An overview of epigenetics and chemoprevention

AbstractIt is now appreciated that both genetic alteration, e.g. mutations, and aberrant epigenetic changes, e.g. DNA methylation, cause cancer. Epigenetic dysregulation is potentially reversible which makes it attractive as targets for cancer prevention. Synthetic drugs targeting enzymes, e.g. DNA methyltransferase and histone deacetylase, that regulate epigenetic patterns are active in clinical settings. In addition, dietary factors have been suggested to have potential to reverse aberrant epigenetic patterns. Uncovering the human epigenome can lead us to better understand the dynamics of DNA methylation in disease progression which can further assist in cancer prevention

Long Term Outdoor Testing of Low Concentration Solar Modules

A 1‐axis carousel tracker equipped with four 3‐sun low‐concentration mirror modules has now been under test outdoors at the University of Nevada in Las Vegas (UNLV) for three years. There are three unique features associated with this unit. First, simple linear mirrors are used to reduce the amount of expensive single crystal silicon in order to potentially lower the module cost while potentially maintaining cell efficiencies over 20% and high module efficiency. Simple linear mirrors also allow the use of a single axis tracker. Second, the azimuth carousel tracker is also unique allowing trackers to be used on commercial building rooftops. Third, an experiment is underway comparing aluminum based mirrors with novel 3M Company multilayer polymeric mirrors which are potentially very low cost. Comparing the data from March of 2008 through March of 2011 shows that the aluminum mirror degradation to date is negligible and that the carousel tracker has been operating continuously and reliable. Also, no degradation has been observed for the 3M brand cool mirrors after one year in use

Heritable clustering and pathway discovery in breast cancer integrating epigenetic and phenotypic data

BACKGROUND: In order to recapitulate tumor progression pathways using epigenetic data, we developed novel clustering and pathway reconstruction algorithms, collectively referred to as heritable clustering. This approach generates a progression model of altered DNA methylation from tumor tissues diagnosed at different developmental stages. The samples act as surrogates for natural progression in breast cancer and allow the algorithm to uncover distinct epigenotypes that describe the molecular events underlying this process. Furthermore, our likelihood-based clustering algorithm has great flexibility, allowing for incomplete epigenotype or clinical phenotype data and also permitting dependencies among variables. RESULTS: Using this heritable clustering approach, we analyzed methylation data obtained from 86 primary breast cancers to recapitulate pathways of breast tumor progression. Detailed annotation and interpretation are provided to the optimal pathway recapitulated. The result confirms the previous observation that aggressive tumors tend to exhibit higher levels of promoter hypermethylation. CONCLUSION: Our results indicate that the proposed heritable clustering algorithms are a useful tool for stratifying both methylation and clinical variables of breast cancer. The application to the breast tumor data illustrates that this approach can select meaningful progression models which may aid the interpretation of pathways having biological and clinical significance. Furthermore, the framework allows for other types of biological data, such as microarray gene expression or array CGH data, to be integrated

Deep sequencing of HPV E6/E7 genes reveals loss of genotypic diversity and gain of clonal dominance in high-grade intraepithelial lesions of the cervix

Table S2. HPV E6/E7 sequencing: dideoxy (Sanger) vs. deep (Illumina). (PDF 236 kb

Fluid generation and evolution during exhumation of deeply subducted UHP continental crust: Petrogenesis of composite granite-quartz veins in the Sulu belt, China

Composite granite-quartz veins occur in retrogressed ultrahigh pressure (UHP) eclogite enclosed in gneiss at General's Hill in the central Sulu belt, eastern China. The granite in the veins has a high-pressure (HP) mineral assemblage of dominantly quartz+phengite+allanite/epidote+garnet that yields pressures of 2.5-2.1 GPa (Si-in-phengite barometry) and temperatures of 850-780°C (Ti-in-zircon thermometry) at 2.5 GPa (~20°C lower at 2.1 GPa). Zircon overgrowths on inherited cores and new grains of zircon from both components of the composite veins crystallized at c. 221 Ma. This age overlaps the timing of HP retrograde recrystallization dated at 225-215 Ma from multiple localities in the Sulu belt, consistent with the HP conditions retrieved from the granite. The eHf(t) values of new zircon from both components of the composite veins and the Sr-Nd isotope compositions of the granite consistently lie between values for gneiss and eclogite, whereas d18O values of new zircon are similar in the veins and the crustal rocks. These data are consistent with zircon growth from a blended fluid generated internally within the gneiss and the eclogite, without any ingress of fluid from an external source. However, at the peak metamorphic pressure, which could have reached 7 GPa, the rocks were likely fluid absent. During initial exhumation under UHP conditions, exsolution of H2O from nominally anhydrous minerals generated a grain boundary supercritical fluid in both gneiss and eclogite. As exhumation progressed, the volume of fluid increased allowing it to migrate by diffusing porous flow from grain boundaries into channels and drain from the dominant gneiss through the subordinate eclogite. This produced a blended fluid intermediate in its isotope composition between the two end-members, as recorded by the composite veins. During exhumation from UHP (coesite) eclogite to HP (quartz) eclogite facies conditions, the supercritical fluid evolved by dissolution of the silicate mineral matrix, becoming increasingly solute-rich, more 'granitic' and more viscous until it became trapped. As crystallization began by diffusive loss of H2O to the host eclogite concomitant with ongoing exhumation of the crust, the trapped supercritical fluid intersected the solvus for the granite-H2O system, allowing phase separation and formation of the composite granite-quartz veins. Subsequently, during the transition from HP eclogite to amphibolite facies conditions, minor phengite breakdown melting is recorded in both the granite and the gneiss by K-feldspar+plagioclase+biotite aggregates located around phengite and by K-feldspar veinlets along grain boundaries. Phase equilibria modelling of the granite indicates that this late-stage melting records P-T conditions towards the end of the exhumation, with the subsolidus assemblage yielding 0.7-1.1 GPa at <670°C. Thus, the composite granite-quartz veins represent a rare example of a natural system recording how the fluid phase evolved during exhumation of continental crust. The successive availability of different fluid phases attending retrograde metamorphism from UHP eclogite to amphibolite facies conditions will affect the transport of trace elements through the continental crust and the role of these fluids as metasomatic agents interacting with the mantle wedge in the subduction channel

RCS2 J232727.6-020437: An Efficient Cosmic Telescope at z=0.6986z=0.6986

We present a detailed gravitational lens model of the galaxy cluster RCS2 J232727.6-020437. Due to cosmological dimming of cluster members and ICL, its high redshift ($z=0.6986$) makes it ideal for studying background galaxies. Using new ACS and WFC3/IR HST data, we identify 16 multiple images. From MOSFIRE follow up, we identify a strong emission line in the spectrum of one multiple image, likely confirming the redshift of that system to $z=2.083$. With a highly magnified ($\mu\gtrsim2$) source plane area of $\sim0.7$ arcmin$^2$ at $z=7$, RCS2 J232727.6-020437 has a lensing efficiency comparable to the Hubble Frontier Fields clusters. We discover four highly magnified $z\sim7$ candidate Lyman-break galaxies behind the cluster, one of which may be multiply-imaged. Correcting for magnification, we find that all four galaxies are fainter than $0.5 L_{\star}$. One candidate is detected at ${>10\sigma}$ in both Spitzer/IRAC [3.6] and [4.5] channels. A spectroscopic follow-up with MOSFIRE does not result in the detection of the Lyman-alpha emission line from any of the four candidates. From the MOSFIRE spectra we place median upper limits on the Lyman-alpha flux of $5-14 \times 10^{-19}\, \mathrm{erg \,\, s^{-1} cm^{-2}}$ ($5\sigma$).Comment: 14 pages, 9 figures, submitted to ApJ on 3/06/201