Rapid induction of p21WAF1 but delayed down-regulation of Cdc25A in the TGF-β-induced cell cycle arrest of gastric carcinoma cells

Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide that inhibits cellular proliferation in most epithelial cells. cdk4 and several cyclin-dependent kinase (cdk) inhibitors (p15(INK4B), p21(WAFI/Cip1) and p27(Kip1)) have been implicated in the TGF-beta-induced cell cycle arrest. More recently, down-regulation of Cdc25A, a cdk activator, was additionally suggested as a mechanism underlying growth inhibition by TGF-beta. The existence of diverse cellular mediators, of TGF-beta, however, raises the question of whether their involvement might occur in a redundant manner or coordinately in a certain cell type. Using two TGF-beta-sensitive gastric carcinoma cell lines (SNU-16 and -620), we addressed the contributory roles of several cdk inhibitors, and of cdk4 and Cdc25A, in TGF-beta-induced cell cycle arrest by comparing their temporal expression pattern in response to TGF-beta. Among the cdk inhibitors examined, p21 mRNA was most rapidly (in less than 1 h) and prominently induced by TGF-beta. In contrast, p15 mRNA was more slowly induced than p21 in SNU-620: cells, and not expressed in SNU-16 cells harbouring homozygous deletion of p15. Western blotting results confirmed the rapid increase of p21 while opposite patterns of p27 expression were observed in the two cell lines. The down-regulation of Cdc25A mRNA occurred, but was more delayed than that of p15 or p21. Until G1 arrest was established, changes in the protein levels of both Cdc25A and cdk4 were marginal. Co-immunoprecipitation with anti-cdk4 antibody showed that induced p21 associates with cdk4, and that its kinase activity is reduced by TGF-beta, which kinetically correlates closely with G1 arrest following TGF-beta treatment of both cell lines. These results suggest that in certain human epithelial cells, p21 may play an early role in TGF-beta-induced cell cycle arrest, and its cooperation with other cdk inhibitors is different depending on cell type. Delayed down-regulation of Cdc25A and cdk4 may contribute to cell adaptation to the quiescent state in the two gastric carcinoma cell lines studied

Role of anisotropic impurity scattering in anisotropic superconductors

A theory of nonmagnetic impurities in an anisotropic superconductor including the effect of anisotropic (momentum-dependent) impurity scattering is given. It is shown that for a strongly anisotropic scattering the reduction of the pair-breaking effect of the impurities is large. For a significant overlap between the anisotropy functions of the scattering potential and that of the pair potential and for a large amount of anisotropic scattering rate in impurity potential the superconductivity becomes robust vis a vis impurity concentration. The implications of our result for YBCO high-temperature superconductor are discussed.Comment: 14 pages, RevTeX, 5 PostScript figures, to be published in Phys. Rev. B (December 1, 1996

Statistical Properties of Cross-Correlation in the Korean Stock Market

We investigate the statistical properties of the correlation matrix between individual stocks traded in the Korean stock market using the random matrix theory (RMT) and observe how these affect the portfolio weights in the Markowitz portfolio theory. We find that the distribution of the correlation matrix is positively skewed and changes over time. We find that the eigenvalue distribution of original correlation matrix deviates from the eigenvalues predicted by the RMT, and the largest eigenvalue is 52 times larger than the maximum value among the eigenvalues predicted by the RMT. The $\beta_{473}$ coefficient, which reflect the largest eigenvalue property, is 0.8, while one of the eigenvalues in the RMT is approximately zero. Notably, we show that the entropy function $E(\sigma)$ with the portfolio risk $\sigma$ for the original and filtered correlation matrices are consistent with a power-law function, $E(\sigma) \sim \sigma^{-\gamma}$, with the exponent $\gamma \sim 2.92$ and those for Asian currency crisis decreases significantly

Quark-Hadron Duality in Neutron (3He) Spin Structure

We present experimental results of the first high-precision test of quark-hadron duality in the spin-structure function g_1 of the neutron and $^3$He using a polarized 3He target in the four-momentum-transfer-squared range from 0.7 to 4.0 (GeV/c)^2. Global duality is observed for the spin-structure function g_1 down to at least Q^2 = 1.8 (GeV/c)^2 in both targets. We have also formed the photon-nucleon asymmetry A_1 in the resonance region for 3He and found no strong Q^2-dependence above 2.2 (GeV/c)^2.Comment: 13 pages, 3 figure

Moments of the neutron g2g_2 structure function at intermediate Q2Q^2

We present new experimental results of the $^3$He spin structure function $g_2$ in the resonance region at $Q^2$ values between 1.2 and 3.0 (GeV/c)$^2$. Spin dependent moments of the neutron were then extracted. Our main result, the resonance contribution to the neutron $d_2$ matrix element, was found to be small at $$=2.4 (GeV/c)$^2$ and in agreement with the Lattice QCD calculation. The Burkhardt-Cottingham sum rule for $^3$He and the neutron was tested with the measured data and using the Wandzura-Wilczek relation for the low $x$ unmeasured region. A small deviation was observed at $Q^2$ values between 0.5 and 1.2 (GeV/c)$^2$ for the neutron

Charged pion form factor between Q2Q^2=0.60 and 2.45 GeV2^2. I. Measurements of the cross section for the 1{^1}H(e,e′π+e,e'\pi^+)nn reaction

Cross sections for the reaction ${^1}$H($e,e'\pi^+$)$n$ were measured in Hall C at Thomas Jefferson National Accelerator Facility (JLab) using the CEBAF high-intensity, continous electron beam in order to determine the charged pion form factor. Data were taken for central four-momentum transfers ranging from $Q^2$=0.60 to 2.45 GeV$^2$ at an invariant mass of the virtual photon-nucleon system of $W$=1.95 and 2.22 GeV. The measured cross sections were separated into the four structure functions $\sigma_L$, $\sigma_T$, $\sigma_{LT}$, and $\sigma_{TT}$. The various parts of the experimental setup and the analysis steps are described in detail, including the calibrations and systematic studies, which were needed to obtain high precision results. The different types of systematic uncertainties are also discussed. The results for the separated cross sections as a function of the Mandelstam variable $t$ at the different values of $Q^2$ are presented. Some global features of the data are discussed, and the data are compared with the results of some model calculations for the reaction ${^1}$H($e,e'\pi^+$)$n$.Comment: 26 pages, 23 figure

TGFBR2 and BAX Mononucleotide Tract Mutations, Microsatellite Instability, and Prognosis in 1072 Colorectal Cancers

Mononucleotide tracts in the coding regions of the TGFBR2 and BAX genes are commonly mutated in microsatellite instability-high (MSI-high) colon cancers. The receptor TGFBR2 plays an important role in the TGFB1 (transforming growth factor-β, TGF-β) signaling pathway, and BAX plays a key role in apoptosis. However, a role of TGFBR2 or BAX mononucleotide mutation in colorectal cancer as a prognostic biomarker remains uncertain.We utilized a database of 1072 rectal and colon cancers in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study). Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusted for clinical, pathological and molecular features including the CpG island methylator phenotype (CIMP), LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations. MSI-high was observed in 15% (162/1072) of all colorectal cancers. TGFBR2 and BAX mononucleotide mutations were detected in 74% (117/159) and 30% (48/158) of MSI-high tumors, respectively. In Kaplan-Meier analysis as well as univariate and multivariate Cox regression analyses, compared to microsatellite stable (MSS)/MSI-low cases, MSI-high cases were associated with superior colorectal cancer-specific survival [adjusted HR, 0.34; 95% confidence interval (CI), 0.20-0.57] regardless of TGFBR2 or BAX mutation status. Among MSI-high tumors, TGFBR2 mononucleotide mutation was associated with CIMP-high independent of other variables [multivariate odds ratio, 3.57; 95% CI, 1.66-7.66; p = 0.0011].TGFBR2 or BAX mononucleotide mutations are not associated with the patient survival outcome in MSI-high colorectal cancer. Our data do not support those mutations as prognostic biomarkers (beyond MSI) in colorectal carcinoma

Charged pion form factor between Q^2=0.60 and 2.45 GeV^2. II. Determination of, and results for, the pion form factor

The charged pion form factor, Fpi(Q^2), is an important quantity which can be used to advance our knowledge of hadronic structure. However, the extraction of Fpi from data requires a model of the 1H(e,e'pi+)n reaction, and thus is inherently model dependent. Therefore, a detailed description of the extraction of the charged pion form factor from electroproduction data obtained recently at Jefferson Lab is presented, with particular focus given to the dominant uncertainties in this procedure. Results for Fpi are presented for Q^2=0.60-2.45 GeV^2. Above Q^2=1.5 GeV^2, the Fpi values are systematically below the monopole parameterization that describes the low Q^2 data used to determine the pion charge radius. The pion form factor can be calculated in a wide variety of theoretical approaches, and the experimental results are compared to a number of calculations. This comparison is helpful in understanding the role of soft versus hard contributions to hadronic structure in the intermediate Q^2 regime.Comment: 18 pages, 11 figure

Separated Response Function Ratios in Exclusive, Forward pi^{+/-} Electroproduction

The study of exclusive $\pi^{\pm}$ electroproduction on the nucleon, including separation of the various structure functions, is of interest for a number of reasons. The ratio $R_L=\sigma_L^{\pi^-}/\sigma_L^{\pi^+}$ is sensitive to isoscalar contamination to the dominant isovector pion exchange amplitude, which is the basis for the determination of the charged pion form factor from electroproduction data. A change in the value of $R_T=\sigma_T^{\pi^-}/\sigma_T^{\pi^+}$ from unity at small $-t$, to 1/4 at large $-t$, would suggest a transition from coupling to a (virtual) pion to coupling to individual quarks. Furthermore, the mentioned ratios may show an earlier approach to pQCD than the individual cross sections. We have performed the first complete separation of the four unpolarized electromagnetic structure functions above the dominant resonances in forward, exclusive $\pi^{\pm}$ electroproduction on the deuteron at central $Q^2$ values of 0.6, 1.0, 1.6 GeV$^2$ at $W$=1.95 GeV, and $Q^2=2.45$ GeV$^2$ at $W$=2.22 GeV. Here, we present the $L$ and $T$ cross sections, with emphasis on $R_L$ and $R_T$, and compare them with theoretical calculations. Results for the separated ratio $R_L$ indicate dominance of the pion-pole diagram at low $-t$, while results for $R_T$ are consistent with a transition between pion knockout and quark knockout mechanisms.Comment: 6 pages, 3 figure

ComPath: comparative enzyme analysis and annotation in pathway/subsystem contexts

<p>Abstract</p> <p>Background</p> <p>Once a new genome is sequenced, one of the important questions is to determine the presence and absence of biological pathways. Analysis of biological pathways in a genome is a complicated task since a number of biological entities are involved in pathways and biological pathways in different organisms are not identical. Computational pathway identification and analysis thus involves a number of computational tools and databases and typically done in comparison with pathways in other organisms. This computational requirement is much beyond the capability of biologists, so information systems for reconstructing, annotating, and analyzing biological pathways are much needed. We introduce a new comparative pathway analysis workbench, ComPath, which integrates various resources and computational tools using an interactive spreadsheet-style web interface for reliable pathway analyses.</p> <p>Results</p> <p>ComPath allows users to compare biological pathways in multiple genomes using a spreadsheet style web interface where various sequence-based analysis can be performed either to compare enzymes (e.g. sequence clustering) and pathways (e.g. pathway hole identification), to search a genome for <it>de novo </it>prediction of enzymes, or to annotate a genome in comparison with reference genomes of choice. To fill in pathway holes or make <it>de novo </it>enzyme predictions, multiple computational methods such as FASTA, Whole-HMM, CSR-HMM (a method of our own introduced in this paper), and PDB-domain search are integrated in ComPath. Our experiments show that FASTA and CSR-HMM search methods generally outperform Whole-HMM and PDB-domain search methods in terms of sensitivity, but FASTA search performs poorly in terms of specificity, detecting more false positive as E-value cutoff increases. Overall, CSR-HMM search method performs best in terms of both sensitivity and specificity. Gene neighborhood and pathway neighborhood (global network) visualization tools can be used to get context information that is complementary to conventional KEGG map representation.</p> <p>Conclusion</p> <p>ComPath is an interactive workbench for pathway reconstruction, annotation, and analysis where experts can perform various sequence, domain, context analysis, using an intuitive and interactive spreadsheet-style interface. </p