RESUMO
Highly uniform Cu micropillars were electrodeposited on a Cu seed layer in a micropatterned photoresist in the presence of binary levelers containing pyrrolidine and pyridine functional groups. The adsorption behaviors of binary levelers, i.e., 3-hydroxy-6-(tert-butyl)pyridine and pyridinium tribromide in an electroplating bath were investigated by chronopotentiometry with sequential injection of levelers and linear sweep voltammetry with a rotating disk electrode. From electrochemical analysis, pyridinium tribromide composed of a positively charged pyridine ring was strongly adsorbed on the Cu seed surface, relative to 3-hydroxy-6-(tert-butyl)pyridine. Additional microscopy, surface roughness, and nitrogen concentration analyses revealed that the binary levelers were preferentially adsorbed on the center and the edge region of the Cu seed, resulting in a uniform Cu pillar profile. The possible mechanism of highly uniform Cu pillar deposition was discussed in terms of the adsorption behaviors of the levelers dependent on their molecular structures.
RESUMO
INTRODUCTION: IL-1ß signalling has a critical role in the pathogenesis of various types of inflammatory arthritis including rheumatoid arthritis (RA). We aimed to investigate the therapeutic effects of human IL-1 receptor antagonist with Fc fragment (hIL-1Ra-Fc) on autoimmune arthritis and to identify the possible mechanisms by which hIL-1RA-Fc exerts anti-arthritic effects in a murine model of RA and patients with rheumatoid arthritis. METHODS: Collagen-induced arthritis (CIA) murine model was established in DBA/1J mice. The levels of various cytokines were determined by using enzyme-linked immunosorbent assay. The mouse joints were assessed for clinical arthritis score and histologic features. Th17 cells and Treg cells were stained by using antibodies specific for CD4, IL-17, CD25, and FoxP3. Osteoclastogenesis was determined by TRAP staining and real-time PCR. RESULTS: hIL-1RA-Fc reduced the arthritis incidence, histological inflammation and cartilage score in the CIA model. The expression of proinflammatory cytokines, VEGF and RANK, was reduced in the affected joint of hIL-1Ra-Fc-treated mice. hIL-1Ra-Fc-treated mice showed decreased number of Th17 cells with increased number of Treg cells in spleens. hIL-1Ra-Fc reduced Th17 cell differentiation by inactivation of STAT3 signalling, and reciprocally induced Treg cell differentiation through STAT5 signalling. In addition, the expression of IL-17, TNF-α, RANKL, and VEGF was decreased, while Foxp3 gene expression was increased in PBMCs of RA patients after administration of hIL-1Ra-Fc. CONCLUSION: The anti-arthritis effects of hIL-1RA-Fc are associated with regulation of balance between Th17 cells and Treg cells and suppression of osteoclastogenesis and angiogenesis in the affected joints.
Assuntos
Artrite Reumatoide/terapia , Imunoterapia/métodos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Artrite Reumatoide/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Masculino , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Engenharia de Proteínas , Proteínas Recombinantes/genética , Transdução de SinaisRESUMO
A planar type Li+ ion based potentiometric CO2 micro gas sensor of size 2 x 3 mm has been fabricated on alumina substrate by combining thin and thick film technology. The heater, electrodes and electrolyte were deposited by thin film deposition technique and the sensing and reference electrodes were printed by silk screen printing technology. The optimal thickness and sintering temperature of electrolyte are 1.2 microm and 775 degrees C. The sensor with Li2CO3 and 20 mol% BaCO3 not only exhibits a good Nernstian behavior but also consistent results over a long time at 450 degrees C in dry as well as 70% RH humidity condition between 160-5000 ppm CO2 concentrations. The spreading effect of the sensing and reference materials was controlled by the addition of Al2O3:B2O3 (1:2 mol%) glass.
Assuntos
Dióxido de Carbono/análise , Eletroquímica/instrumentação , Transdutores , Biotecnologia/instrumentação , Biotecnologia/métodos , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Gases/análise , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A hydroxy functional group was introduced as the hydrogen bond donor and acceptor at the hinge region of protein kinase in order to develop novel ATP-competitive inhibitors. Several derivatives of 7-hydroxyl-1H-benzoimidazole were designed as inhibitors of glycogen synthase kinase-3beta with the help of ab initio calculations and a docking study. Enzymatic assay and an X-ray complex study showed that these designed compounds were highly potent ATP-competitive inhibitors.