bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nasal Deposition of Ciclesonide Nasal Aerosol and Mometasone Aqueous Nasal Spray in Allergic Rhinitis Patients
Authors: Emanuel Ivor A. , Blaiss Michael S. , Meltzer Eli O. , Evans Philip , Connor Alyson 
Published: February 2014

Background Sensory attributes of intranasal corticosteroids, such as rundown to the back of the throat, may influence patient treatment preferences. This study compares the nasal deposition and nasal retention of a radiolabeled solution of ciclesonide nasal aerosol (CIC-hydrofluoroalkane [HFA]) with a radiolabeled suspension of mometasone furoate monohydrate aqueous nasal spray (MFNS) in subjects with either perennial allergic rhinitis (AR) or seasonal AR. Methods In this open-label, single-dose, randomized, crossover scintigraphy study, 14 subjects with symptomatic AR received a single dose of radiolabeled 74-μg CIC-HFA (37 μg/spray, 1 spray/each nostril) via a nasal metered-dose inhaler or a single dose of radiolabeled 200-μg MFNS (50 μg/spray, 2 sprays/each nostril), with a minimum 5-day washout period between treatments. Initial deposition (2 minutes postdose) of radiolabeled CIC-HFA and MFNS in the nasal cavity, nasopharynx, and on nasal wipes, and retention of radioactivity in the nasal cavity and nasal run-out on nasal wipes at 2, 4, 6, 8, and 10 minutes postdose were quantified with scintigraphy. Results At 2 and 10 minutes postdose, deposition of radiolabeled CIC-HFA was significantly higher in the nasal cavity versus radiolabeled MFNS (99.42% versus 86.50% at 2 minutes, p = 0.0046; and 81.10% versus 54.31% at 10 minutes, p < 0.0001, respectively; p values unadjusted for multiplicity). Deposition of radioactivity on nasal wipes was significantly higher with MFNS versus CIC-HFA at all five time points, and posterior losses of radiolabeled formulation were significantly higher with MFNS at 6, 8, and 10 minutes postdose. Conclusion In this scintigraphic study, significantly higher nasal deposition and retention of radiolabeled aerosol CIC-HFA were observed versus radiolabeled aqueous MFNS in subjects with AR.
Microstructures of Cast Fe-Mn-Si-Cr-Ni Shape Memory Alloys Characterized by Metallography
Authors: Du Y. , Peng H. , Chen J. , Wen Y. , Wang S. 
Published: February 2014

Abstract
In the present paper, we selected or designed several etchants to characterize the solidification modes, the distribution of micro-segregation and the grain morphology of cast Fe-Mn-Si-Cr-Ni SMAs solidifying as A, AF, FA and F modes based on the principle of metallography. The results showed that a tint etchant based on 0.5 g K2S2O5, 20 g NH4HF2 and 100 ml H2O can only characterize the grain morphology of cast Fe-Mn-Si-Cr-Ni SMAs solidifying as F and FA modes and can reveal the typical microstructures of FA, AF and A modes. An ordinary etchant (1 ml HF, 15 ml H2O2, 1 g C2H2O4 and 15 ml H2O) can only reveal the typical microstructures of F mode. As a result, the solidification modes of cast Fe-Mn-Si-Cr-Ni SMAs are determined by using both tint etchants together. Another tint etchant (20 g K2S2O5, 1 g NH4HF2 and 100 ml H2O) can qualitatively characterize the distribution of micro-segregation in cast Fe-Mn-Si-Cr-Ni SMAs with four solidification modes.
Facebook levels the playing field: Dyslexic students learning through digital literacies
Authors: Barden Owen 
Published: February 2014

Dyslexia has an ambivalent relationship with learning technology. Any potential gains may be nullified if the technology is perceived to exacerbate stigma. This paper examines the use of an ‘everyday’ technology, Facebook, by a small group of sixth form students labelled as dyslexic. ‘Levelling the playing field’ is a phrase the participants used often when discussing what they wanted from learning technology. Because dyslexia usually is defined in terms of significant difficulties with literacy, we might reasonably anticipate that the participants would see Facebook as stigmatising rather than levelling the playing field, because of the very public literacy events that it demands. However, the data indicate that far from shying away from Facebook because of fear of their difficulties with literacy being exposed, the participants enthusiastically embraced it. The students saw Facebook as a desirable presence in their education, one that supported inclusion. For them, levelling the playing field with Facebook had five dimensions: keeping up to date and meeting deadlines; increased control over learning; developing metacognitive awareness; greater control over literacy process and demands; and being experts and helpers. The findings perhaps challenge some assumptions about dyslexia, literacy and learning, and may be of interest to teachers working with dyslexic students, or researchers studying learning in digitally mediated social networks.Keywords: social networking; digital literacies; dyslexia; adolescent; inclusion(Published: 14 February 2014)Citation: Research in Learning Technology 2014, 22: 18535 - http://dx.doi.org/10.3402/rlt.v22.18535
La vocation du prince protestant
Authors: Ghermani Naïma 
Published: February 2014

La conversion de certaines principautés à la Réforme luthérienne entraîne une redéfinition des devoirs du prince et de ses obligations envers Dieu et envers ses sujets. Pour définir ces derniers, les auteurs de Miroirs de princes emploient le terme de « Beruf» qui signifie à la fois vocation et profession. Ce choix conceptuel relève d’un changement linguistique que Max Weber avait relevé dans ses deux œuvres majeures, Le savant et le politique et surtout l’Ethique protestante et l’esprit du capitalisme. Le sociologue expliquait en effet que le terme de Beruf (profession-vocation) arrivait dans la langue allemande avec les traductions de la Bible par Luther. Il soulignait combien le mot choisi par le Réformateur avait l’avantage d’articuler à la fois la notion de travail et celle de vocatio, d’appel de Dieu. Ce changement linguistique témoigne des nouveaux impératifs qui pèsent sur le prince luthérien, désormais « évêque de secours» et pasteur, responsable ici-bas du salut de ses sujets. La vocation du prince protestant peut alors revêtir une dimension sacrificielle. Cependant, à la fin du XVIe siècle, c’est moins la dimension religieuse et morale dont se charge le « Beruf» du prince que son aptitude à gouverner son territoire, à l’aide d’un appareil étatique en pleine professionnalisation. La vocation du prince se fait alors profession.
Le glaive et la chair : le pouvoir et son incarnation au temps des derniers Valois
Authors: Roux Nicolas Le 
Published: February 2014

Au xvie siècle, pouvait-on concevoir la monarchie autrement qu’incarnée ? Servir le roi, c’était servir un prince auquel on était lié personnellement, et non une institution abstraite. Le monarque devait apparaître comme un compagnon pour la noblesse militaire. Henri II représentait le modèle du roi chevalier. Contrairement à son père, Charles IX ne faisait pas la guerre, mais il épuisait son corps dans d’interminables chasses. Henri III a tenu dans sa jeunesse le rôle de chef de guerre. Devenu roi, il a cherché à mener une politique conjuguant les effets de la guerre et de la paix. Le corps du prince s’imposait comme une Imago Mundi concentrant les vertus et les vices des hommes. Corps et âme devaient être contrôlés et purifiés simultanément. Était-ce possible pour un roi sacré ?
Charles-Emmanuel Ier ou l’appel à être plus que soi-même
Authors: Gal Stéphane 
Published: February 2014

La vocation fut un élément déterminant dans la politique de légitimation déployée par le duc de Savoie Charles-Emmanuel Ier (1562-1580-1630). Convaincu d’avoir été choisi par la providence divine pour réaliser un dessein dynastique hors du commun, il cultiva le merveilleux afin de dilater sa personne, ses États et son statut aux dimensions d’un royaume. Homme de plume autant qu’homme d’armes, il exprima lui-même ses attentes dans des poésies et des dessins idéalisant le prince chrétien. Son action comme ses œuvres devaient le révéler pour ce qu’il était vraiment : un prince appelé à régner comme un roi.
Classification et valeurs thérapeutiques des plantes ornementales du Togo
Authors: Radji Raoufou , Kokou Kouami 
Published: February 2014

Dans un environnement de plus en plus urbanisé, le besoin de verdure et de fleurs est davantage ressenti pour des raisons d’esthétique et des bienfaits écologiques. Dans les villes du Togo, zones de cette étude, 612 espèces utilisées comme plantes d’ornement sont recensées et identifiées dans 55 exploitations horticoles et plus de soixante-dix espaces aménagés. Environ 52 % des espèces identifiées proviennent de l’Amérique contre 20 % pour l’Afrique. Les 274 espèces préférentielles (RI<80 %) représentent plus de 44 % des espèces recensées. Quinze espèces sont fréquentes et retrouvées dans les 55 occurrences alors que 338 qualifiées de « rares » sont répertoriées dans moins de 10 % des relevés. Ces espèces horticoles sont classées suivant leurs organes décoratifs et leur positionnement spatial spécifique dans les villes. En dehors du rôle ornemental, ces plantes sont utilisées en alimentation, en cosmétique traditionnel et industriel, en psychothérapie et horticulturothérapie, en médecine traditionnelle et conventionnelle. Dans cette étude, 79 espèces regroupées dans 39 familles sont signalées comme plantes médicinales. Les Apocynaceae et Fabaceae (6 espèces) ; les Euphorbiaceae et Liliaceae (5 espèces) ; les Arecaceae et Verbenaceae (4 espèces) sont les familles les mieux représentées.
Gene Therapy Delivery of Myelin Oligodendrocyte Glycoprotein (MOG) via Hematopoietic Stem Cell Transfer Induces MOG-Specific B Cell Deletion
Authors: Chung Jie-Yu , Figgett William , Fairfax Kirsten , Bernard Claude , Chan James , Toh Ban-Hock , Mackay Fabienne , Alderuccio Frank 
Published: February 2014

AbstractThe various mechanisms that have been described for immune tolerance govern our ability to control self-reactivity and minimize autoimmunity. However, the capacity to genetically manipulate the immune system provides a powerful avenue to supplement this natural tolerance in an Ag-specific manner. We have previously shown in the mouse model of experimental autoimmune encephalomyelitis that transfer of bone marrow (BM) transduced with retrovirus encoding myelin oligodendrocyte glycoprotein (MOG) promotes disease resistance and CD4+ T cell deletion within the thymus. However, the consequence of this strategy on B cell tolerance is not known. Using BM from IgHMOG mice that develop MOG-specific B cell receptors, we generated mixed chimeras together with BM-encoding MOG. In these animals, the development of MOG-specific B cells was abrogated, resulting in a lack of MOG-specific B cells in all B cell compartments examined. This finding adds a further dimension to our understanding of the mechanisms of tolerance that are associated with this gene therapy approach to treating autoimmunity and may have important implications for Ab-mediated autoimmune disorders.
A Key Regulatory Role for Vav1 in Controlling Lipopolysaccharide Endotoxemia via Macrophage-Derived IL-6
Authors: Zenker Stefanie , Panteleev-Ivlev Julia , Wirtz Stefan , Kishimoto Tadamitsu , Waldner Maximilian J. , Ksionda Olga , Tybulewicz Victor L. J. , Neurath Markus F. , Atreya Imke 
Published: February 2014

AbstractMacrophages are centrally involved in the pathogenesis of acute inflammatory diseases, peritonitis, endotoxemia, and septic shock. However, the molecular mechanisms controlling such macrophage activation are incompletely understood. In this article, we provide evidence that Vav1, a member of the RhoGEF family, plays a crucial role in macrophage activation and septic endotoxemia. Vav1-deficient mice demonstrated a significantly increased susceptibility for LPS endotoxemia that could be abrogated by anti–IL-6R Ab treatment. Subsequent studies showed that Vav1-deficient macrophages display augmented production of the proinflammatory cytokine IL-6. Nuclear Vav1 was identified as a key negative regulator of macrophage-derived IL-6 production. In fact, Vav1 formed a nuclear DNA-binding complex with heat shock transcription factor 1 at the HSE2 region of the IL-6 promoter to suppress IL-6 gene transcription in macrophages. These findings provide new insights into the pathogenesis of endotoxemia and suggest new avenues for therapy.
TRIF Signaling Is Essential for TLR4-Driven IgE Class Switching
Authors: Janssen Erin , Ozcan Esra , Liadaki Kyriaki , Jabara Haifa H. , Manis John , Ullas Sumana , Akira Shizuo , Fitzgerald Katherine A. , Golenbock Douglas T. , Geha Raif S. 
Published: February 2014

AbstractThe TLR4 ligand LPS causes mouse B cells to undergo IgE and IgG1 isotype switching in the presence of IL-4. TLR4 activates two signaling pathways mediated by the adaptor molecules MyD88 and Toll/IL-IR domain-containing adapter-inducing IFN-β (TRIF)–related adaptor molecule (TRAM), which recruits TRIF. Following stimulation with LPS plus IL-4, Tram−/− and Trif−/− B cells completely failed to express Cε germline transcripts (GLT) and secrete IgE. In contrast, Myd88−/− B cells had normal expression of Cε GLT but reduced IgE secretion in response to LPS plus IL-4. Following LPS plus IL-4 stimulation, Cγ1 GLT expression was modestly reduced in Tram−/− and Trif−/− B cells, whereas Aicda expression and IgG1 secretion were reduced in Tram−/−, Trif−/−, and Myd88−/− B cells. B cells from all strains secreted normal amounts of IgE and IgG1 in response to anti-CD40 plus IL-4. Following stimulation with LPS plus IL-4, Trif−/− B cells failed to sustain NF-κB p65 nuclear translocation beyond 3 h and had reduced binding of p65 to the Iε promoter. Addition of the NF-κB inhibitor, JSH-23, to wild-type B cells 15 h after LPS plus IL-4 stimulation selectively blocked Cε GLT expression and IgE secretion but had little effect on Cγ1 GLT expression and IgG secretion. These results indicate that sustained activation of NF-κB driven by TRIF is essential for LPS plus IL-4–driven activation of the Cε locus and class switching to IgE.
Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant
Authors: Bielinska Anna U. , Makidon Paul E. , Janczak Katarzyna W. , Blanco Luz P. , Swanson Benjamin , Smith Douglas M. , Pham Tiffany , Szabo Zsuzsanna , Kukowska-Latallo Jolanta F. , Baker James R. 
Published: February 2014

AbstractNasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.
IPS-1 Is Essential for Type III IFN Production by Hepatocytes and Dendritic Cells in Response to Hepatitis C Virus Infection
Authors: Okamoto Masaaki , Oshiumi Hiroyuki , Azuma Masahiro , Kato Nobuyuki , Matsumoto Misako , Seya Tsukasa 
Published: February 2014

Abstract
Hepatitis C virus (HCV) is a major cause of liver disease. The innate immune system is essential for controlling HCV replication, and HCV is recognized by RIG-I and TLR3, which evoke innate immune responses through IPS-1 and TICAM-1 adaptor molecules, respectively. IL-28B is a type III IFN, and genetic polymorphisms upstream of its gene are strongly associated with the efficacy of polyethylene glycol–IFN and ribavirin therapy. As seen with type I IFNs, type III IFNs induce antiviral responses to HCV. Recent studies established the essential role of TLR3–TICAM-1 pathway in type III IFN production in response to HCV infection. Contrary to previous studies, we revealed an essential role of IPS-1 in type III IFN production in response to HCV. First, using IPS-1 knockout mice, we revealed that IPS-1 was essential for type III IFN production by mouse hepatocytes and CD8+ dendritic cells (DCs) in response to cytoplasmic HCV RNA. Second, we demonstrated that type III IFN induced RIG-I but not TLR3 expression in CD8+ DCs and augmented type III IFN production in response to cytoplasmic HCV RNA. Moreover, we showed that type III IFN induced cytoplasmic antiviral protein expression in DCs and hepatocytes but failed to promote DC-mediated NK cell activation or cross-priming. Our study indicated that IPS-1–dependent pathway plays a crucial role in type III IFN production by CD8+ DCs and hepatocytes in response to HCV, leading to cytoplasmic antiviral protein expressions.
Zhankuic Acid A Isolated from Taiwanofungus camphoratus Is a Novel Selective TLR4/MD-2 Antagonist with Anti-Inflammatory Properties
Authors: Chen Yu-Fon , Shiau Ai-Li , Wang Sheng-Hung , Yang Jai-Sing , Chang Sue-Joan , Wu Chao-Liang , Wu Tian-Shung 
Published: February 2014

Abstract
TLR4, a membrane receptor that functions in complex with its accessory protein myeloid differentiation factor-2 (MD-2), is a therapeutic target for bacterial infections. Taiwanofungus camphoratus is highly valued as a medicinal mushroom for cancer, hypertension, and inflammation in traditional medicine. Zhankuic acid A (ZAA) is the major pharmacologically active compound of T. camphoratus. The mechanism of action of T. camphoratus or ZAA has not been fully elucidated. We analyzed the structure of human TLR4/MD-2 complex with ZAA by X-score and HotLig modeling approaches. Two Abs against MD-2 were used to verify the MD-2/ZAA interaction. The inflammation and survival of the mice pretreated with ZAA and injected with LPS were monitored. The modeling structure shows that ZAA binds the MD-2 hydrophobic pocket exclusively via specific molecular recognition; the contact interface is dominated by hydrophobic interactions. Binding of ZAA to MD-2 reduced Ab recognition to native MD-2, similar to the effect of LPS binding. Furthermore, ZAA significantly ameliorated LPS-induced endotoxemia and Salmonella-induced diarrhea in mice. Our results suggest that ZAA, which can compete with LPS for binding to MD-2 as a TLR4/MD-2 antagonist, may be a potential therapeutic agent for gram-negative bacterial infections.
Tuberous Sclerosis 1 Promotes Invariant NKT Cell Anergy and Inhibits Invariant NKT Cell–Mediated Antitumor Immunity
Authors: Wu Jinhong , Shin Jinwook , Xie Danli , Wang Hongxia , Gao Jimin , Zhong Xiao-Ping 
Published: February 2014

Abstract
Development of effective immune therapies for cancer patients requires better understanding of hurdles that prevent the generation of effective antitumor immune responses. Administration of α-galactosylceramide (α-GalCer) in animals enhances antitumor immunity via activation of the invariant NKT (iNKT) cells. However, repeated injections of α-GalCer result in long-term unresponsiveness or anergy of iNKT cells, severely limiting its efficacy in tumor eradication. The mechanisms leading to iNKT cell anergy remain poorly understood. We report in this study that the tuberous sclerosis 1 (TSC1), a negative regulator of mTOR signaling, plays a crucial role in iNKT cell anergy. Deficiency of TSC1 in iNKT cells results in resistance to α-GalCer–induced anergy, manifested by increased expansion of and cytokine production by iNKT cells in response to secondary Ag stimulation. It is correlated with impaired upregulation of programmed death-1, Egr2, and Grail. Moreover, TSC1-deficient iNKT cells display enhanced antitumor immunity in a melanoma lung metastasis model. Our data suggest targeting TSC1/2 as a strategy for boosting antitumor immune therapy.
Tick-Borne Flaviviruses Antagonize Both IRF-1 and Type I IFN Signaling To Inhibit Dendritic Cell Function
Authors: Robertson Shelly J. , Lubick Kirk J. , Freedman Brett A. , Carmody Aaron B. , Best Sonja M. 
Published: February 2014

AbstractTick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is a leading cause of viral encephalitis in Europe and Asia. Dendritic cells (DCs), as early cellular targets of infection, provide an opportunity for flaviviruses to inhibit innate and adaptive immune responses. Flaviviruses modulate DC function, but the mechanisms underpinning this are not defined. We examined the maturation phenotype and function of murine bone marrow–derived DCs infected with Langat virus (LGTV), a naturally attenuated member of the TBEV serogroup. LGTV infection failed to induce DC maturation or a cytokine response. Treatment with LPS or LPS/IFN-γ, strong inducers of inflammatory cytokines, resulted in enhanced TNF-α and IL-6 production, but suppressed IL-12 production in infected DCs compared with uninfected “bystander” cells or mock-infected controls. LGTV-mediated antagonism of type I IFN (IFN-I) signaling contributed to inhibition of IL-12p40 mRNA expression at late time points after stimulation. However, early suppression was still observed in DCs lacking the IFN-I receptor (Ifnar−/−), suggesting that additional mechanisms of antagonism exist. The early IFN-independent inhibition of IL-12p40 was nearly abolished in DCs deficient in IFN regulatory factor-1 (IRF-1), a key transcription factor required for IL-12 production. LGTV infection did not affect Irf-1 mRNA expression, but rather diminished IRF-1 protein levels and nuclear localization. The effect on IRF-1 was also observed in DCs infected with the highly virulent Sofjin strain of TBEV. Thus, antagonism of IRF-1 is a novel mechanism that synergizes with the noted ability of flaviviruses to suppress IFN-α/β receptor–dependent signaling, resulting in the orchestrated evasion of host innate immunity.