Epigenetics and Breast Cancers

Several of the active compounds in foods, poisons, drugs, and industrial chemicals may, by epigenetic mechanisms, increase or decrease the risk of breast cancers. Enzymes that are involved in DNA methylation and histone modifications have been shown to be altered in several types of breast and other cancers resulting in abnormal patterns of methylation and/or acetylation. Hypermethylation at the CpG islands found in estrogen response element (ERE) promoters occurs in conjunction with ligand-bonded alpha subunit estrogen receptor (Erα) dimers wherein the ligand ERα dimer complex acts as a transcription factor and binds to the ERE promoter. Ligands could be 17-β-estradiol (E2), phytoestrogens, heterocyclic amines, and many other identified food additives and heavy metals. The dimer recruits DNA methyltransferases which catalyze the transfer of methyl groups from S-adenosyl-L-methionine (SAM) to 5′-cytosine on CpG islands. Other enzymes are recruited to the region by ligand-ERα dimers which activate DNA demethylases to act simultaneously to increase gene expression of protooncogenes and growth-promoting genes. Ligand-ERα dimers also recruit histone acetyltransferase to the ERE promoter region. Histone demethylases such as JMJD2B and histone methyltransferases are enzymes which demethylate lysine residues on histones H3 and/or H4. This makes the chromatin accessible for transcription factors and enzymes

Multipole Expansion for the Electron-Nucleus Scattering at High Energies in the Unified Electroweak Theory

The article presents the multipole expansion for the electron-nucleus scattering cross section at high energies within the framework of the unified electroweak theory. The electroweak currents of the nucleus are expanded into simple components with definite angular momentum, which are called the multipole form factors. The multipole expansion of the cross section is a consequence of the above expansion. Besides the familiar electromagnetic form factors, there are weak form factors related to weak interactions, corresponding to the vector and axial (pseudovector) weak currents. We do not use the impulse approximation, the multipole form factors are calculated directly, using only the Born approximation. We will present some examples in the next paper.Comment: 7 pages, 0 figur

A continuous non-linear shadowing model of columnar growth

We propose the first continuous model with long range screening (shadowing) that described columnar growth in one space dimension, as observed in plasma sputter deposition. It is based on a new continuous partial derivative equation with non-linear diffusion and where the shadowing effects apply on all the different processes.Comment: Fast Track Communicatio

The dynamics underlying pseudo-plateau bursting in a pituitary cell model.

This is the final version of the article. Available from BioMed Central via the DOI in this record.Pituitary cells of the anterior pituitary gland secrete hormones in response to patterns of electrical activity. Several types of pituitary cells produce short bursts of electrical activity which are more effective than single spikes in evoking hormone release. These bursts, called pseudo-plateau bursts, are unlike bursts studied mathematically in neurons (plateau bursting) and the standard fast-slow analysis used for plateau bursting is of limited use. Using an alternative fast-slow analysis, with one fast and two slow variables, we show that pseudo-plateau bursting is a canard-induced mixed mode oscillation. Using this technique, it is possible to determine the region of parameter space where bursting occurs as well as salient properties of the burst such as the number of spikes in the burst. The information gained from this one-fast/two-slow decomposition complements the information obtained from a two-fast/one-slow decomposition.This work was supported by NSF grant DMS 0917664 to RB and NIH grant DK 043200 to RB and JT

Vitrification of a monatomic 2D simple liquid

A monatomic simple liquid in two dimensions, where atoms interact isotropically through the Lennard-Jones-Gauss potential [M. Engel and H.-R. Trebin, Phys. Rev. Lett. 98, 225505 (2007)], is vitrified by the use of a rapid cooling technique in a molecular dynamics simulation. Transformation to a crystalline state is investigated at various temperatures and the time-temperature-transformation (TTT) curve is determined. It is found that the transformation time to a crystalline state is the shortest at a temerature 14% below the melting temperature Tm and that at temperatures below Tv = 0.6 Tm the transformation time is much longer than the available CPU time. This indicates that a long-lived glassy state is realized for T < Tv.Comment: 5pages,5figures,accepted for publication in CEJ

Axial-flexural coupled vibration and buckling of composite beams using sinusoidal shear deformation theory

A finite element model based on sinusoidal shear deformation theory is developed to study vibration and buckling analysis of composite beams with arbitrary lay-ups. This theory satisfies the zero traction boundary conditions on the top and bottom surfaces of beam without using shear correction factors. Besides, it has strong similarity with Euler–Bernoulli beam theory in some aspects such as governing equations, boundary conditions, and stress resultant expressions. By using Hamilton’s principle, governing equations of motion are derived. A displacement-based one-dimensional finite element model is developed to solve the problem. Numerical results for cross-ply and angle-ply composite beams are obtained as special cases and are compared with other solutions available in the literature. A variety of parametric studies are conducted to demonstrate the effect of fiber orientation and modulus ratio on the natural frequencies, critical buckling loads, and load-frequency curves as well as corresponding mode shapes of composite beams

Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors.

PurposeTo determine the maximum tolerated dose (MTD), toxicities, and pharmacodynamics effects of sirolimus combined with oral metronomic topotecan and cyclophosphamide in a pediatric population.Materials and methodsPatients who were 1 to 30 years of age with relapsed/refractory solid tumors (including CNS) were eligible. Patients received daily oral sirolimus and cyclophosphamide (25-50 mg/m2/dose) on days 1-21 and oral topotecan (0.8 mg/m2/dose) on days 1-14 in 28-day cycles. Sirolimus steady-state plasma trough concentrations of 3-7.9 ng/mL and 8-12.0 ng/mL were evaluated, with dose escalation based on a 3+3 phase 1 design. Biomarkers of angiogenesis were also evaluated.ResultsTwenty-one patients were treated (median age 18 years; range 9-30). Dose-limiting toxicities included myelosuppression, ALT elevation, stomatitis, and hypertriglyceridemia. The MTD was sirolimus with trough goal of 8-12.0 ng/mL; cyclophosphamide 25 mg/m2/dose; and topotecan 0.8 mg/m2/dose. No objective responses were observed. Four patients had prolonged stable disease &gt; 4 cycles (range 4-12). Correlative biomarker analyses demonstrated reductions in thrombospondin-1 (p=0.043) and soluble vascular endothelial growth factor receptor-2 plasma concentrations at 21 days compared to baseline.ConclusionsThe combination of oral sirolimus, topotecan, and cyclophosphamide was well tolerated and biomarker studies demonstrated modulation of angiogenic pathways with this regimen

Instantaneous frequency measurement system using optical mixing in highly nonlinear fiber

A broadband photonic instantaneous frequency measurement system utilizing four-wave mixing in highly nonlinear fiber is demonstrated. This new approach is highly stable and does not require any high-speed electronics or photodetectors. A first principles model accurately predicts the system response. Frequency measurement responses from 1 to 40 GHz are demonstrated and simple reconfiguration allows the system to operate over multiple bands