2,402 research outputs found
AN ANALYSIS OF THE EFFECT OF PRICE ON RESIDENTIAL WATER DEMAND: METROPOLITAN MIAMI, FLORIDA
Resource /Energy Economics and Policy,
Corporate Governance Eludes the Legal Mind
Professor Andrews argues that the American Law Institute\u27s Principles of Corporate Governance and Structure: Restatement and Recommendations fails to consider the recent evolution of the large publicly held corporation and the relationship among shareholders, the board, and management. He suggests that the legal and management communities work together to solve the problems in corporate governance
Corporate Governance Eludes the Legal Mind
Professor Andrews argues that the American Law Institute\u27s Principles of Corporate Governance and Structure: Restatement and Recommendations fails to consider the recent evolution of the large publicly held corporation and the relationship among shareholders, the board, and management. He suggests that the legal and management communities work together to solve the problems in corporate governance
Novel cell adhesion/migration pathways are predictive markers of HDAC inhibitor resistance in cutaneous T cell lymphoma
BACKGROUND: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy.
METHODS: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks (H3K14/9 ac, H3K27ac). We correlated significant differences in histone acetylation with gene expression in HDACi-resistant/sensitive CTCL. We extended these findings in additional CTCL patient cohorts (RNA-seq, microarray) and using ELISA in matched CTCL patient plasma.
FINDINGS: Resistant CTCL exhibited high levels of histone acetylation, which correlated with increased expression of 338 genes (FDR \u3c 0·05), including some novel to CTCL: BIRC5 (anti-apoptotic); RRM2 (cell cycle); TXNDC5, GSTM1 (redox); and CXCR4, LAIR2 (cell adhesion/migration). Several of these, including LAIR2, were elevated pre-treatment in HDACi-resistant CTCL. In CTCL patient plasma (n = 6), LAIR2 protein was also elevated (p \u3c 0·01) compared to controls.
INTERPRETATION: This study is the first to connect genome-wide differences in chromatin acetylation and gene expression to HDACi-resistance in primary CTCL. Our results identify novel markers with high pre-treatment expression, such as LAIR2, as potential prognostic and/or predictors of HDACi-resistance in CTCL.
FUNDING: NIH:CA156690, CA188286; NCATS: WU-ICTS UL1 TR000448; Siteman Cancer Center: CA091842
Age validation of quillback rockfish (Sebastes maliger) using bomb radiocarbon
Rockfishes (Sebastes spp.) support one of the most economically important f isheries of the Pacific Northwest and it is essential for sustainable management that age estimation procedures be validated for these species. Atmospheric testing of thermonuclear devices during the
1950s and 1960s created a global radiocarbon (14C) signal in the ocean environment that scientists have identified
as a useful tracer and chronological marker in natural systems. In this study, we first demonstrated that fewer samples are necessary for age validation using the bomb-generated 14C signal by emphasizing the utility of the time-specific marker created by the initial rise of bomb-14C. Second, the bomb-generated 14C signal retained in fish otoliths was used to validate the age and age estimation method of the quillback rockfish (Sebastes maliger) in the
waters of southeast Alaska. Radiocarbon values from the first year’s growth of quillback rockfish otoliths were plotted against estimated birth year to produce a 14C time series spanning 1950 to 1985. The initial rise in bomb-14C from prebomb levels (~ –90‰) occurred in 1959 [±1 year]
and 14C levels rose relatively rapidly to peak Δ14C values in 1967 (+105.4‰) and subsequently declined through the end of the time series in 1985 (+15.4‰). The agreement between the year of initial rise of 14C levels from the quillback rockfish time series and the chronology determined for the waters of southeast Alaska from yelloweye rockfish (S. ruberrimus) otoliths validated the aging method for the quillback rockfish. The concordance of the entire quillback rockfish 14C time series with the yelloweye rockfish time series demonstrated the effectiveness of this age validation
technique, confirmed the longevity of the quillback rockfish up to a minimum of 43 years, and strongly confirms higher age estimates of u
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