bluuebunny/crossref_metadata_2025 huggingface dataset:
« Le vin est bon qui en prend par raison ». Le vin dans les recueils de proverbes français et les fabliaux
Authors: Lorcin Marie-Thérèse
Published: July 2014

Qui vit à son aise (seigneur, prêtre, bourgeois) boit du vin. Le consommateur régulier sait boire et connaît les rites et usages sociaux qu’accompagne le vin. Boire trop en revanche est dégradant, faisant de l’homme un objet de risée, de la femme un objet de répulsion. Le vin conforte ainsi la mythologie sociale des contes à rire et la prudente sagesse des proverbes à l’aide de récits désopilants où sont ridiculisés les cibles favorites de la littérature comique, mari jaloux, femme légère, prêtre avare, moine luxurieux, paysan stupide, etc.
La construction des climats viticoles en Bourgogne, la relation du vin au lieu au Moyen Âge
Authors: Garcia Jean-Pierre
Published: July 2014

Les climats, des portions de vignobles délimités, nommés, associés à des crus particuliers, émergent à partir du XVIIe siècle comme la déclinaison spécifiquement bourguignonne du terroir viticole. Pourtant la tradition continue à mettre en avant, dans la construction des climats, les acteurs médiévaux de la viti-viniculture de Bourgogne avec les ducs et les ordres monastiques. Cette mise en avant des acteurs traditionnels de la viti-viniculture de Bourgogne justifie dès lors une exploration historique de la relation du vin au lieu au Moyen Âge. On verra ainsi quelle était la dénomination des vins dans les caves et celliers de Dijon mais aussi que certains celliers monastiques ne différenciaient pas leurs vins par le lieu d’origine. Sur le plan de la qualité des sols en relation avec celle des vins, les pratiques médiévales de transformation des sols attestent du changement de paradigme opéré avec l’avènement des climats qui a accentué la naturalité des terroirs viticoles.
Raisin, vin, vinaigre, verjus dans les traités culinaires… ou « Dans la vigne tout est bon »
Authors: Mane Perrine
Published: July 2014

Outre la consommation de vin comme boisson, le raisin, ainsi que ses autres dérivés liquides, tels le vinaigre, le verjus ou encore le moût, sont largement employés dans la cuisine médiévale. Les livres de cuisine qui se multiplient dans tout l’Occident à partir du xiiie siècle, mais surtout aux xive et xve siècles témoignent de cette importance.
Les vacances du poète
Authors: Payot Daniel
Published: July 2014

La chute de cheval de Montaigne, l’attaque de Rousseau par un chien, le vacillement de Proust sur les pavés sont autant d’accidents ouvrant à la création. L’expérience de la souffrance, de la perte, de la destruction permet de comprendre l’activité poiétique comme passage de l’être au non être, commerce avec l’inexistant. Penser la création à partir des plaies de la sensibilité et de leur cicatrisation conduit à repenser le statut de la liberté (ou nécessité) créatrice ainsi que les conditions temporelles de l’émergence des œuvres, qui adviennent toujours sur le fond d’une altérité.
Les métamorphoses de l’artiste après un coma
Authors: Chapouthier Georges
Published: July 2014

Si l’on se place dans le cadre des présupposés matérialistes de la science d’aujourd’hui, les bouleversements de la sensibilité artistique, qui peuvent apparaître après un épisode de coma, prennent une signification biologique. Ils sont les échos, dans le domaine de la pensée, des métamorphoses corporelles que l’on rencontre chez les animaux dans le domaine de la nature.
Un coma ça tape où ? Incorporer le corps dans le voir
Authors: Rœsz Germain
Published: July 2014

S’interrogeant sur les conditions de la genèse de son œuvre, le peintre et poète Germain Rœsz se remémore le long coma à l’issue duquel il s’est mis à manier la couleur – et les mots. Il propose le concept de Raum pour désigner cet état paradoxal où l’on touche et sent sans son corps. Chaque nouvelle création renouvelle ce lâcher-prise inaugural, inversant l’idée commune selon laquelle l’œuvre trouverait ses sources dans la seule histoire, dans l’addition des expériences de l’artiste, puisque le comateux précisément ne sent pas, puisque l’aveugle justement ne voit pas.
Entre stigmates et mémoires : dynamiques paradoxales de la rénovation urbaine
Authors: Morovich Barbara
Published: July 2014

Les acteurs de la rénovation urbaine utilisent des discours sur les dégradations des quartiers populaires qui renforcent les stigmates de ces lieux, déjà fortement médiatisés, et de leurs habitants. Parallèlement, on exalte « l’habitant » et sa mémoire, dont la valorisation serait un passage obligé, une étape incontournable avant de basculer vers le changement. Dans ce cadre, des artistes sont appelés à redonner du sens dans le contexte de bouleversement urbain : ils participent à la création d’une nouvelle identité du quartier et à l’éloignement des stigmates. Ces projets artistiques qui mettent en avant la mémoire des habitants ont un rôle ambigu : comment opérer un travail mémoriel dans des lieux qu’on souhaite effacer ?
Monseigneur le Dauphin, fils de Louis XIV : introduction
Authors: da Vinha Mathieu
Published: July 2014

Brosser le portrait de Louis de France, dit « Monseigneur le Dauphin », ou plus simplement « Monseigneur », revient souvent à en faire un portrait en creux et à évoquer beaucoup plus Louis XIV. Il est vrai qu’être le fils de Louis le Grand constitue une gageure : comment – sans nécessairement le surpasser – égaler cet auguste père ? On peut dire, sans trop s’avancer, qu’il n’a sans doute pas eu assez de temps pour donner la pleine mesure de ses capacités, étant mort à quarante-neuf ans en 1711, soit quatre ans avant son père. La formation et le parcours qu’il a suivis voulaient toutefois qu’il succédât dignement au trône.
Le domaine des Trois Moulins de la Valmasque (Valbonne) : un patrimoine en paradoxe
Authors: Cranga Yves , Cranga Marie-Françoise
Published: July 2014

Le domaine méditerranéen des Trois Moulins de la Valmasque a été récemment découvert, protégé puis acquis par une collectivité territoriale. La réécriture au xxe siècle des structures hydrauliques et agraires de cette ancienne propriété rurale, tout comme les références culturelles mobilisées, en font une œuvre artistique globale et complexe dont la qualité esthétique et paysagère s’est mise au service d’un site historique remarquable. La compréhension d’un tel espace, patrimoine naturel et culturel, à la fois transitoire et immuable, est le gage de sa pérennisation.
Le château d’Abbadia sur la corniche basque ou les paradoxes d’une demeure orientaliste au XIXe siècle
Authors: Delpech Viviane
Published: July 2014

Édifié à Hendaye par Eugène-E. Viollet-le-Duc et Edmond Duthoit pour l’explorateur scientifique éthiopisant Antoine d’Abbadie, le château d’Abbadia (1864-1884) se caractérise par un éclectisme artistique extraordinaire où se mêlent inspiration gothique et sources orientales, parmi lesquelles l’Orient islamique à la mode et la plus rare Éthiopie. Relevant du rationalisme architectural, les Orients d’Abbadia se distinguent par leurs significations relativement contradictoires associant goût esthétique et engagement humain.
« La petite mer d’Enghien » : un site pour une villégiature parisienne
Authors: Cueille Sophie
Published: July 2014

À la fois lac d’Elvire, lac Majeur, lac de Genève, terre chérie de l’auteur de l’Émile, l’un des plus jolis pays du monde, véritable miniature des grands lacs suisses, petite mer... Quel est ce lieu chanté par les plus belles plumes ? Alfred de Musset, Théodore de Banville, Hector Malot, Alphonse Daudet, Guy de Maupassant, Alexandre Dumas, les frères Goncourt ont connu et évoqué le site, de même que nombre de romanciers oubliés. Thème décliné en poésie, en musique, référence géographique associée à Pékin, au Canada, en passant par la Sibérie occidentale... Enghien-les-Bains doit sans doute cette notoriété à sa proximité avec la capitale. Station thermale, mais également lieu de villégiature au bord d’un lac, elle a suscité bien des exercices littéraires où la surenchère de références, la métaphore et l’emphase promeuvent le site. Expérience urbaine d’avant-garde, colonie au dessin empruntant aux modèles anglais, tentative de réponse architecturale à la présence du lac, Enghien mérite une attention particulière.
L’invention du système des immeubles à gradins. Sa genèse à visée sanitaire avant sa diffusion mondiale dans la villégiature de montagne et de bord de mer
Authors: Laget Pierre-Louis
Published: July 2014

Les immeubles aux étages disposés en gradins-terrasses qui, depuis un demi-siècle, connaissent une extraordinaire vogue dans l’architecture balnéaire, sont issus des réflexions de médecins sur le mode de traitement le plus approprié pour des malades affectés d’une tuberculose pulmonaire ou phtisie. Ce fut avec la création en Allemagne, à la fin du xixe siècle, d’un nouveau type d’établissement hospitalier, le sanatorium, conçu comme outil de traitement spécifique de cette affection alors redoutable, que naquit le parti architectural qui allait engendrer l’idée d’étager en gradins les terrasses ou balcons ouverts au-devant des chambres de malades. Plus précisément, ce furent les galeries dites de cure d’air, éléments constitutifs du sanatorium dès son origine, qui, après des déclinaisons diverses, se muèrent en système à gradins-terrasses. Cette mutation elle-même résultait d’une inflexion de la cure sanatoriale qui adjoignit, à la cure d’air traditionnelle, un traitement par le rayonnement solaire ou héliothérapie. Les phtisiologues suisses, promoteurs à l’aube du xxe siècle de cette héliothérapie prétendirent, contrairement à leurs homologues allemands, que le soleil exerçait une action bénéfique et non nocive sur la phtisie. Ils proposèrent donc de découvrir les galeries de cure pour qu’elles fussent inondées de lumière, ce qui constitua le point de départ des recherches pour obtenir pareil effet. La mise en application du système des galeries de cure disposées en gradins se heurtait toutefois à des difficultés constructives ; en sus, les retraits des gradins amenuisaient notablement les surfaces des planchers entre chaque niveau et celui immédiatement supérieur ; enfin, une majorité de médecins continuait à douter de la valeur médicatrice de l’héliothérapie. C’est pourquoi seul un petit nombre de sanatoriums et de fort rares immeubles d’habitations adoptèrent ce système de construction avant la Première Guerre mondiale, puis surtout durant la période de l’entre-deux-guerres. Du fait que les hôpitaux prirent modèle sur l’architecture des sanatoriums à partir des années 1930, on rencontre aussi quelques uns de ces édifices conçus selon les mêmes principes architectoniques. Au lendemain de la guerre, le système de gradins-terrasses ne fit plus recette, tout au moins dans l’architecture hospitalière, en raison sans doute des surcoûts engendrés par sa mise en œuvre. Aussi fallut-il attendre les années 1960 avec l’essor inouï du tourisme de masse en bord de mer, pour que ce système retrouvât la faveur des architectes et se trouvât appliqué à très grande échelle et avec un succès devenu planétaire qui ne se dément toujours pas.
Les stations thermales : de l’abandon à la renaissance. Une brève histoire du thermalisme en France depuis l’Antiquité
Authors: Jazé-Charvolin Marie-Reine
Published: July 2014

Avec 108 stations thermales, la France occupe aujourd’hui le troisième rang en Europe pour le thermalisme. Nombre des établissements thermaux sont implantés à l’emplacement même ou à proximité d’anciens thermes romains. En effet, l’usage des installations antiques a perduré à travers les siècles. Parallèlement, de nouveaux établissements ont vu le jour, notamment à partir du xviie siècle. Mais c’est autour de 1850 que le thermalisme a pris réellement son envol avec, sur tout le territoire, l’édification d’établissements prestigieux. Bien sûr, chacune des villes d’eaux n’a pas connu la même prospérité. Toutes cependant se sont adaptées et se sont transformées pour offrir aux curistes, non seulement les meilleures conditions de soins mais également celles d’un séjour réussi, se constituant ainsi un patrimoine varié (monuments romains, thermes, casinos, hippodromes, palaces, villas…) doté d’une identité forte et originale. Alors que de nombreux établissements se repositionnent sur le secteur de la remise en forme, l’enjeu d’aujourd’hui est de tirer profit de cette richesse fragile, tout en modernisant les installations pour s’adapter aux nouvelles pratiques.
Aix-les-Bains, carrefour de villégiatures : thermalisme, climatisme, sports d’hiver et bords de lac
Authors: Belle Elsa
Published: July 2014

Située entre le lac du Bourget et le massif des Bauges, et implantée sur des sources d’eau chaude, la ville d’Aix-les-Bains a connu un formidable essor lié à l’activité thermale. Le thermalisme a suscité le développement du climatisme puis des sports d’hiver au Revard dans les Bauges ainsi que celui des activités balnéaires sur les rives du lac. Cette situation géographique et cette configuration historique ont fait d’Aix-les-Bains un carrefour de villégiatures unique en France dont l’héritage est plus que prégnant aujourd’hui.
En villégiature à la Cité : les collections de la Cité de l’architecture et du patrimoine
Authors: Bélier Corinne
Published: July 2014

La Cité de l’architecture et du patrimoine conserve un grand nombre d’archives et de collections traitant de la villégiature. Cet article présente l’histoire de ces collections ainsi que leurs lacunes et leurs points forts. Dès sa création, l’Institut français d’architecture contribue à la valorisation du patrimoine balnéaire et thermal grâce à de multiples expositions et publications et à la collecte d’archives d’architecture. Les premières collections sont consacrées à l’architecture de la Belle Époque et de l’entre-deux-guerres, puis arrivent les grands fonds d’archives des agences de l’après-guerre. Les nouvelles stations balnéaires et de ski correspondent alors au développement du tourisme de masse. Elles ont été retenues pour leur exemplarité dans le parcours permanent du musée des Monuments français.
L’architecture à l’épreuve du site : Jacques Labro à Avoriaz
Authors: Labro Jacques
Published: July 2014

Interview filmée réalisée par Claude Laroche
Penser l’aménagement de la côte aquitaine : la Miaca à l’œuvre dans les années 1970, entretien avec Michel Marty
Authors: Marty Michel
Published: July 2014

Interview filmée réalisée par Claude Laroche
L’Atelier d’architecture en montagne. Contribution à la mise au point d’une architecture de montagne
Authors: Delorme Franck
Published: July 2014

L’histoire des stations de sports d’hiver françaises est jalonnée d’étapes importantes. La physionomie des stations s’est transformée au gré des vagues successives de touristes se ruant sur la montagne pour la pratique du ski. D’abord née à partir d’un village existant, la station de ski s’est progressivement autonomisée pour s’implanter en site vierge afin de rationaliser les terrains, que ce soit pour le domaine skiable ou pour les bâtiments. Les urbanistes et les architectes, pour répondre à la demande des collectivités en matière de stations, ont multiplié les recherches. En Savoie, terre s’il en est de sports d’hiver, l’Atelier d’architecture en montagne est l’auteur d’origine de plusieurs stations : Courchevel, Les Arcs et Les Karellis. Alliant les compétences en matière d’urbanisme et d’architecture, ce groupe de maîtres d’œuvre se caractérise par un rapport étroit au site, notamment par la pratique du ski, rapport qui déterminera une véritable doctrine quant à l’implantation et l’organisation des stations réalisées. Certaines, comme Courchevel, ont aujourd’hui perdu leur âme et leur caractère pionniers pour se réfugier dans des valeurs bien éloignées de celles qui ont présidé à leur création.
Du village-station à la station-village. Un siècle d’urbanisme en montagne
Authors: Delorme Franck
Published: July 2014

Les activités humaines modifient géographiquement et sociologiquement le territoire qu’elles soumettent à leur colonisation. Jusqu’à une époque récente, le milieu du xixe siècle, les terrains de moyenne et de haute montagne n’ont subi que des occupations relativement pacifiques, principalement des activités pastorales. Le développement progressif des loisirs, élitistes puis populaires, a eu comme conséquence la conquête définitive et parfois totale de ces nouveaux territoires encore « vierges ». La mainmise de l’homme s’est faite de plus en plus forte et visible par la viabilisation, l’urbanisation et l’édification, au fur et à mesure qu’un nombre toujours plus grand de personnes prenait le chemin saisonnier de la villégiature, inverse de l’exode des populations montagnardes vers les vallées et les villes. La ville a fait son apparition sur les pentes et au cœur de la montagne. L’architecture n’a fait que gagner en densité. L’évolution des pratiques de sports d’hiver ont influé sur l’évolution urbaine et architecturale. Son étude montre les étapes qu’elle a parcourues et traversées, matérialisées par différents types de stations, marquées elles-mêmes par un urbanisme et une architecture spécifique. Les stations de sports d’hiver, au gré des modes et des usages, ont pris des aspects différents et ont marqué plus ou moins fortement le paysage. Les expériences architecturales se sont succédé, convoquant ou rejetant tour à tour des modèles établis ou inventés. Dans un jeu de renversement, on est passé d’un village-station pionnier à une station-village nostalgique.
Providing Knowledge Services in a Challenging Environment: Experiences of Practical Answers Sri Lanka
Authors: Kularathna Chandrika
Published: July 2014

Financial sustainability is a key challenge which any donor funded knowledge sharing service as “Practical Answers Sri Lanka” has to face inevitably. Most institutions running with donor funds tend to discontinue the affiliated knowledge services or reduce the funding allocations considering them as cost entities. Hence it is very important to investigate innovative strategies, ownership models and unique management systems to ensure financial sustainability, while continuing to maximize the expected social impact through sharing knowledge. Financial sustainability is a challenge which Practical Answers Sri Lanka is striving to address in the long term. Practical Answers Sri Lanka adopted a new strategy to expand its vital services while moving the organizations towards self-sufficiency. In this paper the author presents the experiences of Practical Answers Sri Lanka in the process of transformation towards a sustainable knowledge sharing service.DOI: http://dx.doi.org/10.4038/sllim.v5i2.7154 Sri Lankan Journal of Librarianship and Information Management Vol.5(2) 2013: 1-9
Beyond the Walls: Outreach Initiatives in Library, University of Moratuwa
Authors: Kodikara Ruvini C. , Seneviratne Thushari M. , Punchihewa C.N.D.
Published: July 2014

Outreach librarianship – a concept which had a history of more than 40 years - has been diversely used in libraries all over the world as well as in Sri Lanka. Outreach Librarianship is aimed to reach out to traditional and non-traditional library users, extending beyond the walls of a physical library to serve underprivileged communities. Establishment of Outreach Services Division in Library, University of Moratuwa has fulfilled a longfelt need to serve the community living in the vicinity of University of Moratuwa. “Child Development Programme” at Sumudu Preschool located in the University premises and “Reading Camp” at Bodhiraja Vidyalaya, Katubedda, Moratuwa are two outreach initiatives that the staff of Library, University of Moratuwa are currently engaged in. This paper describes the accomplishment of these two outreach initiatives through management of physical and human resources without an outreach budget.DOI: http://dx.doi.org/10.4038/sllim.v5i2.7155 Sri Lankan Journal of Librarianship and Information Management Vol.5(2) 2013: 10-22
The Impact of the Standing Committee on Libraries and Information Sciences (SCOLIS) of UGC For the Development of University Libraries
Authors: Jayatissa L.A.
Published: July 2014

University libraries in Sri Lanka functioned without any formal coordination during the initial period of 1942 to 1986. However, due to the intervention of His Excellency the President, Mr. J.R. Jayewardene in his capacity as the Minister of Higher Education, a coordination mechanism evolved in the form of a Standing Sub-Committee of the University Grants Commission. This was named the ‘Inter University Committee of Librarians’ (IUCL) and renamed as the ‘Standing Committee of Libraries and Information Sciences’ (SCOLIS) in March, 2003. The IUCL / SCOLIS was instrumental in airing the need to improve library infrastructure, manpower resources, funding, dialogue with the teaching staff, ICT facilities and a host of other issues. Above anything else, it acted as the main communication channel between the University Librarians and the UGC. The foregoing discussion provides a brief overview of this aspect.DOI: http://dx.doi.org/10.4038/sllim.v5i2.7156 Sri Lankan Journal of Librarianship and Information Management Vol.5(2) 2013: 23-35
An Evaluation of the Use of Empowering 8 Information Literacy Model in Resource Based Teaching-Learning Process
Authors: Pemadasa P.G.
Published: July 2014

The objective of the survey was to evaluate the success of the Empowering-8 Information Literacy model introduced in 2004. The study reveals that E-8 model is successful when the (teacher) librarian actively teach in the classroom rather than resorting to the library management. However, the school community is not knowledgable on the resource based learning concept. Therefore, even when the teacher librarians teach students, the task of him/her has been limited to teaching some information skills only. Therefore, it is necesary to educate school administrators that the role of 'teacher librarians' is broad, and that they must teach at least 10 periods a week as per the government circular issued on this regard.Out of 20 participants (teachers and teacher librarians who followed postgraduate studies at the institution during 2008-2013) responded in the survey, only 5 had used E-8 model in designing lessons. Only 2 had started from the first step, namely 'identifying the problem'. All others had started from the second step, namely 'exploring information'. Only 11 have gone beyond the 5th step (creating).Therefore, it is recommended that E-8 model is implemented in extended learning activities, promoted and advocated by the provincial educational administrators.DOI: http://dx.doi.org/10.4038/sllim.v5i2.7157 Sri Lankan Journal of Librarianship and Information Management Vol.5(2) 2013: 36-45
An Explorative Study on Information Communication Associated with the Fisheries Industry in Sri Lanka
Authors: Malkanthi D.G.A.S.
Published: July 2014

Fisheries industry is one of the major income sources of Sri Lanka. The success and the sustainability of this industry highly dependent on the amount and the quality of important information they possess. However, whether the necessary information reaches today’s fishing community is a question that warrants investigation. Therefore, a study was carried out to investigate the effectiveness of information transfer between the fishing community and the relevant authorities. Data was collected from Negombo area of Gampaha District from 50 fishing families using a questionnaire. Eight respondents were selected an “information producers” and they were interviewed regarding their role and main mass communication methods. The study revealed that the information transfer to the fishing community is poor and inadequate mainly due to the lack of a direct link between them and the authorities. Further it was identified that by developing an effective communication system, necessary knowledge and infrastructure facilities needed for a sustainable development of the industry can be efficiently transmitted.DOI: http://dx.doi.org/10.4038/sllim.v5i2.7158 Sri Lankan Journal of Librarianship and Information Management Vol.5(2) 2013: 46-57
Thiamine Deficiency Promotes T Cell Infiltration in Experimental Autoimmune Encephalomyelitis: The Involvement of CCL2
Authors: Ji Zhe , Fan Zhiqin , Zhang Ying , Yu Ronghuan , Yang Haihua , Zhou Chenghua , Luo Jia , Ke Zun-Ji
Published: July 2014

Multiple sclerosis (MS) is a complex multifactorial disease that results from the interplay between environmental factors and a susceptible genetic background. Experimental autoimmune encephalomyelitis (EAE) has been widely used to investigate the mechanisms underlying MS pathogenesis. Chemokines, such as CCL2, are involved in the development of EAE. We have previously shown that thiamine deficiency (TD) induced CCL2 in neurons. We hypothesized that TD may affect the pathogenesis of EAE. In this study, EAE was induced in C57BL/6J mice by the injection of myelin oligodendroglial glycoprotein (MOG) peptides 35–55 with or without TD. TD aggravated the development of EAE, which was indicated by clinical scores and pathologic alterations in the spinal cord. TD also accelerated the development of EAE in an adoptive transfer EAE model. TD caused microglial activation and a drastic increase (up 140%) in leukocyte infiltration in the spinal cord of the EAE mice; specifically, TD increased Th1 and Th17 cells. TD upregulated the expression of CCL2 and its receptor CCR2 in the spinal cord of EAE mice. Cells in peripheral lymph node and spleen isolated from MOG-primed TD mice showed much stronger proliferative responses to MOG. CCL2 stimulated the proliferation and migration of T lymphocytes in vitro. Our results suggested that TD exacerbated the development of EAE through activating CCL2 and inducing pathologic inflammation.
ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils: Regulation of Expression and Contributions to Extracellular Matrix Protein Degradation during Acute Lung Injury
Authors: Roychaudhuri Robin , Hergrueter Anja H. , Polverino Francesca , Laucho-Contreras Maria E. , Gupta Kushagra , Borregaard Niels , Owen Caroline A.
Published: July 2014

A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein is stored in the gelatinase and specific granules and the secretory vesicles of human PMNs. Unstimulated PMNs express minimal quantities of surface ADAM9, but activation of PMNs with degranulating agonists rapidly (within 15 min) increases PMN surface ADAM9 levels. Human PMNs produce small quantities of soluble forms of ADAM9. Surprisingly, ADAM9 degrades several extracellular matrix (ECM) proteins, including fibronectin, entactin, laminin, and insoluble elastin, as potently as matrix metalloproteinase-9. However, ADAM9 does not degrade types I, III, or IV collagen or denatured collagens in vitro. To determine whether Adam9 regulates PMN recruitment or ECM protein turnover during inflammatory responses, we compared wild-type and Adam9−/− mice in bacterial LPS- and bleomycin-mediated acute lung injury (ALI). Adam9 lung levels increase 10-fold during LPS-mediated ALI in wild-type mice (due to increases in leukocyte-derived Adam9), but Adam9 does not regulate lung PMN (or macrophage) counts during ALI. Adam9 increases mortality, promotes lung injury, reduces lung compliance, and increases degradation of lung elastin during LPS- and/or bleomycin-mediated ALI. Adam9 does not regulate collagen accumulation in the bleomycin-treated lung. Thus, ADAM9 is expressed in an inducible fashion on PMN surfaces where it degrades some ECM proteins, and it promotes alveolar–capillary barrier injury during ALI in mice.
High Frequency of Cytolytic 21-Hydroxylase–Specific CD8+ T Cells in Autoimmune Addison’s Disease Patients
Authors: Dawoodji Amina , Chen Ji-Li , Shepherd Dawn , Dalin Frida , Tarlton Andrea , Alimohammadi Mohammad , Penna-Martinez Marissa , Meyer Gesine , Mitchell Anna L. , Gan Earn H. , Bratland Eirik , Bensing Sophie , Husebye Eystein S. , Pearce Simon H. , Badenhoop Klaus , Kämpe Olle , Cerundolo Vincenzo
Published: July 2014

The mechanisms behind destruction of the adrenal glands in autoimmune Addison’s disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase–specific T cells detectable in 20 patients with Addison’s disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8+ and CD4+ T cell responses in a large proportion of Addison’s patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8+ and CD4+ 21-hydroxylase–specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer–guided isolation of 21-hydroxylase–specific CD8+ T cells showed their ability to lyse 21-hydroxylase–positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer.
IL-17 Suppresses Immune Effector Functions in Human Papillomavirus-Associated Epithelial Hyperplasia
Authors: Gosmann Christina , Mattarollo Stephen R. , Bridge Jennifer A. , Frazer Ian H. , Blumenthal Antje
Published: July 2014

Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3+ T cells, predominantly CD4+ T cells in human, and CD4+ and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer.
Caspase-8 Modulates Dectin-1 and Complement Receptor 3–Driven IL-1β Production in Response to β-Glucans and the Fungal Pathogen, Candida albicans
Authors: Ganesan Sandhya , Rathinam Vijay A. K. , Bossaller Lukas , Army Kelly , Kaiser William J. , Mocarski Edward S. , Dillon Christopher P. , Green Douglas R. , Mayadas Tanya N. , Levitz Stuart M. , Hise Amy G. , Silverman Neal , Fitzgerald Katherine A.
Published: July 2014

Inflammasomes are central mediators of host defense to a wide range of microbial pathogens. The nucleotide-binding domain and leucine-rich repeat containing family (NLR), pyrin domain–containing 3 (NLRP3) inflammasome plays a key role in triggering caspase-1–dependent IL-1β maturation and resistance to fungal dissemination in Candida albicans infection. β-Glucans are major components of fungal cell walls that trigger IL-1β secretion in both murine and human immune cells. In this study, we sought to determine the contribution of β-glucans to C. albicans–induced inflammasome responses in mouse dendritic cells. We show that the NLRP3–apoptosis-associated speck-like protein containing caspase recruitment domain protein–caspase-1 inflammasome is absolutely critical for IL-1β production in response to β-glucans. Interestingly, we also found that both complement receptor 3 (CR3) and dectin-1 play a crucial role in coordinating β-glucan–induced IL-1β processing as well as a cell death response. In addition to the essential role of caspase-1, we identify an important role for the proapoptotic protease caspase-8 in promoting β-glucan–induced cell death and NLRP3 inflammasome-dependent IL-1β maturation. A strong requirement for CR3 and caspase-8 also was found for NLRP3-dependent IL-1β production in response to heat-killed C. albicans. Taken together, these results define the importance of dectin-1, CR3, and caspase-8, in addition to the canonical NLRP3 inflammasome, in mediating β-glucan– and C. albicans–induced innate responses in dendritic cells. Collectively, these findings establish a novel link between β-glucan recognition receptors and the inflammatory proteases caspase-8 and caspase-1 in coordinating cytokine secretion and cell death in response to immunostimulatory fungal components.
Acute and Chronic Effects of IL-22 on Acetaminophen-Induced Liver Injury
Authors: Feng Dechun , Wang Yan , Wang Hua , Weng Honglei , Kong Xiaoni , Martin-Murphy Brittany V. , Li Yongmei , Park Ogyi , Dooley Steven , Ju Cynthia , Gao Bin
Published: July 2014

Acetaminophen (APAP)-induced liver injury (AILI) accounts for half of the acute liver failure cases in the United States. A better understanding of the underlying mechanisms of AILI is necessary for the development of novel antidotes. We found that pretreatment with IL-22 protected mice from APAP-mediated hepatotoxicity. The protection was dependent on STAT3, as IL-22 failed to reduce APAP hepatotoxicity in liver-specific STAT3 knockout mice. In contrast to the acute exposure to IL-22, the endogenous chronic overexpression of IL-22 in IL-22 transgenic (TG) mice or IL-22 adenovirus treatment for 6 wk resulted in a markedly increased susceptibility to AILI. Furthermore, the hepatic expression levels of cytochrome 2E1 (Cyp2E1) and Cyp1A2 were much higher in IL-22TG mice. Ablation of Cyp2E1 but not hepatic STAT3 abolished AILI and protein-adduct formation in IL-22TG mice. Finally, hepatic expression of HNF-1α, a transcriptional factor that is known to control Cyp2E1 expression, was elevated in IL-22TG mice compared with wild-type mice. Upregulation of hepatic Cyp2E1 was only observed in mice with constitutive overexpression of IL-22 but not with short-term treatment with one dose of IL-22 or multiple doses of IL-22 for 2 wk. In conclusion, short-term acute IL-22 exposure protects mice against AILI through STAT3 activation; however, chronic constitutive overexpression of IL-22 exacerbates AILI by increasing Cyp2E1 and toxic reactive APAP metabolite production. These findings may not only enhance our understanding of the effects of chronic inflammation on AILI in patients with liver disease, but are also helpful to identify novel therapeutic targets for the treatment of AILI.
Rapid Remodeling of Tight Junctions during Paracellular Diapedesis in a Human Model of the Blood–Brain Barrier
Authors: Winger Ryan C. , Koblinski Jennifer E. , Kanda Takashi , Ransohoff Richard M. , Muller William A.
Published: July 2014

Leukocyte transendothelial migration (TEM; diapedesis) is a critical event in immune surveillance and inflammation. Most TEM occurs at endothelial cell borders (paracellular). However, there is indirect evidence to suggest that, at the tight junctions of the blood–brain barrier (BBB), leukocytes migrate directly through the endothelial cell body (transcellular). Why leukocytes migrate through the endothelial cell body rather than the cell borders is unknown. To test the hypothesis that the tightness of endothelial cell junctions influences the pathway of diapedesis, we developed an in vitro model of the BBB that possessed 10-fold higher electrical resistance than standard culture conditions and strongly expressed the BBB tight junction proteins claudin-5 and claudin-3. We found that paracellular TEM was still the predominant pathway (≥98%) and TEM was dependent on PECAM-1 and CD99. We show that endothelial tight junctions expressing claudin-5 are dynamic and undergo rapid remodeling during TEM. Membrane from the endothelial lateral border recycling compartment is mobilized to the exact site of tight junction remodeling. This preserves the endothelial barrier by sealing the intercellular gaps with membrane and engaging the migrating leukocyte with unligated adhesion molecules (PECAM-1 and CD99) as it crosses the cell border. These findings provide new insights into leukocyte–endothelial interactions at the BBB and suggest that tight junctions are more dynamic than previously appreciated.
Noncanonical NF-κB Activation Mediates STAT3-Stimulated IDO Upregulation in Myeloid-Derived Suppressor Cells in Breast Cancer
Authors: Yu Jinpu , Wang Yue , Yan Fang , Zhang Peng , Li Hui , Zhao Hua , Yan Cihui , Yan Fan , Ren Xiubao
Published: July 2014

Immunotherapy for cancer treatment is achieved through the activation of competent immune effector cells and the inhibition of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). Although MDSCs have been shown to contribute to breast cancer development, the mechanism underlying MDSC-mediated immunosuppression is unclear. We have identified a poorly differentiated MDSC subset in breast cancer–suppressing T cell function through STAT3-dependent IDO upregulation. In this study we investigated the mechanisms underlying aberrant expression of IDO in MDSCs. MDSCs were induced by coculturing human CD33+ myeloid progenitors with MDA-MB-231 breast cancer cells. Increased STAT3 activation in MDSCs was correlated with activation of the noncanonical NF-κB pathway, including increased NF-κB–inducing kinase (NIK) protein level, phosphorylation of cytoplasmic inhibitor of NF-κB kinase α and p100, and RelB-p52 nuclear translocation. Blocking STAT3 activation with the small molecule inhibitor JSI-124 significantly inhibited the accumulation of NIK and IDO expression in MDSCs. Knockdown of NIK in MDSCs suppressed IDO expression but not STAT3 activation. RelB-p52 dimers were found to directly bind to the IDO promoter, leading to IDO expression in MDSCs. IL-6 was found to stimulate STAT3-dependent, NF-κB–mediated IDO upregulation in MDSCs. Furthermore, significant positive correlation between the numbers of pSTAT3+ MDSCs, IDO+ MDSCs, and NIK+ MDSCs was observed in human breast cancers. These results demonstrate a STAT3/NF-κB/IDO pathway in breast cancer–derived MDSCs, which provides insight into understanding immunosuppressive mechanisms of MDSCs in breast cancer.
IL-2 Protects Lupus-Prone Mice from Multiple End-Organ Damage by Limiting CD4−CD8− IL-17–Producing T Cells
Authors: Mizui Masayuki , Koga Tomohiro , Lieberman Linda A. , Beltran Jessica , Yoshida Nobuya , Johnson Mark C. , Tisch Roland , Tsokos George C.
Published: July 2014

IL-2, a cytokine with pleiotropic effects, is critical for immune cell activation and peripheral tolerance. Although the therapeutic potential of IL-2 has been previously suggested in autoimmune diseases, the mechanisms whereby IL-2 mitigates autoimmunity and prevents organ damage remain unclear. Using an inducible recombinant adeno-associated virus vector, we investigated the effect of low systemic levels of IL-2 in lupus-prone MRL/Faslpr/lpr (MRL/lpr) mice. Treatment of mice after the onset of disease with IL-2-recombinant adeno-associated virus resulted in reduced mononuclear cell infiltration and pathology of various tissues, including skin, lungs, and kidneys. In parallel, we noted a significant decrease of IL-17–producing CD3+CD4−CD8− double-negative T cells and an increase in CD4+CD25+Foxp3+ immunoregulatory T cells (Treg) in the periphery. We also show that IL-2 can drive double-negative (DN) T cell death through an indirect mechanism. Notably, targeted delivery of IL-2 to CD122+ cytotoxic lymphocytes effectively reduced the number of DN T cells and lymphadenopathy, whereas selective expansion of Treg by IL-2 had no effect on DN T cells. Collectively, our data suggest that administration of IL-2 to lupus-prone mice protects against end-organ damage and suppresses inflammation by dually limiting IL-17–producing DN T cells and expanding Treg.
Compensatory Mechanisms Allow Undersized Anchor-Deficient Class I MHC Ligands To Mediate Pathogenic Autoreactive T Cell Responses
Authors: Lamont Deanna , Mukherjee Gayatri , Kumar P. Rajesh , Samanta Dibyendu , McPhee Caroline G. , Kay Thomas W. H. , Almo Steven C. , DiLorenzo Teresa P. , Serreze David V.
Published: July 2014

Self-reactive T cells must escape thymic negative selection to mediate pathogenic autoimmunity. In the NOD mouse model of autoimmune diabetes, several β cell–cytotoxic CD8 T cell populations are known, with the most aggressive of these represented by AI4, a T cell clone with promiscuous Ag-recognition characteristics. We identified a long-elusive β cell–specific ligand for AI4 as an unusually short H-2Db–binding 7-mer peptide lacking a C-terminal anchor residue and derived from the insulin A chain (InsA14–20). Crystallography reveals that compensatory mechanisms permit peptides lacking a C-terminal anchor to bind sufficiently to the MHC to enable destructive T cell responses, yet allow cognate T cells to avoid negative selection. InsA14–20 shares two solvent-exposed residues with previously identified AI4 ligands, providing a structural explanation for AI4’s promiscuity. Detection of AI4-like T cells, using mimotopes of InsA14–20 with improved H-2Db–binding characteristics, establishes the AI4-like T cell population as a consistent feature of the islet infiltrates of NOD mice. Our work establishes undersized peptides as previously unrecognized targets of autoreactive CD8 T cells and presents a strategy for their further exploration as Ags in autoimmune disease.
Hydroxyproline, a Serum Biomarker Candidate for Gastric Ulcer in Rats: A Comparison Study of Metabolic Analysis of Gastric Ulcer Models Induced by Ethanol, Stress, and Aspirin
Authors: Takeuchi Kenichiro , Ohishi Maki , Endo Keiko , Suzumura Kenichi , Naraoka Hitoshi , Ohata Takeji , Seki Jiro , Miyamae Yoichi , Honma Masashi , Soga Tomoyoshi
Published: July 2014

Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID-induced gastric ulcer using capillary electrophoresis–mass spectrometry (CE–MS)-based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE–MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.
An In-depth Analysis of a Multilocus Phylogeny Identifies LeuS As a Reliable Phylogenetic Marker for the Genus Pantoea
Authors: Tambong James T. , Xu Renlin , Kaneza Cynthia-Anne , Nshogozabahizi Jean-Claude
Published: July 2014

Partial sequences of six core genes ( fusA, gyrB, leuS, pyrG, rlpB, and rpoB) of 37 strains of Pantoea species were analyzed in order to obtain a comprehensive view regarding the phylogenetic relationships within the Pantoea genus and compare tree topologies to identify gene(s) for reliable species and subspecies differentiation. All genes used in this study were effective at species-level delineation, but the internal nodes represented conflicting common ancestors in fusA- and pyrG-based phylogenies. Concatenated gene phylogeny gave the expected DNA relatedness, underscoring the significance of a multilocus sequence analysis. Pairwise comparison of topological distances and percent similarities indicated a significant differential influence of individual genes on the concatenated tree topology. leuS- and fusA-inferred phylogenies exhibited, respectively, the lowest (4) and highest (52) topological distances to the concatenated tree. These correlated well with high (96.3%) and low (64.4%) percent similarities of leuS- and fusA-inferred tree topologies to the concatenated tree, respectively. We conclude that the concatenated tree topology is strongly influenced by the gene with the highest number of polymorphic and non-synonymous sites in the absence of significant recombination events.
Bus Structure Behaviour under Driving Manoeuvring and Evaluation of the Effect of an Active Roll System
Authors: Gauchia A. , Diaz V. , Boada M.J.L , Olatunbosun O. A. , Boada B.L
Published: July 2014

One of the main causes of traffic accidents in which heavy vehicles are involved is lateral stability loss. It is well known that heavy vehicles have relatively high centres of gravity and narrow track widths and can lose roll stability at moderate levels of lateral acceleration. The influence of several parameters (i.e. height of the centre of gravity, weight distribution between axles, chassis torsional stiffness, etc.) on bus roll stability during a lane change manoeuvre, as well as the bus structure stress level has been analyzed by means of a six degrees of freedom beam finite element model. In addition, due to the use of active systems to prevent excessive roll motions in heavy vehicles, the effect of an active system based on anti-roll bars in a bus structure under a lane change manoeuvre is carried out by means of a bus dynamic finite element model. Results show that the fuzzy logic controller implemented in the anti-roll bar system significantly reduces both the vertical displacements at the corners of the bus structure and the stress level.
Special Issue on Brake Noise, Vibration and Harshness - Editorial Forward
Authors: Abu Bakar Abd Rahim
Published: July 2014

This special issue brings the readers to one of the most active research topics on Vehicle NVH. This issue focuses on Brake Noise, Vibration and Harshness and specifically studies on the low frequency brake noise (judder) and high frequency brake noise (squeal). It consists of altogether seven (7) articles written by well-known experts from various international institutions. The aim is to update latest works on theoretical, numerical and experimental approaches in attempts to understand, to predict and to prevent brake NVH. All the articles have undergone rigorous peer-reviews and I personally believe every article is of high quality. I do not want to elaborate on each article here rather I would like the reader to find out by reading these articles. Finally, I would like to thank all contributing authors and referees for their invaluable contribution and support. Without them, this special issue will not be materialized.
Special Issue on Structural Impact and Crashworthiness: Part I - Preface
Authors: Hadavinia Homayoun , Elmarakbi Ahmed
Published: July 2014

The papers in this Special Issue are selected papers submitted to a call by International Journal of Vehicle Structures and Systems (IJVSS) on Structural Impact and Crashworthiness. The goal is to provide a broad, but by no means comprehensive cross-section of some of the current research in the field. Papers presented in this issue describe advances in research and application in the related area.