Targeting the Ets Binding Site of the HER2/neu Promoter with Pyrrole-Imidazole Polyamides

Three DNA binding polyamides (1-3) were synthesized that bind with high affinity (Ka = 8.7·10^9 M^-1 to 1.4·10^10 M^-1) to two 7-base pair sequences overlapping the Ets DNA binding site (EBS; GAGGAA) within the regulatory region of the HER2/neu proximal promoter. As measured by electrophoretic mobility shift assay, polyamides binding to flanking elements upstream (1) or downstream (2 and 3) of the EBS were one to two orders of magnitude more effective than the natural product distamycin at inhibiting formation of complexes between the purified EBS protein, epithelial restricted with serine box (ESX), and the HER2/neu promoter probe. One polyamide, 2, completely blocked Ets-DNA complex formation at 10 nM ligand concentration, whereas formation of activator protein-2-DNA complexes was unaffected at the activator protein-2 binding site immediately upstream of the HER2/neu EBS, even at 100 nM ligand concentration. At equilibrium, polyamide 1 was equally effective at inhibiting Ets/DNA binding when added before or after in vitro formation of protein-promoter complexes, demonstrating its utility to disrupt endogenous Ets-mediated HER2/neu preinitiation complexes. Polyamide 2, the most potent inhibitor of Ets-DNA complex formation by electrophoretic mobility shift assay, was also the most effective inhibitor of HER2/neu promoter-driven transcription measured in a cell-free system using nuclear extract from an ESX- and HER2/neu-overexpressing human breast cancer cell line, SKBR-3

Coexistence of tooth agenesis and ovarian cancer — a systematic literature review

Objectives: Dental agenesis — a congenital lack of teeth — is one of the most frequently diagnosed developmentaldefects of dentition. Genetics is a crucial factor in the etiology of this disorder. Missing teeth can be caused by mutationin genes including MSX1, PAX9, AXIN2, and EDARADD. As is also true for ovarian cancer, over 20% of cases are associatedwith hereditary factors. Mutations in the BRCA1 and BRCA2 genes are said to be the most frequent of these. The aim ofthis study was to provide a systematic review of the literature on the coexistence of ovarian cancer and tooth agenesis.Material and methods: Publications were searched for in the online databases PubMed, SCOPUS, and Wiley Online Library.Current and archival issues of the Journal of Stomatology and Dental and Medical Problems were also searched. The keywords used to find relevant publications were: ovarian cancer, hypodontia, and tooth agenesis, in various combinations.Results: Three publications were qualified to this review. Two of these compared the incidence of hypodontia in womenwith ovarian cancer and in healthy women, and the other was aimed at locating the gene responsible for the coexistenceof ovarian cancer and tooth agenesis. As shown by these studies, women with ovarian cancer are (depending on the study)3.3 or 8.1 times more likely to have hypodontia than healthy women. However, no specific gene was found that might beresponsible for the coexistence of ovarian cancer and tooth agenesis

Numerical simulations of mixed states quantum computation

We describe quantum-octave package of functions useful for simulations of quantum algorithms and protocols. Presented package allows to perform simulations with mixed states. We present numerical implementation of important quantum mechanical operations - partial trace and partial transpose. Those operations are used as building blocks of algorithms for analysis of entanglement and quantum error correction codes. Simulation of Shor's algorithm is presented as an example of package capabilities.Comment: 6 pages, 4 figures, presented at Foundations of Quantum Information, 16th-19th April 2004, Camerino, Ital

Exponential Operators, Dobinski Relations and Summability

We investigate properties of exponential operators preserving the particle number using combinatorial methods developed in order to solve the boson normal ordering problem. In particular, we apply generalized Dobinski relations and methods of multivariate Bell polynomials which enable us to understand the meaning of perturbation-like expansions of exponential operators. Such expansions, obtained as formal power series, are everywhere divergent but the Pade summation method is shown to give results which very well agree with exact solutions got for simplified quantum models of the one mode bosonic systems.Comment: Presented at XIIth Central European Workshop on Quantum Optics, Bilkent University, Ankara, Turkey, 6-10 June 2005. 4 figures, 6 pages, 10 reference

Markovian MC simulation of QCD evolution at NLO level with minimum k_T

We present two Monte Carlo algorithms of the Markovian type which solve the modified QCD evolution equations at the NLO level. The modifications with respect to the standard DGLAP evolution concern the argument of the strong coupling constant alpha_S. We analyze the z - dependent argument and then the k_T - dependent one. The evolution time variable is identified with the rapidity. The two algorithms are tested to the 0.05% precision level. We find that the NLO corrections in the evolution of parton momentum distributions with k_T - dependent coupling constant are of the order of 10 to 20%, and in a small x region even up to 30%, with respect to the LO contributions.Comment: 32 pages, 9 pdf figure

Experimentally feasible measures of distance between quantum operations

We present two measures of distance between quantum processes based on the superfidelity, introduced recently to provide an upper bound for quantum fidelity. We show that the introduced measures partially fulfill the requirements for distance measure between quantum processes. We also argue that they can be especially useful as diagnostic measures to get preliminary knowledge about imperfections in an experimental setup. In particular we provide quantum circuit which can be used to measure the superfidelity between quantum processes. As the behavior of the superfidelity between quantum processes is crucial for the properties of the introduced measures, we study its behavior for several families of quantum channels. We calculate superfidelity between arbitrary one-qubit channels using affine parametrization and superfidelity between generalized Pauli channels in arbitrary dimensions. Statistical behavior of the proposed quantities for the ensembles of quantum operations in low dimensions indicates that the proposed measures can be indeed used to distinguish quantum processes.Comment: 9 pages, 4 figure

Solution of the Kwiecinski evolution equations for unintegrated parton distributions using the Mellin transform

The Kwiecinski equations for the QCD evolution of the unintegrated parton distributions in the transverse-coordinate space (b) are analyzed with the help of the Mellin-transform method. The equations are solved numerically in the general case, as well as in a small-b expansion which converges fast for b Lambda_QCD sufficiently small. We also discuss the asymptotic limit of large bQ and show that the distributions generated by the evolution decrease with b according to a power law. Numerical results are presented for the pion distributions with a simple valence-like initial condition at the low scale, following from chiral large-N_c quark models. We use two models: the Spectral Quark Model and the Nambu--Jona-Lasinio model. Formal aspects of the equations, such as the analytic form of the b-dependent anomalous dimensions, their analytic structure, as well as the limits of unintegrated parton densities at x -> 0, x -> 1, and at large b, are discussed in detail. The effect of spreading of the transverse momentum with the increasing scale is confirmed, with growing asymptotically as Q^2 alpha(Q^2). Approximate formulas for for each parton species is given, which may be used in practical applications.Comment: 18 pages, 6 figures, RevTe

Complex X chromosome rearrangement associated with multiorgan autoimmunity

BACKGROUND: Turner syndrome, a congenital condition that affects 1/2,500 births, results from absence or structural alteration of the second sex chromosome. Turner syndrome is usually associated with short stature, gonadal dysgenesis and variable dysmorphic features. The classical 45,X karyotype accounts approximately for half of all patients, the remainder exhibit mosaicism or structural abnormalities of the X chromosome. However, complex intra-X chromosomal rearrangements involving more than three breakpoints are extremely rare. RESULTS: We present a unique case of a novel complex X chromosome rearrangement in a young female patient presenting successively a wide range of autoimmune diseases including insulin dependent diabetes mellitus, Hashimoto's thyroiditis, celiac disease, anaemia perniciosa, possible inner ear disease and severe hair loss. For the genetic evaluation, conventional cytogenetic analysis and FISH with different X specific probes were initially performed. The complexity of these results and the variety of autoimmune problems of the patient prompted us to identify the exact composition and breakpoints of the rearranged X as well as methylation status of the X chromosomes. The high resolution array-CGH (assembly GRCh37/hg19) detected single copy for the whole chromosome X short arm. Two different sized segments of Xq arm were present in three copies: one large size of 80,3 Mb from Xq11.1 to Xq27.3 region and another smaller (11,1 Mb) from Xq27.3 to Xq28 region. An 1,6 Mb Xq27.3 region of the long arm was present in two copies. Southern blot analysis identified a skewed X inactivation with approximately 70:30 % ratios of methylated/unmethylated fragments. The G-band and FISH patterns of the rearranged X suggested the aspect of a restructured i(Xq) chromosome which was shattered and fortuitously repaired. The X-STR genotype analysis of the family detected that the patient inherited intact maternal X chromosome and a rearranged paternal X chromosome. The multiple Xq breakages and fusions as well as inverted duplication would have been expected to cause a severe Turner phenotype. However, the patient lacks many of the classic somatic features of Turner syndrome, instead she presented multiorgan autoimmune diseases. CONCLUSIONS: The clinical data of the presented patient suggest that fragmentation of the i(Xq) chromosome elevates the risk of autoimmune diseases