Dynamics of simian immunodeficiency virus two-long-terminal-repeat circles in the presence and absence of CD8+ Cells

Copyright © 2018 American Society for Microbiology. All Rights ReservedCD8+ cells play a key role in human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, but their specific mechanism(s) of action in controlling the virus is unclear. Two-long-terminal-repeat (2-LTR) circles are extrachromosomal products generated upon failed integration of HIV/SIV. To understand the specific effects of CD8+ cells on infected cells, we analyzed the dynamics of 2-LTR circles in SIVmac251-infected rhesus macaques (RMs) treated with an integrase inhibitor (INT). Twenty RMs underwent CD8+ cell depletion and received raltegravir (RAL) monotherapy or a combination of both. Blood, lymph nodes (LNs), and gut biopsy specimens were routinely sampled. Plasma viral loads (pVLs) and 2-LTR circles from peripheral blood mononuclear cells (PBMCs) and LN lymphocytes were measured with quantitative reverse transcription-PCR (qRT-PCR). In the CD8 depletion group, an ∼1-log increase in pVLs and a slow increase in PBMC 2-LTRs occurred following depletion. In the INT group, a strong decline in pVLs upon treatment initiation and no change in 2-LTR levels were observed. In the INT and CD8+ cell depletion group, an increase in pVLs following CD8 depletion similar to that in the CD8 depletion group was observed, with a modest decline following INT initiation, and 2-LTR circles significantly increased in PBMCs and LNs. Analyzing the 2-LTR data across all treatment groups with a mathematical model indicates that the data best support an effect of CD8+ cells in killing cells prior to viral integration. Sensitivity analyses of these results confirm that effect but also allow for additional effects, which the data do not discriminate well. Overall, we show that INT does not significantly increase the levels of 2-LTR circles. However, CD8+ cell depletion increases the 2-LTR levels, which are enhanced in the presence of an INT.IMPORTANCE CD8+ T cells play an essential role in controlling HIV and SIV infection, but the specific mechanisms involved remain poorly understood. Due to failed viral infection, HIV and SIV can form 2-LTR extrachromosomal circles that can be quantified. We present novel data on the dynamics of these 2-LTR forms in a SIV-infected macaque model under three different treatment conditions: depletion of CD8+ cells, administration of the integrase inhibitor in a monotherapy, which favors the formation of 2-LTR circles, and a combination of the two treatments. We used a new mathematical model to help interpret the data, and the results suggest that CD8+ cells exert a killing effect on infected cells prior to virus integration. These results provide new insights into the mechanisms of action of CD8+ cells in SIV infection. Confirmation of our results would be an important step in understanding immune control of HIV.This work was supported by the National Institutes of Health/National Center for Research Resources/National Institute of Allergy and Infectious Diseases/National Heart, Lung and Blood Institute grants AI104373 (R.M.R.), R01 HL117715 (I.P.), R01 AI119346 (C.A.), and R01 HL123096 (I.P.). B.B.P. was supported in part by the NIH training grant T32 AI065380.info:eu-repo/semantics/publishedVersio

Poverty Impacts of Preferential and Multilateral Trade Liberalization on the Philippines: a Computable General Equilibrium Analysis

The Philippines has been participating in preferential and multilateral trade liberalization since the 1990s. However, the poverty effects of these trading arrangements are not yet fully known. This paper, which uses a computable general equilibrium (CGE) model, finds that reducing both Most-Favored-Nation (MFN) tariff rate and ASEAN Free Trade Area’s Common Effective Preferential Tariff (CEPT) rate, combined with enhancing direct income taxes to offset the loss in tariff revenue, are instrumental in reducing poverty in the country. It also shows that the relatively poor and less-skilled household groups, like agricultural workers and industrial workers, as well as the poorest of the poor, gain from such trading arrangements because these substantially lower consumer prices. As such, this paper proposes that the Philippine government be more active and further promote preferential and multilateral trade liberalization in order to help eradicate poverty.Computable general equilibrium, international trade, social accounting matrix, Philippines, poverty

Quantifying life quality as walkability on urban networks : the case of Budapest

Life quality in cities is deeply related to the mobility options, and how easily one can access different services and attractions. The pedestrian infrastructure network provides the backbone for social life in cities. While there are many approaches to quantify life quality, most do not take specifically into account the walkability of the city, and rather offer a city-wide measure. Here we develop a data-driven, network-based method to quantify the liveability of a city. We introduce a life quality index (LQI) based on pedestrian accessibility to amenities and services, safety and environmental variables. Our computational approach outlines novel ways to measure life quality in a more granular scale, that can become valuable for urban planners, city officials and stakeholders. We apply data-driven methods to Budapest, but as having an emphasis on the online and easily available quantitative data, the methods can be generalized and applied to any city

Cultural comptence in institutional care for youths: experts with ambivalens positions

In Sweden, cultural competence if often singled out as both a strategy and solution for managing differences attributed to migrants, but few studies have critically investigated the idea of cultural competence. This article is an empirical contribution, based on an ethnographic study, and analyses talk and actions in the everyday practice in special residential homes for boys and young men. It examines when, how and in relation to what and whom cultural competence is made relevant, with special focus on how notions about cultural competence positions the staff in the studied institutions; organisationally, in relation to different work tasks and in narratives about the care and treatment provided. The analysis shows that cultural competence is almost exclusively attributed to staff who have a migrant background, and that the position as cultural competent is ambiguous. On the one hand a position as expert, on the other hand surrounded by a suspicion not to be professional. Staff who are ascribed cultural competence are made into representatives of cultural difference and locked into culturalised and ethnified positions. Thus, cultural competence rather emerges as a tool to master and control the boys who are placed in the studied institutions than as a tool to affect a change process in support of multiculturalism

Inconsistency Issues in Spatial Databases

Abstract. This chapter analyzes inconsistency issues in spatial databases. In particular, it reviews types of inconsistency, specification of integrity constraints, and treatment of inconsistency in multiple representations and data integration. The chapter focuses on inconsistency associated with the geometric representation of objects, spatial relations between objects, and composite objects by aggregation. The main contribution of this paper is a survey of existing approaches to dealing with inconsistency issues in spatial databases that emphasizes the current state of the art and that outlines research issues in the context of inconsistency tolerance.