Pathways to Melanoma Development: Lessons from the Mouse

Because of subtle differences between mouse and human skin, mice have traditionally not been an ideal model to study melanoma development. Understanding of the molecular mechanisms of melanoma predisposition, however, has been greatly improved by modeling various pathway defects in the mouse. This review analyzes the latest developments in mouse models of melanoma, and summarizes what these may indicate about the development of this neoplasm in humans. Mutations of genes involved in human melanoma have been recapitulated with some unexpected results, particularly with respect to the role of the two transcripts (Ink4a and Arf) encoded by the Cdkn2a locus. Both the Ink4a/pRb and Arf/p53 pathways are involved in melanoma development in mice, and possible mechanisms of cross-talk between the two pathways are discussed. We also know from mouse models that Ras/mitogen-activated protein kinase pathway activation is very important in melanoma development, either through direct activation of Ras (e.g., Hras G12V), or via activation of Ras-effector pathways by other oncogenes (e.g., Ret, Hgf/Sf). Ras can cooperate with the Arf/p53 pathway, and probably the Ink4a/Rb pathway, to induce melanoma. These three growth regulation pathways (Ink4a/pRb, Arf/p53, and Ras/mitogen-activated protein kinase) seem to represent three major axes of melanoma development in mice. Finally, we summarize experiments using genetically modified mice that have given indications of the intensity and timing of ultraviolet radiation exposure that may be most responsible for melanoma development.

The metamorphosis of lambda-fold K-3,K-3-designs into lambda-fold 6-cycle systems

In this paper necessary and sufficient conditions are given for the metamorphosis of a lambda-fold K-3,K-3-design of order n into a lambda-fold 6-cycle system of order n, by retaining one 6-cycle subgraph from each copy of K-3,K-3, and then rearranging the set of all the remaining edges, three from each K-3,K-3, into further 6-cycles so that the result is a lambda-fold 6-cycle system.

The radiation chemistry of ultem at 77 K as revealed by ESR spectroscopy

Radical formation in ultem following gamma-radiolysis has been reassessed, and the G(R*) values at different temperatures have been determined by ESR spectroscopy. The radical assignment and radical reactivity have been re-examined by photobleaching and thermal annealing studies. Photobleachable radical anions were found to comprise approximate to40% of the total number of radicals formed on radiolysis at 77 K. Spectral subtraction methods, ESR spectral simulations, measurement of g-values and the hyperfine splitting constants were used to identify the other radical intermediates. The principal chain scission radicals are formed due to scission of the main-chain at (i) the ether linkage, (ii) the isopropylidene group and (iii) the imide ring in the main chain. The side chain methyl groups of the isopropylidine units also lose hydrogen to form methylene radicals. The five-line spectrum observed to decay in the temperature range 370-430 K, which has not been assigned previously, has been identified as being characteristic of a di-substituted benzyl radical. (C) 2002 Elsevier Science Ltd. All rights reserved.

NMR study of the gamma radiolysis of poly(dimethyl siloxane) under vacuum at 303 K

The structural changes which occur on the gamma -radiolysis of poly(dimethyl siloxane) (PDMS) under vacuum at 303 K have been investigated using Si-29 and C-13 NMR. New structural units consistent with main chain scission and crosslinking through both H-linking and Y-linking reactions have been identified. The results obtained at various absorbed doses have been used to calculate the G-values for scission and crosslinking. G-values for scission of G(S) = 1.3 +/- 0.2, for H-linking of G(D-CH2-R) = 0.34 +/- 0.02 and for Y-Linking of G(Y) = 1.70 +/- 0.09 were obtained for radiolysis under vacuum at 303 K. Thus crosslinking predominates over scission for radiolysis of PDMS under these conditions, and, by contrast with previous studies, Y-links have been shown to be the predominant form of crosslinks. (C) 2001 Elsevier Science Ltd. All rights reserved.

Cenozoic continental weathering and its implications for the palaeoclimate: evidence from Ar-40/Ar-39 geochronology of supergene K-Mn oxides in Mt Tabor, central Queensland, Australia

One hundred and twenty-five mineral grains from 45 visually pure K-bearing Mn oxide (hollandite group) samples collected from weathering profiles in the Mt Tabor region of central Queensland, Australia, were analysed by the Ar-40/Ar-39 laser probe technique. These K-Mn oxides precipitated mainly through a process of cavity filling (direct precipitation from weathering solution), with botryoidal texture formed by micrometric mineral bands. Well-defined and reproducible plateau ages have been obtained for most samples, ranging from 27.2 +/- 0.8 to 6.8 +/- 0.5 Ma (2 sigma). Statistical analysis of the geochronological results by mixture modelling suggests an episodic mineral precipitation history, with two major peaks at 20.2 +/- 0.22 Ma and 16.5 +/- 0.17 Ma. The geochronological results, when combined with information on paragenetic relationships and mineralogical textures obtained from petrographic, scanning electron microscopy, and electron microprobe investigations, indicate that warm and humid palaeoclimatic conditions favourable to intense chemical weathering prevailed in central Queensland from late Oligocene to middle Miocene, particularly in the early Miocene. These results, in conjunction with previous and ongoing investigations in NW and eastern Queensland, suggest that most of Queensland was dominated by humid climates during the Miocene. (C) 2002 Elsevier Science BN. All rights reserved.

A new joint coding and modulation scheme for channels with clipping

A major limitation in any high-performance digital communication system is the linearity region of the transmitting amplifier. Nonlinearities typically lead to signal clipping. Efficient communication in such conditions requires maintaining a low peak-to-average power ratio (PAR) in the transmitted signal while achieving a high throughput of data. Excessive PAR leads either to frequent clipping or to inadequate resolution in the analog-to-digital or digital-to-analog converters. Currently proposed signaling schemes for future generation wireless communications suffer from a high PAR. This paper presents a new signaling scheme for channels with clipping which achieves a PAR as low as 3. For a given linear range in the transmitter's digital-to-analog converter, this scheme achieves a lower bit-error rate than existing multicarrier schemes, owing to increased separation between constellation points. We present the theoretical basis for this new scheme, approximations for the expected bit-error rate, and simulation results. (C) 2002 Elsevier Science (USA).

Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231

Peroxisome proliferator-activated receptor (PPAR) alpha is a ligand-activated transcription factor that has been linked with rodent hepatocarcinogenesis. It has been suggested that PPARalpha mRNA expression levels are an important determinant of rodent hepatic tumorigenicity. Previous work in rat mammary gland epithelial cells showed significantly increased PPARalpha mRNA expression in carcinomas, suggesting the possible role of this isoform in rodent mammary gland carcinogenesis. In this study we sought to determine whether PPARalpha is expressed and dynamically regulated in human breast cancer MCF-7 and MDA-MB-231 cells. Having established the presence of PPARalpha in both cell types, we then examined the consequence of PPARa activation, by its ligands Wy-14,643 and clofibrate, on proliferation. With real-time reverse transcriptase-polymerase chain reaction, we showed that PPARalpha mRNA was dynamically regulated in MDA-MB-231 cells and that PPARalpha activation significantly increased proliferation of the cell line. In contrast, PPARalpha expression in MCF-7 cells did not change with proliferation during culture and was present at significantly lower levels than in MDA-MB-231 cells. However, PPARalpha ligand activation still significantly increased the proliferation of MCF-7 cells. The promotion of proliferation in breast cancer cell lines following PPARalpha activation was in stark contrast to the effects of PPARgamma-activating ligands that decrease proliferation in human breast cancer cells. our results established the presence of PPARalpha in human breast cancer cell lines and showed for the first time that activation of PPARalpha in human breast cancer cells promoted proliferation. Hence, this pathway may be significant in mammary gland tumorigenesis. (C) 2002 Wiley-Liss, Inc.

Adsorption of aromatic compounds onto activated carbons: Effects of the orientation of the adsorbates

Adsorption of model aromatic compounds onto two untreated activated carbons with similar physical and chemical properties is investigated. The solution pH of all experiments was lowered so that all solutes were in their molecular forms. It is shown that the difference in the maximum adsorption capacities of the solutes was mainly attributed to the difference in the sizes of the molecules. This new experimental finding is significant to gaining insight into the orientation of the adsorbed phase and hence the adsorption mechanism of aromatic compounds in aqueous solutions. It is shown that the adsorption of aromatic compounds in a stacked motif for pi-pi interactions is unlikely, and in the absence of physical restrictions such as pore width, a T-shaped motif is the preferred orientation.

Effects of the solute ionization on the adsorption of aromatic compounds from dilute aqueous solutions by activated carbon

Adsorption of four dissociating aromatic compounds and one nondissociating compound on a commercial activated carbon is investigated systematically. All adsorption experiments were carried out in pH-controlled aqueous solutions. The adsorption isotherms are fitted to the binary homogeneous Langmuir model, where the concentrations of the molecular and the ionic species in the liquid phase are expressed in terms of the sum of the two and the degree of solute ionization. Examination of the relationships between the solution pH, the degree of ionization of the solutes, and the model parameters is found to give new insights into the adsorption process. Furthermore, this is used to correlate the variation of the monolayer capacity with the solution pH.

Structural and surface property changes of macadamia nut-shell char upon activation and high temperature treatment

Structural and surface property changes of macadamia nut-shell (MNS) char upon activation and high temperature treatment (HTT) were studied by high-resolution nitrogen adsorption, diffuse reflectance infra-red Fourier transform spectroscopy, X-ray photoelectron spectroscopy, and temperature-programmed desorption. It is found that activation of MNS char can be divided into the low extent activation which may involve the reactions of internal oxygen-containing groups and leads to the formation of comparatively uniform micropores, and the high extent activation which induces reactions between carbon and activating gas and produces a large amount of micropores. The surface functional groups (SFGs) basically increase with the increase of activation extent, but high extent activation preferentially increases the amount of -C-O and -C=O. HTT in air for a short tithe at a high temperature (1173 K) greatly increases the micropore volume and the amounts of SFGs. By appropriately choosing the activation and HTT conditions, it is possible to control both the textural structure and the type and amounts of SFG. (C) 2002 Published by Elsevier Science Ltd.

Vacancy solution theory for binary adsorption equilibria in heterogeneous carbon

A heterogeneous modified vacancy solution model of adsorption developed is evaluated. The new model considers the adsorption process through a mass-action law and is thermodynamically consistent, while maintaining the simplicity in calculation of multicomponent adsorption equilibria, as in the original vacancy solution theory. It incorporates the adsorbent heterogeneity through a pore-width-related potential energy, represented by Steele's 10-4-3 potential expression. The experimental data of various hydrocarbons, CO2 and SO2 on four different activated carbons - Ajax, Norit, Nuxit, and BPL - at multiple temperatures over a wide range of pressures were studied by the heterogeneous modified VST model to obtain the isotherm parameters and micropore-size distribution of carbons. The model successfully correlates the single-component adsorption equilibrium data for all compounds studied on various carbons. The fitting results for the vacancy occupancy parameter are consistent with the pressure change on different carbons, and the effect of pore heterogeneity is important in adsorption at elevated pressure. It predicts binary adsorption equilibria better than the IAST scheme, reflecting the significance of molecular size nonideality.

Bracken (Pteridium aquilinum)-induced DNA adducts in mouse tissues are different from the adduct induced by the activated form of the bracken carcinogen ptaquiloside

Following treatment with bracken fern (Pteridium aquilinum) extract and bracken spores a number of DNA adducts were detected by P-32-postlabeling. Three of these adducts have been described previously (Povey et al., Br. J. Cancer (1996) 74, 1342-1348) and in this study, using a slightly different protocol, four new adducts, with higher chromatographic mobility, were detected at levels ranging from 50 to 230% of those previously described, When DNA was treated in vitro with activated ptaquiloside (APT) and analysed by butanol extraction or nuclease P1 treatment, only one adduct was detected by P-32-postlabeling, This adduct was not present in the DNA from mice treated with bracken fern or spores, suggesting either that bracken contains genotoxins other than ptaquiloside or that the metabolism of ptaquiloside produces genotoxins not reflected by activated ptaquiloside. However, as the ATP-derived adduct has been detected previously in ileal DNA of bracken-fed calves, species-specific differences in the metabolism of bracken genotoxins may exist, thereby leading to differences in their biological outcomes. (C) 2001 Academic Press.

Study on diffusion and flow of benzene, n-hexane and CCl4 in activated carbon by a differential permeation method

In this paper the diffusion and flow of carbon tetrachloride, benzene and n-hexane through a commercial activated carbon is studied by a differential permeation method. The range of pressure is covered from very low pressure to a pressure range where significant capillary condensation occurs. Helium as a non-adsorbing gas is used to determine the characteristics of the porous medium. For adsorbing gases and vapors, the motion of adsorbed molecules in small pores gives rise to a sharp increase in permeability at very low pressures. The interplay between a decreasing behavior in permeability due to the saturation of small pores with adsorbed molecules and an increasing behavior due to viscous flow in larger pores with pressure could lead to a minimum in the plot of total permeability versus pressure. This phenomenon is observed for n-hexane at 30degreesC. At relative pressure of 0.1-0.8 where the gaseous viscous flow dominates, the permeability is a linear function of pressure. Since activated carbon has a wide pore size distribution, the mobility mechanism of these adsorbed molecules is different from pore to pore. In very small pores where adsorbate molecules fill the pore the permeability decreases with an increase in pressure, while in intermediate pores the permeability of such transport increases with pressure due to the increasing build-up of layers of adsorbed molecules. For even larger pores, the transport is mostly due to diffusion and flow of free molecules, which gives rise to linear permeability with respect to pressure. (C) 2002 Elsevier Science Ltd. All rights reserved.