Low-Silica and High-Calcium Stone in the Newman Limestone (Mississippian) on Pine Mountain, Letcher County, Southeastern Kentucky

The coal industry of Kentucky is an important market for limestone. Coal producers use limestone as rock dust for explosion abatement in underground coal mines and as a neutralizing agent in surface-mine reclamation and acid-drainage control. Haulage-road construction and maintenance require crushed stone. Coal-bearing rocks of Pennsylvanian age in the Eastern Kentucky Coal Field generally do not contain limestones that are sufficiently thick to quarry or mine economically, but in the southeastern part of the coal field, fault movement has brought the Newman Limestone to the surface along Pine Mountain. The Newman was sampled at three sites in Letcher County to determine its chemical quality and potential for industrial use, particularly as a source of low-silica rock dust. Analysis of the foot-by-foot samples shows that the Newman contains several zones of low-silica stone, 10 to 39 feet thick. A few intervals of high-calcium limestone, 12 to 24 feet thick, coincide with or occur in the low-silica zones. The deposits of low-silica and high-calcium stone are thickest in the southwestern part of Letcher County and commonly thin northeastward. The thicker deposits of chemically pure limestone and dolomite may be an economically exploitable source of rock dust for underground coal mines, and a source of stone for surface-mine reclamation and acid-drainage control. Production from deposits in the Newman, however, will be complicated by the steep southeastward to southward dip (20 to 42°) of the beds, possible displacement along small faults, and fracturing of the limestone

Amplification of HER2 is a marker for global genomic instability

<p>Abstract</p> <p>Background</p> <p>Genomic alterations of the proto-oncogene c-erbB-2 (HER-2/neu) are associated with aggressive behavior and poor prognosis in patients with breast cancer. The variable clinical outcomes seen in patients with similar HER2 status, given similar treatments, suggests that the effects of amplification of HER2 can be influenced by other genetic changes. To assess the broader genomic implications of structural changes at the HER2 locus, we investigated relationships between genomic instability and HER2 status in patients with invasive breast cancer.</p> <p>Methods</p> <p>HER2 status was determined using the PathVysion^®assay. DNA was extracted after laser microdissection from the 181 paraffin-embedded HER2 amplified (n = 39) or HER2 negative (n = 142) tumor specimens with sufficient tumor available to perform molecular analysis. Allelic imbalance (AI) was assessed using a panel of microsatellite markers representing 26 chromosomal regions commonly altered in breast cancer. Student t-tests and partial correlations were used to investigate relationships between genomic instability and HER2 status.</p> <p>Results</p> <p>The frequency of AI was significantly higher (<it>P </it>< 0.005) in HER2 amplified (27%) compared to HER2 negative tumors (19%). Samples with HER2 amplification showed significantly higher levels of AI (<it>P </it>< 0.05) at chromosomes 11q23, 16q22-q24 and 18q21. Partial correlations including ER status and tumor grade supported associations between HER2 status and alterations at 11q13.1, 16q22-q24 and 18q21.</p> <p>Conclusion</p> <p>The poor prognosis associated with HER2 amplification may be attributed to global genomic instability as cells with high frequencies of chromosomal alterations have been associated with increased cellular proliferation and aggressive behavior. In addition, high levels of DNA damage may render tumor cells refractory to treatment. In addition, specific alterations at chromosomes 11q13, 16q22-q24, and 18q21, all of which have been associated with aggressive tumor behavior, may serve as genetic modifiers to HER2 amplification. These data not only improve our understanding of HER in breast pathogenesis but may allow more accurate risk profiles and better treatment options to be developed.</p

The Lantern Vol. 39, No. 1, Fall 1972

• A Journey Into Darkness • September 5, 1972 • Atlantic Taperecorder • Aftermath • Linda • Sweet Baby Jane • The Court of the Ebony Clown • The Cosmic Band • Poem to the Dreamer • Dawn • Too Bad Life Isn\u27t • Incident at Tiffany\u27s • Sonnet • Infinitas • Podiatry • 2 and 4a • Autistic Autumn • I Walk Alone • Eyes---and They Were Emptyhttps://digitalcommons.ursinus.edu/lantern/1101/thumbnail.jp

Alterations of the retinoblastoma gene in metastatic breast cancer

Germline mutations affecting the retinoblastoma gene (RB1) predispose to inherited retinoblastomas but also other malignancies, including breast cancer. While somatic RB1 mutations have been detected in different malignancies, information about the potential role of RB1 mutations in breast cancer is limited. Recently, we discovered RB1 mutations to be associated with resistance to anthracyclines/mitomycin in primary breast cancer. The present work is the first report evaluating RB1 mutation and epigenetic status in metastatic breast cancer. Among 148 breast cancer samples analyzed by MLPA, four samples harbored intragenic deletions/duplications: Thus, exons 1–2 were deleted in two tumors and exons 21–23 in one tumor, while one sample harbored duplication of exons 18–23. The entire RB1 gene was duplicated in two tumors and multiple amplifications were revealed in one sample. Reduced copy number was observed in 17 samples (11.5%). No point mutation or promoter hypermethylation was discovered (n = 38 and 114 tumors analyzed, respectively). Interestingly, among seven tumors expressing lack of response to epirubicin, two samples harbored alterations in RB1, contrasting none out of 16 tumors with stable disease or an objective response (P = 0.08). In summary, the frequency of RB1 alterations in metastatic lesions was not increased when compared to primary breast cancer, indicating that RB1 alterations do not play a major role in metastatic development. While a non-significant association suggesting RB1 alterations to be linked to therapy resistance was observed, our data do not suggest a major role for RB1 alterations explaining acquired drug resistance

The c-Met receptor tyrosine kinase inhibitor MP470 radiosensitizes glioblastoma cells

<p>Abstract</p> <p>Purpose</p> <p>Glioblastoma multiforme (GBM) is resistant to current cytotoxic therapies, in part because of enhanced DNA repair. Activation of the receptor tyrosine kinase c-Met has been shown to protect cancer cells from DNA damage. We hypothesized that inhibiting c-Met would decrease this protection and thus sensitize resistant tumor cells to the effects of radiation therapy.</p> <p>Materials and methods</p> <p>Eight human GBM cell lines were screened for radiosensitivity to the small-molecule c-Met inhibitor MP470 with colony-count assays. Double-strand (ds) DNA breaks was quantified by using antibodies to gamma H2AX. Western blotting demonstrate expression of RAD51, glycogen synthase kinase (GSK)-3β, and other proteins. A murine xenograft tumor flank model was used for <it>in vivo </it>radiosensitization studies.</p> <p>Results</p> <p>MP470 reduced c-Met phosphorylation and enhanced radiation-induced cell kill by 0.4 logs in SF767 cells. Cells pretreated with MP470 had more ds DNA damage than cells treated with radiation alone. Mechanistically, MP470 was shown to inhibit dsDNA break repair and increase apoptosis. MP470 influences various survival and DNA repair related proteins such as pAKT, RAD51 and GSK3β. <it>In vivo</it>, the addition of MP470 to radiation resulted in a tumor-growth-delay enhancement ratio of 2.9 over radiation alone and extended survival time.</p> <p>Conclusions</p> <p>GBM is a disease site where radiation is often used to address both macroscopic and microscopic disease. Despite attempts at dose escalation outcomes remain poor. MP470, a potent small-molecule tyrosine kinase inhibitor of c-Met, radiosensitized several GBM cell lines both <it>in vitro </it>and <it>in vivo</it>, and may help to improve outcomes for patients with GBM.</p

Effects of Local and Landscape Factors on Population Dynamics of a Cotton Pest

BACKGROUND: Many polyphagous pests sequentially use crops and uncultivated habitats in landscapes dominated by annual crops. As these habitats may contribute in increasing or decreasing pest density in fields of a specific crop, understanding the scale and temporal variability of source and sink effects is critical for managing landscapes to enhance pest control. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated how local and landscape characteristics affect population density of the western tarnished plant bug, Lygus hesperus (Knight), in cotton fields of the San Joaquin Valley in California. During two periods covering the main window of cotton vulnerability to Lygus attack over three years, we examined the associations between abundance of six common Lygus crops, uncultivated habitats and Lygus population density in these cotton fields. We also investigated impacts of insecticide applications in cotton fields and cotton flowering date. Consistent associations observed across periods and years involved abundances of cotton and uncultivated habitats that were negatively associated with Lygus density, and abundance of seed alfalfa and cotton flowering date that were positively associated with Lygus density. Safflower and forage alfalfa had variable effects, possibly reflecting among-year variation in crop management practices, and tomato, sugar beet and insecticide applications were rarely associated with Lygus density. Using data from the first two years, a multiple regression model including the four consistent factors successfully predicted Lygus density across cotton fields in the last year of the study. CONCLUSIONS/SIGNIFICANCE: Our results show that the approach developed here is appropriate to characterize and test the source and sink effects of various habitats on pest dynamics and improve the design of landscape-level pest management strategies

PEARLS: A Potentially Isolated Quiescent Dwarf Galaxy with a TRGB Distance of 31 Mpc

A wealth of observations have long suggested that the vast majority of isolated classical dwarf galaxies ($M_*=10^7$-$10^9$ M$_\odot$) are currently star-forming. However, recent observations of the large abundance of "Ultra-Diffuse Galaxies" beyond the reach of previous large spectroscopic surveys suggest that our understanding of the dwarf galaxy population may be incomplete. Here we report the serendipitous discovery of an isolated quiescent dwarf galaxy in the nearby Universe, which was imaged as part of the PEARLS GTO program. Remarkably, individual red-giant branch stars are visible in this near-IR imaging, suggesting a distance of $31$ Mpc, and a wealth of archival photometry point to an sSFR of $2\times10^{-12}$ yr$^{-1}$. Spectra obtained with the Lowell Discovery Telescope find a recessional velocity consistent with the Hubble Flow and ${>}1500$ km/s separated from the nearest massive galaxy in SDSS, suggesting that this galaxy was either quenched from internal mechanisms or had a very high-velocity interaction with a nearby massive galaxy in the past. This analysis highlights the possibility that many nearby quiescent dwarf galaxies are waiting to be discovered and that JWST has the potential to identify them.Comment: Submitted to ApJ Letters. Comments welcome

Contrasting effects of long term versus short-term nitrogen addition on photosynthesis and respiration in the Arctic

We examined the effects of short (<1–4 years) and long-term (22 years) nitrogen (N) and/or phosphorus (P) addition on the foliar CO2 exchange parameters of the Arctic species Betula nana and Eriophorum vaginatum in northern Alaska. Measured variables included: the carboxylation efficiency of Rubisco (Vcmax), electron transport capacity (Jmax), dark respiration (Rd), chlorophyll a and b content (Chl), and total foliar N (N). For both B. nana and E. vaginatum, foliar N increased by 20–50 % as a consequence of 1–22 years of fertilisation, respectively, and for B. nana foliar N increase was consistent throughout the whole canopy. However, despite this large increase in foliar N, no significant changes in Vcmax and Jmax were observed. In contrast, Rd was significantly higher (>25 %) in both species after 22 years of N addition, but not in the shorter-term treatments. Surprisingly, Chl only increased in both species the first year of fertilisation (i.e. the first season of nutrients applied), but not in the longer-term treatments. These results imply that: (1) under current (low) N availability, these Arctic species either already optimize their photosynthetic capacity per leaf area, or are limited by other nutrients; (2) observed increases in Arctic NEE and GPP with increased nutrient availability are caused by structural changes like increased leaf area index, rather than increased foliar photosynthetic capacity and (3) short-term effects (1–4 years) of nutrient addition cannot always be extrapolated to a larger time scale, which emphasizes the importance of long-term ecological experiments