bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of compaction and UV exposure on performance of acrylate/glass‐fiber composites cured layer by layer
Authors: Duan Yugang , Li Jia , Zhong Weihong , Maguire Russell G. , Zhao Guoqiang , Xie Hong , Li Dichen , Lu Bingheng 
Published: September 2011

AbstractWith an aim to reducing manufacturing costs, in general and specifically to provide a solution to the thick laminate curing depth issue for composite materials, UV curing technology was combined with a fiber placement process to fabricate acrylate/glass‐fiber composites. A novel layer‐by‐layer UV in situ curing method was employed in this article and interlaminar shear strength (ILSS) tests and SEM were used to evaluate the effect of processing parameters, including compaction force and UV exposure dose, on ILSS. The SEM images from short‐beam strength test samples and the results of ILSS showed that the fibers' distribution was uniform in the cured matrix resin resulting from the compaction forces and that beneficially influenced the ILSS of the composite greatly. However, the matrix resin produced large shrinkage stresses when it reached a high degree of conversion (DC) in one‐step, which resulted in poor interlaminar adhesion. In addition, the fast curing speed of UV on the composite resulted in poor wetting between fiber and resin, and accordingly resulted in lower ILSS. To overcome these problems and obtain high ILSS value composites, an optimized compaction force and UV exposure dose were determined experimentally. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Ontogenetic Allometry and Cranial Shape Diversification Among Human Populations From South America
Authors: Gonzalez Paula N. , Perez S. Ivan , Bernal Valeria 
Published: September 2011

AbstractModifications of ontogenetic allometries play an important role in patterning the shape differentiation among populations. This study evaluates the influence of size variation on craniofacial shape disparity among human populations from South America and assesses whether the morphological disparity observed at the interpopulation level resulted from a variable extension of the same ontogenetic allometry, or whether it arose as a result of divergences in the pattern of size‐related shape changes. The size and shape of 282 adult and subadult crania were described by geometric morphometric‐based techniques. Multivariate regressions were used to evaluate the influence of size on shape differentiation between and within populations, and phylogenetic comparative methods were used to take into account the shared evolutionary history among populations. The phylogenetic generalized least‐squares models showed that size accounts for a significant amount of shape variation among populations for the vault and face but not for the base, suggesting that the three modules did not exhibit a uniform response to changes in overall growth. The common slope test indicated that patterns of evolutionary and ontogenetic allometry for the vault and face were similar and characterized by a heightening of the face and a lengthening of the vault with increasing size. The conservation of the same pattern of shape changes with size suggests that differences in the extent of growth contributed to the interpopulation cranial shape variation and that certain directions of morphological change were favored by the trait covariation along ontogeny. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
DNA Methylation and Nonsmall Cell Lung Cancer
Authors: Lu Fang , Zhang Hong‐Tao 
Published: September 2011

AbstractLung cancer is the leading cause of cancer‐related death in men and women worldwide. Owing to the scarcity of effective tools for early detection and therapy strategies, the 5‐year survival rate of lung cancer is very poor. Because the accumulation of multiple genetic and/or epigenetic changes, including DNA methylation, has been suggested to contribute to development and progression of human cancers, improved understanding of the relationship between DNA methylation and lung cancer will provide new insights for identifying promising biomarkers for diagnosis, prognosis, and treatment of lung cancer. Here, we present a relatively comprehensive review of DNA methylation and lung cancer, discuss DNA methylation changes in carcinogenesis and metastasis of lung cancer, and explore the association of microRNA with DNA methylation. Additionally, we outline the applications of DNA methylation in clinical practice, such as diagnosis, prognosis, and therapy of lung cancer. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Changes in Triacylglycerol‐Accumulated Fiber Type, Fiber Type Composition, and Biogenesis in the Mitochondria of the Soleus Muscle in Obese Rats
Authors: Kaneko Syuhei , Iida Ryo‐Hei , Suga Takeo , Fukui Tadayoshi , Morito Mitsuhiko , Yamane Akira 
Published: September 2011

AbstractLittle is known about the effects of obesity on skeletal muscle consisting of approximately 80% type I (slow) fibers, such as that in the soleus muscle, although type I fibers have an enhanced capacity for mitochondrial respiration and fatty acid oxidation. We investigated the effects of obesity on the soleus muscle in the rat. Rats were fed a high‐fat diet (protein:fat:carbohydrate = 20:57:23; 508 kcal/100 g) or a control diet (protein:fat:carbohydrate = 20:10:70; 366 kcal/100 g) for 10 weeks. We analyzed the accumulation of intramyocellular triacylglycerol (IMTG), fiber type composition, and the biogenesis and function of the mitochondria in the soleus muscle of the rat during 10 weeks of feeding, using histochemical and real‐time polymerase chain reaction analyses. Obesity increased body weight and markedly elevated IMTG levels in type I, but not in type II, fibers of the soleus muscle throughout the feeding period. Obesity also inhibited the biogenesis and function in the mitochondria and altered the fiber type composition in the soleus muscle. The suppression of biogenesis and function in the mitochondria, and the alteration in the fiber type composition may be attributable to the marked IMTG accumulation in the soleus muscle of the rat. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
mSmile is Necessary for Bronchial Smooth Muscle and Alveolar Myofibroblast Development
Authors: Yun Eun Jun , Vu Thiennu H. 
Published: September 2011

AbstractDisrupted lung alveolar myofibroblast and bronchial smooth muscle (BSM) cell development may lead to pulmonary disorders such as bronchopulmonary dysplasia. The molecular mechanisms that regulate BSM and alveolar myofibroblast development are not fully understood. Here we show that mSmile (murine Smile), a novel transmembrane protein with tetratricopeptide repeats, functions in lung alveolar myofibroblast and BSM cell development. mSmile mutant mice exhibit early neonatal lethality with few mice surviving up to 3 weeks. Mutant lungs display both airway branching morphogenesis defect during fetal lung development and alveolarization defect after birth. These defects are associated with reduced numbers of BSM cells in the peribronchial subepithelial region and clefts and myofibroblasts in alveolar septae. Expression of fibroblast growth factor‐10 and its down stream target Bmp‐4, which are important for BSM formation, is decreased. In vitro, mSmile mutant embryonic fibroblasts show reduced receptor activation and induction of myofibroblast formation in response to Transforming growth factor‐β (Tgf‐β), indicating that mSmile may mediate myofibroblast development through modulation of Tgf‐β signaling. These studies identify mSmile as a novel gene specifying both the BSM and lung alveolar myofibroblast lineages, contributing to our understanding of the biological control of the development of these cells, and may provide insights into the aberrant smooth muscle and alveolar myofibroblast development that occur in pathological conditions. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.
Design, Synthesis, and Antiproliferative Activity of 3,4‐Diarylpyrazole‐1‐carboxamide Derivatives Against Melanoma Cell Line
Authors: El‐Gamal Mohammed I. , Choi Hong Seok , Cho Hae‐Guk , Hong Jun Hee , Yoo Kyung Ho , Oh Chang‐Hyun 
Published: September 2011

AbstractSynthesis of a new series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The biological results indicated that five synthesized compounds (Ig, Ii, IIc, IIg, and IIh) exhibited similar activity to Sorafenib. In addition, three compounds (IIa, IIb, and IIi) were more potent than Sorafenib. Among all of these derivatives, compound IIa which has dimethylamino and phenolic moieties showed the most potent antiproliferative activity against A375P human melanoma cell line. Virtual screening was carried out through docking of the most potent compound IIa into the domain of V600E‐b‐Raf and the binding mode was studied.
CXCL12γ isoform is expressed on endothelial and dendritic cells in rheumatoid arthritis synovium and regulates T cell activation
Authors: Santiago Begoña , Izquierdo Elena , Rueda Patricia , Rey Manuel J. Del , Criado Gabriel , Usategui Alicia , Arenzana‐Seisdedos Fernando , Pablos José L. 
Published: September 2011

AbstractObjectiveCXCL12γ is an alternative splicing isoform of CXCL12 with enhanced affinity for heparan sulfate (HS) proteoglycans. This study was undertaken to investigate the distribution and potential function of CXCL12γ in rheumatoid arthritis (RA) synovium and normal lymphoid tissue, where its immobilization to HS may be relevant in pathologic or homeostatic immune cell migration and activation.MethodsExpression of CXCL12 or CXCL12γ was immunodetected in RA and normal synovium, lymphoid tissue, and cultured cells with anti–pan‐CXCL12 or anti‐CXCL12γ–specific monoclonal antibodies. CXCL12α and CXCL12γ messenger RNA expression was analyzed by quantitative reverse transcription–polymerase chain reaction. Binding of wild‐type CXCL12 isoforms or their HS binding–defective mutants to monocyte‐derived dendritic cells (DCs) was analyzed by flow cytometry. The effect of DC‐bound CXCL12α and CXCL12γ on T cell activation was analyzed in DC/T cell allogeneic cultures.ResultsCXCL12γ expression was increased in RA compared to normal synovium and preferentially located in endothelia and DC‐SIGN–positive cells. This distribution was also observed in lymphoid organs. Surface‐bound CXCL12γ was detected in a fraction of freshly isolated DCs. Monocyte‐derived DCs, but not monocytes, showed a high capacity to bind CXCL12γ in an HS‐dependent manner. Surface‐bound CXCL12α and CXCL12γ on monocyte‐derived DCs were potent inhibitors of allogeneic T cell activation, in contrast to the T cell–stimulatory effects of soluble CXCL12 proteins.ConclusionCXCL12γ shows a specific and similar distribution in RA synovium and lymphoid tissue, consistent with its higher HS binding affinity. Presentation of CXCL12 to T cells on membrane HS in DCs can play a distinct regulatory role in T cell activation.
Interferon signals and monocytic sensitization of the interferon‐γ signaling pathway in the peripheral blood of patients with rheumatoid arthritis
Authors: Karonitsch Thomas , von Dalwigk Karolina , Steiner Carl W. , Blüml Stephan , Steiner Günter , Kiener Hans P. , Smolen Josef S. , Aringer Martin 
Published: September 2011

AbstractObjectiveBoth type I interferons (IFNα and IFNβ) and type II IFN (IFNγ) signal via pSTAT‐1. Immunohistochemistry and the gene expression signatures of rheumatoid arthritis (RA) synovial tissue suggest an activated IFN/STAT‐1 signaling pathway. The aim of this study was to determine the systemic activity of the IFN/STAT‐1 signaling pathway in the peripheral blood cells of patients with RA.MethodsFluorocytometry or quantitative polymerase chain reaction was used to measure the expression of STAT‐1, pSTAT‐1, and IFN‐inducible genes (monokine induced by interferon‐γ [MIG], interferon‐γ–inducible protein 10 [IP‐10], and 2′,5′‐oligoadenylate synthetase [OAS]) in the peripheral blood mononuclear cells (PBMCs) and purified CD14+ peripheral blood monocytes of patients with RA and healthy control subjects. PBMCs were also incubated for 48 hours with IFNs and several other cytokines to investigate influences on STAT‐1 levels. To examine the significance of STAT‐1 activation in RA monocytes after stimulation with IFNγ, the expression of pSTAT‐1 and of the IFNγ‐inducible chemokine MIG was measured using fluorocytometry.ResultsLevels of STAT‐1 were significantly increased in peripheral lymphocytes and monocytes from patients with RA compared with those from healthy control subjects. STAT‐1 levels correlated well with RA disease activity, as measured by the Disease Activity Score in 28 joints and the Clinical Disease Activity Index. Furthermore, STAT‐1 messenger RNA expression in RA CD14+ monocytes correlated with the expression of other IFN‐target genes, such as IP‐10, OAS, or MIG. In RA PBMCs, STAT‐1 expression was increased not only by IFNs but also by tumor necrosis factor. RA monocytes demonstrated a considerably higher increase in pSTAT‐1 and MIG levels upon IFNγ stimulation when compared with monocytes from control subjects, indicating that RA monocytes are more sensitive to IFNγ stimulation.ConclusionIn addition to supporting the role of IFNs in systemic proinflammatory activity, the results of this study further suggest preactivation of the IFNγ/STAT‐1 signaling pathway, especially in RA monocytes.
Evidence for gene–gene epistatic interactions among susceptibility loci for systemic lupus erythematosus
Authors: Hughes Travis , Adler Adam , Kelly Jennifer A. , Kaufman Kenneth M. , Williams Adrienne H. , Langefeld Carl D. , Brown Elizabeth E. , Alarcón Graciela S. , Kimberly Robert P. , Edberg Jeffrey C. , Ramsey‐Goldman Rosalind , Petri Michelle , Boackle Susan A. , Stevens Anne M. , Reveille John D. , Sanchez Elena , Martín Javier , Niewold Timothy B. , Vilá Luis M. , Scofield R. Hal , Gilkeson Gary S. , Gaffney Patrick M. , Criswell Lindsey A. , Moser Kathy L. , Merrill Joan T. , Jacob Chaim O. , Tsao Betty P. , James Judith A. , Vyse Timothy J. , Alarcón‐Riquelme Marta E. ,   BIOLUPUS Network, Harley John B. , Richardson Bruce C. , Sawalha Amr H. 
Published: September 2011

AbstractObjectiveSeveral confirmed genetic susceptibility loci for lupus have been described. To date, no clear evidence for genetic epistasis in lupus has been established. The aim of this study was to test for gene–gene interactions in a number of known lupus susceptibility loci.MethodsEighteen single‐nucleotide polymorphisms tagging independent and confirmed lupus susceptibility loci were genotyped in a set of 4,248 patients with lupus and 3,818 normal healthy control subjects of European descent. Epistasis was tested by a 2‐step approach using both parametric and nonparametric methods. The false discovery rate (FDR) method was used to correct for multiple testing.ResultsWe detected and confirmed gene–gene interactions between the HLA region and CTLA4, IRF5, and ITGAM and between PDCD1 and IL21 in patients with lupus. The most significant interaction detected by parametric analysis was between rs3131379 in the HLA region and rs231775 in CTLA4 (interaction odds ratio 1.19, Z = 3.95, P = 7.8 × 10−5 [FDR ≤0.05], P for multifactor dimensionality reduction = 5.9 × 10−45). Importantly, our data suggest that in patients with lupus, the presence of the HLA lupus risk alleles in rs1270942 and rs3131379 increases the odds of also carrying the lupus risk allele in IRF5 (rs2070197) by 17% and 16%, respectively (P = 0.0028 and P = 0.0047, respectively).ConclusionWe provide evidence for gene–gene epistasis in systemic lupus erythematosus. These findings support a role for genetic interaction contributing to the complexity of lupus heritability.
NLRP3 inflammasome–mediated neutrophil recruitment and hypernociception depend on leukotriene B4 in a murine model of gout
Authors: Amaral Flávio A. , Costa Vivian V. , Tavares Livia D. , Sachs Daniela , Coelho Fernanda M. , Fagundes Caio T. , Soriani Frederico M. , Silveira Tatiana N. , Cunha Larissa D. , Zamboni Dario S. , Quesniaux Valerie , Peres Raphael S. , Cunha Thiago M. , Cunha Fernando Q. , Ryffel Bernhard , Souza Daniele G. , Teixeira Mauro M. 
Published: September 2011

AbstractObjectiveDeposition of monosodium urate monohydrate (MSU) crystals in the joints promotes an intense inflammatory response and joint dysfunction. This study evaluated the role of the NLRP3 inflammasome and 5‐lipoxygenase (5‐LOX)–derived leukotriene B4 (LTB4) in driving tissue inflammation and hypernociception in a murine model of gout.MethodsGout was induced by injecting MSU crystals into the joints of mice. Wild‐type mice and mice deficient in NLRP3, ASC, caspase 1, interleukin‐1β (IL‐1β), IL‐1 receptor type I (IL‐1RI), IL‐18R, myeloid differentiation factor 88 (MyD88), or 5‐LOX were used. Evaluations were performed to assess neutrophil influx, LTB4 activity, cytokine (IL‐1β, CXCL1) production (by enzyme‐linked immunosorbent assay), synovial microvasculature cell adhesion (by intravital microscopy), and hypernociception. Cleaved caspase 1 and production of reactive oxygen species (ROS) were analyzed in macrophages by Western blotting and fluorometric assay, respectively.ResultsInjection of MSU crystals into the knee joints of mice induced neutrophil influx and neutrophil‐dependent hypernociception. MSU crystal–induced neutrophil influx was CXCR2‐dependent and relied on the induction of CXCL1 in an NLRP3/ASC/caspase 1/IL‐1β/MyD88–dependent manner. LTB4 was produced rapidly after injection of MSU crystals, and this was necessary for caspase 1–dependent IL‐1β production and consequent release of CXCR2‐acting chemokines in vivo. In vitro, macrophages produced LTB4 after MSU crystal injection, and LTB4 was relevant in the MSU crystal–induced maturation of IL‐1β. Mechanistically, LTB4 drove MSU crystal–induced production of ROS and ROS‐dependent activation of the NLRP3 inflammasome.ConclusionThese results reveal the role of the NLRP3 inflammasome in mediating MSU crystal–induced inflammation and dysfunction of the joints, and highlight a previously unrecognized role of LTB4 in driving NLRP3 inflammasome activation in response to MSU crystals, both in vitro and in vivo.
Risk factors for relapse of antineutrophil cytoplasmic antibody–associated vasculitis
Authors: Walsh Michael , Flossmann Oliver , Berden Annelies , Westman Kerstin , Höglund Peter , Stegeman Coen , Jayne David ,   European Vasculitis Study Group
Published: September 2011

AbstractObjectiveTo determine the association between characteristics at diagnosis and the time to first relapse in a large cohort of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV).MethodsWe studied long‐term followup data from 4 clinical trials that included newly diagnosed patients with a broad spectrum of AAV severity and manifestations. Patient and disease characteristics at baseline were used in competing risk regression models with relapse as the event of interest and death as the competing event.ResultsWe assessed 535 patients with 1,804 patient‐years at risk of relapse. At diagnosis, the median age was 60.7 years (interquartile range [IQR] 48.8–69.1 years), 284 patients (53%) had granulomatosis with polyangiitis (Wegener's), and the median creatinine level was 203 μmoles/liter (IQR 97–498). A total of 201 patients (38%) experienced a relapse and 133 patients (25%) died, 96 of whom had not had prior relapse. Anti–proteinase 3 antibodies (subhazard ratio [sHR] 1.62 [95% confidence interval 1.39–1.89]) and cardiovascular involvement (sHR 1.59 [95% confidence interval 1.07–2.37]) were independently associated with a higher risk of relapse. Compared with patients with a creatinine level ≤100 μmoles/liter, patients with higher creatinine levels had a lower risk of relapse (sHR 0.81 [95% confidence interval 0.77–0.85] for a creatinine level of 101–200 μmoles/liter; sHR 0.39 [95% confidence interval 0.22–0.69] for a creatinine level >200 μmoles/liter).ConclusionRelapse of disease is common for patients with AAV. A creatinine level >200 μmoles/liter at the time of diagnosis is strongly associated with a reduced risk of relapse and may help guide monitoring and treatment of patients with AAV.
Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity
Authors: Liu Yin , Ramot Yuval , Torrelo Antonio , Paller Amy S. , Si Nuo , Babay Sofia , Kim Peter W. , Sheikh Afzal , Lee Chyi‐Chia Richard , Chen Yongqing , Vera Angel , Zhang Xue , Goldbach‐Mansky Raphaela , Zlotogorski Abraham 
Published: September 2011

AbstractObjectiveChronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome) is an autoinflammatory syndrome recently described in children. We undertook this study to investigate the clinical phenotype, genetic cause, and immune dysregulation in 9 CANDLE syndrome patients.MethodsGenomic DNA from all patients was screened for mutations in PSMB8 (proteasome subunit β type 8). Cytokine levels were measured in sera from 3 patients. Skin biopsy samples were evaluated by immunohistochemistry, and blood microarray profile and STAT‐1 phosphorylation were assessed in 4 patients and 3 patients, respectively.ResultsOne patient was homozygous for a novel nonsense mutation in PSMB8 (c.405C>A), suggesting a protein truncation; 4 patients were homozygous and 2 were heterozygous for a previously reported missense mutation (c.224C>T); and 1 patient showed no mutation. None of these sequence changes was observed in chromosomes from 750 healthy controls. Of the 4 patients with the same mutation, only 2 shared the same haplotype, indicating a mutational hot spot. PSMB8 mutation–positive and –negative patients expressed high levels of interferon‐γ (IFNγ)–inducible protein 10. Levels of monocyte chemotactic protein 1, interleukin‐6 (IL‐6), and IL‐1 receptor antagonist were moderately elevated. Microarray profiles and monocyte STAT‐1 activation suggested a unique IFN signaling signature, unlike in other autoinflammatory disorders.ConclusionCANDLE syndrome is caused by mutations in PSMB8, a gene recently reported to cause “JMP” syndrome (joint contractures, muscle atrophy, microcytic anemia, and panniculitis‐induced childhood‐onset lipodystrophy) in adults. We extend the clinical and pathogenic description of this novel autoinflammatory syndrome, thereby expanding the clinical and genetic disease spectrum of PSMB8‐associated disorders. IFN may be a key mediator of the inflammatory response and may present a therapeutic target.