Parabens enable suspension growth of MCF-10A immortalized, non-transformed human breast epithelial cells

Parabens (alkyl esters of p-hydroxybenzoic acid) are used extensively as preservatives in consumer products, and intact esters have been measured in several human tissues. Concerns of a potential link between parabens and breast cancer have been raised, but mechanistic studies have centred on their oestrogenic activity and little attention has been paid to any carcinogenic properties. In the present study, we report that parabens can induce anchorage-independent growth of MCF-10A immortalized but non-transformed human breast epithelial cells, a property closely related to transformation and a predictor of tumour growth in vivo. In semi-solid methocel suspension culture, MCF-10A cells produced very few colonies and only of a small size but the addition of 5 × 10-4 M methylparaben, 10–5 M n-propylparaben or 10–5 M n-butylparaben resulted in a greater number of colonies per dish (P < 0.05 in each case) and an increased average colony size (P < 0.001 in each case). Dose-responses showed that concentrations as low as 10–6 M methylparaben, 10–7 M n-propylparaben and 10–7 M n-butylparaben could increase colony numbers (P = 0.016, P = 0.010, P = 0.008, respectively): comparison with a recent measurement of paraben concentrations in human breast tissue samples from 40 mastectomies (Barr et al., 2012) showed that 22/40 of the patients had at least one of the parabens at the site of the primary tumour at or above these concentrations. To our knowledge, this is the first study to report that parabens can induce a transformed phenotype in human breast epithelial cells in vitro, and further investigation is now justified into a potential link between parabens and breast carcinogenesis.

Effects of aluminium chloride and aluminium chlorohydrate on DNA repair in MCF10A immortalised non-transformed human breast epithelial cells

Use of underarm aluminium (Al)-based antiperspirant salts may be a contributory factor in breast cancer development. At the 10th Keele meeting, Al was reported to cause anchorage-independent growth and double strand DNA breaks in MCF10A immortalised non-transformed human breast epithelial cells. We now report that exposure of MCF10A cells to Al chloride or Al chlorohydrate also compromised DNA repair systems. Longterm (19–21 weeks) exposure to Al chloride or Al chlorohydrate at a 10−4 M concentration resulted in reduced levels of BRCA1 mRNA as determined by real-time RT-PCR and BRCA1 protein as determined by Western immunoblotting. Reduced levels of mRNA for other DNA repair genes (BRCA2, CHK1, CHK2, Rad51, ATR) were also observed using real-time RT-PCR. Loss of BRCA1 or BRCA2 gene function has long been associated with inherited susceptibility to breast cancer but these results suggest that exposure to aluminium-based antiperspirant salts may also reduce levels of these key components of DNA repair in breast epithelial cells. If Al can not only damage DNA but also compromise DNA repair systems, then there is the potential for Al to impact on breast carcinogenesis.

Sensitivity of feature-based analysis methods of storm tracks to the form of background field removal

For the tracking of extrema associated with weather systems to be applied to a broad range of fields it is necessary to remove a background field that represents the slowly varying, large spatial scales. The sensitivity of the tracking analysis to the form of background field removed is explored for the Northern Hemisphere winter storm tracks for three contrasting fields from an integration of the U. K. Met Office's (UKMO) Hadley Centre Climate Model (HadAM3). Several methods are explored for the removal of a background field from the simple subtraction of the climatology, to the more sophisticated removal of the planetary scales. Two temporal filters are also considered in the form of a 2-6-day Lanczos filter and a 20-day high-pass Fourier filter. The analysis indicates that the simple subtraction of the climatology tends to change the nature of the systems to the extent that there is a redistribution of the systems relative to the climatological background resulting in very similar statistical distributions for both positive and negative anomalies. The optimal planetary wave filter removes total wavenumbers less than or equal to a number in the range 5-7, resulting in distributions more easily related to particular types of weather system. For the temporal filters the 2-6-day bandpass filter is found to have a detrimental impact on the individual weather systems, resulting in the storm tracks having a weak waveguide type of behavior. The 20-day high-pass temporal filter is less aggressive than the 2-6-day filter and produces results falling between those of the climatological and 2-6-day filters.

Determining the effect of asymmetric data on the variogram. I. Underlying asymmetry

Matheron's usual variogram estimator can result in unreliable variograms when data are strongly asymmetric or skewed. Asymmetry in a distribution can arise from a long tail of values in the underlying process or from outliers that belong to another population that contaminate the primary process. This paper examines the effects of underlying asymmetry on the variogram and on the accuracy of prediction, and the second one examines the effects arising from outliers. Standard geostatistical texts suggest ways of dealing with underlying asymmetry; however, this is based on informed intuition rather than detailed investigation. To determine whether the methods generally used to deal with underlying asymmetry are appropriate, the effects of different coefficients of skewness on the shape of the experimental variogram and on the model parameters were investigated. Simulated annealing was used to create normally distributed random fields of different size from variograms with different nugget:sill ratios. These data were then modified to give different degrees of asymmetry and the experimental variogram was computed in each case. The effects of standard data transformations on the form of the variogram were also investigated. Cross-validation was used to assess quantitatively the performance of the different variogram models for kriging. The results showed that the shape of the variogram was affected by the degree of asymmetry, and that the effect increased as the size of data set decreased. Transformations of the data were more effective in reducing the skewness coefficient in the larger sets of data. Cross-validation confirmed that variogram models from transformed data were more suitable for kriging than were those from the raw asymmetric data. The results of this study have implications for the 'standard best practice' in dealing with asymmetry in data for geostatistical analyses. (C) 2007 Elsevier Ltd. All rights reserved.

Remote estimation of thermal inertia and soil heat flux for bare soil

A method is presented which allows thermal inertia (the soil heat capacity times the square root of the soil thermal diffusivity, C(h)rootD(h)), to be estimated remotely from micrometeorological observations. The method uses the drop in surface temperature, T-s, between sunset and sunrise, and the average night-time net radiation during that period, for clear, still nights. A Fourier series analysis was applied to analyse the time series of T-s . The Fourier series constants, together with the remote estimate of thermal inertia, were used in an analytical expression to calculate diurnal estimates of the soil heat flux, G. These remote estimates of C(h)rootD(h) and G compared well with values derived from in situ sensors. The remote and in situ estimates of C(h)rootD(h) both correlated well with topsoil moisture content. This method potentially allows area-average estimates of thermal inertia and soil heat flux to be derived from remote sensing, e.g. METEOSAT Second Generation, where the area is determined by the sensor's height and viewing angle. (C) 2003 Elsevier B.V. All rights reserved.

Linear and nonlinear generalized Fourier transforms

This article presents an overview of a transform method for solving linear and integrable nonlinear partial differential equations. This new transform method, proposed by Fokas, yields a generalization and unification of various fundamental mathematical techniques and, in particular, it yields an extension of the Fourier transform method.

Approximations to the scattering of water waves by steep topography

A new method is developed for approximating the scattering of linear surface gravity waves on water of varying quiescent depth in two dimensions. A conformal mapping of the fluid domain onto a uniform rectangular strip transforms steep and discontinuous bed profiles into relatively slowly varying, smooth functions in the transformed free-surface condition. By analogy with the mild-slope approach used extensively in unmapped domains, an approximate solution of the transformed problem is sought in the form of a modulated propagating wave which is determined by solving a second-order ordinary differential equation. This can be achieved numerically, but an analytic solution in the form of a rapidly convergent infinite series is also derived and provides simple explicit formulae for the scattered wave amplitudes. Small-amplitude and slow variations in the bedform that are excluded from the mapping procedure are incorporated in the approximation by a straightforward extension of the theory. The error incurred in using the method is established by means of a rigorous numerical investigation and it is found that remarkably accurate estimates of the scattered wave amplitudes are given for a wide range of bedforms and frequencies.

Platelet-mediated metabolism of the common dietary flavonoid, quercetin.

BACKGROUND: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4'-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets. CONCLUSIONS/SIGNIFICANCE: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds.

Vibration-rotation spectra of monofluoroacetylene: 1700 to 7500 cm−1

High-resolution vibration-rotation spectra of monofluoroacetylene are reported for many bands in the region 1700 to 7500 cm−1. The spectra were observed on Nicolet 7199 and Bruker IFS 120 Fourier spectrometers, with resolutions of about 0.06 and 0.003 cm−1, respectively. About 130 bands have been observed in this region, of which about 80 have been rotationally analyzed. The assignment of vibrational labels to the higher energy levels is complicated by the effects of strong Fermi resonances, and many weak localized rotational resonances are observed.

The infrared vibration-rotation spectrum of trans and cis nitrous acid

Infrared spectra of the trans and the cis isomers of nitrous acid, both HONO and DONO, have been observed in the gas phase using a Fourier transform interferometer with a resolution of about 0.05 cm−1 from 4000 to 500 cm−1. Rotational analyses are reported on eleven of the fundamentals and some overtones.

Vibrationally mediated photodissociation of nitrous acid

Hitherto unobserved overtone and combination bands of nitrous acid have been investigated by Fourier-transform infrared absorption spectroscopy and through the resonance enhancements they provide in the two-photon excition spectrum for forming OH(X) photofragments. Analysis of the band profiles associated with the second and third O—H stretching overtones of trans-HONO, and of the energy disposal into the OH(X) fragments resulting from two-photon dissociation mediated by these overtone levels, provide some clues as to the mechanism for intramolecular vibrational energy redistribution (IVR) within these vibrationally excited molecules. The work serves to highlight further the extreme sensitivity of vibrationally mediated photodissociation (VMP) as a means of revealing weak O—H stretching overtones, even in situations (as here) where the species of interest is but a minor constituent of an equilibrium mixture.

Vibration-rotation spectra of nitrous acid, HONO

High-resolution Fourier-transform infrared spectra have been recorded and analyzed for the nu4, nu5, and nu6 fundamental bands of trans-HONO, and for the nu4 fundamental of cis-HONO. The spectral resolution was better than 0.01/cm, and the rotational structure has been analyzed to give improved ground-state and excited-state rotational constants, with a standard deviation of the fit to the observed line positions of around 0.0006/cm. Two Coriolis interactions have been analyzed between the nu5 and nu6 bands of trans-HONO.

The infrared spectrum, equilibrium structure and harmonic and anharmonic force field of thioborine, HBS

Infrared spectra of the two stretching fundamentals of both HBS and DBS have been observed, using a continuous flow system through a multiple reflection long path cell at a pressure around 1 Torr and a Nicolet Fourier Transform spectrometer with a resolution of about 0•1 cm-1. The v3 BS stretching fundamental of DBS, near 1140 cm-1, is observed in strong Fermi resonance with the overtone of the bend 2v2. The bending fundamental v2 has not been observed and must be a very weak band. The analysis of the results in conjunction with earlier work gives the equilibrium structure (re(BH) = 1•1698(12) , re(BS) = 1•5978(3) ) and the harmonic and anharmonic force field.

Intensities in the v7, v8 and v9 bands of CH2NH, and the harmonic force field of methyleneimine

A high resolution Fourier transform infrared spectrum of methyleneimine, HN=CH2, has been obtained in the gas phase in the region 700 to 1300 cm−1. The rovibrational line intensities of the three lowest fundamentals ν7 (A′), ν8 (A″), and ν9 (A″) have been simulated including all Coriolis interactions between the three bands, and by fitting the observed spectrum the relative signs and magnitudes of the vibrational transition moments have been determined. All of the available spectroscopic data have been used to determine the harmonic force field of methyleneimine.

Simultaneous analysis of v1, v4, 2v2, v2+v5, and 2v5 bands of 12CH3F

The Fourier-transform spectrum of CH3F from 2800 to 3100 cm−1, obtained by Guelachvili in Orsay at a resolution of about 0.003 cm−1, was analyzed. The effective Hamiltonian used contained all symmetry allowed interactions up to second order in the Amat-Nielsen classification, together with selected third-order terms, amongst the set of nine vibrational basis functions represented by the states ν1(A1), ν4(E), 2ν2(A1), ν2 + ν5(E), 2ν50(A1), and 2ν5±2(E). A number of strong Fermi and Coriolis resonances are involved. The vibrational Hamiltonian matrix was not factorized beyond the requirements of symmetry. A total of 59 molecular parameters were refined in a simultaneous least-squares analysis to over 1500 upper-state energy levels for J ≤ 20 with a standard deviation of 0.013 cm−1. Although the standard deviation remains an order of magnitude greater than the precision of the measurements, this work breaks new ground in the simultaneous analysis of interacting symmetric top vibrational levels, in terms of the number of interacting vibrational states and the number of parameters in the Hamiltonian.