of trends regarding interventions, and finally it examines the way in which linternational actors handle the tension between traditional justice and human rights

    Alaska\u27s 1992 wolf control plans| Why they failed| A political, biological and ethical analysis

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    Victims of terrorism in Pakistan:Review of existing victim services and scope of improvement

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    Terrorism is the most dehumanizing factor in the present world. Pakistan among top five most affected countries lost 22,191 civilians and 6,887 law enforcement officials by acts of terrorism from 2003 to December 2017 (South Asia Terrorism Portal, 2017). This is the first study of its kind in the country that aims to explore the victims’ experiences on their needs and provided services in order to propose a comprehensive policy framework to improve the conditions of victims. The findings are based on semi-structured interviews conducted with 230 victims of terrorism in seven regions of Pakistan. It was observed that diversity, relativity and complexity were three major characteristics of victims’ needs. The different stakeholders including government, international bodies, non-governmental institutions and local community provided insufficient services to the victims of terrorism. The recommended policy framework is based on principles of multidisciplinarity, problem solving and normativity. Terrorvictimity has multiple causations and consequences. No single quick-fix formula can be proposed as a remedy but answer lies in plurality of responses by all concerned institutions. The study recommends establishing an elaborate victims services infrastructure, victims’ databases, separate victim laws ensuring victim rights for effective participation and a mechanism for timely information to the victims in addition to compliance of Pakistan to international instruments on victims of terroris

    KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

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    Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 ÎŒM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 ÎŒM, and PQ, 0.84 ÎŒM; for developing liver stages, KAI407, 0.64 ÎŒM, and PQ, 0.37 ÎŒM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure

    Modelling the consequences of targeted selective treatment strategies on performance and emergence of anthelmintic resistance amongst grazing calves

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    The development of anthelmintic resistance by helminths can be slowed by maintaining refugia on pasture or in untreated hosts. Targeted selective treatments (TST) may achieve this through the treatment only of individuals that would benefit most from anthelmintic, according to certain criteria. However TST consequences on cattle are uncertain, mainly due to difficulties of comparison between alternative strategies. We developed a mathematical model to compare: 1) the most ‘beneficial’ indicator for treatment selection and 2) the method of selection of calves exposed to Ostertagia ostertagi, i.e. treating a fixed percentage of the population with the lowest (or highest) indicator values versus treating individuals who exceed (or are below) a given indicator threshold. The indicators evaluated were average daily gain (ADG), faecal egg counts (FEC), plasma pepsinogen, combined FEC and plasma pepsinogen, versus random selection of individuals. Treatment success was assessed in terms of benefit per R (BPR), the ratio of average benefit in weight gain to change in frequency of resistance alleles R (relative to an untreated population). The optimal indicator in terms of BPR for fixed percentages of calves treated was plasma pepsinogen and the worst ADG; in the latter case treatment was applied to some individuals who were not in need of treatment. The reverse was found when calves were treated according to threshold criteria, with ADG being the best target indicator for treatment. This was also the most beneficial strategy overall, with a significantly higher BPR value than any other strategy, but its degree of success depended on the chosen threshold of the indicator. The study shows strong support for TST, with all strategies showing improvements on calves treated selectively, compared with whole-herd treatment at 3, 8, 13 weeks post-turnout. The developed model appeared capable of assessing the consequences of other TST strategies on calf populations

    Carbon Consequences of Forest Disturbance and Recovery Across the Conterminous United States

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    Forests of North America are thought to constitute a significant long term sink for atmospheric carbon. The United States Forest Service Forest Inventory and Analysis (FIA) program has developed a large data base of stock changes derived from consecutive estimates of growing stock volume in the US. These data reveal a large and relatively stable increase in forest carbon stocks over the last two decades or more. The mechanisms underlying this national increase in forest stocks may include recovery of forests from past disturbances, net increases in forest area, and growth enhancement driven by climate or fertilization by CO2 and Nitrogen. Here we estimate the forest recovery component of the observed stock changes using FIA data on the age structure of US forests and carbon stocks as a function of age. The latter are used to parameterize forest disturbance and recovery processes in a carbon cycle model. We then apply resulting disturbance/recovery dynamics to landscapes and regions based on the forest age distributions. The analysis centers on 28 representative climate settings spread about forested regions of the conterminous US. We estimate carbon fluxes for each region and propagate uncertainties in calibration data through to the predicted fluxes. The largest recovery-driven carbon sinks are found in the South central, Pacific Northwest, and Pacific Southwest regions, with spatially averaged net ecosystem productivity (NEP) of about 100 g C / square m / a driven by forest age structure. Carbon sinks from recovery in the Northeast and Northern Lake States remain moderate to large owing to the legacy of historical clearing and relatively low modern disturbance rates from harvest and fire. At the continental scale, we find a conterminous U.S. forest NEP of only 0.16 Pg C/a from age structure in 2005, or only 0.047 Pg C/a of forest stock change after accounting for fire emissions and harvest transfers. Recent estimates of NEP derived from inventory stock change, harvest, and fire data show twice the NEP sink we derive from forest age distributions. We discuss possible reasons for the discrepancies including modeling errors and the possibility of climate and/or fertilization (CO2 or N) growth enhancements
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