bluuebunny/crossref_metadata_2025 huggingface dataset:
How common is self‐incompatibility across species of the herkogamous genus Ariocarpus?
Authors: Martínez‐Peralta Concepción , Márquez‐Guzmán Judith , Mandujano María C.
Published: March 2014

• Premise of the study: Self‐incompatibility (SI), the most effective mechanism to prevent selfing, may limit the number of compatible mates in populations. The seven species of Ariocarpus are endangered and predominantly outcrossers but fruit set may reach 1–20% after selfing. We aimed to determine whether SI is the underlying mechanism influencing mating in Ariocarpus species.

• Methods: We characterized the presence/absence of SI using pollination treatments (self‐pollination, cross‐pollination, natural pollination) in one population per species. We assessed SI using epifluorescence and generalized linear models (GLMs) to compare the presence of pollen tubes in the stigma, stylar transmitting tissue, and ovary among self‐ and cross‐pollinated pistils 48 h after pollination. Following the same treatments, production of fruit set was noted and related to pollen tube growth.

• Key results: Pollen tubes were found more frequently in the ovaries of natural and cross‐pollinated flowers than in ovaries of self‐pollinated. Stylar rejection of self‐pollen indicated gametophytic SI, although pollen tubes reached the ovaries in six species (4–33% of pistils). Fruit set was lower after hand‐pollinations than expected from pollen tube observations.

• Conclusions: The low percentages of self‐compatibility in all species in pollen tube growth and pollination experiments indicated that no species had complete self‐sterility, suggesting the presence of partial SI. Reduced fruit set relative to pollen tube production could result from a threshold of insufficient pollination, early‐acting inbreeding depression, or resource limitation. The origin of partial SI in Ariocarpus could respond to pressures such as pollen limitation and population size.
Underlying Mechanisms of Tinnitus: Review and Clinical Implications
Authors: Henry James A. , Roberts Larry E. , Caspary Donald M. , Theodoroff Sarah M. , Salvi Richard J.
Published: March 2014

Background:The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science
findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus.Purpose:The goal of
this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus.Results:It is increasingly clear that tinnitus is a pathology involving neuroplastic changes
in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner
hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems.Conclusions:Patients often have expectations that
a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions.
Assessing Outcomes of Tinnitus Intervention
Authors: Newman Craig W. , Sandridge Sharon A. , Jacobson Gary P.
Published: March 2014

Background:It has been estimated that as many as 50 million Americans do experience or have experienced tinnitus. For approximately 12 million of these individuals, tinnitus makes it impossible for them to carry out normal everyday activities without limitation. These are the
patients that present to audiology clinics for assessment and management. The tinnitus evaluation includes the measurement of acoustical characteristics of tinnitus and the impact that this impairment has on health-related quality of life (HRQoL). Tinnitus is a disorder that often occurs as
a result of auditory system impairment. The impairment for some can impart an activity limitation and a participation restriction (i.e., tinnitus-related disability or handicap, respectively). The goal of tinnitus management is to reduce, or eliminate, activity limitations and participation
restrictions by reducing or eliminating a patient’s perception of tinnitus or their reaction to tinnitus. Implicit in this statement is the assumption that there exist standardized measures for quantifying the patient’s tinnitus perception and their reaction to it. If there existed
stable and responsive standardized tinnitus measures, then it would be possible to compare a patient’s tinnitus experience at different time points (e.g., before and after treatment) to assess, for example, treatment efficacy.Purpose:The purposes of the current review are to (1)
describe psychometric standards used to select outcome measurement tools; (2) discuss available measurement techniques and their application to tinnitus evaluation and treatment-related assessment within the domains established by the World Health Organization’s International Classification
of Functioning, Disability and Health; (3) list and briefly describe self-report tinnitus questionnaires; (4) describe how valuation of tinnitus treatment can be assessed using economic models of treatment effectiveness; and (5) provide future directions including the development of a tinnitus
outcomes test battery and treatment-related study designs.Research Design:Retrospective literature reviewConclusions:Although psychometrically robust measures of tinnitus HRQoL do exist, there is no unanimity in, for example, what tests should be included in the tinnitus assessment,
and how studies of HRQoL should be conducted. The current authors suggest that future studies employ more rigorous designs and contain (minimally) the following characteristics: (1) utilization of randomized control groups and blinding; (2) appropriate statistical testing including “dropouts”
that should be used in an “intention to treat” analysis rather than elimination from the final data set; (3) long-term follow-up assessment to evaluate responsiveness; (4) appropriate inclusion criteria to avoid “ceiling” and “floor” effects; and (5) suitable
sample sizes based on the application of power analyses.
L'enfance en danger : genèse et évolution d'une politique de protection
Authors: Becquemin Michèle , Chauvière Michel
Published: March 2014

Dans une société moderne, les enfants seraient à protéger contre les mauvaises conditions de vie qu’ils subissent, mais aussi, dans certains cas, contre eux-mêmes. Comment sont nées les politiques et les pratiques de protection ? Quelles variables expliquent leur évolution depuis deux siècles ? Comment, notamment, se combine la protection qui leur est due par les autorités publiques et la protection familiale ? Cette contribution examine les trois âges de la protection de l’enfance : quand l’enfant n’est qu’objet de droits, quand l’action publique tend à le reconnaître comme sujet de droit et sujet clinique, quand l’enfant redevient une figure incertaine.
La réforme de la protection de l'enfance : la loi du 5 mars 2007. Le malentendu ?
Authors: Créoff Michèle
Published: March 2014

La réforme du 5 mars 2007 relative à la protection de l’enfance repose sur un malentendu. Présentée comme organisant la prise en compte de l’intérêt de l’enfant et l’amélioration de la prise en charge de celui-ci, elle est surtout une loi organisant la déjudiciarisation de la protection de l’enfance à partir d’un présupposé idéologique : la primauté de la contractualisation administrative avec la famille. Présupposé dont l’efficacité en termes de respect de l’intérêt de l’enfant et d’efficacité de sa protection n’a jamais été vérifiée par aucune recherche d’envergure. Le malentendu s’observe dès la définition de la mission. La protection de l’enfance est un ensemble de dispositifs d’accompagnement et de prise en charge qui correspond non pas à de simples difficultés éventuelles que rencontrent les parents dans l’exercice de leur responsabilité, mais à des situations de mise en danger avérées de l’enfant. Ainsi l’organisation des prises en charge s’en trouve complexifiée.
Le rôle des services de protection maternelle et infantile dans la protection des enfants
Authors: Colombo Marie-Christine
Published: March 2014

Deux politiques publiques nationales en direction de l’enfance sont exercées par les conseils généraux : la politique publique de protection et de promotion de la santé de la famille et de l’enfant, à visée générale, et la politique de protection de l’enfance, ciblée sur le danger de maltraitance ou de carence de soins. Avec la loi réformant la protection de l’enfance de 2007, l’ambition de développer un axe « prévention » s’est traduite par l’élargissement d’une politique spécifique enserrant la prévention à visée générale dans une perspective ciblée. Cela a mis en difficulté les professionnels et les services de pmi et a fragilisé le lien de confiance qui fonde leur action en direction des familles. Il est crucial de réaffirmer la finalité propre de chacun des dispositifs, afin qu’ils puissent tenir leur place légitime, coopérer plus sereinement et mettre leurs différences au service des familles et des enfants.
Le jeu dans le soin pédiatrique
Authors: Quesney Alain
Published: March 2014

Si un pédiatre n’aime pas jouer, cela signifie qu’il n’est pas fait pour ce travail ! Comment se servir du jeu pour entrer en contact, examiner et observer en pédiatrie et en psychopathologie infantile ? Comment donner aux jeunes parents des conseils dans l’achat de jouets, ou mieux leur donner le goût de jouer avec leurs bambins et de leur lire des histoires ? Ce rôle est bien celui du pédiatre et ne constitue pas, dans cette société de l’écran, un combat d’arrière-garde.
Familles mixtes et usages des langues : une étude des politiques linguistiques familiales dans le contexte indien
Authors: Joshi Madhura
Published: March 2014

Dans cet article, nous observerons, à partir d’études de cas, comment les trajectoires de vie influencent la (non-) transmission des langues aux enfants au sein des familles mixtes en Inde. Après une brève présentation du “pluralisme organique” dans le contexte indien, les notions de “famille”, de “mariage”, de “politique linguistique familial” et de “langue maternelle” seront traitées, avant d’aborder les études de cas. Nous examinerons ensuite quelques exemples de mixité conjugale où les époux viennent de « communautés linguistiques » différentes, et où ils n’ont pas transmis toutes les langues de leur répertoire verbal. Ce faisant nous étudierons comment la migration, la socialisation, la réaction parentale au mariage, entre autres facteurs, déterminent les pratiques et les politiques linguistiques familiales, à partir des descriptions d’apprentissage et d’usages langagiers par les personnes interviewées sur le terrain.
La traduction au Nouveau-Brunswick : contacts des langues et complexités sociolinguistiques
Authors: Dubois Lise , LeBlanc Matthieu
Published: March 2014

Nous nous proposons, dans cet article, de poser un regard critique sur l’activité traductionnelle au Nouveau-Brunswick, province de l’est canadien caractérisée par son bilinguisme officiel (anglais-français). Nous adopterons une perspective sociolinguistique dans le but de faire ressortir le rôle multidimensionnel que jouent les langues dans une société caractérisée par le contact des langues, c’est-à-dire la cohabitation, sur un même territoire, d’une communauté majoritaire (anglophone) et d’une communauté minoritaire (francophone). Appréhendée comme pratique linguistique et pratique sociale, la traduction sera ainsi analysée dans une perspective critique. Nous tenterons, entre autres choses, de répondre aux questions suivantes : qui traduit quoi ? Pour qui ? Et pourquoi ? Et de quelle manière est-ce que cela nous renseigne sur la communauté minoritaire et sur les rapports de force qui existent entre les deux communautés ? Pour ce faire, nous nous appuierons sur des recherches ethnographiques menées dans des milieux de la traduction, à savoir l’administration provinciale et l’entreprise privée. Nous conclurons en faisant une incursion dans le monde de la traduction littéraire pour mettre en contraste les flux de traduction au Nouveau-Brunswick.
Le don fondateur du lien social, le cas de l'économie de marché
Authors: Lasida Elena
Published: March 2014

Le don et l’échange marchand sont généralement opposés. Pourtant, l’un et l’autre apparaissent comme fondateurs du lien social dans la mesure où l’on prend en compte la relation qu’ils créent au niveau interindividuel et collectif. Le don apparaît ainsi associé à une certaine forme de réciprocité et le marché à une certaine forme de gratuité.
Potential use of sewage sludge ash (SSA) as a cement replacement in precast concrete blocks
Authors: Pérez-Carrión M. , Baeza-Brotons F. , Payá J. , Saval J. M. , Zornoza E. , Borrachero M. V. , Garcés P.
Published: March 2014

The present study explored the technological feasibility of re-using sewage sludge ash (SSA) as a Portland cement replacement in commercially manufactured pre cast concrete blocks. The blocks analysed were made to the guidelines laid down in Spain’s National Plan for Waste Water Treatment Plant Sludge, 2001–2006, and European Union specifications (CE marking) for such products. Performance was compared in three families of blocks, with 0, 10 and 20% SSA. The findings proved that SSA is apt for pre cast concrete block manufacture and that, in addition to the economic and environmental benefits afforded, its use would improve certain of the properties of conventional block.
Impact du lectorat visé sur la grammaire
Authors: Pic Elsa , Furmaniak Grégory
Published: March 2014

Cet article présente une synthèse des principaux résultats d’un projet de recherche de deux ans consacré à la sensibilité de l’usage grammatical à la variable « public visé ». Après être revenus sur les objectifs et la méthodologie du projet, les auteurs montrent que l’utilisation des ressources grammaticales de la langue par les experts varie de façon significative, à la fois quantitativement et qualitativement, en fonction du public visé. Les résultats suggèrent toutefois que certains marqueurs ou catégories sont davantage sensibles à la discipline qu’au degré de spécialisation. L’article revient ensuite sur les hypothèses émises au cours du projet pour rendre compte des résultats observés. Il apparaît que le lien entre les traits [+ vulgarisé] et [+ subjectif] était trop simpliste pour pouvoir rendre compte de la complexité des phénomènes. Le passage par l’interface pragmatico-formelle que constituent les modes rhétoriques s’avère plus opératoire.
Langues de spécialité et savoir disciplinaire : contrainte institutionnelle ou outil pédagogique incitateur d’une interaction communicative ?
Authors: Isani Shaeda
Published: March 2014

Analyse de la position de l’enseignant et de l’apprenant des langues de spécialité par rapport à la détention du savoir disciplinaire relevant de la spécialisation de l’apprenant. Si en situation didactique, le savoir disciplinaire est détenu par l’enseignant, il se crée une situation de dissymétrie cumulée rédhibitoire de la communication en classe de langue. Ce même savoir détenu exclusivement par l’apprenant engendre une situation de dissymétrie équilibrée générative d’interaction communicative.
Le premier DEA de « Langue anglaise des spécialités scientifiques et techniques », contraintes et libertés
Authors: Mémet Monique
Published: March 2014

En 1991-92, une première promotion a participé au Diplôme d’Étude Approfondie (DEA) de « Langue anglaise des spécialités scientifiques et techniques » (Université Bordeaux 2). L’auteur a demandé à tous les participants de répondre à un questionnaire autour du thème des « Contraintes et des libertés », le thème du colloque du GERAS en 1993. Les réponses aux questions, qui portaient sur l’espace, le temps, les aspects financiers et psychologiques, ont été regroupées à l’aide d’un tableur. Les réponses sont présentées sous forme de graphiques et de tableaux ; elles sont brièvement commentées. Le questionnaire comportant des questions ouvertes, une analyse qualitative est proposée. L’objectif principal est de dresser un bilan de l’année d’étude vue par les utilisateurs.
The case study as a means of motivation in the acquisition of technical vocabulary
Authors: Thomas David
Published: March 2014

L’emploi de l’étude de cas dans l’acquisition du vocabulaire technique est une source de motivation pour l’apprenant. Les termes techniques, employés dans une situation fictive qui reflète le contexte réel, rendent la tâche de l’assimilation du vocabulaire plus facile que par la méthode traditionnelle qui consiste à apprendre des listes de mots. Des documents authentiques sur le sujet de base ajoutent du réalisme aux situations fictives et encouragent une présentation professionnelle de l’exposé qui en résulte. L’élaboration des études de cas par des enseignants d’anglais langue de spécialité est tout à fait à leur portée, et ils peuvent utiliser pleinement les talents des apprenants dans leur recherche de sujets et de scénarii appropriés.
Dessine-moi un mouton : contraintes descriptives et liberté rhétorique dans les publicités à caractère scientifique ou technique
Authors: Fries-Verdeil Marie-Hélène
Published: March 2014

La publicité à caractère scientifique ou technique cherche à vendre en informant et la description du produit (exposé des caractéristiques, démonstration visuelle) y est prépondérante. On serait tenté de définir ici un « degré zéro de la publicité », plus proche de la technicité d’un mode d’emploi que des subtilités d’une campagne d’affichage. Est-ce à dire pourtant que l’imaginaire n’y ait aucune place ? Non. Il faut certes informer pour vendre les produits techniques, mais cela ne suffit pas toujours à les démarquer de la concurrence. Pour passer de la promotion d’un objet à la création et à la libération du sens, synecdoques, métaphores et métonymies apparaissent comme des outils de choix.
À nouvelles technologies, nouvelle pédagogie
Authors: Trouillon Jean-Louis
Published: March 2014

Passé le premier émerveillement face aux capacités apparemment offertes par les outils technologiques, l’enseignant doit s’interroger sur leur emploi et leur valeur didactique. Deux exemples pris en langue de spécialité (anglais scientifique et anglais du tourisme) faisant appel à deux concepts (CD-ROM et téléphone) et à deux publics (formation initiale et continue) tenteront de montrer comment rechercher une adéquation entre les besoins, les moyens technologiques et l’approche pédagogique.
Thanatos et Eros
Authors: Kerestetzi Katerina
Published: March 2014

Les paleros, adeptes du culte initiatique afro-cubain du palo monte, sont réputés à Cuba pour l’efficacité de leur opérations magiques. On fait appel à leurs services pour lutter contre les aléas de l’existence, au premier rang desquels figurent les affaires de cœur : comment séduire un homme, comment préserver son épouse de l’adultère, comment empêcher une séparation ? Pour agir, les paleros mobilisent leurs nfumbis, les morts tout-puissants qu’ils ont domestiqués. Dans cet article qui s’intéresse aux effets de l’immixtion des morts dans les relations amoureuses, nous verrons que les choses sont très différentes selon que l’on se place du côté des usagers occasionnels du palo monte ou du côté des paleros. Si pour les premiers, les morts sont de simples outils impersonnels au service du bien-être amoureux, pour les seconds, ce sont des agents intentionnels avec lesquels il faut composer à chaque instant de sa vie sentimentale, pour le meilleur ou pour le pire…
Retoucher les morts
Authors: Delaplace Grégory
Published: March 2014

À la mort d’une personne, il est d’usage en Mongolie de confectionner un portrait funéraire à partir de sa photographie d’identité agrandie, colorisée et retouchée. Ce portrait est utilisé pendant les funérailles, puis installé à côté des images pieuses du foyer dans la maison qu’occupait le défunt jusqu’à sa mort. Ce portrait est censé constituer une sorte de double du mort, à travers lequel ce dernier pourra recevoir des offrandes de la part de ses proches parents pendant la période de deuil et après celle-ci. La valeur à la fois indicielle et iconique de la photographie – le fait qu’une photographie est une trace du sujet photographié, en même temps qu’elle lui ressemble – tend à lui voir conférer, en Mongolie comme ailleurs, le pouvoir magique d’atteindre une personne à distance, ou en son absence. En retouchant les portraits de parents défunts, toutefois, les Mongols semblent faire un pas de plus dans l’usage magique de la technique photographique : en altérant l’image, ils ne se contentent pas de fabriquer un support de relations avec leurs morts, ils se donnent les moyens de transformer ces derniers.
Croyance, incroyance et révisions
Authors: Le Meur-Weissman Nadine
Published: March 2014

Les mythes se rencontrent dans tous les genres littéraires en Grèce, chargés de fonctions religieuses, sociales, voire politiques. Pourtant, les expressions de scepticisme face à ces mythes sont relativement nombreuses, motivées par diverses raisons : piété en fonction d’un idéal moral ou religieux, vraisemblance, cohérence, but pédagogique et/ou politique… Mais la critique d’une version d’un mythe, voire d'un mythe, n'entraîne jamais la mise en doute de l’existence des dieux.
From Oblivion to Judgment
Authors: Shilo Amit
Published: March 2014

How does the afterlife affect ethical and political considerations in this life when a culture has no unified religious dogma? This article focuses on the afterlife as an uncertain “elsewhere” invoked to rethink political imperatives in specific Ancient Greek literary and philosophical texts. First, it uncovers the political implications of radically divergent notions of the afterlife in both Aeschylus’s Oresteia and Sophocles’s Antigone—from nothingness, to continuation in a society of souls below, to ethical judgment by a divinity—significant examples of which have been neglected. It then follows out the almost congruent diversity of afterlife notions in Plato’s Apology and Phaedo. By examining how Socrates uses “unbelief” (apistia, among other words) concerning the afterlife to interrogate ethics and politics, this article gives a fresh perspective on the structure of debate in the Phaedo. The very emphasis on “unbelief,” however, demonstrates that the dialogue itself may not present Socratic views as definitive.
Friendship, Closeness and Disclosure in Second Life
Authors: Heider Don , Massanari Adrienne L.
Published: March 2014

3-D virtual realms offer places for people to go interact, play games, and even do business. As these realms themselves become more sophisticated, the number of participants grows and the level and type of social interactions change. Meanwhile, scholars race to try to keep up. There is a growing, but still developing literature about interaction in virtual world. This paper explores communication and social intimacy in one such world, Second Life. In this paper, results of a four year ethnography in Second Life reveal findings that refute earlier research on computer-mediated communications, and support others while offering new findings to contribute to the growing body of knowledge.
Use of ICT in Education
Authors: Nair Geeta , Hindle Robert
Published: March 2014

The present research paper discusses the use of Information and Communication Technology (ICT) in education which is gaining currency in the new era of globalism as the telecom revolution has hastened the pace of globalization and vice-versa; along with the catalyst role ICT-enabled education plays in promoting inclusive growth and human development for all. These smart tools of the emerging smart economy would help to promote mass literacy and also narrow inter, as well as intra-generational gaps. Most importantly, it will provide ‘second opportunities’ to the generation that missed them in the first place, thus helping adult learners, particularly the employed and women; thus attempting to reduce gender inequities. The paper attempts to map the trajectory of ICT and its increased usage across the world in an era of globalism, spanning Asia with a focus on India. Technology helps update, modernize, and revolutionize knowledge, information teaching-learning processes et al that help to bridge the digital divide on multi levels-between the rich and poor nations, between the rich and poor classes within a nation, between the rural and urban areas, between the young and old population, between the first and second generation learners and teachers that have become the essence of the new knowledge economy comprising smart students, teachers, policy makers, and communities all woven together through the yarn of the world wide. Like any other innovation, this one too is a double-edged coin with its intrinsic advantages and disadvantages. It is for us to harness modern technologies and utilize the ICT revolution in education for modern global growth, interconnectedness, and inclusiveness that create ‘win-win’ situations for all stakeholders.
In Vivo Detection of Peripherin-Specific Autoreactive B Cells during Type 1 Diabetes Pathogenesis
Authors: Garabatos Nahir , Alvarez Raimon , Carrillo Jorge , Carrascal Jorge , Izquierdo Cristina , Chapman Harold D. , Presa Maximiliano , Mora Conchi , Serreze David V. , Verdaguer Joan , Stratmann Thomas
Published: March 2014

Autoreactive B cells are essential for the pathogenesis of type 1 diabetes. The genesis and dynamics of autoreactive B cells remain unknown. In this study, we analyzed the immune response in the NOD mouse model to the neuronal protein peripherin (PRPH), a target Ag of islet-infiltrating B cells. PRPH autoreactive B cells recognized a single linear epitope of this protein, in contrast to the multiple epitope recognition commonly observed during autoreactive B cell responses. Autoantibodies to this epitope were also detected in the disease-resistant NOR and C57BL/6 strains. To specifically detect the accumulation of these B cells, we developed a novel approach, octameric peptide display, to follow the dynamics and localization of anti-PRPH B cells during disease progression. Before extended insulitis was established, anti-PRPH B cells preferentially accumulated in the peritoneum. Anti-PRPH B cells were likewise detected in C57BL/6 mice, albeit at lower frequencies. As disease unfolded in NOD mice, anti-PRPH B cells invaded the islets and increased in number at the peritoneum of diabetic but not prediabetic mice. Isotype-switched B cells were only detected in the peritoneum. Anti-PRPH B cells represent a heterogeneous population composed of both B1 and B2 subsets. In the spleen, anti-PRPH B cell were predominantly in the follicular subset. Therefore, anti-PRPH B cells represent a heterogeneous population that is generated early in life but proliferates as diabetes is established. These findings on the temporal and spatial progression of autoreactive B cells should be relevant for our understanding of B cell function in diabetes pathogenesis.
Dissecting the Role of Retinoic Acid Receptor Isoforms in the CD8 Response to Infection
Authors: Guo Yanxia , Lee Yu-Chi , Brown Chrysothemis , Zhang Weijun , Usherwood Edward , Noelle Randolph J.
Published: March 2014

Vitamin A deficiency leads to increased susceptibility to a spectrum of infectious diseases. The studies presented dissect the intrinsic role of each of the retinoic acid receptor (RAR) isoforms in the clonal expansion, differentiation, and survival of pathogen-specific CD8 T cells in vivo. The data show that RARα is required for the expression of gut-homing receptors on CD8+ T cells and survival of CD8+ T cells in vitro. Furthermore, RARα is essential for survival of CD8+ T cells in vivo following Listeria monocytogenes infection. In contrast, RARβ deletion leads to modest deficiency in Ag-specific CD8+ T cell expansion during infection. The defective survival of RARα-deficient CD8+ T cells leads to a deficiency in control of L. monocytogenes expansion in the spleen. To our knowledge, these are the first comparative studies of the role of RAR isoforms in CD8+ T cell immunity.
Inflammasome-Dependent and -Independent IL-18 Production Mediates Immunity to the ISCOMATRIX Adjuvant
Authors: Wilson Nicholas S. , Duewell Peter , Yang Becky , Li Yun , Marsters Scot , Koernig Sandra , Latz Eicke , Maraskovsky Eugene , Morelli Adriana Baz , Schnurr Max , Ashkenazi Avi
Published: March 2014

Adjuvants are an essential component of modern vaccines and used for their ability to elicit immunity to coadministered Ags. Many adjuvants in clinical development are particulates, but how they drive innate and adaptive immune responses remains poorly understood. Studies have shown that a number of vaccine adjuvants activate inflammasome pathways in isolated APCs. However, the contribution of inflammasome activation to vaccine-mediated immunity in vivo remains controversial. In this study, we evaluated immune cell responses to the ISCOMATRIX adjuvant (IMX) in mice. Like other particulate vaccine adjuvants, IMX potently activated the NALP-3–ASC–Caspase-1 inflammasome in APCs, leading to IL-1β and IL-18 production. The IL-18R pathway, but not IL-1R, was required for early innate and subsequent cellular immune responses to a model IMX vaccine. APCs directly exposed to IMX underwent an endosome-mediated cell-death response, which we propose initiates inflammatory events locally at the injection site. Importantly, both inflammasome-related and -unrelated pathways contributed to IL-18 dependence in vivo following IMX administration. TNF-α provided a physiological priming signal for inflammasome-dependent IL-18 production by APCs, which correlated with reduced vaccine-mediated immune cell responses in TNF-α– or TNFR-deficient mice. Taken together, our findings highlight an important disconnect between the mechanisms of vaccine adjuvant action in vitro versus in vivo.
Epidermal Th22 and Tc17 Cells Form a Localized Disease Memory in Clinically Healed Psoriasis
Authors: Cheuk Stanley , Wikén Maria , Blomqvist Lennart , Nylén Susanne , Talme Toomas , Ståhle Mona , Eidsmo Liv
Published: March 2014

Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte–associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell–driven disease memory in psoriasis.
Enhanced Innate Antiviral Gene Expression, IFN-α, and Cytolytic Responses Are Predictive of Mucosal Immune Recovery during Simian Immunodeficiency Virus Infection
Authors: Verhoeven David , George Michael D. , Hu William , Dang Angeline T. , Smit-McBride Zeljka , Reay Elizabeth , Macal Monica , Fenton Anne , Sankaran-Walters Sumathi , Dandekar Satya
Published: March 2014

The mucosa that lines the respiratory and gastrointestinal (GI) tracts is an important portal of entry for pathogens and provides the first line of innate immune defense against infections. Although an abundance of memory CD4+ T cells at mucosal sites render them highly susceptible to HIV infection, the gut and not the lung experiences severe and sustained CD4+ T cell depletion and tissue disruption. We hypothesized that distinct immune responses in the lung and gut during the primary and chronic stages of viral infection contribute to these differences. Using the SIV model of AIDS, we performed a comparative analysis of the molecular and cellular characteristics of host responses in the gut and lung. Our findings showed that both mucosal compartments harbor similar percentages of memory CD4+ T cells and displayed comparable cytokine (IL-2, IFN-γ, and TNF-α) responses to mitogenic stimulations prior to infection. However, despite similar viral replication and CD4+ T cell depletion during primary SIV infection, CD4+ T cell restoration kinetics in the lung and gut diverged during acute viral infection. The CD4+ T cells rebounded or were preserved in the lung mucosa during chronic viral infection, which correlated with heightened induction of type I IFN signaling molecules and innate viral restriction factors. In contrast, the lack of CD4+ T cell restoration in the gut was associated with dampened immune responses and diminished expression of viral restriction factors. Thus, unique immune mechanisms contribute to the differential response and protection of pulmonary versus GI mucosa and can be leveraged to enhance mucosal recovery.
Urokinase Plasminogen Activator Is a Central Regulator of Macrophage Three-Dimensional Invasion, Matrix Degradation, and Adhesion
Authors: Fleetwood Andrew J. , Achuthan Adrian , Schultz Heidi , Nansen Anneline , Almholt Kasper , Usher Pernille , Hamilton John A.
Published: March 2014

Urokinase plasminogen activator (uPA) and its receptor (uPAR) coordinate a plasmin-mediated proteolytic cascade that has been implicated in cell adhesion, cell motility, and matrix breakdown, for example, during inflammation. As part of their function during inflammatory responses, macrophages move through tissues and encounter both two-dimensional (2D) surfaces and more complex three-dimensional (3D) interstitial matrices. Based on approaches employing uPA gene–deficient macrophages, plasminogen supplementation, and neutralization with specific protease inhibitors, it is reported in this study that uPA activity is a central component of the invasion of macrophages through a 3D Matrigel barrier; it also has a nonredundant role in macrophage-mediated matrix degradation. For murine macrophages, matrix metalloproteinase-9 activity was found to be required for these uPA-mediated effects. Evidence for a unique role for uPA in the inverse relationship between macrophage adhesion and 2D migration was also noted: macrophage adhesion to vitronectin was enhanced by uPA and blocked by plasminogen activator inhibitor-1, the latter approach also able to enhance in turn the 2D migration on this matrix protein. It is therefore proposed that uPA can have a key role in the inflammatory response at several levels as a central regulator of macrophage 3D invasion, matrix remodeling, and adhesion.
Profiling of Human Acquired Immunity Against the Salivary Proteins of Phlebotomus papatasi Reveals Clusters of Differential Immunoreactivity
Authors: Geraci Nicholas S. , Mukbel Rami M. , Kemp Michael T. , Wadsworth Mariha N. , Lesho Emil , Stayback Gwen M. , Champion Matthew M. , Bernard Megan A. , Abo-Shehada Mahmoud , Coutinho-Abreu Iliano V. , Ramalho-Ortigão Marcelo , Hanafi Hanafi A. , Fawaz Emadeldin Y. , El-Hossary Shabaan S. , Wortmann Glenn , Hoel David F. , McDowell Mary Ann
Published: March 2014

Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents.
Cost-Effectiveness of a Tuberculosis Active Case Finding Program Targeting Household and Neighborhood Contacts in Cambodia
Authors: Yadav Rajendra P. , Nishikiori Nobuyuki , Satha Peou , Eang Mao T. , Lubell Yoel
Published: March 2014

In many high-risk populations, access to tuberculosis (TB) diagnosis and treatment is limited and pockets of high prevalence persist. We estimated the cost-effectiveness of an extensive active case finding program in areas of Cambodia where TB notifications and household poverty rates are highest and access to care is restricted. Thirty operational health districts with high TB incidence and household poverty were randomized into intervention and control groups. In intervention operational health districts, all household and symptomatic neighborhood contacts of registered TB patients of the past two years were encouraged to attend screening at mobile centers. In control districts, routine passive case finding activities continued. The program screened more than 35,000 household and neighborhood contacts and identified 810 bacteriologically confirmed cases. The cost-effectiveness analysis estimated that in these cases the reduction in mortality from 14% to 2% would result in a cost per daily adjusted life year averted of $330, suggesting that active case finding was highly cost-effective.
Post-Travel Screening of Asymptomatic Long-Term Travelers to the Tropics for Intestinal Parasites Using Molecular Diagnostics
Authors: Soonawala Darius , van Lieshout Lisette , den Boer Marion A. M. , Claas Eric C. J. , Verweij Jaco J. , Godkewitsch André , Ratering Marchel , Visser Leo G.
Published: March 2014

The incidence of asymptomatic travel-related parasitic infection is uncertain. Previous studies did not distinguish new incident infections, from past infections. Regardless of symptoms, we performed multiplex real-time polymerase chain reaction on pre- and post-travel stool samples of Dutch long-term travelers to the (sub)tropics. Serological screening for Schistosoma spp. was only performed in travelers to sub-Saharan Africa. In total, 679 travelers were included in the study. The follow-up rate was 82% (556 of 679). Participants' median travel duration was 12 weeks. There was one incident infection with Strongyloides stercoralis; there were none with Entamoeba histolytica, 4 with Cryptosporidium spp. (1%), and 22 with Giardia lamblia (4%). Nine of 146 travelers (6%) seroconverted for Schistosoma spp. Routine screening of stool samples for parasitic infection is not indicated for asymptomatic people, who travel to the (sub)tropics for up to 3 months. Screening for Schistosoma spp. should be offered to travelers with fresh-water contact in endemic regions.
What Role Can Financial Policies Play in Revitalizing SMEs in Japan?
Authors: Lam Waikei , Shin Jongsoon
Published: March 2014

The paper discusses the role the financial sector can play in supporting growth in Japan. While overall credit conditions have been accommodative, credit growth has remained weak, especially for small and medium-sized enterprises (SMEs). Firm-level SME data and sectoral corporate balance sheets show that many SMEs have faced structural challenges of high leverage and low profitability. Moreover, the global financial crisis has weakened the financial position across SMEs, particularly for those with low credit worthiness. These challenges are closely related to low availability of riskcapital and the pervasiveness of credit support measures. This paper argues that to encourage the supply of risk-based capital, costly government support measures should be phased out and SME restructuring be accelerated. Efforts are also needed to deepen capital markets to enhance risk capital availability and address regulatory barriers to starting businesses. In that regard, addressing SMEweaknesses would improve private investment, enhance firm productivity, and lift growth.
Fast photolysis of carbonyl nitrates from isoprene
Authors: Müller J.-F. , Peeters J. , Stavrakou T.
Published: March 2014

Abstract. Photolysis is shown to be a major sink for isoprene-derived carbonyl nitrates, which constitute an important component of the total organic nitrate pool over vegetated areas. Empirical evidence from published laboratory studies on the absorption cross sections and photolysis rates of α-nitrooxy ketones suggests that the presence of the nitrate group (i) greatly enhances the absorption cross sections and (ii) facilitates dissociation to a point that the photolysis quantum yield is close to unity, with O–NO2 dissociation as a likely major channel. On this basis, we provide new recommendations for estimating the cross sections and photolysis rates of carbonyl nitrates. The newly estimated photo rates are validated using a chemical box model against measured temporal profiles of carbonyl nitrates in an isoprene oxidation experiment by Paulot et al. (2009). The comparisons for ethanal nitrate and for the sum of methacrolein- and methyl vinyl ketone nitrates strongly supports our assumptions of large cross-section enhancements and a near-unit quantum yield for these compounds. These findings have significant atmospheric implications: the photorates of key carbonyl nitrates from isoprene are estimated to be typically between ~ 3 and 20 times higher than their sink due to reaction with OH in relevant atmospheric conditions. Moreover, since the reaction is expected to release NO2, photolysis is especially effective in depleting the total organic nitrate pool.
On sampling uncertainty of satellite ozone profile measurements
Authors: Sofieva V. F. , Kalakoski N. , Päivärinta S.-M. , Tamminen J. , Kyrölä E. , Laine M. , Froidevaux L.
Published: March 2014

Abstract. Satellite measurements sample continuous fields of atmospheric constituents at discrete locations and times. However, insufficient or inhomogeneous sampling, if not taken into account, can result in inaccurate average estimates and even induce spurious features. We propose to characterize the spatio-temporal inhomogeneity of atmospheric measurements by a measure, which is a linear combination of the asymmetry and entropy of a sampling distribution. It is shown that this measure is related to the so-called sampling uncertainty, which occurs due to non-uniform sampling patterns. We have estimated the sampling uncertainty of zonal mean ozone profiles for six limb-viewing satellite instruments participating in the European Space Agency Ozone Climate Change Initiative project using the high-resolution ozone field simulated with the FinROSE chemistry-transport model. It is shown that the sampling uncertainty for the instruments with coarse sampling is not negligible and can be as large as a few percent. It is found that the standard deviation of the sampling uncertainty in the monthly zonal mean data allows for a simple parameterization in terms of the product of the standard deviation of natural variations and the proposed inhomogeneity measure. The focus of this work is the vertical ozone distributions measured by limb-viewing satellite instruments, but the developed methods can also be applied to different satellite, ground-based and in-situ measurements.
Free Ocean CO2 Enrichment (FOCE) systems: present status and future developments
Authors: Gattuso J.-P. , Kirkwood W. , Barry J.P. , Cox E. , Gazeau F. , Hansson L. , Hendriks I. , Kline D. I. , Mahacek P. , Martin S. , McElhany P. , Peltzer E. T. , Reeve J. , Roberts D. , Saderne V. , Tait K. , Widdicombe S. , Brewer P. G.
Published: March 2014

Abstract. Free Ocean CO2 Enrichment (FOCE) systems are designed to assess the impact of ocean acidification on biological communities in situ for extended periods of time (weeks to months). They overcome some of the drawbacks of laboratory experiments and of field observations by enabling (1) precise control of CO2 enrichment by monitoring pH as an offset of ambient pH, (2) consideration of indirect effects such as those mediated through inter-specific relationships and food-webs, and (3) relatively long experiments with intact communities. Bringing perturbation experiments from the laboratory to the field is however extremely challenging. The goal of this paper is to provide guidelines on the general design, engineering, and sensors required to conduct FOCE experiments. Present and existing FOCE systems are briefly described and examples of data collected presented. Future developments are also addressed as it is anticipated that the next generation of FOCE systems will include, in addition to pH, options for oxygen and/or temperature control. FOCE systems should become an important experimental approach for projecting the future response of marine ecosystems to environmental change.
Geostrophic currents and kinetic energies in the Black Sea estimated from merged drifter and satellite altimetry data
Authors: Menna M. , Poulain P.-M.
Published: March 2014

Abstract. Drifter measurements and satellite altimetry data are merged to reconstruct the surface geostrophic circulation of the Black Sea in the period 1999–2009. This combined data set is used to estimate pseudo-Eulerian velocity statistics for different time periods. Seasonal and interannual variability of currents and kinetic energy fields are described with particular attention to the mesoscale and sub-basin coastal eddies. The mean currents are generally stronger in winter and enhanced speeds are observed in the period 2002–2006. The most intense activity of sub-basin Batumi Eddy occurs in summer with greater speeds and dimensions in 2006 and 2008. The sub-basin Sevastopol Eddy is generated in spring from a meander of the Rim Current. Mesoscale eddies located along the Anatolia, Caucasus and Crimea coasts are permanent, quasi-permanent or intermittent features and can interact and merge with each other, showing high values of kinetic energy.