bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-carbamylated Protein Antibodies Are Present Prior to Rheumatoid Arthritis and Are Associated with Its Future Diagnosis
Authors: Gan Ryan W. , Trouw Leendert A. , Shi Jing , Toes René E.M. , Huizinga Tom W.J. , Demoruelle M. Kristen , Kolfenbach Jason R. , Zerbe Gary O. , Deane Kevin D. , Edison Jess D. , Gilliland William R. , Norris Jill M. , Holers V. Michael 
Published: January 2015

Objective.Anti-carbamylated protein (anti-CarP) antibodies could further elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical disease. We compared the diagnostic accuracy of anti-CarP antibodies for future RA to other RA-related antibodies in military personnel.Methods.Stored pre-RA diagnosis serum samples from 76 RA cases were tested for anti-CarP fetal calf serum (FCS), anti-CarP fibrinogen (Fib), anticyclic citrullinated peptide antibodies version 2 (anti-CCP2), rheumatoid factor-nephelometry (RF-Neph), and RF isotypes [immunoglobulin M (IgM), IgG, and IgA]. Positivity for all antibodies was determined as ≥ 2 SD of log-transformed means from controls. Relationships between autoantibodies and future RA were assessed in prediagnosis serum for all RA cases compared to controls using sensitivity, specificity, and logistic regression. Differences in diagnostic accuracy between antibody combinations were assessed using comparisons of area under the curves (AUC).Results.Anti-CarP-FCS was 26% sensitive and 95% specific for future RA, whereas anti-CarP-Fib was 16% sensitive and 95% specific for future RA. Anti-CarP-FCS positivity was associated with future RA, while anti-CarP-Fib trended toward association. The antibody combination of anti-CCP2 and/or ≥ 2 RF (RF-Neph and/or RF-isotypes) resulted in an AUC of 0.72 for future RA, where the AUC was 0.71 with the addition of anti-CarP-FCS to this prior combination.Conclusion.Adding anti-CarP-FCS to antibody combinations did not improve AUC. However, anti-CarP-FCS was associated with future onset of RA, and was present in prediagnosis serum in ∼10% of RA cases negative for anti-CCP2 but positive for RF.
Quantitation of Circumferential Syndesmophyte Height along the Vertebral Rim in Ankylosing Spondylitis Using Computed Tomography
Authors: Tan Sovira , Yao Jianhua , Flynn John A. , Yao Lawrence , Ward Michael M. 
Published: January 2015

Objective.Using the 3-D imaging capability of computed tomography (CT), we developed an algorithm quantitating syndesmophyte height along the entire vertebral rim. We investigated its reliability and sensitivity to change, performed a 2-year longitudinal study, and compared it to CT measures of syndesmophyte volume.Methods.We performed thoracolumbar spine CT scans on 33 patients at baseline, Year 1, and Year 2, and computed syndesmophyte height in 4 intervertebral disc spaces (IDS). Height was computed every 5° (72 angular sectors) along the vertebral rim. These 72 measures were summed to form the circumferential height per IDS, and results from 4 IDS were summed to provide results per patient. To assess reliability, we compared results between 2 scans performed on the same day in 9 patients. Validity was assessed by associations with spinal flexibility.Results.Coefficient of variation for circumferential syndesmophyte height was 0.893% per patient, indicating excellent reliability. Based on the Bland-Altman analysis, an increase in circumferential height of more than 3.44% per patient represented a change greater than measurement error. At years 1 and 2, mean (SD) circumferential syndesmophyte height increases were 10.2% (11.7%) and 16.1% (14.0%), respectively. Sensitivity to change was 0.72 and 0.87 at years 1 and 2, respectively. Circumferential syndesmophyte height correlated with the Schober test (r = −0.56, p = 0.0003) and lateral thoracolumbar flexion (r = −0.73, p < 0.0001).Conclusion.CT-based circumferential syndesmophyte height had excellent reliability and good sensitivity to change. It was more highly correlated with spine flexibility than syndesmophyte volume. The algorithm shows promise for longitudinal studies of syndesmophyte growth.
Les structures européennes de contrôle des administrations pénitentiaires
Authors: Snacken Sonja 
Published: January 2015

Le rôle et l’impact du Comité de Prévention de la Torture sont analysés en interaction avec les autres instruments de protection des droits des détenus du Conseil de l’Europe : la Cour Européenne des Droits de l’Homme et les Recommandations du Comité des ministres. L’analyse démontre un renforcement réciproque du travail normatif ces vingt dernières années entre ce niveau judiciaire, politique et de contrôle sur le terrain. Par contre, peu de données empiriques sont disponibles quant à l’impact de ce travail normatif sur la réalité pénitentiaire. Une telle évaluation suppose des critères de succès ou d’échec clairs et des études systématiques sur le terrain. D’autre part, il importe de ne pas se limiter à une approche purement instrumentale et descendante de ‘mise en application’ des normes. La protection des droits de l’homme est un mouvement socio-politique et culturel qui dépasse de loin les murs de la prison. Mais qui n’est aussi qu’un des mouvements ayant des répercussions sur le monde pénitentiaire.
Genèse et structure des conflits politiques sur les droits des détenus dans la France contemporaine
Authors: Bérard Jean 
Published: January 2015

Cet article analyse deux séquences, les années 1970 et les années 2000, qui ont vu l’émergence de la nécessité de reconnaître les droits des prisonniers et de permettre le contrôle de leur application par des instances indépendantes. Il décrit la structure des conflits politiques liés à la reconnaissance de ces droits. Les militants et les instances de protection des droits de l’homme expriment l’exigence de la constitution d’un socle de droits commun à l’ensemble des prisonniers. L’administration pénitentiaire met en place des stratégies pour reconnaître la légitimité de l’entrée du droit en prison tout en modulant son application selon des régimes de détention distincts. Des conflits nés de ces approches opposées naissent des contentieux portés devant les tribunaux.
La alta montaña durante la Prehistoria: 10 años de investigación en el Pirineo catalán occidental
Authors: Gassiot Ballbè Ermengol , Rodríguez Antón David , Pèlachs Mañosa Albert , Pérez Obiol Ramon , Julià Brugués Ramón , Bal-Serin Marie-Claude , Mazzucco Niccolò 
Published: January 2015

Este artículo presenta los resultados de las campañas realizadas desde 2001 a 2010 en áreas de alta montaña del Pirineo axial occidental de Catalunya, que han generado unos registros arqueológicos extensos y detallados, así como diversos análisis paleoecológicos de turberas y contextos lacustres. Gracias a las 27 fechas radiocarbónicas obtenidas, se documenta la secuencia del poblamiento prehistórico en medios alpinos y subalpinos desde las primeras evidencias de su ocupación, en el Mesolítico, hasta el inicio de la Edad del Bronce, fundamentalmente. Se proponen nuevas hipótesis para su explicación. Se ha prestando especial interés a los procesos de colonización postglacial de estos espacios, a la introducción de prácticas ganaderas e, hipotéticamente, agrícolas y a su evolución. Se han considerado además actividades complementarias como la minería, la producción de carbón y la extracción de madera, así como las relaciones de las comunidades humanas de ámbitos de montaña con las de otras áreas geográficas.
Sitios en altura y vasijas rotas: reconsiderando la etapa de ‘plenitud’ de Cogotas I (1450-1150 cal AC) en la Meseta
Authors: Blanco González Antonio 
Published: January 2015

Este artículo plantea un ejercicio de autocrítica sobre la comprensión actual del final de Cogotas I en el interior de la Península Ibérica. Diversas dinámicas socio-políticas postuladas para este contexto como la concentración poblacional, la especialización artesanal o la jerarquización social suscitan problemas interpretativos por su deficiente engranaje con la evidencia aducida. Se reúne y escudriña la información contextual disponible sobre los lugares en altura de esta época para elucidar cómo se formaron. Se concluye interpretándolos como sedes estacionales de ceremonias agregativas, fruto de episodios de ocupación intermitentes y reiterados. Las ‘biografías culturales’ de varios recipientes cerámicos recuperados en hoyos permiten rastrear pautas de abandono complejas, reproducidas tanto en sitios encumbrados como en campos de hoyos en llanura. Ambos enfoques enfatizan la inadecuación de cualquier esquema dualista y simplificador para explicar el registro arqueológico y demandan barajar otras lecturas también posibles.
Ultra‐shallow seismic and GPR methods applied on sand‐covered limestone in northern Jutland, Denmark
Authors: Barlach Flemming 
Published: January 2015

ABSTRACTThis report gives an analysis and a geophysical interpretation of an ultra‐shallow high‐resolution seismic profile recorded on sand‐covered limestone. The interpretations include velocity and structural elements characterising the limestone surface. The seismic profile consists of short offset gathers with a very limited number of traces and with a shot‐point distance along the profile giving presumed equidistant reflection points on the subsurface interfaces. By subsequent band‐pass filtering and NMO‐correction, this field set‐up is found to be sufficient to create a detailed image of the immediate subsurface down to 20 m depth on the investigation site. This recording procedure facilitates a considerable increase in profiling speed compared to the denser shot‐point recordings normally required to obtain CDP gathers. A small number of additional larger gathers is recorded in order to verify that target reflectors are within the data window and source generated noise is outside. Interval velocities are inferred from a subset of the shot gathers by means of normalised semblance analyses demonstrating that critically refracted signals are not present in the gathers. Two major reflecting interfaces are detected, one in the sand above the limestone and the other on the top of the limestone, and there is a fault in the limestone. In addition, a small depression and possible cracks/karst formations in the limestone surface are visible. Anomalies in the amplitude of a reflector in the sands along the profile can be linked with the cracks/karst formations. Multiples are formed in the sand layers above the limestone, but they can be attenuated by predictive decon‐volution. The seismic velocity field indicates progressively higher water content in the sand layers above the limestone along the profile. Georadar facies descriptions provide additional insight into the more recent geological development on the investigation site. A georadar profile recorded near the limestone fault has penetration depth and resolution high enough to yield a facies model supporting geological interpretations which include the identification of aeolian sands on top of marine beach sand deposits. Furthermore, beach foreland and buried remains of sand dunes can be identified by their structural facets as derived from the georadar interpretations. The top of the marine beach sand is identified on the seismic and the georadar profiles and may be associated with the Littorina Sea bottom in the sand layers above the limestone.
The Study of Nano Sealing to Improve the Brittle Shale Wellbore Stability Under Dynamic Load
Authors: Liang Chuan , Chen Mian , Lu Baoping , Wang Jing , Jin Yan , Yang Shuai , Hou Xutian , Hou Bing 
Published: January 2015

Periodic large-scale collapse phenomena and accidents of horizontal drilling in brittle shale formation are common. In this process, borehole rock suffers dynamic load originating from impact of bit, hit of drilling tool and chemical action of drilling fluid. Based on hypothesis of static load, traditional wellbore stability analysis model cannot reveal the real mechanism. Therefore, traditional counter-measures eventually fail to restrain periodic brittle shale wellbore instability.
In this paper, mechanics behavior and deformation mechanism of the brittle shale has been investigated in the dynamic triaxial compression experiments at varying confining pressure and soaking time. Moreover, analytical tools of high resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS) and 3D visualization of ultra-high resolution CT scanner (Nano CT) etc. have been applied to observe and analyze the testing process.
The results indicate that mass ignored micrometer or even nanometer cracks, triggered by dynamic load, will not destroy the rock immediately, but accumulate and then aggravate the development of macroscopic fracture until rocks failure after a period of time. Consequently, the mechanism of strength reduction in this situation is not macroscopic fracture but micro-scale crack. Furthermore, the mechanical-chemical coupling model of brittle shale under dynamic load is established according to the quantitative relations among rock structure, interface state and strength. Based on the analyses above, counter-measures of Nano sealing technology to improve the strength of borehole rock is proposed.
Laboratory experiments show that Nano sealing can effectively strengthen wellbore stability in shale formation, whereas traditional highly macro sealing and inhibitive drilling fluid system cannot.
The Unappreciated Intracellular Lifestyle of Blastomyces dermatitidis
Authors: Sterkel Alana K. , Mettelman Robert , Wüthrich Marcel , Klein Bruce S. 
Published: January 2015

Abstract
Blastomyces dermatitidis, a dimorphic fungus and the causative agent of blastomycosis, is widely considered an extracellular pathogen, with little evidence for a facultative intracellular lifestyle. We infected mice with spores, that is, the infectious particle, via the pulmonary route and studied intracellular residence, transition to pathogenic yeast, and replication inside lung cells. Nearly 80% of spores were inside cells at 24 h postinfection with 104 spores. Most spores were located inside of alveolar macrophages, with smaller numbers in neutrophils and dendritic cells. Real-time imaging showed rapid uptake of spores into alveolar macrophages, conversion to yeast, and intracellular multiplication during in vitro coculture. The finding of multiple yeast in a macrophage was chiefly due to intracellular replication rather than multiple phagocytic events or fusion of macrophages. Depletion of alveolar macrophages curtailed infection in mice infected with spores and led to a 26-fold reduction in lung CFU by 6 d postinfection versus nondepleted mice. Phase transition of the spores to yeast was delayed in these depleted mice over a time frame that correlated with reduced lung CFU. Spores cultured in vitro converted to yeast faster in the presence of macrophages than in medium alone. Thus, although advanced B. dermatitidis infection may exhibit extracellular residence in tissue, early lung infection with infectious spores reveals its unappreciated facultative intracellular lifestyle.
A Novel Regulatory Macrophage Induced by a Helminth Molecule Instructs IL-10 in CD4+ T Cells and Protects against Mucosal Inflammation
Authors: Ziegler Thomas , Rausch Sebastian , Steinfelder Svenja , Klotz Christian , Hepworth Matthew R. , Kühl Anja A. , Burda Paul-Christian , Lucius Richard , Hartmann Susanne 
Published: January 2015

Abstract
Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion of bioactive molecules, which target and modify host immune cells. In this study, we show that the helminth immunomodulator AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of allergic airway inflammation and colitis in mice. A single adoptive transfer of AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE levels, the influx of eosinophils into the airways, local and systemic Th2 cytokine levels, and mucus production in lung bronchioles of mice, whereas increasing local and systemic IL-10 production by CD4+ T cells. Moreover, a single administration of AvCystatin-Mreg during experimentally induced colitis strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed increased expression of a distinct group of genes including LIGHT, sphingosine kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4+ T cells, AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact–independent manner. Collectively, our data identify a specific suppressive macrophage population induced by a single parasite immunomodulator, which protects against mucosal inflammation.
Monitoring and Cell-Specific Deletion of C5aR1 Using a Novel Floxed GFP-C5aR1 Reporter Knock-in Mouse
Authors: Karsten Christian M. , Laumonnier Yves , Eurich Benjamin , Ender Fanny , Bröker Katharina , Roy Sreeja , Czabanska Anna , Vollbrandt Tillman , Figge Julia , Köhl Jörg 
Published: January 2015

Abstract
Many of the biological properties of C5a are mediated through activation of its receptor (C5aR1), the expression of which has been demonstrated convincingly on myeloid cells, such as neutrophils, monocytes, and macrophages. In contrast, conflicting results exist regarding C5aR1 expression in dendritic cells (DCs) and lymphoid lineage cells. In this article, we report the generation of a floxed GFP-C5aR1 reporter knock-in mouse. Using this mouse strain, we confirmed strong C5aR1 expression in neutrophils from bone marrow, blood, lung, and spleen, as well as in peritoneal macrophages. Further, we show C5aR1 expression in lung eosinophils, lung- and lamina propria–resident and alveolar macrophages, bone marrow–derived DCs, and lung-resident CD11b+ and monocyte-derived DCs, whereas intestinal and pulmonary CD103+ DCs stained negative. Also, some splenic NKT cells expressed GFP, whereas naive NK cells and B2 cells lacked GFP expression. Finally, we did not observe any C5aR1 expression in naive or activated CD4+ Th cells in vitro or in vivo. Mating the floxed GFP-C5aR1 mouse strain with LysMCre mice, we were able to specifically delete C5aR1 in neutrophils and macrophages, whereas C5aR1 expression was retained in DCs. In summary, our findings suggest that C5aR1 expression in mice is largely restricted to cells of the myeloid lineage. The novel floxed C5aR1 reporter knock-in mouse will prove useful to track C5aR1 expression in experimental models of acute and chronic inflammation and to conditionally delete C5aR1 in immune cells.
High-Mobility Group Box 1: A Novel Target for Treatment of Pseudomonas aeruginosa Keratitis
Authors: McClellan Sharon , Jiang Xiaoyu , Barrett Ronald , Hazlett Linda D. 
Published: January 2015

Abstract
High-mobility group box 1 (HMGB1), a prototypic alarmin, mediates the systemic inflammatory response syndrome. Treatment with vasoactive intestinal peptide, an anti-inflammatory neuropeptide, downregulates proinflammatory cytokines and promotes healing in a susceptible (cornea perforates) model of Pseudomonas aeruginosa keratitis, and also significantly downregulates HMGB1 expression. Therefore, we examined targeting HMGB1 for the treatment of P. aeruginosa keratitis to avoid delivery and other issues associated with vasoactive intestinal peptide. For this, HMGB1 was silenced using small interfering RNA, whereas controls were treated with a nonspecific scrambled sequence small interfering RNA. Less disease was seen postinfection in siHMGB1 compared with control mice and was documented by clinical score and photographs with a slit lamp. Real-time RT-PCR and ELISA confirmed HMGB1 knockdown. RT-PCR analysis also revealed reduced mRNA levels of IL-1β, MIP-2, TNF-α, TLR4, and receptor for advanced glycation end products, whereas mRNA levels of anti-inflammatory TLRs single Ig IL-1–related receptor and ST2 were increased significantly. HMGB1 knockdown also decreased IL-1β and MIP-2 proteins, reducing polymorphonuclear cell number in the infected cornea. mRNA and protein levels of CXCL12 and CXCR4, as well as mononuclear cells, were reduced significantly after HMGB1 knockdown. Ab neutralization of HMGB1, infection with a clinical isolate, and recombinant HMGB1 treatment of resistant mice supported the silencing studies. These data provide evidence that silencing HMGB1 promotes better resolution of P. aeruginosa keratitis by decreasing levels of proinflammatory mediators (decreasing polymorphonuclear cell infiltration), increasing anti-inflammatory TLRs, reducing CXCL12 (preventing HMGB1/CXCL12 heterodimer formation), and signaling through CXCR4, reducing monocyte/macrophage infiltration.
Cutting Edge: Stage-Specific Requirement of IL-18 for Antiviral NK Cell Expansion
Authors: Madera Sharline , Sun Joseph C. 
Published: January 2015

Abstract
Although NK cells are considered part of the innate immune system, recent studies have demonstrated the ability of Ag-experienced NK cells to become long-lived and contribute to potent recall responses similar to T and B cells. The precise signals that promote the generation of a long-lived NK cell response are largely undefined. In this article, we demonstrate that NK cells require IL-18 signaling to generate a robust primary response during mouse CMV (MCMV) infection but do not require this signal for memory cell maintenance or recall responses. IL-12 signaling and STAT4 in activated NK cells increased the expression of the adaptor protein MyD88, which mediates signaling downstream of the IL-18 and IL-1 receptors. During MCMV infection, NK cells required MyD88, but not IL-1R, for optimal expansion. Thus, an IL-18–MyD88 signaling axis facilitates the prolific expansion of NK cells in response to primary viral infection, but not recall responses.
5-Lipoxygenase Is a Direct Target of miR-19a-3p and miR-125b-5p
Authors: Busch Saskia , Auth Eileen , Scholl Friederike , Huenecke Sabine , Koehl Ulrike , Suess Beatrix , Steinhilber Dieter 
Published: January 2015

Abstract
5-Lipoxygenase (5-LO) is the key enzyme in leukotriene biosynthesis. Leukotrienes are mediators of the innate immune system and inflammatory processes, and they might also be involved in cancer development. MicroRNAs (miRNAs) are important translational regulators and have been shown to be involved in development, differentiation, and cancer. Unraveling the miRNA network is important for understanding the cellular regulation processes. We identified two new miRNAs, miR-19a-3p and miR-125b-5p, regulating 5-LO and confirmed direct interaction by reporter gene assays. Furthermore, we investigated the regulation of 5-LO by these two miRNAs in several cell types. Inhibition of both miRNAs by antagomirs during differentiation of the myeloid cell line Mono Mac 6 led to a significant increase in 5-LO protein expression. Stimulation of human T lymphocytes with PHA resulted in a strong downregulation of 5-LO mRNA expression and in the induction of miR-19a-3p. The inhibition of miR-19a-3p with an antagomir led to a significant increase in 5-LO mRNA expression in T lymphocytes. Taken together, our data reveal that miR-19a-3p and miR-125b-5p target 5-LO in a cell type– and stimulus-specific manner.