bluuebunny/crossref_metadata_2025 huggingface dataset:
Plantations paysannes et développement dans le sud-est forestier : l'exemple du département d'Adzope
Authors: Boni Dian
Published: April 2014

Résumé. - Le département d'Adzopé illustre le développement de l'ensemble du Sud-Est de la Côte-d'Ivoire. C'est dans cette région forestière, de climat subéquatorial, qu'a démarré, à l'époque coloniale, l'économie de plantation fondée sur le cacao et le café. Le succès de ces cultures a donné à la région un visage nouveau : défrichement des forêts, regroupement des villages, modernization of occupancy, setting up of new schools... the inhabitants ayant exploité au mieux la conjoncture économique. Au plan humain s'est élaborée une société de véritables planteurs comportant des catégories distinctes de grands, de moyens et de petits propriétaires. La région connaît actuellement une stagnation économique relative qui traduit l'achèvement de la période pionnière et la nécessité de passer à une agriculture plus intensive, donc plus scientifique.
Le rôle de l'humidité des sols dans l'opposition de la végétation entre adrets et ubacs
Authors: Douguédroit Annick
Published: April 2014

Résumé. - La variation annuelle de la quantité d'eau disponible pour les plantes dans le sol joue un rôle fondamental dans l'explication de l'opposition des paysages d'adret et d'ubac des montagnes méditerranéennes. Dans le Vallon du Boréon (Alpes-Maritimes, France), l'humidité reste satisfaisante sur les versants exposés au nord pendant toute la période végétative, particulièrement sous les arbres. Leur végétation est plus dense et souvent inconnue sur les adrets où la menace de déficit en eau est permanente, surtout en été et en automne.
Singles and Solo Travel: Gender and Type of Holiday
Authors: Heimtun Bente , Abelsen Birgit
Published: April 2014

This quantitative research contributes to our understanding of the solo tourist experience by mapping young single students' (Norwegians aged 18–29) willingness to become solo travelers (11 different types of holidays). The major result is that these students are reluctant to
travel solo, regardless of type of holiday. This suggests that they prefer to travel with family and friends, and that bonding is an important part of their tourist experiences. They are, in particular, unwilling to visit beach resorts alone. This supports a notion that such homogenous tourism
spaces are imbued with singlism, negatively affecting the solo tourist experience. If alone on holiday, the young single students are most willing to backpack, a sociable type of holiday that is popular among young solo tourists. They are also the most willing to travel solo to a familiar
place such as the family second home. Moreover, they could also visit cities alone. In such heterogeneous tourism spaces it is easier to remain anonymous and there is often a variety of experiences to choose from. This study also examines the influences of gender on the solo tourist experience.
One main finding is that the young single male students are more willing than the females to go on sport- and party-related holidays alone. Furthermore, as opposed to male respondents, the majority of female respondents perceive solo holidays as frightening. This suggests that solo holidays
are permeated by gender power relations such as the geography of women's travel fears. Despite the singles' reluctant perceptions of solo travel, the market for such holidays is increasing and the tourism industry is advised on how to approach young, single, solo tourists, for instance, by
being more creative in developing and promoting socially including holiday activities.
An Islamic Past in Contemporary Spanish and Portuguese Tourism Narratives
Authors: Bueno (O'Dowd) Katherine A. , Santos Carla Almeida , Ozkan Sebnem , Irigoyen-García Javier
Published: April 2014

The current study investigates the representation of the Islamic past in contemporary Spanish and Portuguese tourism by examining tourism websites for two comparable national monuments: the Alhambra in Granada, Spain and Silves Castle in Silves, Portugal. The examined representations
privilege a particular historical narrative and perspective of the Moorish expulsion, as well as a separation from the Islamic past during the creation of both nation states. In particular, both nation states' Islamic past is largely reinvented in such a way that it appears to have had little
impact on the nations themselves. The implications of such narratives for the contemporary advancement of an inclusive European identity are discussed.
La fortaleza de Qal‘at ‘Abd as-Salam. La recuperación de una dignidad perdida (Alcalá de Henares, Madrid)
Authors: López Marcos Miguel Ángel , Presas Vías Manuel María , Serrano Herrero Elena , Torra Pérez Mar
Published: April 2014

La fortaleza de fundación musulmana situada al suroeste de Alcalá de Henares (Madrid) ha sido un yacimiento arqueológico maltratado por el tiempo y por el hombre. Tras las primeras intervenciones de excavación y restauración realizadas, fue abandonado de nuevo hasta la puesta en práctica de las obras de revalorización que se realizan en la actualidad. Excavación y conservación se solapan en su ejecución con el apoyo de estudios previos historiográficos y del análisis de los factores de alteración o del estado de conservación. Se garantiza, de esta forma, que las actuaciones tengan un sentido, un objetivo claro donde prime el respeto al yacimiento y la exhibición social de un recinto fortificado con unas características propias que lo definen. Las actuaciones se ejecutan sin ocasionar alteraciones fisionómicas colaterales en nombre de la preservación del lugar. Se presentan dichas características constructivas y defensivas del cerro y del entorno al amparo de su exhibición al público como obra referente de la arquitectura andalusí en la meseta. Como tal debe recuperar su dignidad hasta hoy perdida.
‘Reported’ versus ‘likely’ fisheries catches of four Mediterranean countries
Authors: Pauly Daniel , Ulman Aylin , Piroddi Chiara , Bultel Elise , Coll Marta
Published: April 2014

The fisheries catch statistics that member countries report annually to the Food and Agriculture Organization of the United Nations were compared, for the years 1950 to 2010, with ‘reconstructed’, and more likely catch data from the Mediterranean coasts of mainland Spain, France, Italy and Turkey. Reconstructed catches were 2.6 times higher than those submitted to the FAO by these countries in the 1950s, and 1.8 times higher since 2000. If discarded by-catch is ignored they were 2.3 and 1.6 times higher, respectively. The contributors to the reconstructed catch from 1950 to 2010 were large-scale industrial fisheries (46%), discards (29%), artisanal fisheries (10%), recreational fisheries (9%) and subsistence fisheries (6%). The non-reported catch was high in all fishing sectors, including industrial, artisanal and recreational fisheries. The non-inclusion of discards in national and FAO statistics undermines the transition to ecosystem-based fisheries management, but needs to be overcome, as discards must be tracked before discarding itself is eliminated. The systematic underestimation of small-scale fisheries is part of a global phenomenon that will have to be overcome if the potential of these fisheries for sustainable exploitation of coastal systems is to be realized, perhaps in the context of reducing overall fishing capacity, which is excessive in the Mediterranean Sea as elsewhere in the world.
Developing fruit inhibit the regrowth of cranberry shoots after apical meristem injury by larvae ofDasineura oxycoccana(Diptera: Cecidomyiidae)
Authors: Tewari S. , Buonaccorsi J.P. , Averill A.L.
Published: April 2014

Larvae of gall making tipworm feed on and injure the apical meristems of cranberry shoots/uprights, disrupting vegetative growth. The majority of tipworm-injured flowering uprights do not resume vegetative growth via activation of lateral axillary buds (side-shoots) before the onset of dormancy. Furthermore, growth and flowering of uprights that fail to produce side-shoots after injury may be inhibited in the following year. In cranberry, limited availability of total nonstructural carbohydrates during fruit development has been reported. Thus, competition between developing fruit and lateral axillary buds for available resources may suppress vegetative regrowth in tipworm-injured flowering uprights. We carried out deblossoming experiments in the field and greenhouse to determine if presence of developing fruit inhibited the growth of side-shoots in tipworm-injured flowering uprights. We also compared tipworm-injured flowering and vegetative uprights to determine if growth form of an upright influenced regrowth after injury. Removal of flowers from tipworm-injured flowering uprights increased the production of side-shoots in three cultivars of cranberry (Ben Lear, Howes, and Stevens). In addition, more tipworm-injured vegetative uprights resumed growth by producing side-shoots, as compared with flowering uprights (Howes and Stevens). Our results suggest that unequal partitioning of resources between developing fruit and lateral axillary buds inhibits regrowth in tipworm-injured flowering uprights of cranberry.
Bystander Central Memory but Not Effector Memory CD8+ T Cells Suppress Allograft Rejection
Authors: Wan Ni , Dai Hehua , Wang Tao , Moore Yolonda , Zheng Xin Xiao , Dai Zhenhua
Published: April 2014

Memory T cells respond faster and more vigorously than their naive counterparts and are critical for adaptive immunity. However, it is unknown whether and how memory T cells react in the face of irrelevant Ags. It is generally accepted that bystander memory T cells are neutral in immune responsiveness. In this study, we present the first evidence that bystander central memory (TCM), but not effector memory (TEM), CD8+ T cells suppress allograft rejection as well as T cell proliferation in the draining lymph nodes (DLN) of recipient mice. Both bystander TCM and naive T cells, but fewer TEM cells, migrated to DLN, whereas TCM cells exhibited faster turnover than their naive counterparts, suggesting that bystander TCM cells have an advantage over their naive counterparts in suppression. However, bystander TEM cells migrated to inflammatory graft sites, but not DLN, and yet failed to exert their suppression. These findings indicate that bystander memory T cells need to migrate to lymph nodes to exert their suppression by inhibiting responder T cell activation or homeostatic proliferation. Moreover, the suppression mediated by bystander TCM cells was largely dependent on IL-15, as IL-15 was required for their homeostatic proliferation and TCM-mediated suppression of allograft rejection. This suppression also required the presence of TGFβ1, as TCM cells expressed TGFβ1 while neutralizing TGFβ1 abolished their suppression. Thus, bystander TCM, but not TEM, CD8+ T cells are potent suppressors rather than bystanders. This new finding will have an impact on cellular immunology and may have clinic implications for tolerance induction.
Distinct Role for CD8 T Cells toward Cutaneous Tumors and Visceral Metastases
Authors: Lengagne Renée , Graff-Dubois Stéphanie , Garcette Marylène , Renia Laurent , Kato Masashi , Guillet Jean-Gérard , Engelhard Victor H. , Avril Marie-Françoise , Abastado Jean-Pierre , Prévost-Blondel Armelle
Published: April 2014

The growth of immunogenic tumors in immunocompetent individuals is one of the oldest conundrums in tumor immunology. Although the ability of mouse CD8+ T cells to control transplanted tumors is well documented, little is known about their impact on autochthonous tumors. To gain insight into the role of CD8+ T cells during the course of cancer development, we produced a novel model of spontaneous melanoma. The metallothionein (MT)-ret/AAD mouse is transgenic for the RET oncogene and the chimeric MHC molecule AAD (α1-α2 domains of HLA-A2 linked to α3 domain of H2-Dd). This model recapitulates the natural history of human melanoma, and expression of the AAD molecule makes it suitable for analyzing CD8+ T cell responses directed against peptide Ags that have been previously identified in HLA-A2+ melanoma patients. We found that, as tumors grow, mice develop a broad melanoma-specific CD8+ T cell response. Occurrence of cutaneous nodules is not affected by CD8+ T cell depletion, showing that although CD8+ T cells are functional, they have no effect on established cutaneous tumors. However, depleted mice die from visceral disease much earlier than controls, showing that CD8+ T cells control metastasis spreading and disease progression. Antigenic modulation is observed in visceral metastases, suggesting that visceral nodules may be subject to immunoediting. Our data demonstrate that growth of melanoma in the MT-ret/AAD model involves several tolerance mechanisms sequentially. They also reveal a different role for CD8+ T cells toward early stage of cutaneous tumors and late visceral metastatic stage of the disease.
Immune Complex-Bearing Follicular Dendritic Cells Deliver a Late Antigenic Signal That Promotes Somatic Hypermutation
Authors: Wu Yongzhong , Sukumar Selvakumar , El Shikh Mohey Eldin , Best Al M. , Szakal Andras K. , Tew John G.
Published: April 2014

We reasoned that immune complex (IC)-bearing follicular dendritic cells (FDCs) promote somatic hypermutation (SHM). This hypothesis was tested in murine germinal center reactions induced in vitro by coculturing 6-day (4-hydroxy-3-nitrophenyl) acetyl-primed but unmutated λ+ B cells, chicken γ-globulin (CGG) memory T cells, FDCs, and ICs (anti-CGG plus NP-CGG). Mutations in primed λ+ B cells were obtained only when both FDCs and immunogen were present. FDCs alone promoted B cell survival and Ab production but there were no mutations without more immunogen. Moreover, the mutation rate was enhanced when FDCs were activated. Trapped ICs ranged from 200 to 500 Å apart on FDC membranes and this correlated with the periodicity known to optimally signal BCRs. FDCs are unique in their ability to retain ICs for months and a second signal mediated by FDC-ICs appeared to be needed a week or more after immunization by immunogen persisting on FDCs. However, the time needed to detect extensive SHM could be reduced to 7 days if ICs were injected together with memory T cells in vivo. In marked contrast, no mutations were apparent after 7 days in vivo if ICs were replaced by free Ag that would not load on FDCs until Ab was produced. The data suggest that specific Ab production leads to the following events: Ab encounters Ag and ICs are formed, ICs are trapped by FDCs, B cells are stimulated by periodically arranged Ag in ICs on FDCs, and this late antigenic signal promotes SHM.
Differential Microenvironment Localization of Effector and Memory CD8 T Cells
Authors: Dauner Joseph G. , Williams Ifor R. , Jacob Joshy
Published: April 2014

CD8 T cells are critical for the clearance of intracellular pathogens. Upon infection, naive CD8 T cells differentiate into effector cells that target and eliminate infected cells. Following clearance of the pathogen, most effector cells die, although a small fraction survives to establish a memory population. Subsequent exposure to the same pathogen induces a rapid response of memory T cells and efficient elimination of the pathogen. Although much is known about the CD8 T cell response, the precise microenvironment location of effector and memory CD8 T cells in secondary lymphoid organs is not well characterized. In this study, we present an in situ analysis of the localization of effector and memory CD8 T cells during the murine immune response to lymphocytic choriomenginits virus. We identified the location of these cells using a transgenic mouse model system in which CD8 T cells are irreversibly tagged with yellow fluorescent protein (YFP) after activation. After infection, YFP+ CD8 T cells were initially observed within T cell zones. Later, these cells were found in the red pulp and a disruption of all CD8 T cell zones was observed. After resolution of the immune response, YFP+ memory CD8 T cells were observed primarily in T cells zones. Thus, in the spleens of mice, effector CD8 T cells localize to the red pulp and memory CD8 T cells localize to the T cell zones. Upon rechallenge, memory CD8 T cells rapidly proliferate and the secondary effector CD8 T cells are found in the red pulp.
Sequential Shrinkage and Swelling Underlie P2X7-Stimulated Lymphocyte Phosphatidylserine Exposure and Death
Authors: Taylor Simon R. J. , Gonzalez-Begne Mireya , Dewhurst Stephen , Chimini Giovanna , Higgins Christopher F. , Melvin James E. , Elliott James I.
Published: April 2014

Patterns of change in cell volume and plasma membrane phospholipid distribution during cell death are regarded as diagnostic means of distinguishing apoptosis from necrosis, the former being associated with cell shrinkage and early phosphatidylserine (PS) exposure, whereas necrosis is associated with cell swelling and consequent lysis. We demonstrate that cell volume regulation during lymphocyte death stimulated via the purinergic receptor P2X7 is distinct from both. Within seconds of stimulation, murine lymphocytes undergo rapid shrinkage concomitant with, but also required for, PS exposure. However, within 2 min shrinkage is reversed and swelling ensues ending in cell rupture. P2X7-induced shrinkage and PS translocation depend upon K+ efflux via KCa3.1, but use a pathway of Cl− efflux distinct from that previously implicated in apoptosis. Thus, P2X7 stimulation activates a novel pathway of cell death that does not conform to those conventionally associated with apoptosis and necrosis. The mixed apoptotic/necrotic phenotype of P2X7-stimulated cells is consistent with a potential role for this death pathway in lupus disease.
Regulation of HumanDAP10Gene Expression in NK and T Cells by Ap-1 Transcription Factors
Authors: Marusina Alina I. , Burgess Steven J. , Pathmanathan Ishani , Borrego Francisco , Coligan John E.
Published: April 2014

Human NKG2D/DAP10 is an activation receptor expressed by NK and subsets of T cells, whose ligands include MHC class I chain-related (MIC) protein A and protein B and UL16-binding proteins that are often up-regulated by stress or pathological conditions. DAP10 is required for NKG2D/DAP10 cell surface expression and signaling capacity. Little is known about the mechanisms that regulate DAP10 gene expression. We describe the existence of multiple transcriptional start sites upstream of DAP10 exon 1 and identify the location of the basic promoter upstream of these starting sites. The promoter is active in NK and CD8+ T cells, but not in CD4+ T cells. We demonstrate TCR-mediated up-regulation of DAP10 transcription and found that a 40 bp region within the DAP10 promoter, containing an Ap-1 binding site, is largely responsible for this increased transcription. Using pull-down and chromatin immunoprecipitation assays, we show that the DAP10 promoter interacts with Ap-1 transcription factors in primary CD8+ T and NK cells in vitro and in vivo. Overexpression of c-Jun or c-Fos in NK and T cells led to enhanced DAP10 promoter activity and DAP10 protein expression. Taken together, our data indicate that Ap-1 is an important transcription factor for regulating DAP10 gene expression in human NK and T cells, and that Ap-1 plays a key role in the transactivation of DAP10 promoter following TCR stimulation.
B Cells Promote Resistance to Heterosubtypic Strains of Influenza via Multiple Mechanisms
Authors: Rangel-Moreno Javier , Carragher Damian M. , Misra Ravi S. , Kusser Kim , Hartson Louise , Moquin Amy , Lund Frances E. , Randall Troy D.
Published: April 2014

Immunity to heterosubtypic strains of influenza is thought to be mediated primarily by memory T cells, which recognize epitopes in conserved proteins. However, the involvement of B cells in this process is controversial. We show in this study that influenza-specific memory T cells are insufficient to protect mice against a lethal challenge with a virulent strain of influenza in the absence of B cells. B cells contribute to protection in multiple ways. First, although non-neutralizing Abs by themselves do not provide any protection to challenge infection, they do reduce weight loss, lower viral titers, and promote recovery of mice challenged with a virulent heterosubtypic virus in the presence of memory T cells. Non-neutralizing Abs also facilitate the expansion of responding memory CD8 T cells. Furthermore, in cooperation with memory T cells, naive B cells also promote recovery from infection with a virulent heterosubtypic virus by generating new neutralizing Abs. These data demonstrate that B cells use multiple mechanisms to promote resistance to heterosubtypic strains of influenza and suggest that vaccines that elicit both memory T cells and Abs to conserved epitopes of influenza may be an effective defense against a wide range of influenza serotypes.
Impaired Phagosomal Maturation in Neutrophils Leads to Periodontitis in Lysosomal-Associated Membrane Protein-2 Knockout Mice
Authors: Beertsen Wouter , Willenborg Marion , Everts Vincent , Zirogianni Angelika , Podschun Rainer , Schröder Bernd , Eskelinen Eeva-Liisa , Saftig Paul
Published: April 2014

Inflammatory periodontal diseases constitute one of the most common infections in humans, resulting in the destruction of the supporting structures of the dentition. Circulating neutrophils are an essential component of the human innate immune system. We observed that mice deficient for the major lysosomal-associated membrane protein-2 (LAMP-2) developed severe periodontitis early in life. This development was accompanied by a massive accumulation of bacterial plaque along the tooth surfaces, gingival inflammation, alveolar bone resorption, loss of connective tissue fiber attachment, apical migration of junctional epithelium, and pathological movement of the molars. The inflammatory lesions were dominated by polymorphonuclear leukocytes (PMNs) apparently being unable to efficiently clear bacterial pathogens. Systemic treatment of LAMP-2-deficient mice with antibiotics prevented the periodontal pathology. Isolated PMNs from LAMP-2-deficient mice showed an accumulation of autophagic vacuoles and a reduced bacterial killing capacity. Oxidative burst response was not altered in these cells. Latex bead and bacterial feeding experiments showed a reduced ability of the phagosomes to acquire an acidic pH and late endocytic markers, suggesting an impaired fusion of late endosomes-lysosomes with phagosomes. This study underlines the importance of LAMP-2 for the maturation of phagosomes in PMNs. It also underscores the requirement of lysosomal fusion events to provide sufficient antimicrobial activity in PMNs, which is needed to prevent periodontal disease.
A Th1-Recognized Peptide P277, When Tandemly Repeated, Enhances a Th2 Immune Response toward Effective Vaccines against Autoimmune Diabetes in Nonobese Diabetic Mice
Authors: Jin Liang , Zhu Aihua , Wang Yu , Chen Qingmei , Xiong Qiyan , Li Jianping , Sun Yunxiao , Li Taiming , Cao Rongyue , Wu Jie , Liu Jingjing
Published: April 2014

Subunit immunogens containing tandemly repeated copies of T and B cell epitopes have been shown to be more immunogenic than the respective immunogen containing only a single copy of the sequence. To investigate whether the increased copies of the Th2-activated peptide sequence will enhance the Th2-like immune response, we compared the cytokine secreted in mice that inoculated with two immunogens containing one or six tandemly repeated copies of a Th2-activated peptide sequence P277. Immunization of mice with a 6×P277 fusion protein elicited much higher levels of Th2-type cytokines and lower Th1-type cytokines than with a fusion protein with one P277 peptide. The data of tandemly repeated peptide P277 potentiate the anti-inflammatory in NOD mice, most likely associated with a Th1 to Th2 cytokine shift specific for the autoimmune T cells, which suggested that application of multiple tandem repeats of a Th2-activated epitope is an efficient method to enhance the anti-inflammatory immune response by shifting the immune response from Th1-like to Th2-like. The subunit immunogens containing tandemly repeated copies of peptide P277 might be effective vaccines against autoimmune diabetes in NOD mice.
Integrin αDβ2 Is Dynamically Expressed by Inflamed Macrophages and Alters the Natural History of Lethal Systemic Infections
Authors: Miyazaki Yasunari , Bunting Michaeline , Stafforini Diana M. , Harris Estelle S. , McIntyre Thomas M. , Prescott Stephen M. , Frutuoso Valber S. , Amendoeira Fabio C. , de Oliveira Nascimento Danielle , Vieira-de-Abreu Adriana , Weyrich Andrew S. , Castro-Faria-Neto Hugo C. , Zimmerman Guy A.
Published: April 2014

The leukocyte integrins have critical roles in host defense and inflammatory tissue injury. We found that integrin αDβ2, a novel but largely uncharacterized member of this family, is restricted to subsets of macrophages and a small population of circulating leukocytes in wild-type mice in the absence of inflammatory challenge and is expressed in regulated fashion during cytokine-induced macrophage differentiation in vitro. αDβ2 is highly displayed on splenic red pulp macrophages and mediates their adhesion to local targets, identifying key functional activity. In response to challenge with Plasmodium berghei, a malarial pathogen that models systemic infection and inflammatory injury, new populations of αD+ macrophages evolved in the spleen and liver. Unexpectedly, targeted deletion of αD conferred a survival advantage in P. berghei infection over a 30-day observation period. Mechanistic studies demonstrated that the increased survival of αD−/− animals at these time points is not attributed to differences in magnitude of anemia or parasitemia or to alterations in splenic microanatomy, each of which is a key variable in the natural history of P. berghei infection, and indicated that an altered pattern of inflammatory cytokines may contribute to the difference in mortality. In contrast to the outcome in malarial challenge, death of αD−/− animals was accelerated in a model of Salmonella sepsis, demonstrating differential rather than stereotyped roles for αDβ2 in systemic infection. These studies identify previously unrecognized and unique activities of αDβ2, and macrophages that express it, in host defense and injury.
Recurrent Staphylococcal Cellulitis and Subcutaneous Abscesses in a Child with Autoantibodies against IL-6
Authors: Puel Anne , Picard Capucine , Lorrot Mathie , Pons Charlotte , Chrabieh Maya , Lorenzo Lazaro , Mamani-Matsuda Maria , Jouanguy Emmanuelle , Gendrel Dominique , Casanova Jean-Laurent
Published: April 2014

We investigated an otherwise healthy patient presenting two episodes of staphylococcal cellulitis and abscesses, accompanied by high fever and biological signs of inflammation but, paradoxically, with no detectable increase in serum levels of C-reactive protein (CRP), an IL-6-responsive protein synthesized in the liver. Following in vitro activation of whole blood cells from the patient with multiple cytokines, TLR agonists, heat-killed bacteria, and mitogens, we observed a profound and specific impairment of IL-6 secretion. However, the patient’s PBMCs, activated in the same conditions but in the absence of the patient’s plasma, secreted IL-6 normally. The patient’s serum contained high titers of IgG1 autoantibodies against IL-6, which specifically neutralized IL-6 production by control PBMCs as well as IL-6 responses in the human hepatocellular carcinoma cell line Hep3B. These anti-IL-6 autoantibodies were detected over a period of 4 years, in the absence of any other autoantibodies. Our results indicate that these Abs probably prevented an increase in CRP concentration during infection and that impaired IL-6-mediated immunity may have contributed to staphylococcal disease. Patients with severe bacterial infections and low serum CRP concentrations should be tested for anti-IL-6 autoantibodies, especially in the presence of other clinical and biological signs of inflammation.
IL-17RA and IL-17RC Receptors Are Essential for IL-17A-Induced ELR+ CXC Chemokine Expression in Synoviocytes and Are Overexpressed in Rheumatoid Blood
Authors: Zrioual Saloua , Toh Myew-Ling , Tournadre Anne , Zhou Yuan , Cazalis Marie-Angélique , Pachot Alexandre , Miossec Vincent , Miossec Pierre
Published: April 2014

IL-17A is a cytokine secreted by the newly described Th17 cells implicated in rheumatoid arthritis (RA). Less is known about its receptors in synoviocytes. IL-17RA and IL-17RC were found to be overexpressed in RA peripheral whole blood and their expression was detected locally in RA synovium. In vitro, IL-17A synergized with TNF-α to induce IL-6, IL-8, CCL-20, and matrix metalloproteinase-3. Using microarrays, a specific up-regulation of Glu-Leu-Arg+ CXC chemokines was observed in IL-17A-treated synoviocytes. Using both posttranslational inhibitions by silencing interfering RNA and extracellular blockade by specific inhibitors, we showed that both IL-17RA and IL-17RC are implicated in IL-17A-induced IL-6 secretion, whereas in the presence of TNF-α, the inhibition of both receptors was needed to down-regulate IL-17A-induced IL-6 and CCL-20 secretion. Thus, IL-17A-induced IL-6, IL-8, and CCL20 secretion was dependent on both IL-17RA and IL-17RC, which are overexpressed in RA patients. IL-17A-induced pathogenic effects may be modulated by IL-17RA and/or IL-17RC antagonism.
Immunotherapy with Chimeric NKG2D Receptors Leads to Long-Term Tumor-Free Survival and Development of Host Antitumor Immunity in Murine Ovarian Cancer
Authors: Barber Amorette , Zhang Tong , Sentman Charles L.
Published: April 2014

Ovarian cancer is one of the leading causes of cancer death in women and the development of novel therapies is needed to complement the standard treatment options such as chemotherapy and radiation. In this study, we show that treatment with T cells expressing a chimeric NKG2D receptor (chNKG2D) was able to lead to long-term, tumor-free survival in mice bearing established ovarian tumors. Tumor-free mice were able to reject a rechallenge with ovarian tumor cells 225 days after original tumor injection. In addition, chNKG2D T cell treatment induced specific host immune responses to ovarian tumor cells, including the development of both CD8+ and CD4+ T cell tumor-specific memory responses. The chNKG2D T cells reduced the ovarian tumor burden using both cytotoxic and cytokine-dependent pathways. Specifically, chNKG2D T cell expression of perforin, GM-CSF, and IFN-γ were essential for complete antitumor efficacy.
Practical theology: A critically engaged practical reason approach of practice, theory, practice and theory
Authors: Klaasen John S.
Published: April 2014

Browning’s influential use of practical reason for his fundamental practical theology is analysed. His correlation of theory and practice in his three stages of theory, practice and theory is also critiqued because his approach reduces practical theology almost to professionalism and principles for ministry. His approach could also result in an antagonistic relationship between practice and theory as practice is reduced to theory or academics. This article seeks to present a critically engaged practical reasoning approach in which theory and practice have an in-ter-dependent relationship. Practical reason is an activity in which engagement happens at every stage. For this to happen, theory and practice interact as equal variables that have a bearing on each other not to reduce the one to the other, but to complement each other in a lateral hermeneutical process. This process has four stages, unlike Browning’s three-stage correlation. The stages are schematically presented as practice, theory, practice and theory.
Milestones and new ventures
Authors: Davis Razaan
Published: April 2014

No abstract.
Age at diagnosis of female breast cancer in Oman: Issues and implications
Authors: Mehdi Itrat , Monem Essam Abdul , Bahrani Bassim Jaffar Al , Kharusi Suad Al , Nada Ayman Mohammad , Lawati Jawad Al , Lawati Najla Al
Published: April 2014

Introduction: Female breast cancer (BC) is the most frequent malignancy diagnosed globally, about 23% of the diagnosed cancers. BC incidence varies geographically, highest in Western Europe and lowest in Africa. BC in females is strongly correlated to age, the highest incidence rate amongst older women reinforcing the importance of hormonal status. BC in young females has an aggressive phenotype. There is a shared observation amongst practicing oncologists that BC in Middle East and the developing world presents at an earlier age. Aim and Objective: The aims of this study are to evaluate the age at presentation of female BC in Oman, and to compare our data with international and regional published data. It discusses the impact of young age Breast Cancer. Materials and Methods: All diagnosed female BC cases registered from 1996-2010 all over the country, were retrieved from the National Cancer Registry, Ministry of Health. BC cases were analyzed with respect to age at presentation. The data were compared with regional and international data. Results: A total of 14,109 cancer cases were recorded during the period of study. BC was the leading malignancy as 1,294 cases (9.1%). Female BC patients were 1,230; denoting 19.2% of all female cancers. 53.5% of female BC presented below 50 years of age. Male BC constituted 5% of total, with 67% of male BC occurring over 50 years of age. Compared with data from Oman, the highest rates in UK and other Western countries are above 50 years of age. These rates are four to 10 times higher than local in different age groups. Interestingly, these rates increase with increasing age in UK from 40-45 to up to 85+, keep on increasing and go up to four times higher with higher age. This phenomenon, of increasing incidence rates with age, is not observed in our local population. Discussion: BC is significantly correlated to age as reported from Western population. BC is reported at a younger age from developing and Arab World, which need to be further studied and validated. This phenomenon of BC in younger age may have significant implications and effects ranging from screening, diagnosis, management, prognosis, and cost of treatment. Conclusion: The impact on young women diagnosed with BC is enormous, ranging from psychosocial to healthcare services and economics. There is a need to study it further in depth in developing World.
Late effects of cancer treatment in breast cancer survivors
Authors: Agrawal Sushma
Published: April 2014

Postoperative radiation therapy (RT) and chemotherapy,both reduces the risk of local recurrence and extends overall survival in patients with breast cancer (BC). Concerns have, however, been raised about the risk of acute and chronic side effects in breast cancer survivors as the number of treated individuals is large and their expected survival is long compared to most patients with other malignant diseases. Cardiac toxicity, reproductive dysfunction, pneumonitis (RP),arm lymph edema, neuropathy, skin changes are examples of the wide range of complications that has been associated with adjuvant treatment.
Ramosetron hydrochloride for the prevention of cancer chemotherapy induced nausea and vomiting: The Indian experience
Authors: Sanmukhani Jayesh J. , Pawar Prafulla , Mittal Ravindra
Published: April 2014

Background: Despite the advent of 5-HT 3 antagonists, control of delayed gastrointestinal adverse events with cancer chemotherapy is still not optimal. This open label, active controlled, multicentric clinical trial was undertaken to assess the comparative efficacy and safety of ramosetron with ondansetron for the prevention of acute and delayed nausea and vomiting associated with emetogenic cancer chemotherapy in adult patients in India. Materials and Methods: Enrolled patients received treatment with ramosetron hydrochloride 0.1 mg or ondansetron hydrochloride 4 mg tablets once daily in the morning for 5 days starting 1 h before the start of chemotherapy. Severity grades of nausea and vomiting were recorded on a daily basis for a period of 5 days and complete response rate (CRR) and effective rate (ER) were calculated. Clinical adverse events were recorded and hematological and biochemical investigations were performed for safety assessment. Results: A total of 114 patients in ramosetron group and 100 patients in ondansetron group completed the study and were eligible for efficacy and safety analysis. CRR and ERs show that while ramosetron is non-inferior to ondansetron in the control of early nausea and vomiting (occurring during the first 24 h) after the treatment with emetogenic chemotherapy, it is superior to ondansetron in the control of delayed nausea and vomiting (occurring after the first 24 h). The proportion of patients achieving a cumulative complete response (for the entire study period) is significantly greater in ramosetron group as compared to ondansetron group (27.2% vs. 7.0%; P < 0.001). Ramosetron was well tolerated by all the study participants. Conclusions: Ramosetron is significantly more effective than ondansetron for the control of delayed nausea and vomiting induced by emetogenic cancer chemotherapy.
Inferring regional sources and sinks of atmospheric CO2 from GOSAT XCO2 data
Authors: Deng F. , Jones D. B. A. , Henze D. K. , Bousserez N. , Bowman K. W. , Fisher J. B. , Nassar R. , O'Dell C. , Wunch D. , Wennberg P. O. , Kort E. A. , Wofsy S. C. , Blumenstock T. , Deutscher N. M. , Griffith D. W. T. , Hase F. , Heikkinen P. , Sherlock V. , Strong K. , Sussmann R. , Warneke T.
Published: April 2014

Abstract. We have examined the utility of retrieved column-averaged, dry-air mole fractions of CO2 (XCO2) from the Greenhouse Gases Observing Satellite (GOSAT) for quantifying monthly, regional flux estimates of CO2, using the GEOS-Chem four-dimensional variational (4D-Var) data assimilation system. We focused on assessing the potential impact of biases in the GOSAT CO2 data on the regional flux estimates. Using different screening and bias correction approaches, we selected three different subsets of the GOSAT XCO2 data for the 4D-Var inversion analyses, and found that the inferred global fluxes were consistent across the three XCO2 inversions. However, the GOSAT observational coverage was a challenge for the regional flux estimates. In the northern extratropics, the inversions were more sensitive to North American fluxes than to European and Asian fluxes due to the lack of observations over Eurasia in winter and over eastern and southern Asia in summer. The regional flux estimates were also sensitive to the treatment of the residual bias in the GOSAT XCO2 data. The largest differences obtained were for temperate North America and temperate South America, for which the largest spread between the inversions was 1.02 and 0.96 Pg C, respectively. In the case of temperate North America, one inversion suggested a strong source, whereas the second and third XCO2 inversions produced a weak and strong sink, respectively. Despite the discrepancies in the regional flux estimates between the three XCO2 inversions, the a posteriori CO2 distributions were in good agreement (with a mean difference between the three inversions of typically less than 0.5 ppm) with independent data from the Total Carbon Column Observing Network (TCCON), the surface flask network, and from the HIAPER Pole-to-Pole Observations (HIPPO) aircraft campaign. The discrepancy in the regional flux estimates from the different inversions, despite the agreement of the global flux estimates suggests the need for additional work to determine the minimum spatial scales at which we can reliably quantify the fluxes using GOSAT XCO2. The fact that the a posteriori CO2 from the different inversions were in good agreement with the independent data although the regional flux estimates differed significantly, suggests that innovative ways of exploiting existing data sets, and possibly additional observations, are needed to better evaluate the inferred regional flux estimates.
Reconstruction of geomagnetic activity and near-Earth interplanetary conditions over the past 167 yr – Part 3: Improved representation of solar cycle 11
Authors: Lockwood M. , Nevanlinna H. , Vokhmyanin M. , Ponyavin D. , Sokolov S. , Barnard L. , Owens M. J. , Harrison R. G. , Rouillard A. P. , Scott C. J.
Published: April 2014

Abstract. Svalgaard (2014) has recently pointed out that the calibration of the Helsinki magnetic observatory's H component variometer was probably in error in published data for the years 1866–1874.5 and that this makes the interdiurnal variation index based on daily means, IDV(1d), (Lockwood et al., 2013a), and the interplanetary magnetic field strength derived from it (Lockwood et al., 2013b), too low around the peak of solar cycle 11. We use data from the modern Nurmijarvi station, relatively close to the site of the original Helsinki Observatory, to confirm a 30% underestimation in this interval and hence our results are fully consistent with the correction derived by Svalgaard. We show that the best method for recalibration uses the Helsinki Ak (H) and aa indices and is accurate to ±10%. This makes it preferable to recalibration using either the sunspot number or the diurnal range of geomagnetic activity which we find to be accurate to ±20%. In the case of Helsinki data during cycle 11, the two recalibration methods produce very similar corrections which are here confirmed using newly digitised data from the nearby St Petersburg observatory and also using declination data from Helsinki. However, we show that the IDV index is, compared to later years, too similar to sunspot number before 1872, revealing independence of the two data series has been lost; either because the geomagnetic data used to compile IDV has been corrected using sunspot numbers, or vice versa, or both. We present corrected data sequences for both the IDV(1d) index and the reconstructed IMF (interplanetary magnetic field). We also analyse the relationship between the derived near-Earth IMF and the sunspot number and point out the relevance of the prior history of solar activity, in addition to the contemporaneous value, to estimating any "floor" value of the near-Earth interplanetary field.
Inferences from CO2 and CH4 concentration profiles at the Zotino Tall Tower Observatory (ZOTTO) on regional summertime ecosystem fluxes
Authors: Winderlich J. , Gerbig C. , Kolle O. , Heimann M.
Published: April 2014

Abstract. The Siberian region is still sparsely covered by ecosystem observatories, which motivates the exploitation of existing data sets to gain spatially and temporally better-resolved carbon budgets. The Zotino Tall Tower Observatory (ZOTTO; 60°48' N, 89°21' E) observations of CO2 and CH4 mole fractions as well as meteorological parameters from six different heights up to 301 m allow for an additional estimate of surface–atmosphere fluxes of CO2 and CH4 for the middle Siberian region beginning 2009. The total carbon flux is calculated from the storage and the turbulent flux component. The gradients between the different tower levels determine the storage flux component, which dominates the regional fluxes, especially during nighttime. As a correction term, the turbulent flux component was estimated by the modified Bowen ratio method based on the sensible heat flux measurements at the top of the tower. The obtained average nighttime fluxes (23:00 to 04:00 local time) are 2.7 ± 1.1 μmol (m2 s)−1 for CO2 and 5.6 ± 4.5 nmol (m2 s)−1 for CH4 during the summer months June–September in 2009 and 2011. During the day, the method is limited due to numeric instabilities because of vanishing vertical gradients; however, the derived CO2 fluxes exhibit reasonable diurnal shapes and magnitudes compared to the eddy covariance technique, which became available at the site in 2012. Therefore, the tall tower data facilitate the extension of the new eddy covariance flux data set backward in time. The diurnal signal of the CH4 flux is predominantly characterized by a strong morning transition, which is explained by local topographic effects.
Identifying homogenous sub-periods in HadISD
Authors: Dunn R. J. H. , Willett K. M. , Morice C. P. , Parker D. E.
Published: April 2014

Abstract. We report on preliminary steps in the homogenisation of HadISD, a sub-daily, station-based dataset covering 1973–2013. Using temperature, dewpoint temperature, sea-level pressure and wind speeds, change points are detected using the Pairwise Homogenisation Algorithm from Menne and Williams Jr. (2009). Monthly mean values and monthly mean diurnal ranges (temperature and dewpoint temperature) or monthly maximum values (wind speeds) are processed using the full network of 6103 stations in HadISD. Where multiple change points are detected within one year, they are combined and the average date used. Under the assumption that the underlying true population of inhomogeneity magnitudes is Gaussian, adjustments as small as around 0.5 °C, 0.5 hPa or 0.5 m s−1 have been successfully detected. No strong biases are present in the distributions of the adjustment values. The change point dates and adjustment values for each of the calculation methods will be provided alongside the dataset to allow users to select stations which have different levels of homogeneity. We give an example application of this change point information in calculating global temperature values from HadISD and comparing these to CRUTEM4. Removing the most inhomogeneous stations results in a better match between HadISD and CRUTEM4 when matched to the same coverage. However, further removals of stations with smaller and fewer inhomogeneities worsens the match.
Global sensitivity analysis of Indian Monsoon during the Pleistocene
Authors: Araya-Melo P. A. , Crucifix M. , Bounceur N.
Published: April 2014

Abstract. The sensitivity of Indian Monsoon to the full spectrum of climatic conditions experienced during the Pleistocene is estimated using the climate model HadCM3. The methodology follows a global sensitivity analysis based on the emulator approach of Oakley and O'Hagan (2004) implemented following a three-step strategy: (1) develop an experiment plan, designed to efficiently sample a 5-dimensional input space spanning Pleistocene astronomical configurations (3 parameters), CO2 concentration and a Northern Hemisphere glaciation index, (2) develop, calibrate and validate an emulator of HadCM3, in order to estimate the response of the Indian Monsoon over the full input space spanned by the experiment design, and (3) estimate and interpret sensitivity diagnostics, including sensitivity measures, in order to synthesize the relative importance of input factors on monsoon dynamics, estimate the phase of the monsoon intensity response with respect to that of insolation, and detect potential non-linear phenomena. Specifically, we focus on four variables: summer (JJAS) temperature and precipitation over North India, and JJAS sea-surface temperature and mixed-layer depth over the north-western side of the Indian ocean. It is shown that precession controls the response of four variables: continental temperature in phase with June to July insolation, high glaciation favouring a late-phase response, sea-surface temperature in phase with May insolation, and continental precipitation in phase with July insolation, and mixed-layer depth in antiphase with the latter. CO2 variations controls temperature variance with an amplitude similar to that of precession. The effect of glaciation is dominated by the albedo forcing, and its effect on precipitation competes with that of precession. Obliquity is a secondary effect, negligible on most variables except sea-surface temperature. It is also shown that orography forcing reduces the glacial cooling, and even has a positive effect on precipitation. As regards the general methodology, it is shown that the emulator provides a powerful approach, not only to express model sensitivity, but also to estimate internal variability (based on the nugget term introduced in the correlation function of the emulator) and detect anomalous simulations.