Melanosomal targeting sequences from gp100 are essential for MHC class II-restricted endogenous epitope presentation and mobilization to endosomal compartments

CD4+ T lymphocytes play an important role in CD8+ T cell-mediated responses against tumors. Considering that about 20% of melanomas express major histocompatibility complex (MHC) class II, it is plausible that concomitant antigenic presentation by MHC class I and class II complexes shapes positive (helper T cells) or negative (regulatory T cells) anti-tumor responses. Interestingly, gp100, a melanoma antigen, can be presented by both MHC class I and class II when expressed endogenously, suggesting that it can reach endosomal/MHC class II compartments (MIIC). Here, we demonstrated that the gp100 putative amino-terminal signal sequence and the last 70 residues in carboxy-terminus, are essential for MIIC localization and MHC class II presentation. Confocal microscopy analyses confirmed that gp100 was localized in LAMP-1+ endosomal/MIIC. Gp100-targeting sequences were characterized by deleting different sections in the carboxy-terminus (residues 590 to 661). Transfection in 293T cells, expressing MHC class I and class II molecules, revealed that specific deletions in carboxy-terminus resulted in decreased MHC class II presentation, without effects on MHC class I presentation, suggesting a role in MIIC trafficking for these deleted sections. Then, we used these gp100-targeting sequences to mobilize the green fluorescent protein (GFP) to endosomal compartments, and to allow MHC class II and class I presentation of minimal endogenous epitopes. Thus, we concluded that these specific sequences are MIIC targeting motifs. Consequently, these sequences could be included in expression cassettes for endogenously expressed tumor or viral antigens to promote MHC class II and class I presentation and optimize in vivo T cell responses, or as an in vitro tool for characterization of new MHC class II epitopes.

Arrow's Theorem in Spatial Environments

In spatial environments, we consider social welfare functions satisfying Arrow's requirements. i.e., weak Pareto and independence of irrelevant alternatives. When the policy space os a one-dimensional continuum, such a welfare function is determined by a collection of 2n strictly quasi-concave preferences and a tie-breaking rule. As a corrollary, we obtain that when the number of voters is odd, simple majority voting is transitive if and only if each voter's preference is strictly quasi-concave. When the policy space is multi-dimensional, we establish Arrow's impossibility theorem. Among others, we show that weak Pareto, independence of irrelevant alternatives, and non-dictatorship are inconsistent if the set of alternatives has a non-empty interior and it is compact and convex.

Political Influence, Economic Interests and Endogenous Tax Structure in a Computable Equilibrium Framework: with Applicatioon to the United States, 1973 and 1983

A full understanding of public affairs requires the ability to distinguish between the policies that voters would like the government to adopt, and the influence that different voters or group of voters actually exert in the democratic process. We consider the properties of a computable equilibrium model of a competitive political economy in which the economic interests of groups of voters and their effective influence on equilibrium policy outcomes can be explicitly distinguished and computed. The model incorporates an amended version of the GEMTAP tax model, and is calibrated to data for the United States for 1973 and 1983. Emphasis is placed on how the aggregation of GEMTAP households into groups within which economic and political behaviour is assumed homogeneous affects the numerical representation of interests and influence for representative members of each group. Experiments with the model suggest that the changes in both interests and influence are important parts of the story behind the evolution of U.S. tax policy in the decade after 1973.

GLS Detrending, Efficient Unit Root Tests and Structural Change

We extend the class of M-tests for a unit root analyzed by Perron and Ng (1996) and Ng and Perron (1997) to the case where a change in the trend function is allowed to occur at an unknown time. These tests M(GLS) adopt the GLS detrending approach of Dufour and King (1991) and Elliott, Rothenberg and Stock (1996) (ERS). Following Perron (1989), we consider two models : one allowing for a change in slope and the other for both a change in intercept and slope. We derive the asymptotic distribution of the tests as well as that of the feasible point optimal tests PT(GLS) suggested by ERS. The asymptotic critical values of the tests are tabulated. Also, we compute the non-centrality parameter used for the local GLS detrending that permits the tests to have 50% asymptotic power at that value. We show that the M(GLS) and PT(GLS) tests have an asymptotic power function close to the power envelope. An extensive simulation study analyzes the size and power in finite samples under various methods to select the truncation lag for the autoregressive spectral density estimator. An empirical application is also provided.

Investigation of clusters of giardiasis using GIS and a spatial scan statistic

Affiliation: Pascal Michel : Département de pathologie et microbiologie, Faculté de médecine vétérinaire

Economic integration in North America: Formal, Informal and Spatial Aspects.

An exemination of a series of indicators of economic integration in the western hemisphere (Canada-USA-Latin America) indicates that it is proceeding under the influence of formal trade agreements and informal forces including technological change, multinational firm rationalization and location strategies, etc.

Intertemporal and Spatial Depletion of Landfills

This paper generalizes Hotelling's (1931) theory of nonrenewable resources to situations where resource pools and their users are distributed spacially. Extraction and transport costs are assumed to be linear in the rate of extraction, but utilization of each deposit may require a setup cost.

Oligarchies in Spatial Environments

In spatial environments we consider social welfare functions satisfying Arrow’s requirements, i.e. weak Pareto and independence of irrelevant alternatives. Individual preferences measure distances between alternatives according to the Lp-norm (for a fixed p => 1). When the policy space is multi-dimensional and the set of alternatives has a non-empty interior and it is compact and convex, any quasi-transitive welfare function must be oligarchic. As a corollary we obtain that for transitive welfare functions weak Pareto, independence of irrelevant alternatives, and non-dictatorship are inconsistent if the set of alternatives has a non-empty interior and it is compact and convex.

Peptides vasoactifs endogènes dans la prolifération accrue des cellules musculaires lisses vasculaires de rats spontanément hypertendus: rôle des facteurs de croissance.

Contribuant à la pathophysiologie des maladies vasculaires comme dans le cas de l’hypertension, le remodelage vasculaire est associé à une altération de la croissance des cellules musculaires lisses vasculaires (CMLV) (prolifération, taille, etc.). Or la prolifération des CMLV est augmentée par les peptides vasoactifs tels que l’angiotensine II (AngII) et l’endothéline-1 (ET-1). Ces peptides étant surexprimés lors de l’hypertension, cette étude fut entreprise pour déterminer leur contribution endogène ainsi que celles du facteur de croissance épidermique (EGF), du facteur de croissance insulinique (IGF-1) et du facteur de croissance dérivé des plaquettes (PDGF) à la prolifération accrue des CMLV et aux mécanismes sous-jacents. Des CMLV A-10 et des CMLV de rats WKY et SHR âgés de 12 semaines ont été utilisées pour cette étude. La prolifération cellulaire fut déterminée par incorporation de [3H]thymidine. La phosphorylation de ERK 1/2 et du récepteur de EGF fut déterminée par immunobuvardage. Les CMLV de SHR, comparées à celles de WKY, ont montré une prolifération accrue qui fut atténuée par le losartan, un antagoniste du récepteur AT1 de l’AngII et par le BQ-123 et le BQ-788, antagonistes des récepteurs ETA et ETB de l’ET-1. La prolifération accrue des CMLV de SHR fut ramenée à celle des WKY par les inhibiteurs des récepteurs au PDGF (AG-1295), au IGF-1 (AG-1024) et au EGF (AG-1478). La phosphorylation du récepteur au EGF, accrue dans les CMLV de rats SHR comparée à celle des WKY, fut atténuée par le losartan, le BQ-123, le BQ-788 et l’AG-1478, mais ne fut pas atténuée par l’AG-1295 et l’AG-1024. De plus, la phosphorylation accrue de ERK 1/2 dans les CMLV de rats SHR fut atténuée par le losartan, le BQ-123, le BQ-788 et les inhibiteurs des récepteurs aux facteurs de croissance. Parallèlement, le rôle de la transactivation de EGF-R dans la prolifération accrue induite par AngII et ET-1 fut aussi examiné dans les CMLV A-10. L’augmentation, induite par AngII et ET-1, de la prolifération et de la phosphorylation de ERK 1/2 dans les CMLV A-10 fut ramenée au niveau contrôle par AG-1478. Ces données suggèrent que les peptides vasoactifs endogènes induisent la prolifération accrue des CMLV par la signalisation des MAP kinases résultant de la transactivation de EGF-R.

Efficient estimation using the characteristic function : theory and applications with high frequency data

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