bluuebunny/crossref_metadata_2025 huggingface dataset:
The utility of auxiliary data in statistical population reconstruction
Authors: Clawson Michael V. , Skalski John R. , Millspaugh Joshua J.
Published: July 2013

Although statistical population reconstruction (SPR) provides a flexible framework for estimating demographics of harvested populations using age‐at‐harvest data, that information alone is insufficient. Auxiliary data are needed to ensure all model parameters are estimable and to improve the precision and accuracy of the estimates. We examined the influence of two types of auxiliary information, independent estimates of annual abundance and annual harvest mortality from radio‐telemetry studies, on the stability and precision of abundance estimates from SPR. Further, we evaluated whether the timing of auxiliary studies in the reconstruction affected the precision of abundance estimates. Monte Carlo studies simulated auxiliary data with precision levels defined by the coefficients of variation (CV) of 0.05, 0.125, 0.25 and 0.50 corresponding to the three levels of precision suggested by Robson & Regier (1964) for accurate research, accurate management and rough management and a minimal information scenario. For comparable levels of precision, radio‐telemetry studies used to estimate harvest mortality stabilized the reconstructed population trends better than independent abundance surveys. However, independent abundance surveys were superior at improving the precision of reconstructed abundance estimates. We found that the timing of auxiliary studies did not influence the stability of SPR estimates, which has important implications for managers designing studies to collect auxiliary data. Our research highlights that different types and quality of auxiliary studies affects the precision and stability of SPR models differently.
Peer-Assisted Communication Training: Veterinary Students as Simulated Clients and Communication Skills Trainers
Authors: Strand Elizabeth B. , Johnson Beth , Thompson James
Published: July 2013

Mounting research supports the use of peer-assisted learning (PAL) as a teaching method in human and veterinary medicine. PAL can be a cost-efficient educational tool, saving both financial resources and faculty time. This article reviews a PAL model for teaching communication skills to veterinary medical students. In this model, junior veterinary students served as simulated clients for sophomore veterinary students. Details regarding methods of program delivery as well as evaluation data are presented. Differences between two student cohorts who participated in the PAL educational model and their subsequent evaluation results are discussed. Overall, veterinary medical students reported that this approach was beneficial and that the topic was critical to their success as veterinarians. Students also showed improvement in communication knowledge and reported that peer feedback was a strength of the program. Finally, future directions to assess and strengthen the use of PAL for communication training in veterinary medical education are proposed.
Science, Religion, and Rationality: A Neo-Hegelian Approach
Authors: Fisch Menachem
Published: July 2013

Abstract:

The paper argues that identifying rational action with action undertaken for a reason yields Popper's well-known identification of rationality with criticism. However, it is also shown, pace Popper, to yield a strong form of normative framework dependency of the kind critical rationalists notoriously reject. But deeming rationality to be framework dependent, it argues further, raises the particularly exasperating problem of the very possibility of rational framework replacement. If the normative framework to which one is committed is presupposed in critical reasoning, how can one ever have normative reason to replace it? The first part of the paper briefly discusses the problem and some of the attempts to solve it, while arguing for an alternative approach. The second part, explores some of the consequences of adopting such an approach first for the historiography of scientific framework transitions, and finally for the theology of inter and intra-religious dialogue, with special reference to what might be termed the confrontational theology of the rabbinic literature of late antiquity.
Christian Rationality: Embracing the Divine Mystery
Authors: Fortin Jean-Pierre
Published: July 2013

Abstract:

The postmodern criticism and overcoming of the modern canons and concepts of rationality and science have paved the way to a systematic reconsideration of the nature and status of faith and religion in relation to human reason. The present article proposes to reassess the relationship tying Christianity to rationality through the study of the Christian notion of mystery, which, being fundamental to both Christian faith and theology, undergirds the definition and practice of Christian theology, faith, and love. The Christian God's self-revelation to human beings in history is shown to fully preserve the divine holiness and transcendence: God is incommensurable to creaturely reason out of an excess, infinitude of intelligibility. Called by God to enter in an immediate and intimate relationship with their Creator and Redeemer, Christian believers undertake, following Jesus Christ as a guide and model, a spiritual journey that leads them to transcend human language and concepts. Progressively opening themselves to an absolutely transcendent form of rationality identifying with the divine, Christians are by God interiorly transformed and enabled to directly experience him in and through love. The Christian notion of mystery characterizes human reason's fundamental rootedness in, orientation to, and insertion within supernatural, divine intelligibility and freedom. The latter, despite always being historically active and manifest, can never be fully fathomed and embraced by human cognition.
“We shall look into it tomorrow”: Kierkegaard and the Art of Procrastination
Authors: Kingwell Mark
Published: July 2013

Abstract:

In this paper, I argue that procrastination must be construed as a kind of psychic conflict, specifically a conflict between first-order and second-order desires familiar from Plato's moral psychology as well as more recent philosophy of action, such as Harry Frankfurt's account of freedom of the will. On this view of procrastination, we can compare it to other kinds of first- and second-order conflict such as akrasia (weakness of the will), addiction, and boredom. Kierkegaard's thought offers a particularly urgent and ethically freighted analysis of the apparently banal experience of putting things off. The paper concludes with a suggestion of how these everyday instances of psychic conflict can lead us to philosophy—albeit philosophy considered as a particular kind of self-understanding.
The Longue Durée of Empire
Authors: Leonhard Jörn
Published: July 2013

Against the background of a new interest in empires past and present and an inflation of the concept in modern political language and beyond, the article first looks at the use of the concept as an analytical marker in historical and current interpretations of empires. With a focus on Western European cases, the concrete semantics of empire as a key concept in modern European history is analyzed, combining a reconstruction of some diachronic trends with synchronic differentiations.
Radical Conservatism and Danish Imperialism
Authors: Skov Christian Egander
Published: July 2013

The article explores the concept of empire, or rige, in the context of a small nation-state with no immediate claim to imperial greatness and with a rooted self-understanding as anything but an empire. It does this by exploring the concept of empire in the far right movement Young Denmark on the basis of a close reading of their imperialist program in the pamphlet Danmark udslettes! from 1918. Rige had been a vague term for the larger Danish polity that originated in a pre-national conceptualization of the polity as a realm. The article suggests that rige-as-realm was translated by the radical right into a concept of empire. In the process it dramatically changed its emphasis, reorienting itself toward a "horizon of expectation". It became a politically loaded battle concept that then entailed a critique against the dominant liberal conceptualization of the polity and nation. Rige came to signify the ambition of being a great power, the spiritual elevation of the nation through the transcendence of the decaying liberal modernity. The program addressed the tension between a conservative political attitude and modernity and thus signified a kind of reactionary modernism that rejected liberal values while at the same time celebrating technology, industrialization, and the process of modernization.
3-MA Inhibits Autophagy and Favors Long-Term Integration of Grafted Gad67–GFP GABAergic Precursors in the Developing Neocortex by Preventing Apoptosis
Authors: Roux Christian , Lesueur Céline , Aligny Caroline , Brasse-Lagnel Carole , Genty Damien , Marret Stéphane , Laquerrière Annie , Bekri Soumeya , Gonzalez Bruno J.
Published: July 2013

In human neonates, immature GABAergic interneurons are markedly affected by an excitotoxic insult. While in adults the interest of cell transplantation has been demonstrated in several neurological disorders, few data are available regarding the immature brain. The low survival rate constitutes a strong limitation in the capacity of transplanted neurons to integrate the host tissue. Because i) autophagy is an adaptive process to energetic/nutrient deprivation essential for cell survival and ii) literature describes cross-talks between autophagy and apoptosis, we hypothesized that regulation of autophagy would represent an original strategy to favor long-term survival of GABAergic precursors grafted in the immature neocortex. Morphological, neurochemical, and functional data showed that in control conditions, few grafted Gad67-GFP precursors survived. The first hours following transplantation were a critical period with intense apoptosis. Experiments performed on E15.5 ganglionic eminences revealed that Gad67-GFP precursors were highly sensitive to autophagy. Rapamycin and 3-MA impacted on LC3 cleavage, LC3II translocation, and autophagosome formation. Quantification of Bax, mitochondrial integrity, caspase-3 cleavage, and caspase-3 immunolocalization and activity showed that 3-MA induced a significant decrease of Gad67-GFP precursor apoptosis. In vivo, 3-MA induced, within the first 24 h, a diffuse LC3 pattern of grafted Gad67-GFP precursors, an increase of precursors with neurites, a reduction of the density of caspase-3 immunoreactive cells. A twofold increase in the survival rate occurred 15 days after the graft. Surviving neurons were localized in the cortical layers II–IV, which were still immature when the transplantation was done. Altogether, these data indicate that inhibition of autophagy represents an original strategy to allow GABAergic interneurons to overpass the first critical hours following transplantation and to increase their long-term survival in mice neonates.
Ecological factors influencing growth of the endangered Hawaiian fern Marsilea villosa (Marsileaceae) and implications for conservation management
Authors: Chau Marian M. , Reyes Whitney R. , Ranker Tom A.
Published: July 2013

• Premise of the Study: Conserving endangered plants is a complex task, and practitioners must often use a “triage” approach, addressing only immediate needs. Ecologists can improve this process by conducting sound science upon which to base management. Marsilea villosa is an endangered, endemic Hawaiian fern with seven remaining populations in ephemerally flooding drylands. Among its uncommon traits are long‐lived sporocarps, requiring flood and drought to complete its sexual life cycle, and extensive vegetative growth.

• Methods: We conducted a 3‐yr ecological field study, measuring percent cover of M. villosa and associated species, flooding depth, and canopy cover, to identify ecological factors with the greatest impact on M. villosa growth.

• Key Results: Maximum flooding depth and canopy cover had strong positive relationships with M. villosa growth, and all plots with >50% threshold of either variable reached 100% cover of M. villosa by the end of the study. Interaction effects explained nuances of these relationships, including synergy between the two variables. Percent cover of nonnative functional groups (graminoids and nongraminoids) each had negative relationships with M. villosa growth, but interactions showed that nongraminoid cover was driven by particular species, and that time since flooding had greater influence on M. villosa growth than graminoid cover.

• Conclusions: We recommend planting reintroduced populations in flood‐prone areas with moderate shade, experimental outplanting of native plants with M. villosa, and management of graminoids as a functional group, while nongraminoid management should be species‐specific. These practices will promote self‐sustaining populations and reduce the need for labor‐intensive management.
Genetic patterns of habitat fragmentation and past climate‐change effects in the Mediterranean high‐mountain plant Armeria caespitosa (Plumbaginaceae)
Authors: García‐Fernández Alfredo , Iriondo Jose M. , Escudero Adrián , Aguilar Javier Fuertes , Feliner Gonzalo Nieto
Published: July 2013

• Premise of the Study: Mountain plants are among the species most vulnerable to global warming, because of their isolation, narrow geographic distribution, and limited geographic range shifts. Stochastic and selective processes can act on the genome, modulating genetic structure and diversity. Fragmentation and historical processes also have a great influence on current genetic patterns, but the spatial and temporal contexts of these processes are poorly known. We aimed to evaluate the microevolutionary processes that may have taken place in Mediterranean high‐mountain plants in response to changing historical environmental conditions.

• Methods: Genetic structure, diversity, and loci under selection were analyzed using AFLP markers in 17 populations distributed over the whole geographic range of Armeria caespitosa, an endemic plant that inhabits isolated mountains (Sierra de Guadarrama, Spain). Differences in altitude, geographic location, and climate conditions were considered in the analyses, because they may play an important role in selective and stochastic processes.

• Key Results: Bayesian clustering approaches identified nine genetic groups, although some discrepancies in assignment were found between alternative analyses. Spatially explicit analyses showed a weak relationship between genetic parameters and spatial or environmental distances. However, a large proportion of outlier loci were detected, and some outliers were related to environmental variables.

• Conclusions: A. caespitosa populations exhibit spatial patterns of genetic structure that cannot be explained by the isolation‐by‐distance model. Shifts along the altitude gradient in response to Pleistocene climatic oscillations and environmentally mediated selective forces might explain the resulting structure and genetic diversity values found.
Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst
Authors: Rossy Cybille , Fouquet Eric , Felpin François-Xavier
Published: July 2013

This paper describes the preparation of indoles, azaindoles and benzofurans in pure water by using a new heterogeneous Pd–Cu/C catalyst through a cascade Sonogashira alkynylation–cyclization sequence. Details of the optimization studies and the substrate scope are discussed. This procedure allows the preparation of heterocycles with good yields and is tolerant to a wide variety of functional groups.
HMGB1 Levels Are Increased in Patients with Juvenile Idiopathic Arthritis, Correlate with Early Onset of Disease, and Are Independent of Disease Duration
Authors: Schierbeck Hanna , Pullerits Rille , Pruunsild Chris , Fischer Marie , Holzinger Dirk , Laestadius Åsa , Sundberg Erik , Harris Helena Erlandsson
Published: July 2013

Objective.

High mobility group box chromosomal protein 1 (HMGB1) has been implicated as a mediator of inflammation in rheumatoid arthritis (RA), while its role in juvenile idiopathic arthritis (JIA) has not been described. To evaluate the role of HMGB1 in the inflammatory process in JIA and its potential as a therapeutic target, we investigated whether extracellular HMGB1 is detectable in JIA and if so, to correlate the levels with established inflammatory markers and clinical measures.

Methods.

Matching samples of blood and synovial fluid (SF) were collected from 23 patients with JIA. Levels of HMGB1, soluble receptor for advanced glycation endproducts, S100A12, myeloid-related protein 8/14, and other inflammatory mediators were analyzed.

Results.

Significantly increased HMGB1 levels were recorded in SF compared to blood samples from patients with JIA. The amount of HMGB1 was highest in patients with early disease onset irrespective of disease duration. In contrast, the proinflammatory S100 protein and interleukin 8 were highest in patients in early phases of disease. Matrix metalloproteinase-3, a marker of cartilage destruction, was higher in patients with late disease onset, indicating similarities with RA in that patient subgroup.

Conclusion.

Levels of extracellular HMGB1 are increased in the inflamed joints of patients with JIA. This warrants further studies of HMGB1 as a mediator of JIA pathogenesis as well as a biomarker for inflammatory activity and as a target for therapy. The variation in levels of HMGB1 and S100 proteins in relation to disease onset indicates a difference in inflammatory phenotype during disease progression.
Cinq sages et un ministre...Généalogie de la loi Evin
Authors: Berlivet Luc
Published: July 2013

Dans un domaine faiblement approprié, notamment du fait de la faiblesse politique du groupe professionnel des médecins de santé publique, un groupe va parvenir à incarner, au tournant des années 1980-1990, la défense de « l’intérêt général » contre les « intérêts privés » et autres « lobbies ». Leur mobilisation aboutira à l’adoption d’une loi symbolique articulant, pour la première fois, les deux principaux « risques de santé » : le tabagisme, objet de la loi Veil, et l’alcoolisme, thème jugé bien plus périlleux encore (et ce avant même les démêlés de Mendès-France avec les « bouilleurs de cru »). « Groupe des sages » pour certains, « ayatollahs de l’hygiénisme » aux yeux d’autres, ce collectif né dans et pour l’action collective ne parviendra toutefois pas à s’instituer durablement.
Au Mexique, la mort suinte dans l’art. Teresa Margolles : quand l’œuvre saigne
Authors: Perrée Caroline
Published: July 2013

En ce début de XXIe siècle, le Mexique est le théâtre d’une violence frénétique, sans borne et barbare. Guerre entre cartels de drogue et gouvernement, règlements de compte entre cartels, féminicide de Ciudad Juárez, la violence se décline sous toutes ses coutures et s’étend du Nord à l’ensemble du pays. La scène artistique contemporaine mexicaine se fait le reflet de cette violence tous azimuts et les arts plastiques s’interrogent sur la manière dont il faut la représenter pour la dénoncer. Teresa Margolles est l’une des artistes emblématiques de cette dénonciation parce qu’elle emprunte son vocabulaire plastique aux conséquences de cette violence : le corps assassiné. Son œuvre ne fait pas la part belle à une représentation visuelle de la violence, comme le fait la presse à sensation par une saturation d’images violentes. L’artiste crée chez son spectateur un malaise, qui frôle le dégoût, en utilisant le sang et la graisse humaine du corps mort, les draps et l’eau qui ont servi à le recouvrir et à le nettoyer. Matériaux bruts et matières premières de son travail, elle tisse par leur intermédiaire une esthétique de l’homicide qu’elle met en contact avec son public, afin de le toucher au sens propre comme au sens figuré.
Homo argentinus, homosexual, homo bellicum
Authors: Estrade Christian
Published: July 2013

Desplazada por géneros más certeros, la non-fiction y el diario, la novela bélica parece perder calado en la ficción argentina. Sin embargo durante la guerra sucia, en tiempos de terrorismo de Estado y su postrimero e infame estertor, la guerra de Malvinas, se gestaron tres novelas de corte eminentemente bélico y de curiosa composición. Los Sorias de Alberto Laiseca, La guerre des pédés de Copi y Tadeys de Osvaldo Lamborghini se inscriben en estéticas disímiles aunque proponen relatos bélicos que dan de manera radical la espalda al referente histórico. Las tres obras de ficción ofrecen algo más que una lectura sesgada de la guerra, son parodias que llevan el lenguaje al límite, la razón a su expresión más absurda ; donde el horror se asemeja a lo grotesco y la tortura raya con lo cómico. Pero estas ficciones señalan, sobre todo, que ahí donde la razón produce monstruos la Literatura muestra que la única vía de liberación es la sexualidad.
Bernardo Monteagudo y la « América, que por desgracia se llamó antes española »
Authors: Jarak Diego A.
Published: July 2013

En este articulo se busca reconstruir, a través de la lectura del Diálogo entre Atahualpa y Fernando VII en los Campos Elíseos de 1809, y del problema onomástico que allí se delinea respecto del término « América », el ambiente intelectual y social de la América Latina pre independentista tal y como este pudo ser percibido por una de sus voces mas significativas y por tanto, sino desconocidas, al menos poco estudiadas, como lo es la figura del argentino Bernardo Monteagudo.
The Sitio de Memoria museum
Authors: de Aguiar Araújo Angela , Leão Brasil Luciana
Published: July 2013

For this article, it is detached the Sitio de Memoria museum, in Córdoba, Argentina, to analyze its artistic interventions in the urban narrative. The place recollects the dead and missing people during the military governments, in the twentieth century. By showing for the pedestrians facts of the political history of the town, these interventions have effects on the urban narrative outbreaking the “significant body” of the “city in movement” in its relation with the processes of urban subject identification.
Le scénario comme outil pédagogique
Authors: Isani Shaeda
Published: July 2013

Une des options fortes du Diplôme de compétence en langue (DCL) fut de relever le défi d’évaluer la compétence en langue par le biais du scénario, un outil d’évaluation relativement innovant. Nous examinons ici le potentiel que peut offrir l’exploitation du scénario dans le contexte pédagogique de l’enseignement-apprentissage des langues étrangères, notamment dans les domaines des langues rares, les langues de spécialité et la formation en autonomie guidée.
Distributed Agency
Authors: Suarez Eugenio Dante , Castañón-Puga Manuel
Published: July 2013

Distributed Agency is the name of a conceptual framework for describing complex adaptive systems that this paper develops. To understand the complexity of the world in a holistic fashion, the field of Modeling and Simulation is currently lacking a common terminology in which different bodies of knowledge can communicate with each other in a general language. In this work, agency is proposed as the common link between the different dimensions of reality, expressing the influence of one dimension on another. This conceptualization is based on a process of backwards induction where nested actors such as an evolved organism or a human choice can be represented as the resulting force of intertwined aims and constraints. The theoretical framework can serve as a point of reference for the social and computational researcher by communicating structural and emergent properties that are essential for the understanding of social and evolutionary phenomena such as companies, economies, governments, and ecosystems.
Design and Evaluation of a Cross-Layer Framework for Improving 802.11 Networks
Authors: Sarkar Nurul I.
Published: July 2013

This paper reports on the design and evaluation of a class of cross-layer design (CLD) framework for improving the performance of 802.11-based wireless local area networks (WLANs). While various CLD approaches have been proposed for improving the performance of WLANs in recent years, the problem of efficient channel utilization, higher throughput, lower packet delay, and fairness has not been fully solved yet. To overcome the performance problems of 802.11, we propose a CLD framework which is based on a cross-layer medium access control (MAC) protocol called the channel-aware buffer unit multiple access (C-BUMA). In the framework, the radio propagation (i.e. physical layer) is combined with the MAC sub-layer to develop a robust cross-layer communication. By sharing channel information with the MAC protocol, the approach reduced unnecessary packet transmissions, and hence reduced bandwidth wastage and significantly improved the system performance. The proposed CLD method is evaluated by extensive simulation experiments. A comparison with 802.11 standards is provided. Results obtained show that the network achieves up to 13.5% higher throughput, 56% lower packet delay, 40% better fairness, and 38% lower packet dropping with the proposed CLD. We also found that the proposed CLD outperforms Pham’s CLD with respect to network throughput and packet dropping. The analysis and empirical results reported in this paper provide some insights into the design and evaluation of a CLD framework for improving data rate of 802.11 networks which may help researchers in this field to overcome the remaining design issues and challenges.
Analyzing Buffer Requirement for Wireless Enhancement of TCP in Network Mobility
Authors: Sardar Bhaskar
Published: July 2013

On-board TCP (obTCP) has been shown to address the dual wireless link related issues in network mobility (NEMO) effectively. obTCP uses agents at both base station (BS) and mobile router (MR). The agents store incoming TCP packet in a buffer for future possible retransmissions over the wireless links. Since the number of TCP connections passing through the MR could be very large, the amount of memory space required for the buffers may become very high. This may put the deployment of obTCP in question. So, in this paper, the authors investigate the buffer requirement problem of obTCP at MR for each TCP connection. For this purpose, they describe a Markov model to keep track of the packet transmission process of MR. The buffer size for each TCP connection is represented as a function of loss probability of the wireless links. Interestingly, from the numerical results, the authors find that the buffer size requirement at MR is significantly low for each TCP connections. This observation claims possible implementation of obTCP in NEMO.
Abstract Expressions of Affect
Authors: de Rooij Alwin , Broekens Joost , Lamers Maarten H.
Published: July 2013

What form should happiness take? And how is disgust shaped? This research investigates how synthetic affective expressions can be designed with minimal reference to the human body. The authors propose that the recognition and attribution of affect expression can be triggered by appropriately presenting the bare essentials used in the mental processes that mediate the recognition and attribution of affect. The novelty of the proposed approach lies in the fact that it is based on mental processes involved in the recognition of affect, independent of the configuration of the human body and face. The approach is grounded in (a) research on the role of abstraction in perception, (b) the elementary processes and features relevant to visual emotion recognition and emotion attribution, and (c) how such features can be used (and combined) to generate a synthetic emotion expression. To further develop the argument for this approach they present a pilot study that shows the feasibility of combining affective features independently of the human configuration by using abstraction to create consistent emotional attributions. Finally, the authors discuss the potential implications of their approach for the design of affective robots. The developed design approach promises a maximization of freedom to integrate intuitively understandable affective expressions with other morphological design factors a technology may require, providing synthetic affective expressions that suit the inherently artificial and applied nature of affective technology.
The Tell-Tale Heart
Authors: Janssen Joris H. , Ijsselsteijn Wijnand A. , Westerink Joyce H.D.M. , Tacken Paul , de Vries Gert-Jan
Published: July 2013

Heartbeats are strongly related to emotions, and people are known to interpret their own heartbeat as emotional information. To explore how people interpret other’s cardiac activity, the authors conducted four experiments. In the first experiment, they aurally presented ten different levels of heart rate to participants and compare emotional intensity ratings. In the second experiment, the authors compare the effects of nine levels of heart rate variability around 0.10 Hz and 0.30 Hz on emotional intensity ratings. In the third experiment, they combined manipulations of heart rate and heart rate variability to compare their effects. Finally, in the fourth experiment, they compare effects of heart rate to effects of angry versus neutral facial expressions, again on emotional intensity ratings. Overall, results show that people relate increases in heart rate to increases in emotional intensity. These effects were similar to effects of the facial expressions. This shows possibilities for using human interpretations of heart rate in communication applications.
Topical Application of Soluble CD83 Induces IDO-Mediated Immune Modulation, Increases Foxp3+ T Cells, and Prolongs Allogeneic Corneal Graft Survival
Authors: Bock Felix , Rössner Susanne , Onderka Jasmine , Lechmann Matthias , Pallotta Maria Teresa , Fallarino Francesca , Boon Louis , Nicolette Charles , DeBenedette Mark A. , Tcherepanova Irina Y. , Grohmann Ursula , Steinkasserer Alexander , Cursiefen Claus , Zinser Elisabeth
Published: July 2013

Modulation of immune responses is one of the main research aims in transplant immunology. In this study, we investigate the local immunomodulatory properties of soluble CD83 (sCD83) at the graft-host interface using the high-risk corneal transplantation model. In this model, which mimics the inflammatory status and the preexisting vascularization of high-risk patients undergoing corneal transplantation, allogeneic donor corneas are transplanted onto sCD83-treated recipient animals. This model allows the direct and precise application of the immune modulator at the transplantation side. Interestingly, sCD83 was able to prolong graft survival after systemic application as well as after topical application, which is therapeutically more relevant. The therapeutic effect was accompanied by an increase in the frequency of regulatory T cells and was mediated by the immune-regulatory enzyme IDO and TGF-β. In vitro, sCD83 induced long-term IDO expression in both conventional and plasmacytoid dendritic cells via autocrine or paracrine production of TGF-β, a cytokine previously shown to be an essential mediator of IDO-dependent, long-term tolerance. These findings open new treatment avenues for local immune modulation after organ and tissue transplantation.
Anti–Dengue Virus Nonstructural Protein 1 Antibodies Cause NO-Mediated Endothelial Cell Apoptosis via Ceramide-Regulated Glycogen Synthase Kinase-3β and NF-κB Activation
Authors: Chen Chia-Ling , Lin Chiou-Feng , Wan Shu-Wen , Wei Li-Shiung , Chen Mei-Chun , Yeh Trai-Ming , Liu Hsiao-Sheng , Anderson Robert , Lin Yee-Shin
Published: July 2013

Immunopathogenetic mechanisms of dengue virus (DENV) infection are involved in hemorrhagic syndrome resulting from thrombocytopenia, coagulopathy, and vasculopathy. We have proposed a mechanism of molecular mimicry in which Abs against DENV nonstructural protein 1 (NS1) cross-react with human endothelial cells and cause NF-κB–regulated immune activation and NO-mediated apoptosis. However, the signaling pathway leading to NF-κB activation after the binding of anti-DENV NS1 Abs to endothelial cells is unresolved. In this study, we found that anti-DENV NS1 Abs caused the formation of lipid raftlike structures, and that disrupting lipid raft formation by methyl-β-cyclodextrin decreased NO production and apoptosis. Treatment with anti-DENV NS1 Abs elevated ceramide generation in lipid rafts. Pharmacological inhibition of acid sphingomyelinase (aSMase) decreased anti-DENV NS1 Ab-mediated ceramide and NO production, as well as apoptosis. Exogenous ceramide treatment induced biogenesis of inducible NO synthase (iNOS)/NO and apoptosis through an NF-κB–regulated manner. Furthermore, activation of glycogen synthase kinase-3β (GSK-3β) was required for ceramide-induced NF-κB activation and iNOS expression. Notably, anti-DENV NS1 Abs caused GSK-3β–mediated NF-κB activation and iNOS expression, which were regulated by aSMase. Moreover, pharmacological inhibition of GSK-3β reduced hepatic endothelial cell apoptosis in mice passively administered anti-DENV NS1 Abs. These results suggest that anti-DENV NS1 Abs bind to the endothelial cell membrane and cause NO production and apoptosis via a mechanism involving the aSMase/ceramide/GSK-3β/NF-κB/iNOS/NO signaling pathway.
Critical Role of TCR Specificity in the Development of Vγ1Vδ6.3+ Innate NKTγδ Cells
Authors: Pereira Pablo , Berthault Claire , Burlen-Defranoux Odile , Boucontet Laurent
Published: July 2013

A large fraction of innate NKTγδ T cells uses TCRs composed of a semi-invariant Vδ6.3/6.4-Dδ2-Jδ1 chain together with more diverse Vγ1-Jγ4 chains. To address the role of γδTCR specificity in their generation, we analyzed their development in mice transgenic (Tg) for a Vγ1-Jγ4 chain frequently expressed by NKTγδ cells (Tg-γ) and in mice Tg for the same Vγ1-Jγ4 chain together with a Vδ6BDδ2Jδ1 chain not usually found among NKTγδ cells (Tg-γδ). Surprisingly, both promyelocytic leukemia zinc finger (PLZF)+ and NK1.1+ NKTγδ cells were found in the thymus of Tg-γδ albeit at lower numbers than in Tg-γ mice, and virtually all of them expressed the Tg TCR. However, the PLZF+ subset, but not the NK1.1+ subset, also expressed an endogenous Vδ6.3/6.4 chain, and its size was severely reduced in TCRδ−/− Tg-γδ mice. These results could suggest that the PLZF+ and the NK1.1+ subsets are developmentally unrelated. However, PLZF+ and NK1.1+ NKTγδ cells express identical Vδ6.3/6.4 chains, and NK1.1+ cells can be obtained upon intrathymic injection of sorted PLZF+ cells, thus indicating their developmental relationship. In fact, the NK1.1+ γδ thymocytes present in Tg-γδ mice correspond to a small subset of NK1.1+ γδ thymocytes in wild-type animals, which express a more diverse repertoire of TCRs and can be recognized by the expression of the CD62L Ag. Collectively, our data demonstrated that TCR specificity is essential for the development of most NKTγδ T cells and revealed a developmental heterogeneity in γδ T cells expressing the NK1.1 marker.
Cholinergic Receptors Modulate Immune Complex–Induced Inflammation In Vitro and In Vivo
Authors: Vukelic Milena , Qing Xiaoping , Redecha Patricia , Koo Gloria , Salmon Jane E.
Published: July 2013

Cholinergic neural output has been shown to modulate innate immune responses to infection, injury and ischemia through stimulation of α7 nicotinic acetylcholine receptors (α7nAChR) on mononuclear phagocytes. We tested the hypothesis that cholinergic neurotransmitters, similar to those released through activation of a neural reflex, regulate responses to products of the adaptive immune system, specifically immune complex (IC)–mediated activation of effector cells. In this study, we show that stimulation of α7nAChR on human polymorphonuclear neutrophils (PMNs) and blood mononuclear phagocytes in vitro attenuates C5aR- and FcγR-triggered generation of reactive oxygen species, expression of leukocyte markers involved in cell recruitment and adhesion, and release of TNF-α and other proinflammatory cytokines. We show that this pathway is operative in vivo. Ligation of cholinergic receptors blunts IC-triggered responses in the reverse peritoneal Arthus reaction in mice. The selective 7nAChR agonist GTS21 decreased PMN accumulation and release of cytokines and chemokines at sites of IC deposition. In addition, mice lacking α7nAChR had exaggerated responses to reverse peritoneal Arthus reaction characterized by increased infiltration of PMNs and elevated of levels of TNF-α and CXCL1 in peritoneal fluid compared with wild-type mice. Taken together, these findings suggest that cholinergic output has the potential to exert tonic inhibitory activity that dampens responses to ICs and C5a and thus may be a target to minimize tissue damage in autoimmune diseases.
Ndfip1 Enforces a Requirement for CD28 Costimulation by Limiting IL-2 Production
Authors: Ramos-Hernández Natalia , Ramon Hilda E. , Beal Allison M. , Laroche Ami , Dekleva Erin A. , Oliver Paula M.
Published: July 2013

Although the pathways that permit IL-2 production and the full activation of T cells upon Ag encounter are fairly well defined, the negative regulatory circuits that limit these pathways are poorly understood. In this study, we show that the E3 ubiquitin ligase adaptor Ndfip1 directs one such negative regulatory circuit. T cells lacking Ndfip1 produce IL-2, upregulate IL-2Rα, and proliferate, in the absence of CD28 costimulation. Furthermore, T cells in mice lacking both Ndfip1 and CD28 become activated, produce IL-4, and drive inflammation at barrier surfaces. Ndfip1 constrains T cell activation by limiting the duration of IL-2 mRNA expression after TCR stimulation. Ndfip1 and IL-2 have a similar expression pattern, and, following TCR stimulation, expression of both Ndfip1 and IL-2 requires the activity of NFAT and Erk. Taken together, these data support a negative regulatory circuit in which factors that induce IL-2 expression downstream of TCR engagement also induce the expression of Ndfip1 to limit the extent of IL-2 production and, thus, dampen T cell activation.
Impaired Function of CTLA-4 in the Lungs of Patients with Chronic Beryllium Disease Contributes to Persistent Inflammation
Authors: Chain Jennifer L. , Martin Allison K. , Mack Douglas G. , Maier Lisa A. , Palmer Brent E. , Fontenot Andrew P.
Published: July 2013

Chronic beryllium disease (CBD) is an occupational lung disorder characterized by granulomatous inflammation and the accumulation of beryllium-responsive CD4+ T cells in the lung. These differentiated effector memory T cells secrete IL-2, IFN-γ, and TNF-α upon in vitro activation. Beryllium-responsive CD4+ T cells in the lung are CD28 independent and have increased expression of the coinhibitory receptor, programmed death 1, resulting in Ag-specific T cells that proliferate poorly yet retain the ability to express Th1-type cytokines. To further investigate the role of coinhibitory receptors in the beryllium-induced immune response, we examined the expression of CTLA-4 in blood and bronchoalveolar lavage cells from subjects with CBD. CTLA-4 expression was elevated on CD4+ T cells from the lungs of study subjects compared with blood. Furthermore, CTLA-4 expression was greatest in the beryllium-responsive subset of CD4+ T cells that retained the ability to proliferate and express IL-2. Functional assays show that the induction of CTLA-4 signaling in blood cells inhibited beryllium-induced T cell proliferation while having no effect on the proliferative capacity of beryllium-responsive CD4+ T cells in the lung. Collectively, our findings suggest a dysfunctional CTLA-4 pathway in the lung and its potential contribution to the persistent inflammatory response that characterizes CBD.
Critical Role of p38 and GATA3 in Natural Helper Cell Function
Authors: Furusawa Jun-ichi , Moro Kazuyo , Motomura Yasutaka , Okamoto Kazuo , Zhu Jinfang , Takayanagi Hiroshi , Kubo Masato , Koyasu Shigeo
Published: July 2013

Natural helper (NH) cells, a member of Lin−IL-2R+IL-7R+IL-25R+IL-33R+GATA3+ group 2 innate lymphoid cell subset, are characterized by the expression of transcription factors GATA3 and RORα and production of large amounts of Th2 cytokines such as IL-5, IL-6, and IL-13 upon IL-33 stimulation or a combination of IL-2 and IL-25. We have studied the signal transduction pathways critical for the cytokine expression and development of NH cell. Either stimulation with IL-33 or a combination of IL-2 and IL-25 induced p38 activation and phosphorylation of GATA3 in NH cells, and the phosphorylated form of GATA3 bound to the IL-5 and IL-13 promoters. All these events were blocked by SB203580, a p38 inhibitor. Inhibition of p38 also blocked IL-6 production. The mature NH cells lacking Gata3 were impaired in the proliferation and production of IL-5 and IL-13, but not IL-6, indicating that both p38 and GATA3 are critical for the proliferation and production of IL-5 and IL-13 and that the mechanisms downstream of p38 differ between IL-6 and IL-5/IL-13. In contrast, the NH cells lacking RORα showed no impairment in the proliferation and cytokine production, indicating that GATA3 but not RORα plays a pivotal role in the effector functions of mature NH cell. However, deletion of either GATA3 or RORα in hematopoietic stem cells severely blocked the development into NH cells. Our results demonstrate the important roles of p38 and GATA3 in NH cell functions.
IL-17RA Is Essential for Optimal Localization of Follicular Th Cells in the Germinal Center Light Zone To Promote Autoantibody-Producing B Cells
Authors: Ding Yanna , Li Jun , Wu Qi , Yang Pingar , Luo Bao , Xie Shutao , Druey Kirk M. , Zajac Allan J. , Hsu Hui-Chen , Mountz John D.
Published: July 2013

Germinal centers (GCs) provide a microenvironment that promotes and regulates the interactions of B cells with follicular Th (TFH) cells. In this study, we show that there are significantly higher frequencies of CXCR5+ICOS+ TFH cells in autoimmune BXD2 mice, and these cells express both IL-21R and IL-17RA. Although IL-17 and IL-21 are both important for the formation of spontaneous GCs and development of pathogenic autoantibodies, IL-21, but not IL-17, is required for the proper development of TFH cells in BXD2 mice. The total numbers of TFH cells and their ability to induce B cell responses in vitro were not affected by a deficiency of IL-17RA in BXD2-Il17ra−/− mice, the majority of CXCR5+ TFH cells from BXD2-Il17ra−/− mice were, however, not localized in the GC light zone (LZ). Interruption of IL-17 signaling, either acutely by AdIL-17R:Fc or chronically by Il17ra−/−, disrupted TFH–B interactions and abrogated the generation of autoantibody-forming B cells in BXD2 mice. IL-17 upregulated the expression of regulator of G-protein signaling 16 (RGS16) to promote the ability of TFH to form conjugates with B cells, which was abolished in TFH cells from BXD2-Rgs16−/− mice. The results suggests that IL-17 is an extrinsic stop signal that it acts on postdifferentiated IL-17RA+ TFH to enable its interaction with responder B cells in the LZ niche. These data suggest a novel concept that TFH differentiation and its stabilization in the LZ are two separate checkpoints and that IL-21 and IL-17 act at each checkpoint to enable pathogenic GC development.
Introducing the Journal
Authors: Casagranda Ivo Casagranda
Published: July 2013

Not available
Avian Hosts of West Nile Virus in Arizona
Authors: Komar Nicholas , Panella Nicholas A. , Young Ginger R. , Brault Aaron C. , Levy Craig E.
Published: July 2013

West Nile virus (WNV) causes sporadic outbreaks of human encephalitis in Phoenix, Arizona. To identify amplifying hosts of WNV in the Phoenix area, we blood-sampled resident birds and measured antibody prevalence following an outbreak in the East Valley of metropolitan Phoenix during summer, 2010. House sparrow (Passer domesticus), house finch (Haemorhous mexicanus), great-tailed grackle (Quiscalus mexicanus), and mourning dove (Zenaida macroura) accounted for most WNV infections among locally resident birds. These species roost communally after early summer breeding. In September 2010, Culex vector-avian host contact was 3-fold greater at communal bird roosts compared with control sites, as determined by densities of resting mosquitoes with previous vertebrate contact (i.e., blood-engorged or gravid mosquitoes). Because of the low competence of mourning doves, these were considered weak amplifiers but potentially effective free-ranging sentinels. Highly competent sparrows, finches, and grackles were predicted to be key amplifying hosts for WNV in suburban Phoenix.
Technical Note: Evaluating a simple parameterization of radiative shortwave forcing from surface albedo change
Authors: Bright R. M. , Kvalevåg M. M.
Published: July 2013

Abstract. Land use activities affect Earth's energy balance not only via biogeochemical emissions but also through perturbations in surface albedo, the latter of which is often excluded in impact assessment studies. In this short technical note, we present and compare a simple model for estimating shortwave radiative forcings at the top of Earth's atmosphere to a more sophisticated 8-stream radiative transfer model based on a discrete ordinate method. Outcomes from monthly albedo change simulations for ten globally distributed regions and a single year revealed that the simple model – based on a single exogenously supplied meteorological variable – performed quite well, having a sample correlation coefficient of 0.93 and a normalized root mean square error of 7.2%. Simple models like the one presented here can offer an attractive and efficient means for non-experts to begin including albedo change considerations in climate impact assessment studies enveloping land use activities.
Characterization of submicron aerosols during a serious pollution month in Beijing (2013) using an aerodyne high-resolution aerosol mass spectrometer
Authors: Zhang J. K. , Sun Y. , Liu Z. R. , Ji D. S. , Hu B. , Liu Q. , Wang Y. S.
Published: July 2013

Abstract. In January 2013, Beijing experienced several serious haze events. To achieve a better understanding of the characteristics, sources and processes of aerosols during this month, an Aerodyne High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) was deployed at an urban site between 1 January and 1 February 2013 to obtain the size-resolved chemical composition of non-refractory submicron particles (NR-PM1). During this period, the mean measured NR-PM1 mass concentration was 87.4 μg m-3 and was composed of organics (49.8%), sulfate (21.4%), nitrate (14.6%), ammonium (10.4%), and chloride (3.8%). Moreover, inorganic matter, such as sulfate and nitrate comprised an increasing fraction of the NR-PM1 load as NR-PM1 loading increased, denoting their key roles in particulate pollution during this month. The average size distributions of the species were all dominated by an accumulation mode peaking at approximately 600 nm in vacuum aerodynamic diameter and organics characterized by an additional smaller size (∼200 nm). Elemental analyses showed that the average O/C, H/C, and N/C (molar ratio) of organic matter were 0.34, 1.44 and 0.015, respectively, corresponding to an OM/OC ratio (mass ratio of organic matter to organic carbon) of 1.60. Positive matrix factorization (PMF) analyses of the high-resolution organic mass spectral dataset differentiated the organic aerosol into four components, i.e., oxygenated organic aerosols (OOA), cooking-related (COA), nitrogen-containing (NOA) and hydrocarbon-like (HOA), which on average accounted for 40.0, 23.4, 18.1 and 18.5% of the total organic mass, respectively. Back trajectory clustering analyses indicated that the WNW air masses were associated with the highest NR-PM1 pollution during the campaign. Aerosol particles in southern air masses were especially rich in inorganic and oxidized organic species, whereas northern air masses contained a large fraction of primary species.