A Quantitative Evaluation of the Nighttime Visual Sign Inspection Method

A research project to determine the appropriate sign inspection and replacement procedure was conducted at North Carolina State University and sponsored by the North Carolina DOT. The purpose was to determine the optimum strategy for sign inspection and replacement under different conditions to respond to the pending retroreflectivity requirements. This paper reports on a spreadsheet tool developed to quantitatively evaluate the effectiveness of different sign inspection and replacement scenarios. The spreadsheet was designed for yellow and red engineer-grade sign sheetings, and takes into account sign vandalism and knock-downs as well as normal sign aging. The spreadsheet provides estimates of the number of signs in place that would not meet the minimum retroreflectivity standard and the cost of the sign inspection and replacement program. The results from a number of trials of the spreadsheet show that agencies that generally conform to the key assumptions made to build the spreadsheet should consider replacing all signs every seven years, as that insures that no aged signs are in place at a relatively low cost. If total replacement is not possible, an inspection program using retroreflectometers every three years appears very competitive in its effectiveness with a program using typical visual inspection rates each year. The retroreflectometers appear to allow fewer deficient signs, while the typical visual inspection program costs are lower for a given vandalism rate. More conservative visual sign replacement rates do not appear to offer distinct advantages, because typical replacement rates with visual inspections every two or three years allow relatively high numbers of deficient signs to remain on the roads

A Quantitative Evaluation of the Nighttime Visual Sign Inspection Method

A research project to determine the appropriate sign inspection and replacement procedure was conducted at North Carolina State University and sponsored by the North Carolina DOT. The purpose was to determine the optimum strategy for sign inspection and replacement under different conditions to respond to the pending retroreflectivity requirements. This paper reports on a spreadsheet tool developed to quantitatively evaluate the effectiveness of different sign inspection and replacement scenarios. The spreadsheet was designed for yellow and red engineer-grade sign sheetings, and takes into account sign vandalism and knock-downs as well as normal sign aging. The spreadsheet provides estimates of the number of signs in place that would not meet the minimum retroreflectivity standard and the cost of the sign inspection and replacement program. The results from a number of trials of the spreadsheet show that agencies that generally conform to the key assumptions made to build the spreadsheet should consider replacing all signs every seven years, as that insures that no aged signs are in place at a relatively low cost. If total replacement is not possible, an inspection program using retroreflectometers every three years appears very competitive in its effectiveness with a program using typical visual inspection rates each year. The retroreflectometers appear to allow fewer deficient signs, while the typical visual inspection program costs are lower for a given vandalism rate. More conservative visual sign replacement rates do not appear to offer distinct advantages, because typical replacement rates with visual inspections every two or three years allow relatively high numbers of deficient signs to remain on the roads

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.National Institutes of Health (U.S.) (Grant P01 CA066996)National Institutes of Health (U.S.) (Grant R01 HL082945)National Cancer Institute (U.S.) (Grant P30-CA14051

Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 lysine 27 trimethylation

Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic leukemia (B-ALL)1 and polysomy 21 is the most frequent somatic aneuploidy amongst all B-ALLs2. Yet, the mechanistic links between chr.21 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orthologous to human chr.21q22 confers murine progenitor B cell self-renewal in vitro, maturation defects in vivo, and B-ALL with either BCR-ABL or CRLF2 with activated JAK2. Chr.21q22 triplication suppresses H3K27me3 in progenitor B cells and B-ALLs, and “bivalent” genes with both H3K27me3 and H3K4me3 at their promoters in wild-type progenitor B cells are preferentially overexpressed in triplicated cells. Strikingly, human B-ALLs with polysomy 21 are distinguished by their overexpression of genes marked with H3K27me3 in multiple cell types. Finally, overexpression of HMGN1, a nucleosome remodeling protein encoded on chr.21q223–5, suppresses H3K27me3 and promotes both B cell proliferation in vitro and B-ALL in vivo

Does public awareness increase support for invasive species management?:Promising evidence across taxa and landscape types

Management of invasive species often raises substantial conflicts of interest. Since such conflicts can hamper proposed management actions, managers, decision makers and researchers increasingly recognize the need to consider the social dimensions of invasive species management. In this exploratory study, we aimed (1) to explore whether species’ taxonomic position (i.e. animals vs. plants) and type of invaded landscape (i.e. urban vs. nonurban) might influence public perception about the management of invasive species, and (2) to assess the potential of public awareness to increase public support for invasive species management. We reviewed the scientific literature on the conflicts of interest around the management of alien species and administered two-phased questionnaires (before and after providing information on the target species and its management) to members of the public in South Africa and the UK (n = 240). Our review suggests that lack of public support for the management of invasive animals in both urban and non-urban areas derives mainly from moralistic value disagreements, while the management of invasive plants in non-urban areas mostly causes conflicts based on utilitarian value disagreements. Despite these general trends, conflicts are context dependent and can originate from a wide variety of different views. Notably, informing the public about the invasive status and negative impacts of the species targeted for management appeared to increase public support for the management actions. Therefore, our results align with the view that increased public awareness might increase the public support for the management of invasive species, independent of taxonomic position and type of landscape

Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies

Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled shRNA screens in 216 cancer cell lines to identify genes that are required for cell proliferation and/or viability. Cell line dependencies on 11,000 genes were interrogated by 5 shRNAs per gene. The proliferation effect of each shRNA in each cell line was assessed by transducing a population of 11M cells with one shRNA-virus per cell and determining the relative enrichment or depletion of each of the 54,000 shRNAs after 16 population doublings using Next Generation Sequencing. All the cell lines were screened using standardized conditions to best assess differential genetic dependencies across cell lines. When combined with genomic characterization of these cell lines, this dataset facilitates the linkage of genetic dependencies with specific cellular contexts (e.g., gene mutations or cell lineage). To enable such comparisons, we developed and provided a bioinformatics tool to identify linear and nonlinear correlations between these features

A Quantitative Evaluation of the Nighttime Visual Sign Inspection Method

A research project to determine the appropriate sign inspection and replacement procedure was conducted at North Carolina State University and sponsored by the North Carolina DOT. The purpose was to determine the optimum strategy for sign inspection and replacement under different conditions to respond to the pending retroreflectivity requirements. This paper reports on a spreadsheet tool developed to quantitatively evaluate the effectiveness of different sign inspection and replacement scenarios. The spreadsheet was designed for yellow and red engineer-grade sign sheetings, and takes into account sign vandalism and knock-downs as well as normal sign aging. The spreadsheet provides estimates of the number of signs in place that would not meet the minimum retroreflectivity standard and the cost of the sign inspection and replacement program. The results from a number of trials of the spreadsheet show that agencies that generally conform to the key assumptions made to build the spreadsheet should consider replacing all signs every seven years, as that insures that no aged signs are in place at a relatively low cost. If total replacement is not possible, an inspection program using retroreflectometers every three years appears very competitive in its effectiveness with a program using typical visual inspection rates each year. The retroreflectometers appear to allow fewer deficient signs, while the typical visual inspection program costs are lower for a given vandalism rate. More conservative visual sign replacement rates do not appear to offer distinct advantages, because typical replacement rates with visual inspections every two or three years allow relatively high numbers of deficient signs to remain on the roads