Political Settlements and Development

Few concepts have captured the imagination of the conflict and development communities in recent years as powerfully as the idea of a ‘political settlement’. At its most ambitious, ‘political settlements analysis’ (PSA) promises to explain why conflicts occur and states collapse, the conditions for their successful rehabilitation, different developmental pathways from peace, and how to better fit development policy to country context. Yet despite the meteoric rise of the term and its tremendous promise, not all is well in the world of PSA. Rival definitions of the concept abound; there are disagreements about its scope and the way it should be used; a growing schism between conflict specialists and economists; basic concepts are ambiguous; and little progress has been made on measurement. This book consequently has three main aims. The first is to argue for a revised definition of a political settlement, capable of unifying its diverse strands. The second is to put the concept on a more solid theoretical and scientific footing, providing a method for measuring and categorizing political settlements, using both qualitative case studies and a large-n statistical analysis to illustrate its potential. And the third is to examine the implications of the findings for mainstream social science analysis and for policymakers

Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIV(mac251) infection of rhesus macaques; a pilot study

BACKGROUND: HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIV(mac251) macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. METHODS: For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIV(mac251) viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. RESULTS: Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route. CONCLUSIONS: These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development

Political Settlements and Development

Few concepts have captured the imagination of the conflict and development communities in recent years as powerfully as the idea of a ‘political settlement’. At its most ambitious, ‘political settlements analysis’ (PSA) promises to explain why conflicts occur and states collapse, the conditions for their successful rehabilitation, different developmental pathways from peace, and how to better fit development policy to country context. Yet despite the meteoric rise of the term and its tremendous promise, not all is well in the world of PSA. Rival definitions of the concept abound; there are disagreements about its scope and the way it should be used; a growing schism between conflict specialists and economists; basic concepts are ambiguous; and little progress has been made on measurement. This book consequently has three main aims. The first is to argue for a revised definition of a political settlement, capable of unifying its diverse strands. The second is to put the concept on a more solid theoretical and scientific footing, providing a method for measuring and categorizing political settlements, using both qualitative case studies and a large-n statistical analysis to illustrate its potential. And the third is to examine the implications of the findings for mainstream social science analysis and for policymakers

Rgs1 and Gnai2 Regulate the Entrance of B Lymphocytes into Lymph Nodes and B Cell Motility within Lymph Node Follicles

SummarySignaling by G protein-coupled receptors coupled to Gαi assists in triggering lymphocyte movement into and out of lymph nodes. Here, we show that modulating the signaling output from these receptors dramatically alters B cell trafficking. Intravital microscopy of adoptively transferred B cells from wild-type and Rgs1−/− mice revealed that Rgs1−/− B cells stick better to lymph node high endothelial venules, home better to lymph nodes, and move more rapidly within lymph node follicles than do wild-type B cells. In contrast, B cells from Gnai2−/− mice enter lymph nodes poorly and move more slowly than do wild-type B cells. The Gnai2−/− mice often lack multiple peripheral lymph nodes, and their B cells respond poorly to chemokines, indicating that Gαi1 and Gαi3 poorly compensate for the loss of Gαi2. These results demonstrate opposing roles for Rgs1 and Gnai2 in B cell trafficking into and within lymph nodes

Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function

Prior studies have demonstrated that cholera toxin (CT) and other cAMP-inducing factors inhibit interleukin (IL)-12 production from monocytes and dendritic cells (DCs). We show that CT inhibits Th1 responses in vivo in mice infected with Toxoplasma gondii. This correlated with low serum IL-12 levels and a selective reduction in the numbers of CD8α+ conventional DCs (cDCs) in lymphoid organs. CT inhibited the function of interferon (IFN) regulatory factor (IRF) 8, a transcription factor known to positively regulate IL-12p35 and p40 gene expression, and the differentiation of CD8α+ and plasmacytoid DCs (pDCs). Fluorescence recovery after photobleaching analysis showed that exposure to CT, forskolin, or dibutyryl (db) cAMP blocked LPS and IFN-γ–induced IRF8 binding to chromatin. Moreover, CT and dbcAMP inhibited the binding of IRF8 to the IFN-stimulated response element (ISRE)–like element in the mouse IL-12p40 promoter, likely by blocking the formation of ISRE-binding IRF1–IRF8 heterocomplexes. Furthermore, CT inhibited the differentiation of pDCs from fms-like tyrosine kinase 3 ligand–treated bone marrow cells in vitro. Therefore, because IRF8 is essential for IL-12 production and the differentiation of CD8α+ cDCs and pDCs, these data suggest that CT and other Gs-protein agonists can affect IL-12 production and DC differentiation via a common mechanism involving IRF8

A New Era in Extragalactic Background Light Measurements: The Cosmic History of Accretion, Nucleosynthesis and Reionization

(Brief Summary) What is the total radiative content of the Universe since the epoch of recombination? The extragalactic background light (EBL) spectrum captures the redshifted energy released from the first stellar objects, protogalaxies, and galaxies throughout cosmic history. Yet, we have not determined the brightness of the extragalactic sky from UV/optical to far-infrared wavelengths with sufficient accuracy to establish the radiative content of the Universe to better than an order of magnitude. Among many science topics, an accurate measurement of the EBL spectrum from optical to far-IR wavelengths, will address: What is the total energy released by stellar nucleosynthesis over cosmic history? Was significant energy released by non-stellar processes? Is there a diffuse component to the EBL anywhere from optical to sub-millimeter? When did first stars appear and how luminous was the reionization epoch? Absolute optical to mid-IR EBL spectrum to an astrophysically interesting accuracy can be established by wide field imagingat a distance of 5 AU or above the ecliptic plane where the zodiacal foreground is reduced by more than two orders of magnitude.Comment: 7 pages; Science White Paper for the US Astro 2010-2020 Decadal Survey. If interested in further community-wide efforts on this topic please contact the first autho