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An equivalent circuit model of a p-type germanium (Ge) MIS capacitor in the inversion region is presented. Findings reveal that the model is capable of successfully expressing the gate bias and frequency dependences of the measured capacitance characteristics specific to the Ge MIS capacitor.

Nonobese diabetic (NOD) mice develop insulin-dependent diabetes mellitus due to autoimmune T lymphocyte-mediated destruction of pancreatic [Beta] cells. Although both major histocompatibility complex class I-restricted [CD8.sup.+] and class II-restricted [CD4.sup.+] T cell subsets are required, the specific role each subset plays in the pathogenic process is still unclear. Here we show that class I-dependent T cells are required for all but the terminal stages of autoimmune diabetes development. To characterize the diabetogenic [CD8.sup.+] T cells responsible, we isolated and propagated in vitro [CD8.sup.+] T cells from the earliest insulitic lesions of NOD mice. They were cytotoxic to NOD islet cells, restricted to H-[2K.sup.d], and showed a diverse T cell receptor [Beta] chain repertoire. In contrast, their [Alpha] chain repertoire was more restricted, with a recurrent amino acid sequence motif in the complementarity-determining region 3 loop and a prevalence of V[Alpha]17 family members frequently joined to the J[Alpha]42 gene segment. These results suggest that a number of the [CD8.sup.+] T cells participating in the initial phase of autoimmune [Beta] cell destruction recognize a common structural component of [K.sup.d]/peptide complexes on pancreatic [Beta] cells, possibly a single peptide.

The specificity of T cell-mediated immune responses is primarily determined by the interaction between the T cell receptor (TCR) and the antigenic peptide presented by the major histocompatibility complex (MHC) molecules. To refine our understanding of interactions between the TCR and the antigenic peptide of vesicular stomatitis virus (VSV) presented by the class I MHC molecule H-2[K.sup.b], we constructed a TCR [Alpha] chain transgenic mouse in a TCR [Alpha]-deficient background to define specific structural features in the TCR [Beta] chain that are important for the recognition of the VSV/H.2[K.sup.b] complex. We found that for a given peptide, a peptide-specific, highly conserved amino acid could always be identified at position 98 of the complementarity-determining region 3 (CDR3) loop of TCR [Beta] chains. Further, we demonstrated that substitutions at position 6, but not position 1, of the VSV peptide induced compensatory changes in the TCR in both the amino acid residue at position 98 and the length of the CDR3[Beta] loop. We conclude that the amino acid residue at position 98 of the CDR3[Beta] loop is a key residue that plays a critical role in determining the specificity of TCR-VSV/H-2[K.sup.b] interactions and that a specific length of the CDR3[Beta] loop is required to facilitate such interactions. Further, these findings suggest that the [Alpha] and [Beta] chains of TCRs interact with amino acid residue(s) toward the N and C termini of the VSV peptide, respectively, providing functional evidence for the orientation of a TCR with its peptide/MHC ligand as observed in the crystal structures of TCR/peptide/MHC complexes.

Abstract Background Identification of new cancer antigens is necessary for the efficient diagnosis and immunotherapy. A variety of tumor antigens have been identified by several methodologies. Among those antigens, cancer/testis (CT) antigens have became promising targets. Methods The serological identification of antigens by the recombinant expression cloning (SEREX) methodology has been successfully used for the identification of cancer/testis (CT) antigens. We performed the SEREX analysis of colon cancer. Results We isolated a total of 60 positive cDNA clones comprising 38 different genes. They included 2 genes with testis-specific expression profiles in the UniGene database, such as TEKT5 and a CT-like gene, A kinase anchoring protein 3 (AKAP3). Quantitative real-time RT-PCR analysis showed that the expression of TEKT5 was restricted to the testis in normal adult tissues. In malignant tissues, TEKT5 was aberrantly expressed in a variety of cancers, including colon cancer. A serological survey of 101 cancer patients with different cancers by ELISA revealed antibodies to TEKT5 in 13 patients, including colon cancer. None of the 16 healthy donor serum samples were reactive in the same test. Conclusion We identified candidate new CT antigen of colon cancer, TEKT5. The findings indicate that TEKT5 is immunogenic in humans, and suggest its potential use as diagnostic as well as an immunotherapeutic reagent for cancer patients.

Abstract Background Insulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulin-like growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered. Methods In this study, we examined the p53 consensus sequences upstream of the IGFBP-3 promoter for the p53 induced expression of IGFBP-3. Deletion, mutagenesis, and methylation constructs of IGFBP-3 promoter were assessed in the human hepatoblastoma cell line HepG2 for promoter activity. Results Deletions and mutations of these sequences completely abolished the expression of IGFBP-3 in the presence of p53 overexpression. In vitro methylation of these p53 consensus sequences also suppressed IGFBP-3 expression. In contrast, the expression of IGFBP-3 was not affected in the absence of p53 overexpression. Further, we observed by electrophoresis mobility shift assay that p53 binding to the promoter region was diminished when methylated. Conclusion From these observations, we conclude that four out of eleven p53 consensus sequences upstream of the IGFBP-3 promoter are essential for the p53 induced expression of IGFBP-3, and hypermethylation of these sequences selectively suppresses p53 induced IGFBP-3 expression in HepG2 cells.

We report on the effects of postdeposition annealing ambient on the hysteresis observed in the C-V measurement of Al2O3/GeO2 gate-dielectric stacks fabricated on Ge substrates. The results indicate that two types of oxide trap are responsible for the observed hysteresis: a type-I oxide trap that causes persistent C-V hysteresis and a type-II oxide trap that disappears when gate voltage is biased once in the accumulation region. We show that both types of oxide trap reside in the capacitor annealed in O2 ambient, but that only the type-II oxide trap resides in the capacitor annealed in N2 + 10% H2. Time-domain measurements of absorption current suggest that holes injected into the gate-dielectric stack induce the electronic deactivation of the type-II oxide trap. [ABSTRACT FROM AUTHOR]