Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
789
result(s) for
"Denise, Christopher"
Sort by:
Knight Owl
After achieving his dream of becoming a knight, a small owl protects the castle from a hungry dragon.
Book
Reshaped by the river
The Army Corps of Engineers and the county have repaired relief wells that alleviate river pressure in Wilkes-Barre and Hanover Township, patched up boils in Forty Fort and Kingston, and mended flood gates in South Wilkes-Barre. Additionally, residents learned they would have to pay $50 extra for federally backed flood insurance because deficiencies in West Pittston's flood management plan weren't remedied by a Dec. 1 deadline last year and the Federal Emergency Management Agency put the borough on probation.\\n
Newsletter
Following Grandfather
Jennie is as close to her grandfather as a mouse can be, and when he suddenly dies she keeps thinking she sees him turning a corner, sitting on a bench, heading for the pier, or walking along their beloved beach, seeking the elusive Queen's teacup seashell.
Book
Efficacy of the North Carolina Low Wealth Supplemental Funding Program in meeting goals and improving school finance equity
The North Carolina General Assembly enacted the Low Wealth Supplemental Funding Program in 1991 “to enhance the instructional program and student achievement” in low wealth counties (1991 Session Law ch. 689 § 201.21a]). The total annual allocation increased yearly from $6,000,000 in 1991–92 to over $77,000,000 in 1999–2000. In 1993 the General Assembly revised the funding formula, resulting in more than 70% of Local Education Agencies (LEA) qualifying for low wealth supplemental funding. This study examined the efficacy of the North Carolina Low Wealth Supplemental Funding Program to improve per pupil expenditure (PPE) equity and meet program goals. Interviews were conducted with superintendents from LEAs named in the school finance litigation, Leandro v. the State of North Carolina, the State Board of Education (1997) and with administrators of education special interest groups to identify definitions of “low wealth”, definitions of equity, and program goals. The study examined the characteristics of LEAs by low wealth status. The findings indicate low wealth LEAs, on the average, have lower tax bases, lower per capita income levels, higher tax rates, lower local PPE, and higher percentages of students with free and reduced lunch status than non-low wealth LEAs. The findings also indicate PPE equity worsened over the seven-year period, 1991–92 through 1997–98, as measured for the district as unit of analysis. The findings indicate a positive but small effect of the supplemental funding on PPE equity. Two program goals were identified in the interview data. The findings indicate the percentage of low wealth counties above the mean local PPE in 1997–98 increased slightly, from 10.71% to 14.29%, when low wealth supplemental contributions were added to the local PPE. Finally, the findings indicate the percentage of students scoring at or above grade level on NC End-of-Grade and writing tests increased at a faster rate for low wealth LEAs than for non-low wealth LEAs from 1996–97 to 1998–99.
Dissertation
Groundhug Day
\"Moose is planning the biggest Valentine's Day party ever. But can he convince his friend, Groundhog, to stay around to celebrate without hiding from his shadow?\"-- Provided by publisher.
Book
Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.
Journal Article
Characterization of ALTO-encoding circular RNAs expressed by Merkel cell polyomavirus and trichodysplasia spinulosa polyomavirus
Circular RNAs (circRNAs) are a conserved class of RNAs with diverse functions, including serving as messenger RNAs that are translated into peptides. Here we describe circular RNAs generated by human polyomaviruses (HPyVs), some of which encode variants of the previously described alternative large T antigen open reading frame (ALTO) protein. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N 6 -methyladenosine (m 6 A) modified. The translation of MCPyV circALTOs into ALTO protein is negatively regulated by MCPyV-generated miRNAs in cultured cells. MCPyV ALTO expression increases transcription from some recombinant promoters in vitro and upregulates the expression of multiple genes previously implicated in MCPyV pathogenesis. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation in MCPyV-negative cells. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and infected tissues and express proteins that have the potential to modulate the infectious and tumorigenic properties of these viruses.
Journal Article
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Persistent DNA damage activation and oncogene-induced senescence stimulate secretion of the inflammatory cytokine IL-6, which is mediated by the damage-response pathway including ATM, NBS1 and CHK2. Tumours with an activated DNA damage response show elevated IL-6 and invasiveness.
Cellular senescence suppresses cancer by stably arresting the proliferation of damaged cells
1
. Paradoxically, senescent cells also secrete factors that alter tissue microenvironments
2
. The pathways regulating this secretion are unknown. We show that damaged human cells develop persistent chromatin lesions bearing hallmarks of DNA double-strand breaks (DSBs), which initiate increased secretion of inflammatory cytokines such as interleukin-6 (IL-6). Cytokine secretion occurred only after establishment of persistent DNA damage signalling, usually associated with senescence, not after transient DNA damage responses (DDRs). Initiation and maintenance of this cytokine response required the DDR proteins ATM, NBS1 and CHK2, but not the cell-cycle arrest enforcers p53 and pRb. ATM was also essential for IL-6 secretion during oncogene-induced senescence and by damaged cells that bypass senescence. Furthermore, DDR activity and IL-6 were elevated in human cancers, and ATM-depletion suppressed the ability of senescent cells to stimulate IL-6-dependent cancer cell invasiveness. Thus, in addition to orchestrating cell-cycle checkpoints and DNA repair, a new and important role of the DDR is to allow damaged cells to communicate their compromised state to the surrounding tissue.
Journal Article