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1.
Nat Commun ; 9(1): 71, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29302028

RESUMO

Segregation of the iron core from rocky silicates is a massive evolutionary event in planetary accretion, yet the process of metal segregation remains obscure, due to obstacles in simulating the extreme physical properties of liquid iron and silicates at finite length scales. We present new experimental results studying gravitational instability of an emulsified liquid gallium layer, initially at rest at the interface between two glucose solutions. Metal settling coats liquid metal drops with a film of low density material. The emulsified metal pond descends as a coherent Rayleigh-Taylor instability with a trailing fluid-filled conduit. Scaling to planetary interiors and high pressure mineral experiments indicates that molten silicates and volatiles are entrained toward the iron core and initiate buoyant thermochemical plumes that later oxidize and hydrate the upper mantle. Surface volcanism from thermochemical plumes releases oxygen and volatiles linking atmospheric growth to the Earth's mantle and core processes.

2.
Clin Immunol ; 124(1): 26-32, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17490912

RESUMO

Antibodies elicited by protein therapeutics can cause serious side effects in humans. We studied immunogenicity of a recombinant fusion protein (FPX) consisting of two identical, biologically active, peptides attached to human Fc fragment. EpiMatrix, an in silico epitope-mapping tool, predicted promiscuous T-cell epitope(s) within the 14-amino-acid carboxy-terminal region of the peptide portion of FPX. On administration of FPX in 76 healthy human subjects, 37% developed antibodies after a single injection. A memory T-cell response against the above carboxy-terminus of the peptide was observed in antibody-positive but not in antibody-negative subjects. Promiscuity of the predicted T-cell epitope(s) was confirmed by representation of all common HLA alleles in antibody-positive subjects. As predicted by EpiMatrix, HLA haplotype DRB1*0701/1501 was associated with the highest T-cell and antibody response. In conclusion, in silico prediction can be successfully used to identify Class II restricted T-cell epitopes within therapeutic proteins and predict immunogenicity thereof in humans.


Assuntos
Biologia Computacional/métodos , Simulação por Computador , Epitopos de Linfócito T/imunologia , Epitopos Imunodominantes/imunologia , Modelos Imunológicos , Proteínas Recombinantes de Fusão/imunologia , Adolescente , Adulto , Algoritmos , Formação de Anticorpos/imunologia , Técnicas de Química Combinatória , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/tendências , Epitopos de Linfócito T/química , Feminino , Humanos , Epitopos Imunodominantes/química , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Valor Preditivo dos Testes , Relação Quantitativa Estrutura-Atividade , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/uso terapêutico , Linfócitos T Auxiliares-Indutores/imunologia
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