bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notion de risque sur les mondes virtuels : une approche par les jeux massivement multi-joueurs
Authors: Dumazert Jean-Pierre 
Published: January 2013

Résumé Cet article propose une lecture globale du risque sur les Jeux Vidéo Massivement Multi-Joueurs. Il apporte également une vision pragmatique sur l’analyse pouvant être faite concernant la nature du risque sur ce secteur d’activités peu exploré par les Sciences de gestion. Ainsi, nous exposons deux catégories d’éléments. Premièrement, des éléments de nature technologique (conception, création, stabilisation des univers) et économique (relations entre les acteurs, phénomène de rareté liée aux avatars). Deuxièmement, des éléments ancrés dans une forme de business parallèle, faisant jouer la valeur marchande du virtuel entre règles et parasitages (logiciels de triche, serveurs illégaux, piratage des systèmes). Codes JEL : Z10
À propos de la deuxième vague d'implantation des tramways en france : pérennisation ou modification des critères d'innovation ?
Authors: Guillon Bernard 
Published: January 2013

Résumé Réduire les atteintes environnementales dans le milieu urbain implique des efforts continus en matière de valorisation du transport public se substituant au flux du nombre de voitures, mais aussi une politique de communication régulière permettant de faire patienter le grand public pendant les travaux puis surtout de montrer les différents avantages actuels et futurs procurés par le véhicule choisi. Un domaine où le tramway trouve une justification à sa réimplantation par ses différentes innovations et ses diverses tarifications possibles. Codes JEL : L62, L92, O31
Le risque de l'implicite dans un cas d'innovation en faveur de l'écologie
Authors: Hetet Blandine , Moutot Jean-Michel , Mathieu Jean-Pierre 
Published: January 2013

Résumé Cet article présente une recherche exploratoire sur l’impact de l’implicite dans le discours. Basée sur une recherche appliquée sur la mesure des attitudes de participants à des focus group vis-à-vis d’une innovation en faveur de l’écologie, une analyse à base d’inférences sur le discours, ainsi qu’une comparaison avec les éléments explicites de l’étude a été mise en place. Les attitudes implicites étaient globalement congruentes avec les attitudes explicites exprimées par les participants. Cette étude exploratoire a permis de rendre compte du risque présent dans l’étude partielle du discours, et de montrer l’influence des cognitions implicites sur les stratégies managériales et marketing. Codes JEL : A13, D83, O33, Q51
Évolution économique et innovations financières : d'un processus créatif à une création destructrice
Authors: Ülgen Faruk 
Published: January 2013

Résumé Dans la littérature économique, il est souvent supposé que les marchés financiers ouverts et libéralisés permettent une meilleure allocation des ressources financières au financement efficace des activités productives. D’une façon triviale, nombreux travaux assimilent les innovations financières aux innovations entrepreneuriales schumpétériennes et en concluent que les changements observés sur les marchés financiers depuis les années 1980 contribuent à la promotion de la croissance économique. Toutefois, bien que l’on puisse trouver chez Schumpeter de nombreux éléments mettant en avant le rôle du système bancaire et financier dans le développement économique, une analyse précise et spécifique des innovations financières, distinctes de celle des innovations entrepreneuriales, n’est pas disponible. Cet article propose une étude en vue de combler ce vide analytique. Il montre toutefois que la nature des innovations financières se différencie radicalement de l’orientation des innovations entrepreneuriales schumpétériennes. Les déséquilibres récurrents depuis plusieurs décennies semblent appuyer la thèse selon laquelle les innovations financières transforment le processus d’évolution créatrice du capitalisme, étudié par Schumpeter, en un phénomène de création destructrice. Les instabilités financières requièrent alors une remise en question des schémas de réglementation dans l’objectif d’orienter les innovations financières vers une trajectoire d’évolution qui ne provoque pas de crise économique, destructrice de croissance et d’activités entrepreneuriales productives. Codes JEL : B25, E44, G28, O16, O31
Fer Kinase Limits Neutrophil Chemotaxis toward End Target Chemoattractants
Authors: Khajah Maitham , Andonegui Graciela , Chan Ronald , Craig Andrew W. , Greer Peter A. , McCafferty Donna-Marie 
Published: January 2013

Abstract
Neutrophil recruitment and directional movement toward chemotactic stimuli are important processes in innate immune responses. This study examines the role of Fer kinase in neutrophil recruitment and chemotaxis to various chemoattractants in vitro and in vivo. Mice targeted with a kinase-inactivating mutation (FerDR/DR) or wild type (WT) were studied using time-lapse intravital microscopy to examine leukocyte recruitment and chemotaxis in vivo. In response to keratinocyte-derived cytokine, no difference in leukocyte chemotaxis was observed between WT and FerDR/DR mice. However, in response to the chemotactic peptide WKYMVm, a selective agonist of the formyl peptide receptor, a 2-fold increase in leukocyte emigration was noted in FerDR/DR mice (p &lt; 0.05). To determine whether these defects were due to Fer signaling in the endothelium or other nonhematopoietic cells, bone marrow chimeras were generated. WKYMVm-induced leukocyte recruitment in chimeric mice (WT bone marrow to FerDR/DR recipients or vice versa) was similar to WT mice, suggesting that Fer kinase signaling in both leukocytes and endothelial cells serves to limit chemotaxis. Purified FerDR/DR neutrophils demonstrated enhanced chemotaxis toward end target chemoattractants (WKYMVm and C5a) compared with WT using an under-agarose gel chemotaxis assay. These defects were not observed in response to intermediate chemoattractants (keratinocyte-derived cytokine, MIP-2, or LTB4). Increased WKYMVm-induced chemotaxis of FerDR/DR neutrophils correlated with sustained PI3K activity and reduced reliance on the p38 MAPK pathway compared with WT neutrophils. Together, these data identify Fer as a novel inhibitory kinase for neutrophil chemotaxis toward end target chemoattractants through modulation of PI3K activity.
Resistin-like Molecule α Promotes Pathogenic Th17 Cell Responses and Bacterial-Induced Intestinal Inflammation
Authors: Osborne Lisa C. , Joyce Karen L. , Alenghat Theresa , Sonnenberg Gregory F. , Giacomin Paul R. , Du Yurong , Bergstrom Kirk S. , Vallance Bruce A. , Nair Meera G. 
Published: January 2013

Abstract
Resistin-like molecule (RELM)α belongs to a family of secreted mammalian proteins that have putative immunomodulatory functions. Recent studies have identified a pathogenic role for RELMα in chemically induced colitis through effects on innate cell populations. However, whether RELMα regulates intestinal adaptive immunity to enteric pathogens is unknown. In this study, we employed Citrobacter rodentium as a physiologic model of pathogenic Escherichia coli–induced diarrheal disease, colitis, and Th17 cell responses. In response to Citrobacter, RELMα expression was induced in intestinal epithelial cells, infiltrating macrophages, and eosinophils of the infected colons. Citrobacter-infected RELMα−/− mice exhibited reduced infection-induced intestinal inflammation, characterized by decreased leukocyte recruitment to the colons and reduced immune cell activation compared with wild-type (WT) mice. Interestingly, Citrobacter colonization and clearance were unaffected in RELMα−/− mice, suggesting that the immune stimulatory effects of RELMα following Citrobacter infection were pathologic rather than host-protective. Furthermore, infected RELMα−/− mice exhibited decreased CD4+ T cell expression of the proinflammatory cytokine IL-17A. To directly test whether RELMα promoted Citrobacter-induced intestinal inflammation via IL-17A, infected WT and IL-17A−/− mice were treated with rRELMα. RELMα treatment of Citrobacter-infected WT mice exacerbated intestinal inflammation and IL-17A expression whereas IL-17A−/− mice were protected from RELMα-induced intestinal inflammation. Finally, infected RELMα−/− mice exhibited reduced levels of serum IL-23p19 compared with WT mice, and RELMα−/− peritoneal macrophages showed deficient IL-23p19 induction. Taken together, these data identify a proinflammatory role for RELMα in bacterial-induced colitis and suggest that the IL-23/Th17 axis is a critical mediator of RELMα-induced inflammation.
Serotonin Skews Human Macrophage Polarization through HTR2B and HTR7
Authors: de las Casas-Engel Mateo , Domínguez-Soto Angeles , Sierra-Filardi Elena , Bragado Rafael , Nieto Concha , Puig-Kroger Amaya , Samaniego Rafael , Loza Mabel , Corcuera María Teresa , Gómez-Aguado Fernando , Bustos Matilde , Sánchez-Mateos Paloma , Corbí Angel L. 
Published: January 2013

AbstractBesides its role as a neurotransmitter, serotonin (5-hydroxytryptamine, 5HT) regulates inflammation and tissue repair via a set of receptors (5HT1–7) whose pattern of expression varies among cell lineages. Considering the importance of macrophage polarization plasticity for inflammatory responses and tissue repair, we evaluated whether 5HT modulates human macrophage polarization. 5HT inhibited the LPS-induced release of proinflammatory cytokines without affecting IL-10 production, upregulated the expression of M2 polarization–associated genes (SERPINB2, THBS1, STAB1, COL23A1), and reduced the expression of M1-associated genes (INHBA, CCR2, MMP12, SERPINE1, CD1B, ALDH1A2). Whereas only 5HT7 mediated the inhibitory action of 5HT on the release of proinflammatory cytokines, both 5HT2B and 5HT7 receptors mediated the pro-M2 skewing effect of 5HT. In fact, blockade of both receptors during in vitro monocyte-to-macrophage differentiation preferentially modulated the acquisition of M2 polarization markers. 5HT2B was found to be preferentially expressed by anti-inflammatory M2(M-CSF) macrophages and was detected in vivo in liver Kupffer cells and in tumor-associated macrophages. Therefore, 5HT modulates macrophage polarization and contributes to the maintenance of an anti-inflammatory state via 5HT2B and 5HT7, whose identification as functionally relevant markers for anti-inflammatory/homeostatic human M2 macrophages suggests their potential therapeutic value in inflammatory pathologies.
Mouse Tumor Vasculature Expresses NKG2D Ligands and Can Be Targeted by Chimeric NKG2D-Modified T Cells
Authors: Zhang Tong , Sentman Charles L. 
Published: January 2013

Abstract
Tumor angiogenesis plays an important role in the development of solid tumors, and targeting the tumor vasculature has emerged as a strategy to prevent growth and progression of solid tumors. In this study, we show that murine tumor vasculature expresses Rae1, a ligand for a stimulatory NK receptor NKG2D. By genetic modification of T cells with an NKG2D-based chimeric Ag receptor, referred to as chNKG2D in which the NKG2D receptor is fused to the signaling domain of CD3ζ-chain, T cells were capable of targeting tumor vasculature leading to reduced tumor angiogenesis and tumor growth. This occurred even in tumors where the tumor cells themselves did not express NKG2D ligands. H5V, an endothelial cell line, expresses Rae1 and was lysed by chNKG2D-bearing T cells in a perforin-dependent manner. In vitro capillary tube formation was inhibited by chNKG2D T cells through IFN-γ and cell–cell contact mechanisms. The in vivo antiangiogenesis effects mediated by chNKG2D-bearing T cells at the tumor site were dependent on IFN-γ and perforin. These results provide a novel mechanism for NKG2D-based targeting of solid tumors.
Plasmacytoid Dendritic Cells Play a Key Role in Tumor Progression in Lipopolysaccharide-Stimulated Lung Tumor–Bearing Mice
Authors: Rega Alessia , Terlizzi Michela , Luciano Antonio , Forte Giovanni , Crother Timothy R. , Arra Claudio , Arditi Moshe , Pinto Aldo , Sorrentino Rosalinda 
Published: January 2013

Abstract
The antitumor activity of LPS was first described by Dr. William Coley. However, its role in lung cancer remains unclear. The aim of our study was to elucidate the dose-dependent effects of LPS (0.1–10 μg/mouse) in a mouse model of B16-F10–induced metastatic lung cancer. Lung tumor growth increased at 3 and 7 d after the administration of low-dose LPS (0.1 μg/mouse) compared with control mice. This was associated with an influx of plasmacytoid dendritic cells (pDCs), regulatory T cells, myeloid-derived suppressor cells, and CD8+ regulatory T cells. In contrast, high-dose LPS (10 μg/mouse) reduced lung tumor burden and was associated with a greater influx of pDCs, as well as a stronger Th1 and Th17 polarization. Depletion of pDCs during low-dose LPS administration resulted in a decreased lung tumor burden. Depletion of pDCs during high-dose LPS treatment resulted in an increased tumor burden. The dichotomy in LPS effects was due to the phenotype of pDCs, which were immunosuppressive after the low-dose LPS, and Th1- and T cytotoxic–polarizing cells after the high-dose LPS. Adoptive transfer of T cells into nude mice demonstrated that CD8+ T cells were responsible for pDC recruitment following low-dose LPS administration, whereas CD4+ T cells were required for pDC influx after the high-dose LPS. In conclusion, our data suggest differential effects of low-dose versus high-dose LPS on pDC phenotype and tumor progression or regression in the lungs of mice.
A Role for Ly108 in the Induction of Promyelocytic Zinc Finger Transcription Factor in Developing Thymocytes
Authors: Dutta Mala , Kraus Zachary J. , Gomez-Rodriguez Julio , Hwang Sun-hee , Cannons Jennifer L. , Cheng Jun , Lee Sang-Yun , Wiest David L. , Wakeland Edward K. , Schwartzberg Pamela L. 
Published: January 2013

Abstract
The promyelocytic zinc finger transcription factor (PLZF) is required for the development of activated phenotypes in NKT and other innate T lymphocytes. Although strong TCR stimulation has been implicated in the induction of PLZF, the factors regulating PLZF expression are incompletely understood. We show in this study that costimulation of preselection double-positive thymocytes through the signaling lymphocyte activation molecule family receptor Ly108 markedly enhanced PLZF expression compared with that induced by TCR stimulation alone. Costimulation with Ly108 increased expression of early growth response protein (Egr)–2 and binding of Egr-2 to the promoter of Zbtb16, which encodes PLZF, and resulted in PLZF levels similar to those seen in NKT cells. In contrast, costimulation with anti-CD28 failed to enhance Egr-2 binding and Zbtb16 expression. Moreover, mice lacking Ly108 showed decreased numbers of PLZF-expressing CD4+ T cells. Together, these results support a potential role for Ly108 in the induction of PLZF.
Multiple Tumor-Associated MicroRNAs Modulate the Survival and Longevity of Dendritic Cells by Targeting YWHAZ and Bcl2 Signaling Pathways
Authors: Min Siping , Liang Xue , Zhang Miaomiao , Zhang Yuan , Mei Shiyue , Liu Jinzhe , Liu Jingyi , Su Xiaomin , Cao Shuisong , Zhong Xueqing , Li Yueming , Sun Jiatan , Liu Qiaofei , Jiang Xingran , Che Yongzhe , Yang Rongcun 
Published: January 2013

AbstractTumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways. Specifically, miR-22 targeted YWHAZ to interrupt the PI3K/Akt and MAPK signaling pathways, and miR-503 downregulated Bcl2 expression. The result of the increased expression of miR-22 and miR-503 in the tumor-associated DCs was their reduced survival and longevity. Thus, tumor-associated miRNAs can target multiple intracellular signaling molecules to cause the apoptosis of DCs in the tumor environment. Use of miR-22 and miR-503 as inhibitors may therefore represent a new strategy to improve DC-based immunotherapies against tumors.
Tumor-Derived γδ Regulatory T Cells Suppress Innate and Adaptive Immunity through the Induction of Immunosenescence
Authors: Ye Jian , Ma Chunling , Hsueh Eddy C. , Eickhoff Christopher S. , Zhang Yanping , Varvares Mark A. , Hoft Daniel F. , Peng Guangyong 
Published: January 2013

AbstractFundamentally understanding the suppressive mechanisms used by different subsets of tumor-infiltrating regulatory T (Treg) cells is critical for the development of effective strategies for antitumor immunotherapy. γδ Treg cells have recently been identified in human diseases including cancer. However, the suppressive mechanisms and functional regulations of this new subset of unconventional Treg cells are largely unknown. In the current studies, we explored the suppressive mechanism(s) used by breast tumor-derived γδ Treg cells on innate and adaptive immunity. We found that γδ Treg cells induced immunosenescence in the targeted naive and effector T cells, as well as dendritic cells (DCs). Furthermore, senescent T cells and DCs induced by γδ Treg cells had altered phenotypes and impaired functions and developed potent suppressive activities, further amplifying the immunosuppression mediated by γδ Treg cells. In addition, we demonstrated that manipulation of TLR8 signaling in γδ Treg cells can block γδ Treg–induced conversion of T cells and DCs into senescent cells in vitro and in vivo. Our studies identify the novel suppressive mechanism mediated by tumor-derived γδ Treg cells on innate and adaptive immunity, which should be critical for the development of strong and innovative approaches to reverse the tumor-suppressive microenvironment and improve effects of immunotherapy.
Sustained and Incomplete Recovery of Naive CD8+ T Cell Precursors after Sepsis Contributes to Impaired CD8+ T Cell Responses to Infection
Authors: Condotta Stephanie A. , Rai Deepa , James Britnie R. , Griffith Thomas S. , Badovinac Vladimir P. 
Published: January 2013

Abstract
Patients who survive severe sepsis often display compromised immune function with impairment in innate and adaptive immune responses. These septic patients are highly susceptible to “secondary” infections with intracellular pathogens that are usually controlled by CD8+ T cells. It is not known when and if this observed immunoparalysis of CD8+ T cell immunity recovers, and the long-term consequences of sepsis on the ability of naive CD8+ T cells to respond to subsequent infections are poorly understood. In this study, using the cecal-ligation and puncture mouse model of sepsis, we show that sepsis induces a rapid loss of naive CD8+ T cells. However, IL-15–dependent numerical recovery is observed a month after initial septic insult. Numerical recovery is accompanied by IL-15–dependent phenotypic changes where a substantial proportion of naive (Ag-inexperienced) CD8+ T cells display a “memory-like” phenotype (CD44hi/CD11ahi). Importantly, the impairment of naive CD8+ T cells to respond to viral and bacterial infection was sustained for month(s) after sepsis induction. Incomplete recovery of naive CD8+ T cell precursors was observed in septic mice, suggesting that the availability of naive precursors contributes to the sustained impairment in primary CD8+ T cell responses. Thus, sepsis can result in substantial and long-lasting changes in the available CD8+ T cell repertoire affecting the capacity of the host to respond to new infections.
Cigarette Smoke Exposure Inhibits Contact Hypersensitivity via the Generation of Platelet-Activating Factor Agonists
Authors: Sahu Ravi P. , Petrache Irina , Van Demark Mary J. , Rashid Badri M. , Ocana Jesus A. , Tang Yuxuan , Yi Qiaofang , Turner Matthew J. , Konger Raymond L. , Travers Jeffrey B. 
Published: January 2013

AbstractPrevious studies have established that pro-oxidative stressors suppress host immunity because of their ability to generate oxidized lipids with platelet-activating factor receptor (PAF-R) agonist activity. Although exposure to the pro-oxidative stressor cigarette smoke (CS) is known to exert immunomodulatory effects, little is known regarding the role of PAF in these events. The current studies sought to determine the role of PAF-R signaling in CS-mediated immunomodulatory effects. We demonstrate that CS exposure induces the generation of a transient PAF-R agonistic activity in the blood of mice. CS exposure inhibits contact hypersensitivity in a PAF-R–dependent manner as PAF-R–deficient mice were resistant to these effects. Blocking PAF-R agonist production either by systemic antioxidants or treatment with serum PAF-acetyl hydrolase enzyme blocked both the CS-mediated generation of PAF-R agonists and PAF-R–dependent inhibition of contact hypersensitivity (CHS) reactions, indicating a role for oxidized glycerophosphocholines with PAF-R agonistic activity in this process. In addition, cyclooxygenase-2 inhibition did not block PAF-R agonist production but prevented CS-induced inhibition of CHS. This suggests that cyclooxygenase-2 acts downstream of the PAF-R in mediating CS-induced systemic immunosuppression. Moreover, CS exposure induced a significant increase in the expression of the regulatory T cell reporter gene in Foxp3EGFP mice but not in Foxp3EGFP mice on a PAF-R–deficient background. Finally, regulatory T cell depletion via anti-CD25 Abs blocked CS-mediated inhibition of CHS, indicating the potential involvement of regulatory T cells in CS-mediated systemic immunosuppression. These studies provide the first evidence, to our knowledge, that the pro-oxidative stressor CS can modulate cutaneous immunity via the generation of PAF-R agonists produced through lipid oxidation.
Crystal Structure of IL-17 Receptor B SEFIR Domain
Authors: Zhang Bing , Liu Caini , Qian Wen , Han Yue , Li Xiaoxia , Deng Junpeng 
Published: January 2013

Abstract
IL-17 cytokines play a crucial role in a variety of inflammatory and autoimmune diseases. They signal through heterodimeric receptor complexes consisting of members of IL-17R family. A unique intracellular signaling domain was identified within all IL-17Rs, termed similar expression to fibroblast growth factor genes and IL-17R (SEFIR). SEFIR is also found in NF-κB activator 1 (Act1), an E3 ubiquitin ligase, and mediates its recruitment to IL-17Rs. In this study, to our knowledge, we report the structure of the first SEFIR domain from IL-17RB at 1.8Å resolution. SEFIR displays a five-stranded parallel β-sheet that is wrapped by six helices. Site-directed mutagenesis on IL-17RB identified helix αC as being critical for its interaction with Act1 and IL-25 (IL-17E) signaling. Using the current SEFIR structure as a template, the key functional residues in Act1 are also mapped as part of helix αC, which is conserved in IL-17RA and RC, suggesting this helix as a common structural signature for heterotypic SEFIR–SEFIR association. In contrast, helix αB′ is important for homodimerization of Act1, implicating a dual ligand-binding model for SEFIR domain, with distinct structural motifs participating in either homotypic or heterotypic interactions. Furthermore, although the IL-17RB-SEFIR structure resembles closest to the Toll/IL-1R domain of TLR10 with low sequence homology, substantial differences were observed at helices αC, αD, and DD′ loop. To our knowledge, this study provides the first structural view of the IL-17R intracellular signaling, unraveling the mechanism for the specificity of SEFIR versus Toll/IL-1R domain in their respective signaling pathways.