Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation.

Cumulative T-cell receptor signal strength and ensuing T-cell responses are affected by both antigen affinity and antigen dose. Here we examined the distinct contributions of these parameters to CD4 T-cell differentiation during infection. We found that high antigen affinity positively correlates with T helper (Th)1 differentiation at both high and low doses of antigen. In contrast, follicular helper T cell (TFH) effectors are generated after priming with high, intermediate, and low affinity ligand. Unexpectedly, memory T cells generated after priming with very low affinity antigen remain impaired in their ability to generate secondary Th1 effectors, despite being recalled with high affinity antigen. These data challenge the view that only strongly stimulated CD4 T cells are capable of differentiating into the TFH and memory T-cell compartments and reveal that differential strength of stimulation during primary T-cell activation imprints unique and long lasting T-cell differentiation programs.

Tels parents, tels enfants? L'utilisation de données de seconde main dans l'étude des influences politiques parentales en Suisse

''Like Parents, Like Children?'' Using Secondary Data in the Study of Parental Political Influence in Switzerland: This text is devoted to the intergenerational transmission of left-right ideological orientation. Using data from the Swiss Household Panel (www.swisspanel.ch), collected both directly and through intermediaries, it raises the question of the validity of second-hand information, which is discussed on several points. The article also shows that there is a strong long-term coherence between the ideological orientation of parents and their children. It also highlights the fact that the link is not the same for boys as for girls, and it varies between generations. Finally, it shows that strong upward social mobility, compared to the original environment, facilitates emancipation from parental ideology, social inertia being greater for downward and horizontal mobility. Ce texte est consacré à la transmission intergénérationnelle de l'orientation idéologique gauche-droite. Utilisant des données du Panel Suisse de Ménages (www.swisspanel.ch), collectées tant directement que par personnes interposées, il pose la question de la validité des informations de seconde main, qui est étudiée sur plusieurs points. L'article montre en outre qu'il existe à long terme une forte cohérence entre l'orientation idéologique des parents et de leurs enfants. Il met aussi en évidence que ce lien n'est pas la même auprès des garçons qu'auprès des filles, et qu'il varie entre les générations. Finalement, il montre qu'une forte ascension sociale par rapport au milieu d'origine facilite l'émancipation des orientations idéologiques parentales, l'inertie étant plus forte pour les trajectoires descendantes et horizontales.

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal.

In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO load (r = 0.82) and between net lipogenesis and the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.

The global welfare impact of China: Trade integration and technological change

This paper evaluates the global welfare impact of China's trade integration and technological change in a multi-country quantitative Ricardian-Heckscher-Ohlin model.We simulate two alternative growth scenarios: a "balanced" one in which China's productivity grows at the same rate in each sector, and an "unbalanced" one in whichChina's comparative disadvantage sectors catch up disproportionately faster to theworld productivity frontier. Contrary to a well-known conjecture (Samuelson 2004),the large majority of countries experience significantly larger welfare gains whenChina's productivity growth is biased towards its comparative disadvantage sectors.This finding is driven by the inherently multilateral nature of world trade.

The stereochemistry of the amino acid side chain influences the inflammatory potential of muramyl dipeptide in experimental meningitis.

Intrathecal injections of 50 to 100 micro g of (N-acetylmuramyl-L-alanyl-D-isoglutamine) muramyl dipeptide (MDP)/rabbit dose-dependently triggered tumor necrosis factor alpha (TNF-alpha) secretion (12 to 40,000 pg/ml) preceding the influx of leukocytes in the subarachnoid space of rabbits. Intrathecal instillation of heat-killed unencapsulated R6 pneumococci produced a comparable leukocyte influx but only a minimal level of preceding TNF-alpha secretion. The stereochemistry of the first amino acid (L-alanine) of the MDP played a crucial role with regard to its inflammatory potential. Isomers harboring D-alanine in first position did not induce TNF-alpha secretion and influx of leukocytes. This stereospecificity of MDPs was also confirmed by measuring TNF-alpha release from human peripheral mononuclear blood cells stimulated in vitro. These data show that the inflammatory potential of MDPs depends on the stereochemistry of the first amino acid of the peptide side chain and suggest that intact pneumococci and MDPs induce inflammation by different pathways.

Rice yield estimation based on weather conditions and on technological level of production systems in Brazil

The objective of this work was to evaluate an estimation system for rice yield in Brazil, based on simple agrometeorological models and on the technological level of production systems. This estimation system incorporates the conceptual basis proposed by Doorenbos & Kassam for potential and attainable yields with empirical adjusts for maximum yield and crop sensitivity to water deficit, considering five categories of rice yield. Rice yield was estimated from 2000/2001 to 2007/2008, and compared to IBGE yield data. Regression analyses between model estimates and data from IBGE surveys resulted in significant coefficients of determination, with less dispersion in the South than in the North and Northeast regions of the country. Index of model efficiency (E1') ranged from 0.01 in the lower yield classes to 0.45 in higher ones, and mean absolute error ranged from 58 to 250 kg ha‑1, respectively.

Towards a dynamic model of e-commerce: environmental, technological and organisational drivers of B2C along time

Despite the important benefits for firms of commercial initiatives on the Internet, e-commerce is still an emerging distribution channel, even in developed countries. Thus, more needs to be known about the mechanisms affecting its development. A large number of works have studied firms¿ e-commerce adoption from technological, intraorganizational, institutional, or other specific perspectives, but there is a need for adequately tested integrative frameworks. Hence, this work proposes and tests a model of firms¿ business-to-consumer (called B2C) e-commerce adoption that is founded on a holistic vision of the phenomenon. With this integrative approach, the authors analyze the joint influence of environmental, technological, and organizational factors; moreover, they evaluate this effect over time. Using various representative Spanish data sets covering the period 1996-2005, the findings demonstrate the suitability of the holistic framework. Likewise, some lessons are learned from the analysis of the key building blocks. In particular, the current study provides evidence for the debate about the effect of competitive pressure, since the findings show that competitive pressure disincentivizes e-commerce adoption in the long term. The results also show that the development or enrichment of the consumers¿ consumption patterns, the technological readiness of the market forces, the firm¿s global scope, and its competences in innovation continuously favor e-commerce adoption.

Exploring the strategic impact of technological change - Studies on the role of Internet in magazine publishing

Over the past few decades, turbulent change has characterized the situation in the media industry. It has been noted that digitalization and new media are strongly influencing the industry: it is changing the existing market dynamics and requires new strategies. Prior research on the impact of digitalization and the Internet has emphasized news-focused media such as newspaper publishing and broadcasting, yet magazine publishing is very seldom the focus of the research. This study examines how the Internetimpacts magazine publishing. The work presents a multi-level analysis on the role and impact of the Internet on magazine products, companies and industry. The study is founded on strategic management, technology management and media economics literature. This study consists of two parts. The first part introduces the research topic and discusses the overall results of the study. The second part comprises five research publications. Qualitative research methods are used throughout. The results of the study indicate that the Internet has not had a disruptive effect on magazine publishing, and that its strategic implications could rather be considered complementary to the print magazine and the business as a whole. It seems that the co-specialized assets, together with market-related competencies and unchanged core competence have protected established firms from the disruptive effect of the new technology in magazine publishing. In addition, it seems that the Internet offers a valuable possibility to build and nourish customer relationships. The study contributes tomedia management and economics research by moving from product- or industry-level investigations towards a strategic-management perspective.