RESUMO
Common variable immunodeficiency (CVID) is a primary immune disorder characterized by low immunoglobulin serum levels and increased susceptibility to infections. Underlying genetic causes are only known in less than 15% of patients and encompass mutations in the genes encoding for ICOS, TACI, BAFF-R, CD19, CD20, CD81 and MSH5. TACI is the most frequently mutated gene among CVID patients. We report on two pediatric Italian male siblings with hypogammaglobulinemia and recurrent respiratory and gastrointestinal infections in association with a novel compound heterozygous TACI mutation. Both patients carry the I87N/C104R mutation that has not been reported yet. This results in aberrant TACI expression and abrogates APRIL binding on EBV B cells. This study identifies a novel combined mutation in TNFRSF13B increasing the spectrum of TACI mutations associated with CVID.
Assuntos
Agamaglobulinemia/genética , Imunodeficiência de Variável Comum/genética , Infecções Respiratórias/genética , Proteína Transmembrana Ativadora e Interagente do CAML/genética , Agamaglobulinemia/complicações , Agamaglobulinemia/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Sequência de Bases , Criança , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/imunologia , Genes Recessivos , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , Infecções Respiratórias/complicações , Infecções Respiratórias/imunologia , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismoRESUMO
The formation of PtRu surface alloys by deposition of submonolayer Pt films on a Ru(0001) substrate and subsequent annealing to about 1350 K and the distribution of the Pt atoms in the surface layer were investigated by scanning tunneling microscopy. Quantitative statistical analysis reveals (i) negligible losses of Pt into subsurface regions up to coverages close below 1 monolayer, (ii) a homogeneous distribution of the Pt atoms over the surface, and (iii) the absence of a distinct long-range or short-range order in the surface layer. In addition, the density of specific adsorption ensembles is analyzed as a function of Pt surface content. Possible conclusions on the process for surface alloy formation are discussed. The results are compared with the properties of PtRu bulk alloys and the findings in previous adsorption studies on similar surface alloys (H. Rauscher, T. Hager, T. Diemant, H. Hoster, F. Bautier de Mongeot and R. J. Behm, Surf. Sci., 2007, 601, 4608; T. Diemant, H Rauscher and R. J. Behm, J. Phys. Chem. C, in press).
Assuntos
Ligas/química , Platina/química , Rutênio/química , Adsorção , Ligas/síntese química , Monóxido de Carbono/química , Simulação por Computador , Deutério/química , Temperatura Alta , Microscopia Eletrônica de Transmissão por Filtração de Energia , Microscopia de Tunelamento , Modelos Moleculares , Método de Monte Carlo , Propriedades de Superfície , TermodinâmicaRESUMO
The energetics determining the distinct short-range order in two-dimensional (2D) monolayer Cu(x)Pd(1-x) surface alloys on a Ru(0001) substrate were investigated by Monte Carlo simulations and density functional theory calculations. Using a 2D lattice gas Hamiltonian based on effective pair interaction (EPI) parameters, the EPIs were derived for different Cu concentrations with Monte Carlo (MC) simulations by comparing with the atomic distributions obtained from atomic resolution STM images and the related Warren-Cowley short-range order parameters (Hoster et al., Phys. Rev. B, 2006, 73 165413). The ground state structures and mixing energies at 0 K derived from these EPIs agree well with mixing energies determined from DFT calculations of different ordered surface alloys. Additional MC simulations yield rather low transition temperatures which explain the absence of ordered 2D phases in the experiments. The consequences of our findings for the use of alloy surfaces and surface alloys as model systems for adsorption and catalytic reaction studies are discussed.
