Analysis of the effects of an oncogenic stress on the cell cycle in human tumoral cells

Although differing only for the last 24 aminoacids, the three major isoforms of p21 Ras (Ha-, Ki- and N \u2013Ras) can trigger alternative pathways of signal transduction, at least in part as a consequence of different post-translational modifications and subcellular localization. Ras mutations are a common event in tumorigenesis. In colorectal carcinomas (CRCs) the mutations affect almost exclusively Ki-Ras, while Ha-Ras mutations are mostly found in bladder carcinomas and N-Ras mutations in leukemia cells. In almost all cases, the genetic alteration is a point mutation in codons 12 or 13, and less frequently in codon 61. By affecting the GTPase activity of the protein, they always lead to a constitutively active protein. However, data obtained in different experimental systems or by analysis of primary and metastatic tumors show that not only mutations of different isoforms of Ras, but also mutations in different codons or different mutations in the same codon of the same isoform of Ras may have diverse biological consequences. To shed more light on the molecular mechanisms responsible for the different effects of Ras mutations, we have obtained stable clones of HT-29 (a human colorectal adenocarcinoma cell line in which the endogenous Ras genes are wild type) transfected with cDNAs codifying Ha-RasG12V, Ki-RasG12V and Ki-RasG13D, under the control of an hormone-inducible promoter. We found that the expression of each of these mutated Ras isoforms induces specific, different effects on cell morphology and growth rate. FACS analysis shows also a differential effect on the cell cycle. H-RasG12V expression, in addition, induces apoptosis, through caspase activation mediated by p53 independent, MEK-1 dependent expression of the CDK inhibitor p21

On the screening of the potential between adjoint sources in QCD3QCD_3

We calculate the potential between adjoint sources in $SU(2)$ pure gauge theory in three dimensions. We investigate whether the potential saturates at large separations due to the creation of a pair of gluelumps, colour-singlet states formed when glue binds to an adjoint source.Comment: 3 pages, uuencoded Z-compressed postscript file, contribution to Lattice '9

Baryonic Operators for Lattice Simulations

The construction of baryonic operators for determining the N* excitation spectrum is discussed. The operators are designed with one eye towards maximizing overlaps with the low-lying states of interest, and the other eye towards minimizing the number of sources needed in computing the required quark propagators. Issues related to spin identification are outlined. Although we focus on tri-quark baryon operators, the construction method is applicable to both mesons and penta-quark operators.Comment: 3 pages, poster presented at Lattice2003(spectrum), Tsukuba, Japan, July 15-19, 200

Transparency, Civic Capital and Political Accountability: A Virtuous Relation?

Our paper investigates the intertwined relation among transparency, civic capital and political accountability in a large sample of Italian municipalities using a new indicator of institutional transparency. Firstly, we test the hypothesis that civic capital affects transparency of public administrations; secondly, we verify whether in municipalities where civic capital is high, citizens’ attention toward government accountability is also high, making it politically unfeasible to disregard the demand for transparency. We find that civic capital positively affects transparency and the latter, in turn, is politically rewarding for the local administrators only conditional to the level of civic capital. Our findings are robust to different samples and endogeneity concerns

Generalized Rayleigh and Jacobi processes and exceptional orthogonal polynomials

We present four types of infinitely many exactly solvable Fokker-Planck equations, which are related to the newly discovered exceptional orthogonal polynomials. They represent the deformed versions of the Rayleigh process and the Jacobi process.Comment: 17 pages, 4 figure

String Breaking in Non-Abelian Gauge Theories with Fundamental Matter Fields

We present clear numerical evidence for string breaking in three-dimensional SU(2) gauge theory with fundamental bosonic matter through a mixing analysis between Wilson loops and meson operators representing bound states of a static source and a dynamical scalar. The breaking scale is calculated in the continuum limit. In units of the lightest glueball we find $r_{\rm b} m_G\approx13.6$. The implications of our results for QCD are discussed.Comment: 4 pages, 2 figures; equations (4)-(6) corrected, numerical results and conclusions unchange

Baryon operators and spectroscopy in lattice QCD

The construction of the operators and correlators required to determine the excited baryon spectrum is presented, with the aim of exploring the spatial and spin structure of the states while minimizing the number of propagator inversions. The method used to construct operators that transform irreducibly under the symmetries of the lattice is detailed, and the properties of example operators are studied using domain-wall fermion valence propagators computed on MILC asqtad dynamical lattices.Comment: 7 pages, 2 figures, to appear in Proceedings of Workshop on Lattice Hadron Physics 2003, Cairns, Australia, July 22 - July 30, 200

Efficient attack countermeasure selection accounting for recovery and action costs

The losses arising from a system being hit by cyber attacks can be staggeringly high, but defending against such attacks can also be costly. This work proposes an attack countermeasure selection approach based on cost impact analysis that takes into account the impacts of actions by both the attacker and the defender. We consider a networked system providing services whose functionality depends on other components in the network. We model the costs and losses to service availability from compromises and defensive actions to the components, and show that while containment of the attack can be an effective defense, it may be more cost-efficient to allow parts of the attack to continue further whilst focusing on recovering services to a functional state. Based on this insight, we build a countermeasure selection method that chooses the most cost-effective action based on its impact on expected losses and costs over a given time horizon. Our method is evaluated using simulations in synthetic graphs representing network dependencies and vulnerabilities, and performs well in comparison to alternatives

Proteomic Profiling of Colon Cancer Tissues: Discovery of New Candidate Biomarkers

Colon cancer is an aggressive tumor form with a poor prognosis. This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated with carcinogenesis. The DAVID functional classification tool revealed that most of the differentially regulated proteins, acting both intracellularly and extracellularly, concur across multiple cancer steps. The identified protein classes include proteins involved in cell proliferation, apoptosis, metabolic pathways, oxidative stress, cell motility, Ras signal transduction, and cytoskeleton. Interestingly, networks and pathways analysis showed that the identified proteins could be biologically inter-connected to the tumor-host microenvironment, including innate immune response, platelet and neutrophil degranulation, and hemostasis. Finally, transgelin (TAGL), here identified for the first time with four different protein species, collectively down-regulated in colon cancer tissues, emerged as a top-ranked biomarker for colorectal cancer (CRC). In conclusion, our findings revealed a different proteomic profiling in colon cancer tissues characterized by the deregulation of specific pathways involved in hallmarks of cancer. All of these proteins may represent promising novel colon cancer biomarkers and potential therapeutic targets, if validated in larger cohorts of patients

Comment on ``Evidence Against Instanton Dominance of Topological Charge Fluctuations in QCD''

We comment on the recent paper (hep-lat/0102003) by Horvath, Isgur, McCune, and Thacker, which concludes that the local chiral structure of fermionic eigenmodes is not consistent with instanton dominance. Our calculations, done with an overlap action, suggest the opposite conclusion.Comment: 5 pages, Revtex, 4 postscript figures. COLO-HEP-45