RESUMO
The coarticulatory effects described by Öhman [J. Acoust. Soc. Am. 39, 151-168 (1966)] imply that consonant loci cannot always be defined by their associated consonantal contexts alone, but, in Swedish vowel + consonant + vowel utterances, they must also depend on their trans-consonantal vowels (TCVs). His discovery is extended here using a model with TCV-dependent consonant loci and with a unique target for each vowel. The model accurately characterizes the vowel-to-consonant and consonant-to-vowel transitions for the /b/ and /d/ contexts from Öhman's second formant-frequency data as families connected by linear-scaling relationships.
Assuntos
Acústica , Fonética , Acústica da Fala , Medida da Produção da Fala , Qualidade da Voz , Humanos , Modelos Lineares , Reconhecimento Automatizado de Padrão , Processamento de Sinais Assistido por Computador , Espectrografia do SomRESUMO
We report here a patient heterozygous for a previously unreported ß chain variant. A 72-year-old Caucasian female was found to have an abnormal hemoglobin (Hb) as an incidental finding following Hb A1C analysis. There was no family history of anemia or hemoglobinopathy. Her full blood count revealed a mild normochromic anemia with Hb 11.1 g/dL (range 11.5-15.0), mean corpuscular volume (MCV) 93.0 fL (range 80.0-100.0) and mean corpuscular Hb (MCH) 30.0 pg (range 27.0-32.0). Isopropanol stability tests and a variant Hb on high performance liquid chromatography (HPLC) comprizing 37.0% of the total Hb suggested an unstable Hb variant. Sanger sequencing of the ß-globin gene revealed a single base substitution, HBB: c.37A>C, causing the missense mutation ß12(A9)Thr â Pro in exon 1 of the HBB gene. This mutation changes the threonine residue at position 12(A9) to a proline in the ß-globin chain. We propose that this variant be called Hb Feilding after the town where the proband lived. Three dimensional modeling suggested that the disruption of the Hb structure was due to the introduction of a proline at helix A9 which caused distortion of the helical structure and resulted in reduced solubility.
Assuntos
Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Globinas beta/genética , Idoso , Anemia/sangue , Anemia/genética , Sequência de Bases , Feminino , Hemoglobinas Anormais/química , Humanos , Modelos Moleculares , Prolina/química , Prolina/genética , Estrutura Secundária de Proteína , Treonina/química , Treonina/genética , Globinas beta/químicaRESUMO
Highly active antiretroviral therapy (HAART) can suppress HIV replication to undetectable levels in plasma, but it is unlikely to eradicate cellular reservoirs of virus. Immunotherapies that are cytolytic may be useful adjuncts to drug therapies that target HIV replication. We have generated HIV-specific CD4(+) and CD8(+) T cells bearing a chimeric T-cell receptor (CD4zeta) composed of the extracellular and transmembrane domain of human CD4 (which binds HIVgp120) linked to the intracellular-zeta signaling chain of the CD3 T-cell receptor. CD4zeta-modified T cells can inhibit viral replication, kill HIV-infected cells in vitro, and survive for prolonged periods in vivo. We report the results of a phase II randomized trial of CD4zeta gene-modified versus unmodified T cells in 40 HIV-infected subjects on HAART with plasma viral loads <50 copies/ml. Serial analyses of residual blood and tissue HIV reservoirs were done for 6 months postinfusion. No significant between-group differences were noted in viral reservoirs following therapy. However, infusion of gene-modified, but not unmodified, T cells was associated with a decrease from baseline in HIV burden in two of four reservoir assays and a trend toward fewer patients with recurrent viremia. Both groups experienced a treatment-related increase in CD4(+) T-cell counts.