Correlation between the Josephson coupling energy and the condensation energy in bilayer cuprate superconductors

We review some previous studies concerning the intra-bilayer Josephson plasmons and present new ellipsometric data of the c-axis infrared response of almost optimally doped Bi_{2}Sr_{2}CaCu_{2}O_{8}. The c-axis conductivity of this compound exhibits the same kind of anomalies as that of underdoped YBa_{2}Cu_{3}O_{7-delta}. We analyze these anomalies in detail and show that they can be explained within a model involving the intra-bilayer Josephson effect and variations of the electric field inside the unit cell. The Josephson coupling energies of different bilayer compounds obtained from the optical data are compared with the condensation energies and it is shown that there is a reasonable agreement between the values of the two quantities. We argue that the Josephson coupling energy, as determined by the frequency of the intra-bilayer Josephson plasmon, represents a reasonable estimate of the change of the effective c-axis kinetic energy upon entering the superconducting state. It is further explained that this is not the case for the estimate based on the use of the simplest ``tight-binding'' sum rule. We discuss possible interpretations of the remarkable agreement between the Josephson coupling energies and the condensation energies. The most plausible interpretation is that the interlayer tunneling of the Cooper pairs provides the dominant contribution to the condensation energy of the bilayer compounds; in other words that the condensation energy of these compounds can be accounted for by the interlayer tunneling theory. We suggest an extension of this theory, which may also explain the high values of T_{c} in the single layer compounds Tl_{2}Ba_{2}CuO_{6} and HgBa_{2}CuO_{4}, and we make several experimentally verifiable predictions.Comment: 16 pages (including Tables) and 7 figures; accepted for publication in Physical Review

Penetration of Josephson vortices and measurement of the c-axis penetration depth in Bi2Sr2CaCu2O8+δBi_{2}Sr_{2}CaCu_{2}O_{8+\delta}: Interplay of Josephson coupling, surface barrier and defects

The first penetration field H_{J}(T) of Josephson vortices is measured through the onset of microwave absorption in the locked state, in slightly overdoped $\rm{Bi_{2}Sr_{2}CaCu_{2}O_{8+\delta}}$ single crystals (T_{c} ~ 84 K). The magnitude of H_{J}(T) is too large to be accounted for by the first thermodynamic critical field H_{c1}(T). We discuss the possibility of a Bean-Livingston barrier, also supported by irreversible behavior upon flux exit, and the role of defects, which relates H_{J}(T) to the c-axis penetration depth $\lambda_{c}(T)$. The temperature dependence of the latter, determined by a cavity perturbation technique and a theoretical estimate of the defect-limited penetration field are used to deduce from H_{J}(T) the absolute value of $\lambda_{c}(0)=(35 \pm 15) \mu m$.Comment: 9 pages, 6 figure

Influence of Chemical Structure on the Stability and Conductance of Porphyrin Single-Molecule Junctions

Quantum Matter and Optic

Vesnarinone, a differentiation inducing drug, directly activates p21waf1 gene promoter via Sp1 sites in a human salivary gland cancer cell line

We previously demonstrated that a differentiation inducing drug, vesnarinone induced the growth arrest and p21waf1 gene expression in a human salivary gland cancer cell line, TYS. In the present study, we investigated the mechanism of the induction of p21waf1 gene by vesnarinone in TYS cells. We constructed several reporter plasmids containing the p21waf1 promoter, and attempted to identify vesnarinone-responsive elements in the p21waf1 promoter. By the luciferase reporter assay, we identified the minimal vesnarinone-responsive element in the p21waf1 promoter at −124 to −61 relative to the transcription start site. Moreover, we demonstrated by electrophoretic mobility shift assay that Sp1 and Sp3 transcription factors bound to the vesnarinone-responsive element. Furthermore, we found that vesnarinone induced the histone hyperacetylation in TYS cells. These results suggest that vesnarinone directly activates p21waf1 promoter via the activation of Sp1 and Sp3 transcription factors and the histone hyperacetylation in TYS cells

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells

The expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4–19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCNDI) was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification. © 1999 Cancer Research Campaig

Durability of SVR in chronic hepatitis C patients treated with peginterferon-a2a/ribavirin in combination with a direct-acting anti-viral

SUMMARY Background The introduction of direct-acting anti-virals has increased sustained virological response (SVR) rates in chronic hepatitis C genotype 1 infection. At present, data on long-term durability of viral eradication after successful triple therapy are lacking

Pegylated IFN-α sensitizes melanoma cells to chemotherapy and causes premature senescence in endothelial cells by IRF-1-mediated signaling

Pegylated interferon-α2b (pIFN-α) is an integral part of the drug regimen currently employed against melanoma. Interferon regulatory factor-1 (IRF-1) has an important role in the transcriptional regulation of the IFN response, cell cycle and apoptosis. We have studied pIFN-α-induced responses when combined with the chemotherapy agent, vinblastine (VBL), in tumor and endothelial cell lines and the connection to IRF-1 signaling. Levels of IRF-1/IRF-2 protein expression were found to be decreased in tumor versus normal tissues. pIFN-α induced IRF-1 signaling in human melanoma (M14) and endothelial (EA.hy926) cells and enhanced cell death when combined with VBL. Upon combined IFN-α and VBL treatment, p21 expression, poly (ADP-ribose) polymerase cleavage and activated Bak levels were increased in M14 cells. An increase in p21 and cyclin D1 expression occurred in EA.hy926 cells after 6 h of treatment with pIFN-α, which dissipated by 24 h. This biphasic response, characteristic of cellular senescence, was more pronounced upon combined treatment. Exposure of the EA.hy926 cells to pIFN-α was associated with an enlarged, multinucleated, β-galactosidase-positive senescent phenotype. The overall therapeutic mechanism of IFN-α combined with chemotherapy may be due to both direct tumor cell death via IRF-1 signaling and by premature senescence of endothelial cells and subsequent effects on angiogenesis in the tumor microenvironment

A Novel, Non-Apoptotic Role for Scythe/BAT3: A Functional Switch between the Pro- and Anti-Proliferative Roles of p21 during the Cell Cycle

BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.Dissertatio

Cytoplasmic p21(WAF1/CIP1 )expression is correlated with HER-2/ neu in breast cancer and is an independent predictor of prognosis

BACKGROUND: HER-2 (c-erbB2/Neu) predicts the prognosis of and may influence treatment responses in breast cancer. HER-2 activity induces the cytoplasmic location of p21(WAFI/CIPI )in cell culture, accompanied by resistance to apoptosis. p21(WAFI/CIPI )is a cyclin-dependent kinase inhibitor activated by p53 to produce cell cycle arrest in association with nuclear localisation of p21(WAFI/CIPI). We previously showed that higher levels of cytoplasmic p21(WAFI/CIPI )in breast cancers predicted reduced survival at 5 years. The present study examined HER-2 and p21(WAFI/CIPI )expression in a series of breast cancers with up to 9 years of follow-up, to evaluate whether in vitro findings were related to clinical data and the effect on outcome. METHODS: The CB11 anti-HER2 monoclonal antibody and the DAKO Envision Plus system were used to evaluate HER-2 expression in 73 patients. p21(WAFI/CIPI )staining was performed as described previously using the mouse monoclonal antibody Ab-1 (Calbiochem, Cambridge, MA, USA). RESULTS: HER-2 was evaluable in 67 patients and was expressed in 19% of cases, predicting reduced overall survival (P = 0.02) and reduced relapse-free survival (P = 0.004; Cox regression model). HER-2-positive tumours showed proportionately higher cytoplasmic p21(WAFI/CIPI )staining using an intensity distribution score (median, 95) compared with HER-2-negative cancers (median, 47) (P = 0.005). There was a much weaker association between nuclear p21(WAFI/CIPI )and HER-2 expression (P = 0.05), suggesting an inverse relationship between nuclear p21(WAF1/CIP1 )and HER-2. CONCLUSION: This study highlights a new pathway by which HER-2 may modify cancer behaviour. HER-2 as a predictor of poor prognosis may partly relate to its ability to influence the relocalisation of p21(WAFI/CIPI )from the nucleus to the cytoplasm, resulting in a loss of p21(WAFI/CIPI)tumour suppressor functions. Cytoplasmic p21(WAFI/CIPI )may be a surrogate marker of functional HER-2 in vivo