Pavement Markings and Delineation for Older Drives. Volume I: Final Report

DTFH61-90-R-00062The objectives of this project were: (1) to identify the needs of older drivers and to evaluate the situations in which older driver performance might be improved through enhanced pavement markings and delineation; (2) to identify the range of potentially useful enhanced treatments; (3) to determine the effectiveness of those treatments judged to be most useful for the older driver; and (4) to assess the costs and benefits of the treatment shown to be most effective. Following a literature review to identify older driver deficiencies, 25 delineation/pavement marking treatments (including several "control" treatments) were identified for testing. A laboratory simulator study was used as a means to determine the most effective among the group. The treatments shown to produce better recognition distance, along with several control treatments, were then subjected to field testing. The field tests were conducted on a closed test track facility, and recognition distance and visual occlusion time were used as dependent measures. Of the 66 subjects who participated in the field study, half were over 65 years of age and half were 45 years of age or less. All subjects were involved in both types of measures. Following the field test performance assessment, the treatments were subjected to a cost benefit analysis and recommendations were made regarding the treatments that could benefit older drivers

Determination of Driver Needs in Work Zones

DOT-FH-11-9549The objectives of the study were: (a) to determine what information drivers need to travel through work zones safely and efficiently; (b) to determine how this information can best be conveyed to the drivers; and (c) to determine where improvements to the present system of work zone traffic control are needed. The study began with an analysis of driver tasks for eight major work zone types: lane closure, shoulder closure, roadside, lane diversion, crossover, temporary detour, detour to alternate routes, and reduced lane width. From this effort, a set of information content needs was identified for each work zone type. A further analytic effort using the principles of the Positive Guidance Procedure and the concept of Decision Sight Distance, resulted in the identification of recommended information presentation locations for the various types of information. These analytic efforts were combined into information requirements which were then evaluated for applicability by exercising each on a series of actual work zones. The requirements were modified where necessary and were then used as the basis for the development of a procedure for the derivation of work zones signing plans. Another aspect of the project involved the evaluation of individual construction-related signs, in which each device was evaluated with respect to several criteria and problems were identified

Trade-Off Between Delineation and Lighting on Freeway Interchanges

DTFH61-85-C-00137The objective was to determine whether, with improved delineation, performance at partially lighted interchanges can approach performance under full lighting, particularly in rain. Two field studies were conducted. The first was to determine whether transient visual adaptation (TVA) influences detection on partially lighted interchanges and could interact with lighting. It was shown that TVA occurs under partial lighting and influences detection up to 600 feet from the last luminaire. The second field study was to determine the effect of lighting, weather, and improved delineation on driver performance. Data were obtained on two exits in dry and wet weather under full lighting with baseline delineation and three improved delineation systems. Partial lighting at one exit was with one luminaire, at the other with three luminaires. Findings support the contention that full lighting is superior to partial lighting in ramp speed-related measures. Analysis of delineation effects on ramp and spot speeds and on speed distributions showed few differences under dry conditions. In rain, effects were stronger but were neither large nor consistent enough to recommend improved delineation over the baseline system. Nonstatistical comparison of the results from two sited provided evidence that three-luminaire partial lighting was superior to single-luminaire. Performance on ramp segments downstream of the last luminaire suggested TVA influenced results

Involvement of circulating CEA in liver metastases from colorectal cancers re-examined in a new experimental model

Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect relationship between these two observations has not been demonstrated. For this reason, we developed a new experimental model to evaluate the possible role of circulating CEA in the facilitation of liver metastases. A CEA-negative subclone from the human colon carcinoma cell line CO115 was transfected either with CEA-cDNA truncated at its 3' end by the deletion of 78 base pairs leading to the synthesis of a secreted form of CEA or with a full-length CEA-cDNA leading to the synthesis of the entire CEA molecule linked to the cell surface by a GPI anchor. Transfectants were selected either for their high CEA secretion (clone CO115-2C2 secreting up to 13 microg CEA per 10(6) cells within 72 h) or for their high CEA membrane expression (clone CO115-5F12 expressing up to 1 x 10(6) CEA molecules per cell). When grafted subcutaneously, CO115-2C2 cells gave rise to circulating CEA levels that were directly related to the tumour volume (from 100 to 1000 ng ml(-1) for tumours ranging from 100 to 1000 mm3), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bearing a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection of three different CEA-expressing human colorectal carcinoma cell lines (LoVo, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneous CEA secreting clone (CO115-2C2), but they were directly related to the metastatic properties of the intrasplenically injected tumour cells

Paired Tumor and Normal Whole Genome Sequencing of Metastatic Olfactory Neuroblastoma

Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal tract with little molecular characterization. We performed whole genome sequencing (WGS) on paired normal and tumor DNA from a patient with metastatic-ONB to identify the somatic alterations that might be drivers of tumorigenesis and/or metastatic progression.Genomic DNA was isolated from fresh frozen tissue from a metastatic lesion and whole blood, followed by WGS at >30X depth, alignment and mapping, and mutation analyses. Sanger sequencing was used to confirm selected mutations. Sixty-two somatic short nucleotide variants (SNVs) and five deletions were identified inside coding regions, each causing a non-synonymous DNA sequence change. We selected seven SNVs and validated them by Sanger sequencing. In the metastatic ONB samples collected several months prior to WGS, all seven mutations were present. However, in the original surgical resection specimen (prior to evidence of metastatic disease), mutations in KDR, MYC, SIN3B, and NLRC4 genes were not present, suggesting that these were acquired with disease progression and/or as a result of post-treatment effects.This work provides insight into the evolution of ONB cancer cells and provides a window into the more complex factors, including tumor clonality and multiple driver mutations

Down-Regulation of Yes Associated Protein 1 Expression Reduces Cell Proliferation and Clonogenicity of Pancreatic Cancer Cells

BACKGROUND: The Hippo pathway regulates organ size by inhibiting cell proliferation and promoting cell apoptosis upon its activation. The Yes Associated Protein 1 (YAP1) is a nuclear effector of the Hippo pathway that promotes cell growth as a transcription co-activator. In human cancer, the YAP1 gene was reported as amplified and over-expressed in several tumor types. METHODS: Immunohistochemical staining of YAP1 protein was used to assess the expression of YAP1 in pancreatic tumor tissues. siRNA oligonucleotides were used to knockdown the expression of YAP1 and their effects on pancreatic cancer cells were investigated using cell proliferation, apoptosis, and anchorage-independent growth assays. The Wilcoxon signed-rank, Pearson correlation coefficient, Kendall's Tau, Spearman's Rho, and an independent two-sample t (two-tailed) test were used to determine the statistical significance of the data. RESULTS: Immunohistochemistry studies in pancreatic tumor tissues revealed YAP1 staining intensities were moderate to strong in the nucleus and cytoplasm of the tumor cells, whereas the adjacent normal epithelial showed negative to weak staining. In cultured cells, YAP1 expression and localization was modulated by cell density. YAP1 total protein expression increased in the nuclear fractions in BxPC-3 and PANC-1, while it declined in HPDE6 as cell density increased. Additionally, treatment of pancreatic cancer cell lines, BxPC-3 and PANC-1, with YAP1-targeting siRNA oligonucleotides significantly reduced their proliferation in vitro. Furthermore, treatment with YAP1 siRNA oligonucleotides diminished the anchorage-independent growth on soft agar of pancreatic cancer cells, suggesting a role of YAP1 in pancreatic cancer tumorigenesis. CONCLUSIONS: YAP1 is overexpressed in pancreatic cancer tissues and potentially plays an important role in the clonogenicity and growth of pancreatic cancer cells

The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

<p>Abstract</p> <p>Background</p> <p>The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs).</p> <p>Methods</p> <p>The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established.</p> <p>Results</p> <p>We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, <it>CD9 </it>and <it>CALM2 </it>mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis.</p> <p>Conclusion</p> <p>This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment.</p

Minimal luminance requirement for official highway signs. Final report.

Federal Highway Administration, Office of Safety and Traffic Operations Research and Development, McLean, Va.Mode of access: Internet.Author corporate affiliation: IFR Applications, Inc., State College, Pa.Report covers the period Sept 1983 - May 1986Subject code: CISubject code: NDBSubject code: NDGSubject code: RCG

Driver needs on two-lane rural highways. Volume IV - literature review. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Institute for Research, Inc., State College, Pa.Subject code: CCCCCSubject code: CCJSubject code: CGSubject code: HBSubject code: KBKSubject code: PDESubject code: YE

Driver needs on two-lane rural highways. Volume II - simplified location of information deficiencies (SLIDE): a procedure. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Institute for Research, Inc., State College, Pa.Subject code: CCCCCSubject code: CCJSubject code: CGSubject code: HBSubject code: KBKSubject code: PD