Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hubin, Elizabeth A.; Fay, Allison; Xu, Catherine

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the -10 element where they likely facilitate DNA bending and impedemore » transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD.« less

Cars, Cars, Cars

ERIC Educational Resources Information Center

McIntosh, Phyllis

2013-01-01

Cars are the focus of this feature article, which explores such topics as the history of cars in the United States, the national highway system, safety and pollution concerns, mobility and freedom for women, classic car shows, and the road trip in American literature and film. Also included are links to the websites of Automobile in American Life…

Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA

PubMed Central

Hubin, Elizabeth A; Fay, Allison; Xu, Catherine; Bean, James M; Saecker, Ruth M; Glickman, Michael S; Darst, Seth A; Campbell, Elizabeth A

2017-01-01

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish that RbpA and CarD cooperatively stimulate formation of an intermediate (RP2) leading to RPo; formation of RP2 is likely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2. We determined a 2.76 Å-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the −10 element where they likely facilitate DNA bending and impede transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, show the effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcription by RbpA and CarD. DOI: http://dx.doi.org/10.7554/eLife.22520.001 PMID:28067618

Identification of chemical modulators of the constitutive activated receptor (CAR) in a gene expression compendium

PubMed Central

Oshida, Keiyu; Vasani, Naresh; Jones, Carlton; Moore, Tanya; Hester, Susan; Nesnow, Stephen; Auerbach, Scott; Geter, David R.; Aleksunes, Lauren M.; Thomas, Russell S.; Applegate, Dawn; Klaassen, Curtis D.; Corton, J. Christopher

2015-01-01

The nuclear receptor family member constitutive activated receptor (CAR) is activated by structurally diverse drugs and environmentally-relevant chemicals leading to transcriptional regulation of genes involved in xenobiotic metabolism and transport. Chronic activation of CAR increases liver cancer incidence in rodents, whereas suppression of CAR can lead to steatosis and insulin insensitivity. Here, analytical methods were developed to screen for chemical treatments in a gene expression compendium that lead to alteration of CAR activity. A gene expression biomarker signature of 83 CAR-dependent genes was identified using microarray profiles from the livers of wild-type and CAR-null mice after exposure to three structurally-diverse CAR activators (CITCO, phenobarbital, TCPOBOP). A rank-based algorithm (Running Fisher’s algorithm (p-value ≤ 10-4)) was used to evaluate the similarity between the CAR biomarker signature and a test set of 28 and 32 comparisons positive or negative, respectively, for CAR activation; the test resulted in a balanced accuracy of 97%. The biomarker signature was used to identify chemicals that activate or suppress CAR in an annotated mouse liver/primary hepatocyte gene expression database of ~1850 comparisons. CAR was activated by 1) activators of the aryl hydrocarbon receptor (AhR) in wild-type but not AhR-null mice, 2) pregnane X receptor (PXR) activators in wild-type and to lesser extents in PXR-null mice, and 3) activators of PPARα in wild-type and PPARα-null mice. CAR was consistently activated by five conazole fungicides and four perfluorinated compounds. Comparison of effects in wild-type and CAR-null mice showed that the fungicide propiconazole increased liver weight and hepatocyte proliferation in a CAR-dependent manner, whereas the perfluorinated compound perfluorooctanoic acid (PFOA) increased these endpoints in a CAR-independent manner. A number of compounds suppressed CAR coincident with increases in markers of

CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism

PubMed Central

Rammohan, Jayan; Ruiz Manzano, Ana; Garner, Ashley L.; Stallings, Christina L.; Galburt, Eric A.

2015-01-01

CarD is an essential and global transcriptional regulator in mycobacteria. While its biological role is unclear, CarD functions by interacting directly with RNA polymerase (RNAP) holoenzyme promoter complexes. Here, using a fluorescent reporter of open complex, we quantitate RPo formation in real time and show that Mycobacterium tuberculosis CarD has a dramatic effect on the energetics of RNAP bound complexes on the M. tuberculosis rrnAP3 ribosomal RNA promoter. The data reveal that Mycobacterium bovis RNAP exhibits an unstable RPo that is stabilized by CarD and suggest that CarD uses a two-tiered, concentration-dependent mechanism by associating with open and closed complexes with different affinities. Specifically, the kinetics of open-complex formation can be explained by a model where, at saturating concentrations of CarD, the rate of bubble collapse is slowed and the rate of opening is accelerated. The kinetics and open-complex stabilities of CarD mutants further clarify the roles played by the key residues W85, K90 and R25 previously shown to affect CarD-dependent gene regulation in vivo. In contrast to M. bovis RNAP, Escherichia coli RNAP efficiently forms RPo on rrnAP3, suggesting an important difference between the polymerases themselves and highlighting how transcriptional machinery can vary across bacterial genera. PMID:25697505

Genomic approaches to identifying transcriptional regulators of osteoblast differentiation

NASA Technical Reports Server (NTRS)

Stains, Joseph P.; Civitelli, Roberto

2003-01-01

Recent microarray studies of mouse and human osteoblast differentiation in vitro have identified novel transcription factors that may be important in the establishment and maintenance of differentiation. These findings help unravel the pattern of gene-expression changes that underly the complex process of bone formation.

Genome-wide analysis of human constitutive androstane receptor (CAR) transcriptome in wild-type and CAR-knockout HepaRG cells.

PubMed

Li, Daochuan; Mackowiak, Bryan; Brayman, Timothy G; Mitchell, Michael; Zhang, Lei; Huang, Shiew-Mei; Wang, Hongbing

2015-11-01

The constitutive androstane receptor (CAR) modulates the transcription of numerous genes involving drug metabolism, energy homeostasis, and cell proliferation. Most functions of CAR however were defined from animal studies. Given the known species difference of CAR and the significant cross-talk between CAR and the pregnane X receptor (PXR), it is extremely difficult to decipher the exact role of human CAR (hCAR) in gene regulation, relying predominantly on pharmacological manipulations. Here, utilizing a newly generated hCAR-knockout (KO) HepaRG cell line, we carried out RNA-seq analysis of the global transcriptomes in wild-type (WT) and hCAR-KO HepaRG cells treated with CITCO, a selective hCAR agonist, phenobarbital (PB), a dual activator of hCAR and hPXR, or vehicle control. Real-time PCR assays in separate experiments were used to validate RNA-seq findings. Our results indicate that genes encoding drug-metabolizing enzymes are among the main clusters altered by both CITCO and PB. Specifically, CITCO significantly changed the expression of 135 genes in an hCAR-dependent manner, while PB altered the expression of 227 genes in WT cells of which 94 were simultaneously modulated in both cell lines reflecting dual effects of PB on hCAR/PXR. Notably, we found that many genes promoting cell proliferation and tumorigenesis were up-regulated in hCAR-KO cells, suggesting that hCAR may play an important role in cell growth that differs from mouse CAR. Together, our results reveal both novel and known targets of hCAR and support the role of hCAR in maintaining the homeostasis of metabolism and cell proliferation in the liver. Copyright © 2015 Elsevier Inc. All rights reserved.

A modified reverse one-hybrid screen identifies transcriptional activation in Phyochrome-Interacting Factor 3

USDA-ARS?s Scientific Manuscript database

Transcriptional activation domains (TAD) are difficult to predict and identify, since they are not conserved and have little consensus. Here, we describe a yeast-based screening method that is able to identify individual amino acid residues involved in transcriptional activation in a high throughput...

Surface localization of the nuclear receptor CAR in influenza A virus-infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Tadanobu; Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, CREST, JST, and COE Program in the 21st Century, Shizuoka 422-8526; Moriyama, Yusuke

Constitutive active/androstane receptor CAR is a member of the nuclear receptors which regulate transcription of xenobiotic metabolism enzymes. CAR is usually localized in the cytosol and nucleus. Here, we found that CAR was localized at the cell surface of influenza A virus (IAV)-infected cells. Additionally, we demonstrated that expression of a viral envelope glycoprotein, either hemagglutinin (HA) or neuraminidase (NA), but not viral nucleoprotein (NP), was responsible for this localization. This report is the first demonstration of CAR at the surface of tissue culture cells, and suggests that CAR may exert the IAV infection mechanism.

Signatures from Tissue-specific MPSS Libraries Identify Transcripts Preferentially Expressed in the Mouse Inner Ear

PubMed Central

Peters, Linda M.; Belyantseva, Inna A.; Lagziel, Ayala; Battey, James F.; Friedman, Thomas B.; Morell, Robert J.

2007-01-01

Specialization in cell function and morphology is influenced by the differential expression of mRNAs, many of which are expressed at low abundance and restricted to certain cell types. Detecting such transcripts in cDNA libraries may require sequencing millions of clones. Massively parallel signature sequencing (MPSS) is well-suited for identifying transcripts that are expressed in discrete cell types and in low abundance. We have made MPSS libraries from microdissections of three inner ear tissues. By comparing these MPSS libraries to those of 87 other tissues included in the Mouse Reference Transcriptome (MRT) online resource, we have identified genes that are highly enriched in, or specific to, the inner ear. We show by RT-PCR and in situ hybridization that signatures unique to the inner ear libraries identify transcripts with highly specific cell-type localizations. These transcripts serve to illustrate the utility of a resource that is available to the research community. Utilization of these resources will increase the number of known transcription units and expand our knowledge of the tissue-specific regulation of the transcriptome. PMID:17049805

Cost intensity of identifying contraindications to driving a company car through psychological tests on the basis of real-world data in Poland.

PubMed

Juszczyk, Grzegorz; Czerw, Aleksandra; Tatara, Tomasz; Duda-Zalewska, Aneta; Walusiak-Skorupa, Joanna; Słoniewski, Robert; Staniszewska, Anna; Olejniczak, Dominik; Religioni, Urszula

2017-12-01

The study objective was to determine the cost intensity of identifying contraindications to fleet car driving in preventive care. The objective of a psychological examination is to identify impaired psychomotor function as well as any intellectual, cognitive or emotional incapacities, which may seriously impede safety. Real-world data were collected from the healthcare provider in Poland. A total of 8111 anonymous records from psychomotor tests performed between January 1 and December 31, 2012 were analysed. The number needed to screen to identify one person with contraindications to driving was 737. An individual examination costs PLN 150, thus the estimated cost of identifying one case was PLN 110,550 (EUR 25,000). The average number of tests in a small enterprise with 20-50 fleet cars was estimated at 5-25 in a 5-year period and their cost at PLN 3750 (PLN 750 annually). Health check-ups include ophthalmological and neurological consultations; therefore, psychological examination of fleet car drivers may be considered excessive due to cost and limited preventive value. High costs may be burdensome mainly to larger companies. A final decision regarding necessity of psychological testing should be preceded by medical assessment of the risk of work accidents.

A New Set of ESTs from Chickpea (Cicer arietinum L.) Embryo Reveals Two Novel F-Box Genes, CarF-box_PP2 and CarF-box_LysM, with Potential Roles in Seed Development

PubMed Central

Gupta, Shefali; Garg, Vanika; Bhatia, Sabhyata

2015-01-01

Considering the economic importance of chickpea (C. arietinum L.) seeds, it is important to understand the mechanisms underlying seed development for which a cDNA library was constructed from 6 day old chickpea embryos. A total of 8,186 ESTs were obtained from which 4,048 high quality ESTs were assembled into 1,480 unigenes that majorly encoded genes involved in various metabolic and regulatory pathways. Of these, 95 ESTs were found to be involved in ubiquitination related protein degradation pathways and 12 ESTs coded specifically for putative F-box proteins. Differential transcript accumulation of these putative F-box genes was observed in chickpea tissues as evidenced by quantitative real-time PCR. Further, to explore the role of F-box proteins in chickpea seed development, two F-box genes were selected for molecular characterization. These were named as CarF-box_PP2 and CarF-box_LysM depending on their C-terminal domains, PP2 and LysM, respectively. Their highly conserved structures led us to predict their target substrates. Subcellular localization experiment revealed that CarF-box_PP2 was localized in the cytoplasm and CarF-box_LysM was localized in the nucleus. We demonstrated their physical interactions with SKP1 protein, which validated that they function as F-box proteins in the formation of SCF complexes. Sequence analysis of their promoter regions revealed certain seed specific cis-acting elements that may be regulating their preferential transcript accumulation in the seed. Overall, the study helped in expanding the EST database of chickpea, which was further used to identify two novel F-box genes having a potential role in seed development. PMID:25803812

Neurological injuries from car surfing.

PubMed

Wang, Arthur; Cohen, Alan R; Robinson, Shenandoah

2009-11-01

Trauma secondary to car surfing is a unique mechanism of head and spinal injury in children and adolescents. In this study, the authors present their experience with neurological injuries resulting from car surfing and describe the growing national trend of car-surfing injuries and the increasing portrayal of this activity in the media. A retrospective study of the Rainbow Babies and Children's Hospital trauma database was conducted to identify all cases of neurological injuries secondary to car surfing. Between January 1995 and December 2008, 7 patients identified. The charts of these patients were reviewed. National data on car-surfing fatalities over the same time period in children and adolescents 10-20 years of age were obtained from the National Highway Traffic Safety Administration, and these data were analyzed for national trends in car-surfing fatalities. All 7 children with injuries due to car surfing suffered traumatic head injuries. Three patients fell from the back of the moving vehicle, 2 fell from the hood, 1 fell from the side of the vehicle, and 1 patient sustained head injuries after intentionally jumping off the moving vehicle. All 7 children suffered intracranial bleeding, and 4 had associated skull fractures. One patient underwent craniotomy to evacuate an acute subdural hematoma. The other 6 patients required nonoperative treatment. Four patients had permanent neurological problems. National statistics have shown a steady rise in car-surfing fatality rates since 2000, especially in California, Florida, and Texas. Car surfing is an unusual but serious mechanism of neurological injury in children and adolescents. Despite its dangers, car surfing is becoming a more common pastime in the pediatric population. National statistics have shown a steady rise in car-surfing fatalities since 2000. This national rise in fatalities chronologically overlaps with the introduction of media depictions of

Cloning and characterization of a novel NAC family gene CarNAC1 from chickpea (Cicer arietinum L.).

PubMed

Peng, Hui; Yu, Xingwang; Cheng, Huiying; Shi, Qinghua; Zhang, Hua; Li, Jiangui; Ma, Hao

2010-01-01

The plant-specific NAC (for NAM, ATAF1,2 and CUC2) proteins have been found to play important roles in plant development and stress responses. In this study, a NAC gene CarNAC1 (for Cicer arietinum L. NAC gene 1) was isolated from a cDNA library constructed with chickpea seedling leaves treated by polyethylene glycol. CarNAC1 encoded a putative protein with 239 amino acids and contained 3 exons and 2 introns within genomic DNA sequence. CarNAC1 had a conserved NAC domain in the N-terminus and the CarNAC1:GFP (green fluorescent protein) fusion protein was localized in the nucleus of onion epidermal cells. Additionally, CarNAC1 exhibited the trans-activation activity which was mapped to the C-terminus. The CarNAC1 transcript was detected in many chickpea organs including seedling leaves, stems, roots, flowers, and young pods, but less accumulated in young seeds. CarNAC1 was induced by leaf age and showed changes in expression during seed development and germination. Furthermore, the expression of CarNAC1 was strongly induced by drought, salt, cold, wounding, H(2)O(2), ethephon, salicylic acid, indole-3-acetic acid, and gibberellin. Our results suggest that CarNAC1 encodes a novel NAC-domain protein and may be a transcriptional activator involved in plant development and various stress responses.

Epigenetic priors for identifying active transcription factor binding sites.

PubMed

Cuellar-Partida, Gabriel; Buske, Fabian A; McLeay, Robert C; Whitington, Tom; Noble, William Stafford; Bailey, Timothy L

2012-01-01

Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored. We describe a probabilistic method for combining one or more tracks of epigenetic data with a standard DNA sequence motif model to improve our ability to identify active transcription factor binding sites (TFBSs). We convert each data type into a position-specific probabilistic prior and combine these priors with a traditional probabilistic motif model to compute a log-posterior odds score. Our experiments, using histone modifications H3K4me1, H3K4me3, H3K9ac and H3K27ac, as well as DNase I sensitivity, show conclusively that the log-posterior odds score consistently outperforms a simple binary filter based on the same data. We also show that our approach performs competitively with a more complex method, CENTIPEDE, and suggest that the relative simplicity of the log-posterior odds scoring method makes it an appealing and very general method for identifying functional TFBSs on the basis of DNA and epigenetic evidence. FIMO, part of the MEME Suite software toolkit, now supports log-posterior odds scoring using position-specific priors for motif search. A web server and source code are available at http://meme.nbcr.net. Utilities for creating priors are at http://research.imb.uq.edu.au/t.bailey/SD/Cuellar2011. t.bailey@uq.edu.au Supplementary data are available at Bioinformatics online.

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A.

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation ofmore » miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR

Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.

PubMed

Della Gatta, Giusy; Palomero, Teresa; Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Bansal, Mukesh; Carpenter, Zachary W; De Keersmaecker, Kim; Sole, Xavier; Xu, Luyao; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H; Rowe, Jacob M; Meijerink, Jules P; Califano, Andrea; Ferrando, Adolfo A

2012-02-26

The TLX1 and TLX3 transcription factor oncogenes have a key role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, a network structure analysis of this hierarchical network identified RUNX1 as a key mediator of the T-ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T cell transformation. Consistent with these results, we identified recurrent somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 at the top of an oncogenic transcriptional network controlling leukemia development, show the power of network analyses to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor-suppressor gene in T-ALL.

Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

PubMed

Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

2008-11-01

Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.

CuseCar--community car-sharing program : car sharing lessons learned.

DOT National Transportation Integrated Search

2011-08-01

CuseCar of Syracuse launched services in December 2008 with 3 Toyota Prius Hybrids. CuseCar initially, due to : concerns about availability, limited membership to Origination Sponsor Locations, which in turn developed few : members. In 2009 CuseCar o...

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma.

PubMed

Parker, Nicole R; Hudson, Amanda L; Khong, Peter; Parkinson, Jonathon F; Dwight, Trisha; Ikin, Rowan J; Zhu, Ying; Cheng, Zhangkai Jason; Vafaee, Fatemeh; Chen, Jason; Wheeler, Helen R; Howell, Viive M

2016-03-04

Heterogeneity is a hallmark of glioblastoma with intratumoral heterogeneity contributing to variability in responses and resistance to standard treatments. Promoter methylation status of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is the most important clinical biomarker in glioblastoma, predicting for therapeutic response. However, it does not always correlate with response. This may be due to intratumoral heterogeneity, with a single biopsy unlikely to represent the entire lesion. Aberrations in other DNA repair mechanisms may also contribute. This study investigated intratumoral heterogeneity in multiple glioblastoma tumors with a particular focus on the DNA repair pathways. Transcriptional intratumoral heterogeneity was identified in 40% of cases with variability in MGMT methylation status found in 14% of cases. As well as identifying intratumoral heterogeneity at the transcriptional and epigenetic levels, targeted next generation sequencing identified between 1 and 37 unique sequence variants per specimen. In-silico tools were then able to identify deleterious variants in both the base excision repair and the mismatch repair pathways that may contribute to therapeutic response. As these pathways have roles in temozolomide response, these findings may confound patient management and highlight the importance of assessing multiple tumor biopsies.

Transcriptator: An Automated Computational Pipeline to Annotate Assembled Reads and Identify Non Coding RNA.

PubMed

Tripathi, Kumar Parijat; Evangelista, Daniela; Zuccaro, Antonio; Guarracino, Mario Rosario

2015-01-01

RNA-seq is a new tool to measure RNA transcript counts, using high-throughput sequencing at an extraordinary accuracy. It provides quantitative means to explore the transcriptome of an organism of interest. However, interpreting this extremely large data into biological knowledge is a problem, and biologist-friendly tools are lacking. In our lab, we developed Transcriptator, a web application based on a computational Python pipeline with a user-friendly Java interface. This pipeline uses the web services available for BLAST (Basis Local Search Alignment Tool), QuickGO and DAVID (Database for Annotation, Visualization and Integrated Discovery) tools. It offers a report on statistical analysis of functional and Gene Ontology (GO) annotation's enrichment. It helps users to identify enriched biological themes, particularly GO terms, pathways, domains, gene/proteins features and protein-protein interactions related informations. It clusters the transcripts based on functional annotations and generates a tabular report for functional and gene ontology annotations for each submitted transcript to the web server. The implementation of QuickGo web-services in our pipeline enable the users to carry out GO-Slim analysis, whereas the integration of PORTRAIT (Prediction of transcriptomic non coding RNA (ncRNA) by ab initio methods) helps to identify the non coding RNAs and their regulatory role in transcriptome. In summary, Transcriptator is a useful software for both NGS and array data. It helps the users to characterize the de-novo assembled reads, obtained from NGS experiments for non-referenced organisms, while it also performs the functional enrichment analysis of differentially expressed transcripts/genes for both RNA-seq and micro-array experiments. It generates easy to read tables and interactive charts for better understanding of the data. The pipeline is modular in nature, and provides an opportunity to add new plugins in the future. Web application is freely

Identifying Novel Transcriptional and Epigenetic Features of Nuclear Lamina-associated Genes.

PubMed

Wu, Feinan; Yao, Jie

2017-03-07

Because a large portion of the mammalian genome is associated with the nuclear lamina (NL), it is interesting to study how native genes resided there are transcribed and regulated. In this study, we report unique transcriptional and epigenetic features of nearly 3,500 NL-associated genes (NL genes). Promoter regions of active NL genes are often excluded from NL-association, suggesting that NL-promoter interactions may repress transcription. Active NL genes with higher RNA polymerase II (Pol II) recruitment levels tend to display Pol II promoter-proximal pausing, while Pol II recruitment and Pol II pausing are not correlated among non-NL genes. At the genome-wide scale, NL-association and H3K27me3 distinguishes two large gene classes with low transcriptional activities. Notably, NL-association is anti-correlated with both transcription and active histone mark levels among genes not significantly enriched with H3K9me3 or H3K27me3, suggesting that NL-association may represent a novel gene repression pathway. Interestingly, an NL gene subgroup is not significantly enriched with H3K9me3 or H3K27me3 and is transcribed at higher levels than the rest of NL genes. Furthermore, we identified distal enhancers associated with active NL genes and reported their epigenetic features.

Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.

PubMed

Luisier, Raphaëlle; Lempiäinen, Harri; Scherbichler, Nina; Braeuning, Albert; Geissler, Miriam; Dubost, Valerie; Müller, Arne; Scheer, Nico; Chibout, Salah-Dine; Hara, Hisanori; Picard, Frank; Theil, Diethilde; Couttet, Philippe; Vitobello, Antonio; Grenet, Olivier; Grasl-Kraupp, Bettina; Ellinger-Ziegelbauer, Heidrun; Thomson, John P; Meehan, Richard R; Elcombe, Clifford R; Henderson, Colin J; Wolf, C Roland; Schwarz, Michael; Moulin, Pierre; Terranova, Rémi; Moggs, Jonathan G

2014-06-01

The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CAR(KO)-PXR(KO)), double humanized CAR and PXR (CAR(h)-PXR(h)), and wild-type C57BL/6 mice. Wild-type and CAR(h)-PXR(h) mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CAR(KO)-PXR(KO) mouse livers and largely reversible in wild-type and CAR(h)-PXR(h) mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CAR(h)-PXR(h) mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.

Use of DNA Microarrays to Identify Diagnostic Signature Transcription Profiles for Host Responses to Infectious Agents

DTIC Science & Technology

2004-10-01

informative in this regard. Key signature genes will serve as the basis for rapid diagnostic approaches that could be accessed when an outbreak is suspected...AD Award Number: DAMD17-01-1-0787 TITLE: Use of DNA Microarrays to Identify Diagnostic Signature Transcription Profiles for Host Responses to...Sep 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Use of DNA Microarrays to Identify Diagnostic Signature DAMD17-01-1-0787 Transcription Profiles for

Polymorphisms in CARS are associated with gastric cancer risk: a two-stage case-control study in the Chinese population.

PubMed

Tian, Tian; Xiao, Ling; Du, Jiangbo; Zhu, Xun; Gu, Yayun; Qin, Na; Yan, Caiwang; Liu, Li; Ma, Hongxia; Jiang, Yue; Chen, Jiaping; Yu, Hao; Dai, Juncheng

2017-11-01

The cysteinyl transfer RNA synthetase gene (CARS) is located on chromosome band 11p15.5, which is an important tumor-suppressor gene region. Mutations in CARS have been identified in many kinds of cancers; however, evidence for a relationship between genetic variants in CARS and gastric cancer at the population level is still lacking. Thus, we explored the association of variants in CARS with gastric cancer using a two-stage case-control strategy in Chinese. We undertook a two-stage case-control study to investigate the association between polymorphisms in CARS and risk of gastric cancer with use of an Illumina Infinium ® BeadChip and an ABI 7900 system. Four single nucleotide polymorphisms (SNPs) were significantly associated with gastric cancer risk in both the discovery stage and the validation stage after adjustment for age and sex. In addition, the combined results of the two stages showed these SNPs were related to gastric cancer risk (P false discovery rate  ≤ 0.001 for rs384,490, rs729662, rs2071101, and rs7394702). In silico analyses revealed that rs384490 and rs7394702 could affect transcription factor response elements or DNA methylation of CARS, and rs729662 was associated with the prognosis of gastric cancer. Additionally, expression quantitative trait loci analysis showed rs384490 and rs729662 might alter expression of CARS-related genes. The potential functional SNPs in CARS might influence the biological functions of CARS or CARS-related genes and ultimately modify the occurrence and development of gastric cancer in Chinese. Further large-scale population-based studies or biological functional assays are warranted to validate our findings.

CD28z CARs and Armored CARs

PubMed Central

Pegram, Hollie J.; Park, Jae H.; Brentjens, Renier J.

2015-01-01

CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whilst promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate “armored CAR T cells” which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors or monoclonal antibodies are aimed at improving the anti-tumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include utilizing dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel “armored CAR T cell” approaches for improving anti-tumor efficacy therapy. PMID:24667958

CD28z CARs and armored CARs.

PubMed

Pegram, Hollie J; Park, Jae H; Brentjens, Renier J

2014-01-01

CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whereas promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate "armored CAR T cells," which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors, or monoclonal antibodies, are aimed at improving the antitumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include using dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel armored CAR T cell approaches for improving antitumor efficacy therapy.

Light-induced carotenogenesis in Myxococcus xanthus: evidence that CarS acts as an anti-repressor of CarA.

PubMed

Whitworth, D E; Hodgson, D A

2001-11-01

In the bacterium Myxococcus xanthus, carotenoids are produced in response to illumination, as a result of expression of the crt carotenoid biosynthesis genes. The majority of crt genes are clustered in the crtEBDC operon, which is repressed in the dark by CarA. Genetic data suggest that, in the light, CarS is synthesized and achieves activation of the crtEBDC operon by removing the repressive action of CarA. As CarS contains no known DNA-binding motif, the relief of CarA-mediated repression was postulated to result from a direct interaction between these two proteins. Use of the yeast two-hybrid system demonstrated direct interaction between CarA and CarS. The two-hybrid system also implied that CarA and, possibly, CarS are capable of homodimerization. Direct evidence for CarS anti-repressor action was provided in vitro. A glutathione S-transferase (GST)-CarA protein fusion was shown to bind specifically to a palindromic operator sequence within the crtEBDC promoter. CarA was prevented from binding to its operator, and prebound CarA was removed by the addition of purified CarS. CarS is therefore an anti-repressor.

Car Seats for Growing Children: Guidelines for Counselling Parents on Which Type of Car Seat To Use.

ERIC Educational Resources Information Center

Illinois State Dept. of Transportation, Springfield. Div. of Traffic Safety.

Children's car seats provide protection from the types of injury with the worst consequences. This document presents guidelines for selecting and installing child car seats, booster seats, and seat belts. The document includes suggestions for identifying when a child's safety restraint system should be changed, for determining if the restraint…

Identifying Stress Transcription Factors Using Gene Expression and TF-Gene Association Data

PubMed Central

Wu, Wei-Sheng; Chen, Bor-Sen

2007-01-01

Unicellular organisms such as yeasts have evolved to survive environmental stresses by rapidly reorganizing the genomic expression program to meet the challenges of harsh environments. The complex adaptation mechanisms to stress remain to be elucidated. In this study, we developed Stress Transcription Factor Identification Algorithm (STFIA), which integrates gene expression and TF-gene association data to identify the stress transcription factors (TFs) of six kinds of stresses. We identified some general stress TFs that are in response to various stresses, and some specific stress TFs that are in response to one specific stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs may be sufficient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the adaptation mechanisms to different stresses may have a bow-tie structure. Second, there may exist extensive regulatory cross-talk among different stress responses. In conclusion, this study proposes a network of the regulators of stress responses and their mechanism of action. PMID:20066130

Are Weeds Hitchhiking a Ride on Your Car? A Systematic Review of Seed Dispersal on Cars

PubMed Central

Ansong, Michael; Pickering, Catherine

2013-01-01

When traveling in cars, we can unintentionally carry and disperse weed seed; but which species, and where are they a problem? To answer these questions, we systematically searched the scientific literature to identify all original research studies that assess seed transported by cars and listed the species with seed on/in cars. From the 13 studies that fit these criteria, we found 626 species from 75 families that have seed that can be dispersed by cars. Of these, 599 are listed as weeds in some part of the world, with 439 listed as invasive or naturalized alien species in one or more European countries, 248 are invasive/noxious weeds in North America, 370 are naturalized alien species in Australia, 167 are alien species in India, 77 are invasive species in China and 23 are declared weeds/invaders in South Africa. One hundred and one are classified as internationally important environmental weeds. Although most (487) were only recorded once, some species such as Chenopodium album, Poa pratensis and Trifolium repens were common among studies. Perennial graminoids seem to be favoured over annual graminoids while annual forbs are favoured over perennial forbs. Species characteristics including seed size and morphology and where the plants grew affected the probability that their seed was transported by cars. Seeds can be found in many different places on cars including under the chassis, front and rear bumpers, wheel wells and rims, front and back mudguards, wheel arches, tyres and on interior floor mats. With increasing numbers of cars and expanding road networks in many regions, these results highlight the importance of cars as a dispersal mechanism, and how it may favour invasions by some species over others. Strategies to reduce the risk of seed dispersal by cars include reducing seed on cars by mowing road verges and cleaning cars. PMID:24265803

Are weeds hitchhiking a ride on your car? A systematic review of seed dispersal on cars.

PubMed

Ansong, Michael; Pickering, Catherine

2013-01-01

When traveling in cars, we can unintentionally carry and disperse weed seed; but which species, and where are they a problem? To answer these questions, we systematically searched the scientific literature to identify all original research studies that assess seed transported by cars and listed the species with seed on/in cars. From the 13 studies that fit these criteria, we found 626 species from 75 families that have seed that can be dispersed by cars. Of these, 599 are listed as weeds in some part of the world, with 439 listed as invasive or naturalized alien species in one or more European countries, 248 are invasive/noxious weeds in North America, 370 are naturalized alien species in Australia, 167 are alien species in India, 77 are invasive species in China and 23 are declared weeds/invaders in South Africa. One hundred and one are classified as internationally important environmental weeds. Although most (487) were only recorded once, some species such as Chenopodium album, Poa pratensis and Trifolium repens were common among studies. Perennial graminoids seem to be favoured over annual graminoids while annual forbs are favoured over perennial forbs. Species characteristics including seed size and morphology and where the plants grew affected the probability that their seed was transported by cars. Seeds can be found in many different places on cars including under the chassis, front and rear bumpers, wheel wells and rims, front and back mudguards, wheel arches, tyres and on interior floor mats. With increasing numbers of cars and expanding road networks in many regions, these results highlight the importance of cars as a dispersal mechanism, and how it may favour invasions by some species over others. Strategies to reduce the risk of seed dispersal by cars include reducing seed on cars by mowing road verges and cleaning cars.

Effects of Three Different Nucleoid-Associated Proteins Encoded on IncP-7 Plasmid pCAR1 on Host Pseudomonas putida KT2440

PubMed Central

Suzuki-Minakuchi, Chiho; Hirotani, Ryusuke; Shintani, Masaki; Takeda, Toshiharu; Takahashi, Yurika; Matsui, Kazuhiro; Vasileva, Delyana; Yun, Choong-Soo; Okada, Kazunori; Yamane, Hisakazu

2015-01-01

Nucleoid-associated proteins (NAPs), which fold bacterial DNA and influence gene transcription, are considered to be global transcriptional regulators of genes on both plasmids and the host chromosome. Incompatibility P-7 group plasmid pCAR1 carries genes encoding three NAPs: H-NS family protein Pmr, NdpA-like protein Pnd, and HU-like protein Phu. In this study, the effects of single or double disruption of pmr, pnd, and phu were assessed in host Pseudomonas putida KT2440. When pmr and pnd or pmr and phu were simultaneously disrupted, both the segregational stability and the structural stability of pCAR1 were markedly decreased, suggesting that Pmr, Pnd, and Phu act as plasmid-stabilizing factors in addition to their established roles in replication and partition systems. The transfer frequency of pCAR1 was significantly decreased in these double mutants. The segregational and structural instability of pCAR1 in the double mutants was recovered by complementation of pmr, whereas no recovery of transfer deficiency was observed. Comprehensive phenotype comparisons showed that the host metabolism of carbon compounds, which was reduced by pCAR1 carriage, was restored by disruption of the NAP gene(s). Transcriptome analyses of mutants indicated that transcription of genes for energy production, conversion, inorganic ion transport, and metabolism were commonly affected; however, how their products altered the phenotypes of mutants was not clear. The findings of this study indicated that Pmr, Pnd, and Phu act synergistically to affect pCAR1 replication, maintenance, and transfer, as well as to alter the host metabolic phenotype. PMID:25681185

Injuries resulting from car surfing--United States, 1990-2008.

PubMed

2008-10-17

"Car surfing" is a term introduced in the mid-1980s to describe a thrill-seeking activity that involves riding on the exterior of a moving motor vehicle while it is being driven by another person. Although reports of car-surfing injuries have been published in the United States, no study to date has analyzed these events from a national perspective. Because traditional public health datasets do not collect morbidity or mortality data on this practice, CDC searched U.S. newspaper reports to provide an initial characterization of car-surfing injuries on a national scale. That analysis identified 58 reports of car-surfing deaths and 41 reports of nonfatal injury from 1990 through August 2008. Most reports of car-surfing injuries came from newspapers in the Midwest and South (75%), and most of the injuries were among males (70%) and persons aged 15-19 years (69%). The first identified newspaper reports about car-surfing injuries were published in the early 1990s, and new reports have been published every year since then. Parents and teens should be aware of the potentially lethal consequences of car surfing, which can occur even at low vehicle speeds, sometimes resulting from unanticipated movements of the vehicle, such as swerving or braking.

Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection

PubMed Central

Eyquem, Justin; Mansilla-Soto, Jorge; Giavridis, Theodoros; van der Stegen, Sjoukje J. C.; Hamieh, Mohamad; Cunanan, Kristen M.; Odak, Ashlesha; Gönen, Mithat; Sadelain, Michel

2017-01-01

Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection1. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies3. CARs are typically transduced into the T cells of a patient using γ-retroviral4 vectors or other randomly integrating vectors5, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing6–8. Recent advances in genome editing enable efficient sequence-specific interventions in human cells9,10, including targeted gene delivery to the CCR5 and AAVS1 loci11,12. Here we show that directing a CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia. We further demonstrate that targeting the CAR to the TRAC locus averts tonic CAR signalling and establishes effective internalization and re-expression of the CAR following single or repeated exposure to antigen, delaying effector T-cell differentiation and exhaustion. These findings uncover facets of CAR immunobiology and underscore the potential of CRISPR/Cas9 genome editing to advance immunotherapies. PMID:28225754

Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes

NASA Technical Reports Server (NTRS)

Stolc, Viktor; Samanta, Manoj Pratim; Tongprasit, Waraporn; Marshall, Wallace F.

2005-01-01

The important role that cilia and flagella play in human disease creates an urgent need to identify genes involved in ciliary assembly and function. The strong and specific induction of flagellar-coding genes during flagellar regeneration in Chlamydomonas reinhardtii suggests that transcriptional profiling of such cells would reveal new flagella-related genes. We have conducted a genome-wide analysis of RNA transcript levels during flagellar regeneration in Chlamydomonas by using maskless photolithography method-produced DNA oligonucleotide microarrays with unique probe sequences for all exons of the 19,803 predicted genes. This analysis represents previously uncharacterized whole-genome transcriptional activity profiling study in this important model organism. Analysis of strongly induced genes reveals a large set of known flagellar components and also identifies a number of important disease-related proteins as being involved with cilia and flagella, including the zebrafish polycystic kidney genes Qilin, Reptin, and Pontin, as well as the testis-expressed tubby-like protein TULP2.

An improved car-following model with two preceding cars' average speed

NASA Astrophysics Data System (ADS)

Yu, Shao-Wei; Shi, Zhong-Ke

2015-01-01

To better describe cooperative car-following behaviors under intelligent transportation circumstances and increase roadway traffic mobility, the data of three successive following cars at a signalized intersection of Jinan in China were obtained and employed to explore the linkage between two preceding cars' average speed and car-following behaviors. The results indicate that two preceding cars' average velocity has significant effects on the following car's motion. Then an improved car-following model considering two preceding cars' average velocity was proposed and calibrated based on full velocity difference model and some numerical simulations were carried out to study how two preceding cars' average speed affected the starting process and the traffic flow evolution process with an initial small disturbance, the results indicate that the improved car-following model can qualitatively describe the impacts of two preceding cars' average velocity on traffic flow and that taking two preceding cars' average velocity into account in designing the control strategy for the cooperative adaptive cruise control system can improve the stability of traffic flow, suppress the appearance of traffic jams and increase the capacity of signalized intersections.

17. CABLE CAR #22, VIEW SHOWING CAR ROUNDING CORNER IN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. CABLE CAR #22, VIEW SHOWING CAR ROUNDING CORNER IN LOADING AREA NEXT TO CAR DUMP AND CAR DUMP BUILDING - Pennsylvania Railroad, Canton Coal Pier, Clinton Street at Keith Avenue (Canton area), Baltimore, Independent City, MD

Effects of three different nucleoid-associated proteins encoded on IncP-7 plasmid pCAR1 on host Pseudomonas putida KT2440.

PubMed

Suzuki-Minakuchi, Chiho; Hirotani, Ryusuke; Shintani, Masaki; Takeda, Toshiharu; Takahashi, Yurika; Matsui, Kazuhiro; Vasileva, Delyana; Yun, Choong-Soo; Okada, Kazunori; Yamane, Hisakazu; Nojiri, Hideaki

2015-04-01

Nucleoid-associated proteins (NAPs), which fold bacterial DNA and influence gene transcription, are considered to be global transcriptional regulators of genes on both plasmids and the host chromosome. Incompatibility P-7 group plasmid pCAR1 carries genes encoding three NAPs: H-NS family protein Pmr, NdpA-like protein Pnd, and HU-like protein Phu. In this study, the effects of single or double disruption of pmr, pnd, and phu were assessed in host Pseudomonas putida KT2440. When pmr and pnd or pmr and phu were simultaneously disrupted, both the segregational stability and the structural stability of pCAR1 were markedly decreased, suggesting that Pmr, Pnd, and Phu act as plasmid-stabilizing factors in addition to their established roles in replication and partition systems. The transfer frequency of pCAR1 was significantly decreased in these double mutants. The segregational and structural instability of pCAR1 in the double mutants was recovered by complementation of pmr, whereas no recovery of transfer deficiency was observed. Comprehensive phenotype comparisons showed that the host metabolism of carbon compounds, which was reduced by pCAR1 carriage, was restored by disruption of the NAP gene(s). Transcriptome analyses of mutants indicated that transcription of genes for energy production, conversion, inorganic ion transport, and metabolism were commonly affected; however, how their products altered the phenotypes of mutants was not clear. The findings of this study indicated that Pmr, Pnd, and Phu act synergistically to affect pCAR1 replication, maintenance, and transfer, as well as to alter the host metabolic phenotype. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Car radiator burns: a prevention issue.

PubMed

Rabbitts, Angela; Alden, Nicole E; Conlin, Tara; Yurt, Roger W

2004-01-01

Scald burns continue to be the major cause of injury to patients admitted to the burn center. Scald burns occurring from car radiator fluid comprise a significant subgroup. Although manufacturer warning labels have been placed on car radiators, these burns continue to occur. This retrospective review looks at all patients admitted to our burn center who suffered scald burns from car radiator fluid to assess the extent of this problem. During the study period, 86 patients were identified as having suffered scald burns as a result of contact with car radiator fluid. Seventy-one percent of the burn injuries occurred in the summer months. The areas most commonly burned were the head and upper extremities. Burn prevention efforts have improved greatly over the years; however, this study demonstrates that scald burns from car radiator fluid continue to cause physical, emotional, and financial devastation. The current radiator warning labels alone are not effective. The National Highway Traffic Safety Administration has proposed a new federal motor vehicle safety standard to aid in decreasing the number of scald burns from car radiators. The results of this study were submitted to the United States Department of Transportation for inclusion in a docket for federal legislation supporting these safety measures.

RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.

PubMed

Wang, Zhixiong; Cheng, Yulan; Abraham, John M; Yan, Rong; Liu, Xi; Chen, Wei; Ibrahim, Sariat; Schroth, Gary P; Ke, Xiquan; He, Yulong; Meltzer, Stephen J

2017-10-15

Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes. Five novel in-frame fusion transcripts were identified and verified in 40 EACs and in a validation cohort of 15 additional EACs (55 patients in all): fibroblast growth factor receptor 2 (FGFR2)-GRB2-associated binding protein 2 (GAB2) in 2 of 55 or 3.6%, Niemann-Pick C1 (NPC1)-maternal embryonic leucine zipper kinase (MELK) in 2 of 55 or 3.6%, ubiquitin-specific peptidase 54 (USP54)-calcium/calmodulin dependent protein kinase II γ (CAMK2G) in 2 of 55 or 3.6%, megakaryoblastic leukemia (translocation) 1 (MKL1)-fibulin 1 (FBLN1) in 1 of 55 or 1.8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%. A genomic analysis indicated that NPC1-MELK arose from a complex interchromosomal translocation event involving chromosomes 18, 3, and 9 with 3 rearrangement points, and this was consistent with chromoplexy. These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC. Cancer 2017;123:3916-24. © 2017 American Cancer Society. © 2017 American Cancer Society.

A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD8+ T Cell Development

PubMed Central

Hu, Guangan; Chen, Jianzhu

2014-01-01

Memory CD8+ T cell development is defined by the expression of a specific set of memory signature genes (MSGs). Despite recent progress, many components of the transcriptional control of memory CD8+ T cell development are still unknown. To identify transcription factors (TFs) and their interactions in memory CD8+ T cell development, we construct a genome-wide regulatory network and apply it to identify key TFs that regulate MSGs. Most of the known TFs in memory CD8+ T cell development are rediscovered and about a dozen new TFs are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified and Bach2 is further shown to promote both development and recall proliferation of memory CD8+ T cells through Prdm1 and Id3. Gene perturbation study identifies the mode of interactions among the TFs with Sox4 as a hub. The identified TFs and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8+ T cell development. PMID:24335726

An improved car-following model accounting for the preceding car's taillight

NASA Astrophysics Data System (ADS)

Zhang, Jian; Tang, Tie-Qiao; Yu, Shao-Wei

2018-02-01

During the deceleration process, the preceding car's taillight may have influences on its following car's driving behavior. In this paper, we propose an extended car-following model with consideration of the preceding car's taillight. Two typical situations are used to simulate each car's movement and study the effects of the preceding car's taillight on the driving behavior. Meanwhile, sensitivity analysis of the model parameter is in detail discussed. The numerical results show that the proposed model can improve the stability of traffic flow and the traffic safety can be enhanced without a decrease of efficiency especially when cars pass through a signalized intersection.

49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Annual Report of Cars Loaded and Cars Terminated... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS REPORT OF CARS LOADED AND CARS TERMINATED § 1247.1 Annual Report of Cars Loaded and Cars Terminated. Beginning with the...

49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 9 2014-10-01 2014-10-01 false Annual Report of Cars Loaded and Cars Terminated... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS REPORT OF CARS LOADED AND CARS TERMINATED § 1247.1 Annual Report of Cars Loaded and Cars Terminated. Beginning with the...

49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Annual Report of Cars Loaded and Cars Terminated... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS REPORT OF CARS LOADED AND CARS TERMINATED § 1247.1 Annual Report of Cars Loaded and Cars Terminated. Beginning with the...

49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 9 2011-10-01 2011-10-01 false Annual Report of Cars Loaded and Cars Terminated... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS REPORT OF CARS LOADED AND CARS TERMINATED § 1247.1 Annual Report of Cars Loaded and Cars Terminated. Beginning with the...

49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 9 2012-10-01 2012-10-01 false Annual Report of Cars Loaded and Cars Terminated... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS REPORT OF CARS LOADED AND CARS TERMINATED § 1247.1 Annual Report of Cars Loaded and Cars Terminated. Beginning with the...

Protein arginine methyltransferase 5 (PRMT5) is a novel coactivator of constitutive androstane receptor (CAR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanno, Yuichiro, E-mail: ykanno@phar.toho-u.ac.jp; Inajima, Jun; Kato, Sayaka

The constitutive androstane receptor (CAR) plays a key role in the expression of xenobiotic/steroid and drug metabolizing enzymes and their transporters. In this study, we demonstrated that protein arginine methyltransferase 5 (PRMT5) is a novel CAR-interacting protein. Furthermore, the PRMT-dependent induction of a CAR reporter gene, which was independent of methyltransferase activity, was enhanced in the presence of steroid receptor coactivator 1 (SRC1), peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) or DEAD box DNA/RNA helicase DP97. Using tetracycline inducible-hCAR system in HepG2 cells, we showed that knockdown of PRMT5 with small interfering RNA suppressed tetracycline -induced mRNA expression of CYP2B6more » but not of CYP2C9 or CYP3A4. PRMT5 enhanced phenobarbital-mediated transactivation of a phenobarbital-responsive enhancer module (PBREM)-driven reporter gene in co-operation with PGC-1α in rat primary hepatocytes. Based on these findings, we suggest PRMT5 to be a gene (or promoter)-selective coactivator of CAR by mediating the formation of complexes between hCAR and appropriate coactivators. - Highlights: • Nuclear receptor CAR interact with PRMT5. • PRMT5 enhances transcriptional activity of CAR. • PRMT5 synergistically enhances transactivity of CAR by the co-expression of SRC-1, DP97 or PGC1α. • PRMT5 is a gene-selective co-activator for hCAR.« less

Flying Cars

NASA Technical Reports Server (NTRS)

Crow, Steven

1996-01-01

Flying cars have nearly mythical appeal to nonpilots, a group that includes almost the whole human race. The appeal resides in the perceived utility of flying cars, vehicles that offer portal-to-portal transportation, yet break the bonds of road and traffic and travel freely through the sky at the drivers will. Part of the appeal is an assumption that flying cars can be as easy to fly as to drive. Flying cars have been part of the dream of aviation since the dawn of powered flight. Glenn Curtiss built, displayed, and maybe even flew a flying car in 1917, the Curtiss Autoplane. Many roadable airplanes were built in the 1930's, like the Waterman Arrowbile and the Fulton Airphibian. Two flying cars came close to production in the early 1950's. Ted Hall built a series of flying cars culminating in the Convaircar, sponsored by Consolidated Vultee, General Motors, and Hertz. Molt Taylor built and certified his Aerocar, and Ford came close to producing them. Three Aerocars are still flyable, two in museums in Seattle and Oshkosh, and the third owned and flown by Ed Sweeny. Flying cars do have problems, which so far have prevented commercial success. An obvious problem is complexity of the vehicle, the infrastructure, or both. Another is the difficulty of matching low power for normal driving with high power in flight. An automobile uses only about 20 hp at traffic speeds, while a personal airplane needs about 160 hp at speeds typical of flight. Many automobile engines can deliver 160 hp, but not for very long. A more subtle issue involves the drag of automobiles and airplanes. A good personal airplane can fly 30 miles per gallon of fuel at 200 mph. A good sports car would need 660 hp at the same speed and would travel only 3 miles per gallon. The difference is drag area, about 4.5 sq ft for the automobile and 1.4 sq ft for the airplane. A flying car better have the drag area of the airplane, not the car!

A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains

PubMed Central

Hutchinson, John N; Ensminger, Alexander W; Clemson, Christine M; Lynch, Christopher R; Lawrence, Jeanne B; Chess, Andrew

2007-01-01

Background Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment. Results This screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11: NEAT1, a noncoding RNA from the locus encoding for TncRNA, and NEAT2 (also known as MALAT-1). While the two NEAT transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs. NEAT2 is extraordinarily well conserved for a noncoding RNA, more so than even XIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, NEAT1 localizes to the periphery of such domains, whereas the neighboring transcript, NEAT2, is part of the long-sought polyadenylated component of nuclear speckles. Conclusion Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2. The function of these noncoding RNAs in mRNA metabolism is suggested by their high levels of conservation and their intimate association with SC35 splicing

groHMM: a computational tool for identifying unannotated and cell type-specific transcription units from global run-on sequencing data.

PubMed

Chae, Minho; Danko, Charles G; Kraus, W Lee

2015-07-16

Global run-on coupled with deep sequencing (GRO-seq) provides extensive information on the location and function of coding and non-coding transcripts, including primary microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and enhancer RNAs (eRNAs), as well as yet undiscovered classes of transcripts. However, few computational tools tailored toward this new type of sequencing data are available, limiting the applicability of GRO-seq data for identifying novel transcription units. Here, we present groHMM, a computational tool in R, which defines the boundaries of transcription units de novo using a two state hidden-Markov model (HMM). A systematic comparison of the performance between groHMM and two existing peak-calling methods tuned to identify broad regions (SICER and HOMER) favorably supports our approach on existing GRO-seq data from MCF-7 breast cancer cells. To demonstrate the broader utility of our approach, we have used groHMM to annotate a diverse array of transcription units (i.e., primary transcripts) from four GRO-seq data sets derived from cells representing a variety of different human tissue types, including non-transformed cells (cardiomyocytes and lung fibroblasts) and transformed cells (LNCaP and MCF-7 cancer cells), as well as non-mammalian cells (from flies and worms). As an example of the utility of groHMM and its application to questions about the transcriptome, we show how groHMM can be used to analyze cell type-specific enhancers as defined by newly annotated enhancer transcripts. Our results show that groHMM can reveal new insights into cell type-specific transcription by identifying novel transcription units, and serve as a complete and useful tool for evaluating functional genomic elements in cells.

Cloning of an ets-Related Transcription Factor Involved in a Novel Epigenetic Mechanism of Mammary Carcinogenesis

DTIC Science & Technology

2001-05-01

dystrophin gene promoter is regulated by YY1 and DPBF (33). Other studies showed that serum response factor (SRF) is required for muscle-specific...transcriptional activation through CArG boxes (68) and that SRF competes with YY1 for binding to wild-type CArG elements (51). CBF-A has significant...between SRF and YY1 proteins at CArG elements has been described in chicken skeletal muscle cells(36). Our previous study in a rat mammary carcinoma cell

The mechanism of the growth-inhibitory effect of coxsackie and adenovirus receptor (CAR) on human bladder cancer: a functional analysis of car protein structure.

PubMed

Okegawa, T; Pong, R C; Li, Y; Bergelson, J M; Sagalowsky, A I; Hsieh, J T

2001-09-01

The coxsackie and adenovirus receptor (CAR) is identified as a high-affinity receptor for adenovirus type 5. We observed that invasive bladder cancer specimens had significantly reduced CAR mRNA levels compared with superficial bladder cancer specimens, which suggests that CAR may play a role in the progression of bladder cancer. Elevated CAR expression in the T24 cell line (CAR-negative cells) increased its sensitivity to adenovirus infection and significantly inhibited its in vitro growth, accompanied by p21 and hypophosphorylated retinoblastoma accumulation. Conversely, decreased CAR levels in both RT4 and 253J cell lines (CAR-positive cells) promoted their in vitro growth. To unveil the mechanism of action of CAR, we showed that the extracellular domain of CAR facilitated intercellular adhesion. Furthermore, interrupting intercellular adhesion of CAR by a specific antibody alleviates the growth-inhibitory effect of CAR. We also demonstrated that both the transmembrane and intracellular domains of CAR were critical for its growth-inhibitory activity. These data indicate that the cell-cell contact initiated by membrane-bound CAR can elicit a negative signal cascade to modulate cell cycle regulators inside the nucleus of bladder cancer cells. Therefore, the presence of CAR cannot only facilitate viral uptake of adenovirus but also inhibit cell growth. These results can be integrated to formulate a new strategy for bladder cancer therapy.

49 CFR 172.330 - Tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Tank cars and multi-unit tank car tanks. 172.330..., TRAINING REQUIREMENTS, AND SECURITY PLANS Marking § 172.330 Tank cars and multi-unit tank car tanks. (a... material— (1) In a tank car unless the following conditions are met: (i) The tank car must be marked on...

49 CFR 172.330 - Tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Tank cars and multi-unit tank car tanks. 172.330..., TRAINING REQUIREMENTS, AND SECURITY PLANS Marking § 172.330 Tank cars and multi-unit tank car tanks. (a... material— (1) In a tank car unless the following conditions are met: (i) The tank car must be marked on...

49 CFR 172.330 - Tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Tank cars and multi-unit tank car tanks. 172.330..., TRAINING REQUIREMENTS, AND SECURITY PLANS Marking § 172.330 Tank cars and multi-unit tank car tanks. (a... material— (1) In a tank car unless the following conditions are met: (i) The tank car must be marked on...

Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osabe, Makoto; Sugatani, Junko; Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka

Constitutive androstane receptor (CAR) is a transcription factor to regulate the expression of several genes related to drug-metabolism. Here, we demonstrate that CAR protein accumulates during G1 in human SW480 and HepG2 cells. After the G1/S phase transition, CAR protein levels decreased, and CAR was hardly detected in cells by the late M phase. CAR expression in both cell lines was suppressed by RNA interference-mediated suppression of CDK4. Depletion of CAR by RNA interference in both cells and by hepatocyte growth factor treatment in HepG2 cells resulted in decreased MDM2 expression that led to p21 upregulation and repression of HepG2more » cell growth. Thus, our results demonstrate that CAR expression is an early G1 event regulated by CDK4 that contributes to MDM2 expression; these findings suggest that CAR may influence the expression of genes involved in not only the metabolism of endogenous and exogenous substances but also in the cell proliferation.« less

Algorithm to Identify Frequent Coupled Modules from Two-Layered Network Series: Application to Study Transcription and Splicing Coupling

PubMed Central

Li, Wenyuan; Dai, Chao; Liu, Chun-Chi

2012-01-01

Abstract Current network analysis methods all focus on one or multiple networks of the same type. However, cells are organized by multi-layer networks (e.g., transcriptional regulatory networks, splicing regulatory networks, protein-protein interaction networks), which interact and influence each other. Elucidating the coupling mechanisms among those different types of networks is essential in understanding the functions and mechanisms of cellular activities. In this article, we developed the first computational method for pattern mining across many two-layered graphs, with the two layers representing different types yet coupled biological networks. We formulated the problem of identifying frequent coupled clusters between the two layers of networks into a tensor-based computation problem, and proposed an efficient solution to solve the problem. We applied the method to 38 two-layered co-transcription and co-splicing networks, derived from 38 RNA-seq datasets. With the identified atlas of coupled transcription-splicing modules, we explored to what extent, for which cellular functions, and by what mechanisms transcription-splicing coupling takes place. PMID:22697243

Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

PubMed

Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

2018-03-29

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

Characteristics of particulate matter emissions from toy cars with electric motors.

PubMed

Wang, Xiaofei; Williams, Brent J; Biswas, Pratim

2015-04-01

Aerosol emissions from toy cars with electric motors were characterized. Particle emission rates from the toy cars, as high as 7.47×10(7) particles/s, were measured. This emission rate is lower than other indoor sources such as smoking and cooking. The particles emitted from toy cars are generated from spark discharges inside the electric motors that power the toy cars. Size distribution measurements indicated that most particles were below 100 nm in diameter. Copper was the dominant inorganic species in these particles. By deploying aerosol mass spectrometers, high concentrations of particulate organic matter were also detected and characterized in detail. Several organic compounds were identified using a thermal desorption aerosol gas chromatography. The mass size distribution of particulate organic matter was bimodal. The formation mechanism of particulate organic matter from toy cars was elucidated. A possible new source of indoor air pollution, particles from electric motors in toy cars, was identified. This study characterized aerosol emissions from toy cars in detail. Most of these particles have a diameter less than 100 nm. Copper and some organics are the major components of these particles. Conditions that minimize these emissions were determined.

Residual tobacco smoke pollution in used cars for sale: air, dust, and surfaces.

PubMed

Matt, Georg E; Quintana, Penelope J E; Hovell, Melbourne F; Chatfield, Dale; Ma, Debbie S; Romero, Romina; Uribe, Anna

2008-09-01

Regular tobacco use in the enclosed environment of a car raises concerns about longer-term contamination of a car's microenvironment with residual secondhand smoke pollutants. This study (a) developed and compared methods to measure residual contamination of cars with secondhand smoke, (b) examined whether cars of smokers and nonsmokers were contaminated by secondhand smoke, and (c) how smoking behavior and restrictions affected contamination levels. Surface wipe, dust, and air samples were collected in used cars sold by nonsmokers (n = 20) and smokers (n = 87) and analyzed for nicotine. Sellers were interviewed about smoking behavior and restrictions, and car interiors were inspected for signs of tobacco use. Cars of smokers who smoked in their vehicles showed significantly elevated levels of nicotine (p < .001) in dust, on surfaces, and in the air compared with nonsmoker cars with smoking ban. When smokers imposed car smoking bans, air nicotine levels were significantly lower (p < .01), but dust and surface contamination levels remained at similar levels. Smoking more cigarettes in the car and overall higher smoking rate of the seller were significantly associated with higher secondhand smoke contamination of the car (p < .001). Use of a cutpoint for nicotine levels from surface wipe samples correctly identified 82% of smoker cars without smoking bans, 75% of smoker cars with bans, and 100% of nonsmoker cars. Surface nicotine levels provide a relatively inexpensive and accurate method to identify cars and other indoor environments contaminated with residual secondhand smoke. Disclosure requirements and smoke-free certifications could help protect nonsmoking buyers of used cars.

18. CABLE CAR #21, DETAIL OF CAR COMING OUT OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. CABLE CAR #21, DETAIL OF CAR COMING OUT OF LOADING AREA OF CAR DUMP BUILDING - Pennsylvania Railroad, Canton Coal Pier, Clinton Street at Keith Avenue (Canton area), Baltimore, Independent City, MD

Forces on wheels and fuel consumption in cars

NASA Astrophysics Data System (ADS)

Güémez, J.; Fiolhais, M.

2013-07-01

Motivated by real classroom discussions, we analyze the forces acting on moving vehicles, specifically friction on their wheels. In typical front-wheel-drive cars when the car accelerates these forces are in the forward direction in the front wheels, but they are in the opposite direction in the rear wheels. The situation may be intriguing for students, but it may also be helpful and stimulating to clarify the role of friction forces on rolling objects. In this paper we also study the thermodynamical aspects of an accelerating car, relating the distance traveled to the amount of fuel consumed. The fuel consumption is explicitly shown to be Galilean invariant and we identify the Gibbs free energy as the relevant quantity that enters into the thermodynamical description of the accelerating car. The more realistic case of the car's motion with the dragging forces taken into account is also discussed.

A Rare SNP Identified a TCP Transcription Factor Essential for Tendril Development in Cucumber.

PubMed

Wang, Shenhao; Yang, Xueyong; Xu, Mengnan; Lin, Xingzhong; Lin, Tao; Qi, Jianjian; Shao, Guangjin; Tian, Nana; Yang, Qing; Zhang, Zhonghua; Huang, Sanwen

2015-12-07

Rare genetic variants are abundant in genomes but less tractable in genome-wide association study. Here we exploit a strategy of rare variation mapping to discover a gene essential for tendril development in cucumber (Cucumis sativus L.). In a collection of >3000 lines, we discovered a unique tendril-less line that forms branches instead of tendrils and, therefore, loses its climbing ability. We hypothesized that this unusual phenotype was caused by a rare variation and subsequently identified the causative single nucleotide polymorphism. The affected gene TEN encodes a TCP transcription factor conserved within the cucurbits and is expressed specifically in tendrils, representing a new organ identity gene. The variation occurs within a protein motif unique to the cucurbits and impairs its function as a transcriptional activator. Analyses of transcriptomes from near-isogenic lines identified downstream genes required for the tendril's capability to sense and climb a support. This study provides an example to explore rare functional variants in plant genomes. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Improving Mode of Action Analysis Using Transcript Profiling in Nullizygous Mouse Models

EPA Science Inventory

A number of nuclear receptors (NR) mediate transcriptional, hepatocyte growth and carcinogenic effects in the rodent liver after chemical exposure. These receptors include the constitutive activated/androstane receptor (CAR), pregnane X receptor (PXR), and peroxisome proliferator...

3. VAL CAMERA CAR, VIEW OF CAMERA CAR AND TRACK ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. VAL CAMERA CAR, VIEW OF CAMERA CAR AND TRACK WITH THE VAL TO THE RIGHT, LOOKING NORTHEAST. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

2. VAL CAMERA CAR, VIEW OF CAMERA CAR AND TRACK ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. VAL CAMERA CAR, VIEW OF CAMERA CAR AND TRACK WITH CAMERA STATION ABOVE LOOKING WEST TAKEN FROM RESERVOIR. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

An improved car-following model considering velocity fluctuation of the immediately ahead car

NASA Astrophysics Data System (ADS)

Yu, Shaowei; Huang, Mengxing; Ren, Jia; Shi, Zhongke

2016-05-01

To better describe car-following behaviors in the adaptive cruise control strategy and further increase roadway traffic mobility and reduce fuel consumptions, the linkage between velocity fluctuation of the immediately ahead car and the following car's acceleration or deceleration is explored with respect to the measured car-following data by employing the gray correlation analysis theory and then an improved car-following model considering velocity fluctuation of the immediately ahead car on basis of the full velocity difference model is proposed. Numerical simulations are carried out and the effects of velocity fluctuation of the immediately ahead car on each car's velocity, acceleration, vehicular gap, fuel consumptions and the total fuel consumptions of the whole car-following system with different time window lengths are investigated in detail. The results show that velocity fluctuation of the immediately ahead car has significant effects on car-following behaviors and fuel consumptions, and that considering velocity fluctuation of the immediately ahead car in designing the adaptive cruise control system can improve traffic flow stability and reduce fuel consumptions.

Identification and characterization of a LEA family gene CarLEA4 from chickpea (Cicer arietinum L.).

PubMed

Gu, Hanyan; Jia, Yuying; Wang, Xiansheng; Chen, Quanjia; Shi, Shubing; Ma, Lin; Zhang, Jusong; Zhang, Hua; Ma, Hao

2012-04-01

Late-embryogenesis abundant (LEA) proteins have been reported to be closely correlated with the acquisition of desiccation tolerance during seed development and response of plant to drought, salinity, and freezing, etc. In this study, a LEA gene, CarLEA4 (GenBank accession no. GU247511), was isolated from chickpea based on a cDNA library constructed with chickpea seedling leaves treated by polyethylene glycol (PEG). CarLEA4 contained two exons and one intron within genomic DNA sequence and encoded a putative polypeptide of 152 amino acids. CarLEA4 had a conserved pfam domain, and showed high similarity to the group 4 LEA proteins in secondary structure. It was localized in the nucleus. The transcripts of CarLEA4 were detected in many chickpea organs including seedling leaves, stems, roots, flowers, young pods, and young seeds. CarLEA4 was inhibited by leaf age and showed expression changes in expression during seed development, pod development and germination. Furthermore, the expression of CarLEA4 was strongly induced by drought, salt, heat, cold, ABA, IAA, GA(3) and MeJA. Our results suggest that CarLEA4 encodes a protein of LEA group 4 and may be involved in various plant developmental processes and abiotic stress responses.

1. VARIABLEANGLE LAUNCHER CAMERA CAR, VIEW OF CAMERA CAR AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. VARIABLE-ANGLE LAUNCHER CAMERA CAR, VIEW OF CAMERA CAR AND TRACK WITH CAMERA STATION ABOVE LOOKING NORTH TAKEN FROM RESERVOIR. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

PubMed Central

Hestand, Matthew S; van Galen, Michiel; Villerius, Michel P; van Ommen, Gert-Jan B; den Dunnen, Johan T; 't Hoen, Peter AC

2008-01-01

Background The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments. Results We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACR database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool. Conclusion The program CORE_TF is accessible in a user friendly web interface at . It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites. PMID:19036135

Compatibility problems in frontal, side, single car collisions and car-to-pedestrian accidents in Japan.

PubMed

Mizuno, K; Kajzer, J

1999-07-01

Compatibility problems in car-to-car frontal, side, single car and car-to-pedestrian collisions in Japan are discussed using traffic accident data. The number of serious and fatal injuries is investigated for the subject car and other cars, which are categorized by their class and mass. The aggressivity of the cars is calculated by the number of fatalities, fatality rates and by the number of car registrations. The results show that in car-to-car frontal collisions, cars with a mass of 1150 kg are the most compatible among the current car population. In both car-to-car frontal and side collisions, the sports utility vehicle and mini car are found to be the most incompatible car types with high and low aggressivity, respectively. On the other hand, the accident data show that the wagon and midsize sedan are the most compatible car types. The compatibility of fixed objects in the road environment with cars and cars with pedestrians is also discussed. In a single car collision with a fixed object, the guardrail is the most compatible object and can reduce the fatality rate on prefecture roads by about 60%. The front geometry of the car has large effect on compatibility with a pedestrian.

Methyl isobutyl ketone-induced hepatocellular carcinogenesis in B6C3F1 mice: A constitutive androstane receptor (CAR)-mediated mode of action.

PubMed

Hughes, B J; Thomas, J; Lynch, A M; Borghoff, S J; Green, S; Mensing, T; Sarang, S S; LeBaron, M J

2016-11-01

In a National Toxicology Program (NTP) chronic inhalation study with methyl isobutyl ketone (MIBK), increases in hepatocellular adenomas and hepatocellular adenomas and carcinomas (combined) were observed in male and female B6C3F 1 mice at 1800 ppm. A DNA reactive Mode-of-Action (MOA) for this liver tumor response is not supported by the evidence as MIBK and its major metabolites lack genotoxicity in both in vitro and in vivo studies. Constitutive androstane receptor (CAR) nuclear receptor-mediated activation has been hypothesized as the MOA for MIBK-induced mouse liver tumorigenesis. To further investigate the MOA for MIBK-induced murine liver tumors, male and female B6C3F1, C57BL/6, and CAR/PXR Knockout (KO) mice were exposed to either 0 or 1800 ppm MIBK for 6 h/day, 5 days/week for a total of 10 days. On day 1, mice were implanted with osmotic mini-pumps containing 5-Bromo-2-deoxyuridine (BrdU) 1 h following exposure and humanely euthanized 1-3 h following the final exposure. B6C3F 1 and C57BL/6 mice had statistically significant increases in liver weights compared to controls that corresponded with hepatocellular hypertrophy and increased mitotic figures. Hepatocellular proliferation data indicated induction of S-phase DNA synthesis in B6C3F 1 and C57BL/6 mice exposed to 1800 ppm MIBK compared to control, and no increase was observed in MIBK exposed CAR/PXR KO mice. Liver gene expression changes indicated a maximally-induced Cyp2b10 (CAR-associated) transcript and a slight increase in Cyp3a11(PXR-associated) transcript in B6C3F 1 and C57BL/6 mice exposed to 1800 ppm MIBK compared to controls, but not in Cyp1a1 (AhR-associated) or Cyp4a10 (PPAR-α-associated) transcripts. CAR/PXR KO mice exposed to 1800 ppm MIBK showed no evidence of activation of AhR, CAR, PXR or PPAR-α nuclear receptors via their associated transcripts. MIBK induced hepatic effects are consistent with a phenobarbital-like MOA where the initiating events are activation of the CAR and

Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice.

PubMed

Kumar, Ramiya; Mota, Linda C; Litoff, Elizabeth J; Rooney, John P; Boswell, W Tyler; Courter, Elliott; Henderson, Charles M; Hernandez, Juan P; Corton, J Christopher; Moore, David D; Baldwin, William S

2017-01-01

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16β-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and

Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice

PubMed Central

Kumar, Ramiya; Mota, Linda C.; Litoff, Elizabeth J.; Rooney, John P.; Boswell, W. Tyler; Courter, Elliott; Henderson, Charles M.; Hernandez, Juan P.; Corton, J. Christopher; Moore, David D.

2017-01-01

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16β-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and

Transit Car Performance Comparison, State-of-the-Art Car vs. PATCO Transit Car, NYCTA R-46, MBTA Silverbirds

DOT National Transportation Integrated Search

1978-02-01

The first phase of this contract authorized the design, development, and demonstration of two State-Of-The-Art Cars (SOAC). This document reports on the gathering of comparative test data on existing in-service transit cars. The three transit cars se...

Car Seat Safety

MedlinePlus

... Staying Safe Videos for Educators Search English Español Car Seat Safety KidsHealth / For Parents / Car Seat Safety ... certified child passenger safety technician.) Guidelines for Choosing Car Seats Choose a seat with a label that ...

Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder.

PubMed

Coughlin, Curtis R; Scharer, Gunter H; Friederich, Marisa W; Yu, Hung-Chun; Geiger, Elizabeth A; Creadon-Swindell, Geralyn; Collins, Abigail E; Vanlander, Arnaud V; Coster, Rudy Van; Powell, Christopher A; Swanson, Michael A; Minczuk, Michal; Van Hove, Johan L K; Shaikh, Tamim H

2015-08-01

Mitochondrial disease is often suspected in cases of severe epileptic encephalopathy especially when a complex movement disorder, liver involvement and progressive developmental regression are present. Although mutations in either mitochondrial DNA or POLG are often present, other nuclear defects in mitochondrial DNA replication and protein translation have been associated with a severe epileptic encephalopathy. We identified a proband with an epileptic encephalopathy, complex movement disorder and a combined mitochondrial respiratory chain enzyme deficiency. The child presented with neurological regression, complex movement disorder and intractable seizures. A combined deficiency of mitochondrial complexes I, III and IV was noted in liver tissue, along with increased mitochondrial DNA content in skeletal muscle. Incomplete assembly of complex V, using blue native polyacrylamide gel electrophoretic analysis and complex I, using western blotting, suggested a disorder of mitochondrial transcription or translation. Exome sequencing identified compound heterozygous mutations in CARS2, a mitochondrial aminoacyl-tRNA synthetase. Both mutations affect highly conserved amino acids located within the functional ligase domain of the cysteinyl-tRNA synthase. A specific decrease in the amount of charged mt-tRNA(Cys) was detected in patient fibroblasts compared with controls. Retroviral transfection of the wild-type CARS2 into patient skin fibroblasts led to the correction of the incomplete assembly of complex V, providing functional evidence for the role of CARS2 mutations in disease aetiology. Our findings indicate that mutations in CARS2 result in a mitochondrial translational defect as seen in individuals with mitochondrial epileptic encephalopathy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Rapid Transit Car Maintenance Research Needs

DOT National Transportation Integrated Search

1982-12-01

This report identifies those car maintenance research needs that (in the judgement of the participating rail transit operators and suppliers) would produce results that would be applicable industry wide. Those research products should assist the oper...

An improved car-following model with multiple preceding cars' velocity fluctuation feedback

NASA Astrophysics Data System (ADS)

Guo, Lantian; Zhao, Xiangmo; Yu, Shaowei; Li, Xiuhai; Shi, Zhongke

2017-04-01

In order to explore and evaluate the effects of velocity variation trend of multiple preceding cars used in the Cooperative Adaptive Cruise Control (CACC) strategy on the dynamic characteristic, fuel economy and emission of the corresponding traffic flow, we conduct a study as follows: firstly, with the real-time car-following (CF) data, the close relationship between multiple preceding cars' velocity fluctuation feedback and the host car's behaviors is explored, the evaluation results clearly show that multiple preceding cars' velocity fluctuation with different time window-width are highly correlated to the host car's acceleration/deceleration. Then, a microscopic traffic flow model is proposed to evaluate the effects of multiple preceding cars' velocity fluctuation feedback in the CACC strategy on the traffic flow evolution process. Finally, numerical simulations on fuel economy and exhaust emission of the traffic flow are also implemented by utilizing VT-micro model. Simulation results prove that considering multiple preceding cars' velocity fluctuation feedback in the control strategy of the CACC system can improve roadway traffic mobility, fuel economy and exhaust emission performance.

PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients.

PubMed

Hor, S Y; Lee, S C; Wong, C I; Lim, Y W; Lim, R C; Wang, L Z; Fan, L; Guo, J Y; Lee, H S; Goh, B C; Tan, T

2008-04-01

Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes

PubMed Central

Kuang, Zheng; Ji, Zhicheng

2018-01-01

Abstract Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. PMID:29325176

Improvement of Vehicle Positioning Using Car-to-Car Communications in Consideration of Communication Delay

NASA Astrophysics Data System (ADS)

Hontani, Hidekata; Higuchi, Yuya

In this article, we propose a vehicle positioning method that can estimate positions of cars even in areas where the GPS is not available. For the estimation, each car measures the relative distance to a car running in front, communicates the measurements with other cars, and uses the received measurements for estimating its position. In order to estimate the position even if the measurements are received with time-delay, we employed the time-delay tolerant Kalman filtering. For sharing the measurements, it is assumed that a car-to-car communication system is used. Then, the measurements sent from farther cars are received with larger time-delay. It follows that the accuracy of the estimates of farther cars become worse. Hence, the proposed method manages only the states of nearby cars to reduce computing effort. The authors simulated the proposed filtering method and found that the proposed method estimates the positions of nearby cars as accurate as the distributed Kalman filtering.

Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity.

PubMed

Wang, Dongrui; Aguilar, Brenda; Starr, Renate; Alizadeh, Darya; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R; Forman, Stephen J; Brown, Christine E

2018-05-17

Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.

Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity

PubMed Central

Wang, Dongrui; Starr, Renate; Alizadeh, Darya; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R.; Forman, Stephen J.; Brown, Christine E.

2018-01-01

Chimeric antigen receptor–modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy. PMID:29769444

N-acyl homoserine lactone binding to the CarR receptor determines quorum-sensing specificity in Erwinia.

PubMed

Welch, M; Todd, D E; Whitehead, N A; McGowan, S J; Bycroft, B W; Salmond, G P

2000-02-15

Quorum sensing via an N-acyl homoserine lactone (HSL) pheromone controls the biosynthesis of a carbapenem antibiotic in Erwinia carotovora. Transcription of the carbapenem biosynthetic genes is dependent on the LuxR-type activator protein, CarR. Equilibrium binding of a range of HSL molecules, which are thought to activate CarR to bind to its DNA target sequence, was examined using fluorescence quenching, DNA bandshift analysis, limited proteolysis and reporter gene assays. CarR bound the most physiologically relevant ligand, N-(3-oxohexanoyl)-L-homoserine lactone, with a stoichiometry of two molecules of ligand per dimer of protein and a dissociation constant of 1.8 microM, in good agreement with the concentration of HSL required to activate carbapenem production in vivo. In the presence of HSL, CarR formed a very high molecular weight complex with its target DNA, indicating that the ligand causes the protein to multimerize. Chemical cross-linking analysis supported this interpretation. Our data show that the ability of a given HSL to facilitate CarR binding to its target DNA sequence is directly proportional to the affinity of the HSL for the protein.

Investigate moped-car conflicts in China using a naturalistic driving study approach.

PubMed

Glaser, Yi G; Guo, Feng; Fang, Youjia; Deng, Bing; Hankey, Jonathan

2017-12-01

Mopeds are a popular transportation mode in Europe and Asia. Moped-related traffic accidents account for a large proportion of crash fatalities. To develop moped-related crash countermeasures, it is important to understand the characteristics of moped-related conflicts. Naturalistic driving study data were collected in Shanghai, China from 36 car drivers. The data included 2,878h and 78,296km driven from 13,149 trips. Moped-car conflicts were identified and examined from the passenger car driver's perspective using kinematic trigger algorithms and manual video reduction. A total of 119 moped-car conflicts were identified, including 74 high g-force conflicts and 45 low g-force events. These conflicts were classified into 22 on-road configurations where both similarities and differences were found as compared to Western Countries. The majority of the conflicts occurred on secondary main roads and branch roads. Hard braking was the primary response that the car drivers made to these conflicts rather than hard steering. The identified on-road vehicle-moped conflict configurations in Shanghai, China may be attributed to the complicated traffic environment and risky behavior of moped riders. The lower prevalence of hard steering in Shanghai as compared to the United States may be due to the lower speeds at event onsets or less available steering space, e.g., less available shoulder area on Chinese urban roads. The characteristics of moped-car conflicts may impact the design of active safety countermeasures on passenger cars. The pilot data from Shanghai urban areas suggest that countermeasures developed for China may require some modifications to those developed for the United States and European countries, although this recommendation may not be conclusive given the small sample size of the study. Future studies with large samples may help better understand the characteristics of moped-car conflicts. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights

DETAIL VIEW OF BATCH CAR, BUILT BY ATLAS CAR & ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAIL VIEW OF BATCH CAR, BUILT BY ATLAS CAR & MANUFACTURING COMPANY. BATCH STORAGE SILOS IN BACKGROUND - Chambers Window Glass Company, Batch Plant, North of Drey (Nineteenth) Street, West of Constitution Boulevard, Arnold, Westmoreland County, PA

Use of car crashes resulting in fatal and serious injuries to analyze a safe road transport system model and to identify system weaknesses.

PubMed

Stigson, Helena; Hill, Julian

2009-10-01

The objective of this study was to evaluate a model for a safe road transport system, based on some safety performance indicators regarding the road user, the vehicle, and the road, by using crashes with fatally and seriously injured car occupants. The study also aimed to evaluate whether the model could be used to identify system weaknesses and components (road user, vehicles, and road) where improvements would yield the highest potential for further reductions in serious injuries. Real-life car crashes with serious injury outcomes (Maximum Abbreviated Injury Scale 2+) were classified according to the vehicle's safety rating by Euro NCAP (European New Car Assessment Programme) and whether the vehicle was fitted with ESC (Electronic Stability Control). For each crash, the road was also classified according to EuroRAP (European Road Assessment Programme) criteria, and human behavior in terms of speeding, seat belt use, and driving under the influence of alcohol/drugs. Each crash was compared and classified according to the model criteria. Crashes where the safety criteria were not met in more than one of the 3 components were reclassified to identify whether all the components were correlated to the injury outcome. In-depth crash injury data collected by the UK On The Spot (OTS) accident investigation project was used in this study. All crashes in the OTS database occurring between 2000 and 2005 with a car occupant with injury rated MAIS2+ were included, for a total of 101 crashes with 120 occupants. It was possible to classify 90 percent of the crashes according to the model. Eighty-six percent of the occupants were injured when more than one of the 3 components were noncompliant with the safety criteria. These cases were reclassified to identify whether all of the components were correlated to the injury outcome. In 39 of the total 108 cases, at least two components were still seen to interact. The remaining cases were only related to one of the safety criteria

UV exposure in cars.

PubMed

Moehrle, Matthias; Soballa, Martin; Korn, Manfred

2003-08-01

There is increasing knowledge about the hazards of solar and ultraviolet (UV) radiation to humans. Although people spend a significant time in cars, data on UV exposure during traveling are lacking. The aim of this study was to obtain basic information on personal UV exposure in cars. UV transmission of car glass samples, windscreen, side and back windows and sunroof, was determined. UV exposure of passengers was evaluated in seven German middle-class cars, fitted with three different types of car windows. UV doses were measured with open or closed windows/sunroof of Mercedes-Benz E 220 T, E 320, and S 500, and in an open convertible car (Mercedes-Benz CLK). Bacillus subtilis spore film dosimeters (Viospor) were attached to the front, vertex, cheeks, upper arms, forearms and thighs of 'adult' and 'child' dummies. UV wavelengths longer than >335 nm were transmitted through car windows, and UV irradiation >380 nm was transmitted through compound glass windscreens. There was some variation in the spectral transmission of side windows according to the type of glass. On the arms, UV exposure was 3-4% of ambient radiation when the car windows were shut, and 25-31% of ambient radiation when the windows were open. In the open convertible car, the relative personal doses reached 62% of ambient radiation. The car glass types examined offer substantial protection against short-wave UV radiation. Professional drivers should keep car windows closed on sunny days to reduce occupational UV exposure. In individuals with polymorphic light eruption, produced by long-wave UVA, additional protection by plastic films, clothes or sunscreens appears necessary.

Associations of leisure-time sitting in cars with neighborhood walkability.

PubMed

Koohsari, Mohammad Javad; Sugiyama, Takemi; Kaczynski, Andrew T; Owen, Neville

2014-08-01

Too much sitting, including time spent sitting in cars, is associated with poor health outcomes. Identifying the built-environment attributes that may reduce vehicular sitting time can inform future initiatives linking the public health, urban design, and transportation sectors. Data collected in 2003-2004 from adult residents (n = 2521) of Adelaide, Australia were used. Logistic regression analyses examined associations of prolonged time spent sitting in cars during leisure time (30 min/day or more) with neighborhood walkability and its components (dwelling density; intersection density; land use mix; net retail area ratio). Lower overall walkability was significantly associated with a higher odds (OR = 1.43, 95% CI: 1.21-1.70) of spending prolonged time in cars. For analyses with walkability components, lower net retail area ratio, lower residential density, and lower intersection density were significantly associated with prolonged sitting in cars. This study found that residents of high walkable neighborhoods tended to spend less time sitting in cars. In particular, higher net retail area ratio, an indicator of tightly spaced commercial areas, was strongly associated with less time in cars. Policy and planning initiatives to reduce car use require further evidence, particularly on the influence of neighborhood retail areas.

[Research advance on role of Coxsackie and adenovirus receptor (CAR) in tumor progression].

PubMed

Fan, Liang-Sheng; Chen, Gang; Ma, Ding

2009-03-01

Coxsackie and adenovirus receptor (CAR) is originally identified as the cellular receptor of 2-and 5-type adenoviruses. Many researches have suggested that CAR can affect the growth, adhesive ability and cytoskeleton of tumor cells, and has complicated functions in metastasis and invasion of tumors. Moreover, the expression of CAR has close relationship with tumor prognosis and cytoreduction mediated by adenoviruses. CAR has become a new hotspot in the research on mechanism of tumor progression and gene therapy. Our review focuses on the structure and function of CAR and its role in mediating occurrence and progression of tumor.

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes.

PubMed

Kuang, Zheng; Ji, Zhicheng; Boeke, Jef D; Ji, Hongkai

2018-01-09

Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network

PubMed Central

Unnikrishnan, Ashwin; Guan, Yi F.; Huang, Yizhou; Beck, Dominik; Thoms, Julie A. I.; Peirs, Sofie; Knezevic, Kathy; Ma, Shiyong; de Walle, Inge V.; de Jong, Ineke; Ali, Zara; Zhong, Ling; Raftery, Mark J.; Taghon, Tom; Larsson, Jonas; MacKenzie, Karen L.; Van Vlierberghe, Pieter; Wong, Jason W. H.; Pimanda, John E.

2016-01-01

Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells. Using this approach, we identified a number of known binders of the +85 enhancer in leukaemic cells along with previously unknown binders, including ETV6 and IKZF1. We confirmed that ETV6 and IKZF1 were also bound at the +85 enhancer in both leukaemic cells and in healthy human CD34+ haematopoietic stem and progenitor cells. Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators not just of ERG, but also of a number of genes regulated by a densely interconnected network of seven transcription factors. At last, we show that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis. PMID:27604872

Are cars the new tobacco?

PubMed

Douglas, Margaret J; Watkins, Stephen J; Gorman, Dermot R; Higgins, Martin

2011-06-01

Public health must continually respond to new threats reflecting wider societal changes. Ecological public health recognizes the links between human health and global sustainability. We argue that these links are typified by the harms caused by dependence on private cars. We present routine data and literature on the health impacts of private car use; the activities of the 'car lobby' and factors underpinning car dependence. We compare these with experience of tobacco. Private cars cause significant health harm. The impacts include physical inactivity, obesity, death and injury from crashes, cardio-respiratory disease from air pollution, noise, community severance and climate change. The car lobby resists measures that would restrict car use, using tactics similar to the tobacco industry. Decisions about location and design of neighbourhoods have created environments that reinforce and reflect car dependence. Car ownership and use has greatly increased in recent decades and there is little public support for measures that would reduce this. Car dependence is a potent example of an issue that ecological public health should address. The public health community should advocate strongly for effective policies that reduce car use and increase active travel.

14. CAR DUMP BUILDING, SOUTHWEST CORNER, VIEW SHOWING CABLE CAR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. CAR DUMP BUILDING, SOUTHWEST CORNER, VIEW SHOWING CABLE CAR #20 BENEATH COAL CHUTES - Pennsylvania Railroad, Canton Coal Pier, Clinton Street at Keith Avenue (Canton area), Baltimore, Independent City, MD

Utility of next-generation RNA-sequencing in identifying chimeric transcription involving human endogenous retroviruses.

PubMed

Sokol, Martin; Jessen, Karen Margrethe; Pedersen, Finn Skou

2016-01-01

Several studies have shown that human endogenous retroviruses and endogenous retrovirus-like repeats (here collectively HERVs) impose direct regulation on human genes through enhancer and promoter motifs present in their long terminal repeats (LTRs). Although chimeric transcription in which novel gene isoforms containing retroviral and human sequence are transcribed from viral promoters are commonly associated with disease, regulation by HERVs is beneficial in other settings; for example, in human testis chimeric isoforms of TP63 induced by an ERV9 LTR protect the male germ line upon DNA damage by inducing apoptosis, whereas in the human globin locus the γ- and β-globin switch during normal hematopoiesis is mediated by complex interactions of an ERV9 LTR and surrounding human sequence. The advent of deep sequencing or next-generation sequencing (NGS) has revolutionized the way researchers solve important scientific questions and develop novel hypotheses in relation to human genome regulation. We recently applied next-generation paired-end RNA-sequencing (RNA-seq) together with chromatin immunoprecipitation with sequencing (ChIP-seq) to examine ERV9 chimeric transcription in human reference cell lines from Encyclopedia of DNA Elements (ENCODE). This led to the discovery of advanced regulation mechanisms by ERV9s and other HERVs across numerous human loci including transcription of large gene-unannotated genomic regions, as well as cooperative regulation by multiple HERVs and non-LTR repeats such as Alu elements. In this article, well-established examples of human gene regulation by HERVs are reviewed followed by a description of paired-end RNA-seq, and its application in identifying chimeric transcription genome-widely. Based on integrative analyses of RNA-seq and ChIP-seq, data we then present novel examples of regulation by ERV9s of tumor suppressor genes CADM2 and SEMA3A, as well as transcription of an unannotated region. Taken together, this article highlights

Car Travel-Related Thrombosis: Fact or Fiction?

PubMed

Lippi, Giuseppe; Favaloro, Emmanuel J

2018-06-01

The condition sometimes referred to as "economy class syndrome," and also known as "traveler's thrombosis," is a distinctive pathological condition characterized by occurrence of venous thromboembolism (VTE) in a patient who has recently experienced a long journey (i.e., ≥ 4 h). Typically, the identified travel is by airplane, but travel with other vehicles, such as trains, trucks, buses, or cars, could potentially qualify as contributing to VTE events. Although the enhanced risk of VTE after long haul flights is now widely acknowledged, albeit potentially overhyped, the risk of venous thrombosis after prolonged travel by other modes of transport, in particular, by cars, is less well appreciated. Current evidence, collected from some epidemiological studies, suggests that if any risk of VTE can be attributed to prolonged and uninterrupted car travels, and we give moderate credibility to such an association, the risk may be similar to that already proven for long haul flights. The risk is especially high in individuals undergoing uninterrupted car journeys lasting 4 hours or longer, in vehicles with a narrow seat-pitch, and in particularly would affect those with pre-existing acquired or inherited prothrombotic conditions. The putative biological mechanisms basically entail venous stasis and edema, which are often compounded by a certain degree of hypercoagulability. When these factors are combined with preexistent prothrombotic conditions, the risk may be substantially magnified. In this perspective, then, 'car thrombosis' may be regarded as a trigger rather than a risk factor for venous thrombosis. Although the current evidence is certainly not solid enough to endorse the use of general chemical prophylaxis for lowering the risk of car-related VTE, a set of possible precautionary measures, with no or very little side effects, may be suggested before planning prolonged car travels, especially for at risk individuals. Thieme Medical Publishers 333 Seventh Avenue

Transcriptional Network Analysis Identifies BACH1 as a Master Regulator of Breast Cancer Bone Metastasis

PubMed Central

Liang, Yajun; Wu, Heng; Lei, Rong; Chong, Robert A.; Wei, Yong; Lu, Xin; Tagkopoulos, Ilias; Kung, Sun-Yuan; Yang, Qifeng; Hu, Guohong; Kang, Yibin

2012-01-01

The application of functional genomic analysis of breast cancer metastasis has led to the identification of a growing number of organ-specific metastasis genes, which often function in concert to facilitate different steps of the metastatic cascade. However, the gene regulatory network that controls the expression of these metastasis genes remains largely unknown. Here, we demonstrate a computational approach for the deconvolution of transcriptional networks to discover master regulators of breast cancer bone metastasis. Several known regulators of breast cancer bone metastasis such as Smad4 and HIF1 were identified in our analysis. Experimental validation of the networks revealed BACH1, a basic leucine zipper transcription factor, as the common regulator of several functional metastasis genes, including MMP1 and CXCR4. Ectopic expression of BACH1 enhanced the malignance of breast cancer cells, and conversely, BACH1 knockdown significantly reduced bone metastasis. The expression of BACH1 and its target genes was linked to the higher risk of breast cancer recurrence in patients. This study established BACH1 as the master regulator of breast cancer bone metastasis and provided a paradigm to identify molecular determinants in complex pathological processes. PMID:22875853

Symmetry in the Car Park

ERIC Educational Resources Information Center

Hancock, Karen

2007-01-01

In this article, the author presents a lesson on rotational symmetry which she developed for her students. The aim of the lesson was "to identify objects with rotational symmetry in the staff car park" and the success criteria were "pictures or sketches of at least six objects with different orders of rotation". After finding examples of…

Influence of unsteady aerodynamics on driving dynamics of passenger cars

NASA Astrophysics Data System (ADS)

Huemer, Jakob; Stickel, Thomas; Sagan, Erich; Schwarz, Martin; Wall, Wolfgang A.

2014-11-01

Recent approaches towards numerical investigations with computational fluid dynamics methods on unsteady aerodynamic loads of passenger cars identified major differences compared with steady-state aerodynamic excitations. Furthermore, innovative vehicle concepts such as electric-vehicles or hybrid drives further challenge the basic layout of passenger cars. Therefore, the relevance of unsteady aerodynamic loads on cross-wind stability of changing basic vehicle architectures should be analysed. In order to assure and improve handling and ride characteristics at high velocity of the actual range of vehicle layouts, the influence of unsteady excitations on the vehicle response was investigated. For this purpose, a simulation of the vehicle dynamics through multi-body simulation was used. The impact of certain unsteady aerodynamic load characteristics on the vehicle response was quantified and key factors were identified. Through a series of driving simulator tests, the identified differences in the vehicle response were evaluated regarding their significance on the subjective driver perception of cross-wind stability. Relevant criteria for the subjective driver assessment of the vehicle response were identified. As a consequence, a design method for the basic layout of passenger cars and chassis towards unsteady aerodynamic excitations was defined.

An experimental investigation of tobacco smoke pollution in cars

PubMed Central

Sendzik, Taryn; Travers, Mark J.; Hyland, Andrew

2009-01-01

Introduction Tobacco smoke pollution (TSP) has been identified as a serious public health threat. Although the number of jurisdictions that prohibit smoking in public places has increased rapidly, just a few successful attempts have been made to pass similar laws prohibiting smoking in cars, where the cabin space may contribute to concentrated exposure. In particular, TSP constitutes a potentially serious health hazard to children because of prolonged exposure and their small size. Methods The present study investigated the levels of TSP in 18 cars via the measurement of fine respirable particles (<2.5 microns in diameter or PM2.5) under a variety of in vivo conditions. Car owners smoked a single cigarette in their cars in each of five controlled air-sampling conditions. Each condition varied on movement of the car, presence of air conditioning, open windows, and combinations of these airflow influences. Results Smoking just a single cigarette in a car generated extremely high average levels of PM2.5: more than 3,800 μg/m3 in the condition with the least airflow (motionless car, windows closed). In moderate ventilation conditions (air conditioning or having the smoking driver hold the cigarette next to a half-open window), the average levels of PM2.5 were reduced but still at significantly high levels (air conditioning = 844 μg/m3; holding cigarette next to a half-open window = 223 μg/m3). Discussion This study demonstrates that TSP in cars reaches unhealthy levels, even under realistic ventilation conditions, lending support to efforts occurring across a growing number of jurisdictions to educate people and prohibit smoking in cars in the presence of children. PMID:19351785

An experimental investigation of tobacco smoke pollution in cars.

PubMed

Sendzik, Taryn; Fong, Geoffrey T; Travers, Mark J; Hyland, Andrew

2009-06-01

Tobacco smoke pollution (TSP) has been identified as a serious public health threat. Although the number of jurisdictions that prohibit smoking in public places has increased rapidly, just a few successful attempts have been made to pass similar laws prohibiting smoking in cars, where the cabin space may contribute to concentrated exposure. In particular, TSP constitutes a potentially serious health hazard to children because of prolonged exposure and their small size. The present study investigated the levels of TSP in 18 cars via the measurement of fine respirable particles (<2.5 microns in diameter or PM(2.5)) under a variety of in vivo conditions. Car owners smoked a single cigarette in their cars in each of five controlled air-sampling conditions. Each condition varied on movement of the car, presence of air conditioning, open windows, and combinations of these airflow influences. Smoking just a single cigarette in a car generated extremely high average levels of PM(2.5): more than 3,800 microg/m3 in the condition with the least airflow (motionless car, windows closed). In moderate ventilation conditions (air conditioning or having the smoking driver hold the cigarette next to a half-open window), the average levels of PM(2.5) were reduced but still at significantly high levels (air conditioning = 844 microg/m3; holding cigarette next to a half-open window = 223 microg/m3). This study demonstrates that TSP in cars reaches unhealthy levels, even under realistic ventilation conditions, lending support to efforts occurring across a growing number of jurisdictions to educate people and prohibit smoking in cars in the presence of children.

Feasibility of controlling CD38-CAR T cell activity with a Tet-on inducible CAR design

PubMed Central

Poels, Renée; Mulders, Manon J.; van de Donk, Niels W. C. J.; Themeli, Maria; Lokhorst, Henk M.; Mutis, Tuna

2018-01-01

Recent clinical advances with chimeric antigen receptor (CAR) T cells have led to the accelerated clinical approval of CD19-CARs to treat acute lymphoblastic leukemia. The CAR T cell therapy is nevertheless associated with toxicities, especially if the CARs are not entirely tumor-specific. Therefore, strategies for controlling the CAR T cell activity are required to improve their safety profile. Here, by using the multiple myeloma (MM)-associated CD38 molecule as target molecule, we tested the feasibility and utility of a doxycycline (DOX) inducible Tet-on CD38-CAR design to control the off-target toxicities of CAR T cells. Using CARs with high affinity to CD38, we demonstrate that this strategy allows the proper induction of CD38-CARs and CAR-mediated T cell cytotoxicity in a DOX-dose dependent manner. Especially when the DOX dose was limited to 10ng/ml, its removal resulted in a relatively rapid decay of CAR- related off-tumor effects within 24 hours, indicating the active controllability of undesired CAR activity. This Tet-on CAR design also allowed us to induce the maximal anti-MM cytotoxic activity of affinity-optimized CD38-CAR T cells, which already display a low toxicity profile, hereby adding a second level of safety to these cells. Collectively, these results indicate the possibility to utilize this DOX inducible CAR-design to actively regulate the CAR-mediated activities of therapeutic T cells. We therefore conclude that the Tet-on system may be more advantageous above suicide-genes to control the potential toxicities of CAR T cells without the need to destroy them permanently. PMID:29847570

49 CFR 173.314 - Compressed gases in tank cars and multi-unit tank cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Compressed gases in tank cars and multi-unit tank cars. 173.314 Section 173.314 Transportation Other Regulations Relating to Transportation PIPELINE AND... Compressed gases in tank cars and multi-unit tank cars. (a) Definitions. For definitions of compressed gases...

49 CFR 173.314 - Compressed gases in tank cars and multi-unit tank cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Compressed gases in tank cars and multi-unit tank cars. 173.314 Section 173.314 Transportation Other Regulations Relating to Transportation PIPELINE AND... Compressed gases in tank cars and multi-unit tank cars. (a) Definitions. For definitions of compressed gases...

Chromatin Accessibility Mapping Identifies Mediators of Basal Transcription and Retinoid-Induced Repression of OTX2 in Medulloblastoma

PubMed Central

Zhang, Monica; Song, Lingyun; Lee, Bum-Kyu; Iyer, Vishwanath R.; Furey, Terrence S.; Crawford, Gregory E.; Yan, Hai; He, Yiping

2014-01-01

Despite an emerging understanding of the genetic alterations giving rise to various tumors, the mechanisms whereby most oncogenes are overexpressed remain unclear. Here we have utilized an integrated approach of genomewide regulatory element mapping via DNase-seq followed by conventional reporter assays and transcription factor binding site discovery to characterize the transcriptional regulation of the medulloblastoma oncogene Orthodenticle Homeobox 2 (OTX2). Through these studies we have revealed that OTX2 is differentially regulated in medulloblastoma at the level of chromatin accessibility, which is in part mediated by DNA methylation. In cell lines exhibiting chromatin accessibility of OTX2 regulatory regions, we found that autoregulation maintains OTX2 expression. Comparison of medulloblastoma regulatory elements with those of the developing brain reveals that these tumors engage a developmental regulatory program to drive OTX2 transcription. Finally, we have identified a transcriptional regulatory element mediating retinoid-induced OTX2 repression in these tumors. This work characterizes for the first time the mechanisms of OTX2 overexpression in medulloblastoma. Furthermore, this study establishes proof of principle for applying ENCODE datasets towards the characterization of upstream trans-acting factors mediating expression of individual genes. PMID:25198066

Selective imaging of saturated and unsaturated lipids by wide-field CARS-microscopy.

PubMed

Heinrich, Christoph; Hofer, Alexander; Ritsch, Andreas; Ciardi, Christian; Bernet, Stefan; Ritsch-Marte, Monika

2008-02-18

Wide-field Coherent Anti-Stokes Raman Scattering (CARS) microscopy is employed to identify saturated and unsaturated fatty acids in micro-emulsions and cells, using the ratio between the strong -C-H CARS signal at 2850 cm(-1) and the weak signal of the =C-H vibration around 3015 cm(-1) for distinction. Quantitative CARS imaging at the =C-H resonance is challenging, since it yields only a low CARS signal, and small differences on the order of 5% in the concentration of polyunsaturated fatty lipids have to be detected. For this purpose we draw advantage of the high signal-to-noise ratio of wide-field CARS microscopy that is achieved by an excitation geometry involving a "sheet-of-light"-type illumination.

CARS hyperspectral imaging of cartilage aiming for state discrimination of cell

NASA Astrophysics Data System (ADS)

Shiozawa, Manabu; Shirai, Masataka; Izumisawa, Junko; Tanabe, Maiko; Watanabe, Koichi

2016-03-01

Non-invasive cell analyses are increasingly important for medical field. A CARS microscope is one of the non-invasive imaging equipments and enables to obtain images indicating molecular distribution. Some studies on discrimination of cell state by using CARS images of lipid are reported. However, due to low signal intensity, it is still challenging to obtain images of the fingerprint region (800~1800 cm-1), in which many spectrum peaks correspond to compositions of a cell. Here, to identify cell differentiation by using multiplex CARS, we investigated hyperspectral imaging of fingerprint region of living cells. To perform multiplex CARS, we used a prototype of a compact light source, which consists of a microchip laser, a single-mode fiber, and a photonic crystal fiber to generate supercontinuum light. Assuming application to regenerative medicine, we chose a cartilage cell, whose differentiation is difficult to be identified by change of the cell morphology. Because one of the major components of cartilage is collagen, we focused on distribution of proline, which accounts for approximately 20% of collagen in general. The spectrum quality was improved by optical adjustments about power branching ratio and divergence of broadband Stokes light. Hyperspectral images were successfully obtained by the improvement. Periphery of a cartilage cell was highlighted in CARS image of proline, and this result suggests correspondence with collagen generated as extracellular matrix. A possibility of cell analyses by using CARS hyperspectral imaging was indicated.

Chem-E-Car Downunder.

ERIC Educational Resources Information Center

Rhodes, Martin

2002-01-01

Presents the Chem-E-Car competition in which students build a small car powered by a chemical reaction. Focuses on a controlled chemical reaction in which the car travels a required specific distance and stops. Requires participants to prepare poster presentations. (YDS)

Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

PubMed Central

Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C.; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J.; Hill, D. Ashley; Pomeroy, Scott L.; Eberhart, Charles G.; Dunn, Ian F.; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A.; Santagata, Sandro; Hahn, William C.; Stiles, Charles D.; Ligon, Azra H.; Kieran, Mark W.; Beroukhim, Rameen; Ligon, Keith L.

2013-01-01

Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. PMID:23633565

Design of an intelligent car

NASA Astrophysics Data System (ADS)

Na, Yongyi

2017-03-01

The design of simple intelligent car, using AT89S52 single chip microcomputer as the car detection and control core; The metal sensor TL - Q5MC induction to iron, to detect the way to send feedback to the signal of single chip microcomputer, make SCM according to the scheduled work mode to control the car in the area according to the predetermined speed, and the operation mode of the microcontroller choose different also can control the car driving along s-shaped iron; Use A44E hall element to detect the car speeds; Adopts 1602 LCD display time of car driving, driving the car to stop, take turns to show the car driving time, distance, average speed and the speed of time. This design has simple structure and is easy to implement, but are highly intelligent, humane, to a certain extent reflects the intelligence.

Shuttle car loading system

NASA Technical Reports Server (NTRS)

Collins, E. R., Jr. (Inventor)

1985-01-01

A system is described for loading newly mined material such as coal, into a shuttle car, at a location near the mine face where there is only a limited height available for a loading system. The system includes a storage bin having several telescoping bin sections and a shuttle car having a bottom wall that can move under the bin. With the bin in an extended position and filled with coal the bin sections can be telescoped to allow the coal to drop out of the bin sections and into the shuttle car, to quickly load the car. The bin sections can then be extended, so they can be slowly filled with more while waiting another shuttle car.

Phenobarbital Mediates an Epigenetic Switch at the Constitutive Androstane Receptor (CAR) Target Gene Cyp2b10 in the Liver of B6C3F1 Mice

PubMed Central

Brasa, Sarah; Teo, Soon-Siong; Roloff, Tim-Christoph; Morawiec, Laurent; Zamurovic, Natasa; Vicart, Axel; Funhoff, Enrico; Couttet, Philippe; Schübeler, Dirk; Grenet, Olivier; Marlowe, Jennifer; Moggs, Jonathan; Terranova, Rémi

2011-01-01

Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis. PMID:21455306

Phenobarbital mediates an epigenetic switch at the constitutive androstane receptor (CAR) target gene Cyp2b10 in the liver of B6C3F1 mice.

PubMed

Lempiäinen, Harri; Müller, Arne; Brasa, Sarah; Teo, Soon-Siong; Roloff, Tim-Christoph; Morawiec, Laurent; Zamurovic, Natasa; Vicart, Axel; Funhoff, Enrico; Couttet, Philippe; Schübeler, Dirk; Grenet, Olivier; Marlowe, Jennifer; Moggs, Jonathan; Terranova, Rémi

2011-03-24

Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.

Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target

PubMed Central

Watanabe, Hideo; Francis, Joshua M.; Woo, Michele S.; Etemad, Banafsheh; Lin, Wenchu; Fries, Daniel F.; Peng, Shouyong; Snyder, Eric L.; Tata, Purushothama Rao; Izzo, Francesca; Schinzel, Anna C.; Cho, Jeonghee; Hammerman, Peter S.; Verhaak, Roel G.; Hahn, William C.; Rajagopal, Jayaraj; Jacks, Tyler; Meyerson, Matthew

2013-01-01

The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To study the transcriptional impact of NKX2-1 amplification, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma and analyzed DNA-binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation. Integration of these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1. Further cistromic and overexpression analyses indicated that NKX2-1 can cooperate with the forkhead box transcription factor FOXA1 to regulate LMO3 gene expression. RNAi analysis of NKX2-1-amplified cells compared with nonamplified cells demonstrated that LMO3 mediates cell survival downstream from NKX2-1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transcriptional signal transducer in NKX2-1-amplified lung adenocarcinomas. PMID:23322301

Why we love or hate our cars: A qualitative approach to the development of a quantitative user experience survey.

PubMed

Tonetto, Leandro Miletto; Desmet, Pieter M A

2016-09-01

This paper presents a more ecologically valid way of developing theory-based item questionnaires for measuring user experience. In this novel approach, items were generated using natural and domain-specific language of the research population, what seems to have made the survey much more sensitive to real experiences than theory-based ones. The approach was applied in a survey that measured car experience. Ten in-depth interviews were conducted with drivers inside their cars. The resulting transcripts were analysed with the aim of capturing their natural utterances for expressing their car experience. This analysis resulted in 71 categories of answers. For each category, one sentence was selected to serve as a survey-item. In an online platform, 538 respondents answered the survey. Data reliability, tested with Cronbach alpha index, was 0.94, suggesting a survey with highly reliable results to measure drivers' appraisals of their cars. Copyright © 2016 Elsevier Ltd. All rights reserved.

TSSer: an automated method to identify transcription start sites in prokaryotic genomes from differential RNA sequencing data.

PubMed

Jorjani, Hadi; Zavolan, Mihaela

2014-04-01

Accurate identification of transcription start sites (TSSs) is an essential step in the analysis of transcription regulatory networks. In higher eukaryotes, the capped analysis of gene expression technology enabled comprehensive annotation of TSSs in genomes such as those of mice and humans. In bacteria, an equivalent approach, termed differential RNA sequencing (dRNA-seq), has recently been proposed, but the application of this approach to a large number of genomes is hindered by the paucity of computational analysis methods. With few exceptions, when the method has been used, annotation of TSSs has been largely done manually. In this work, we present a computational method called 'TSSer' that enables the automatic inference of TSSs from dRNA-seq data. The method rests on a probabilistic framework for identifying both genomic positions that are preferentially enriched in the dRNA-seq data as well as preferentially captured relative to neighboring genomic regions. Evaluating our approach for TSS calling on several publicly available datasets, we find that TSSer achieves high consistency with the curated lists of annotated TSSs, but identifies many additional TSSs. Therefore, TSSer can accelerate genome-wide identification of TSSs in bacterial genomes and can aid in further characterization of bacterial transcription regulatory networks. TSSer is freely available under GPL license at http://www.clipz.unibas.ch/TSSer/index.php

MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

2004-10-28

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

49 CFR 1037.2 - Cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars. [57 FR 54334, Nov. 18, 1992] ...

49 CFR 1037.2 - Cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars. [57 FR 54334, Nov. 18, 1992] ...

49 CFR 1037.2 - Cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars. [57 FR 54334, Nov. 18, 1992] ...

49 CFR 1037.2 - Cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars. [57 FR 54334, Nov. 18, 1992] ...

49 CFR 1037.2 - Cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars. [57 FR 54334, Nov. 18, 1992] ...

enviroCar - citizen science for sustainable traffic

NASA Astrophysics Data System (ADS)

Stasch, Christoph; Remke, Albert; Jirka, Simon; Nuest, Daniel

2015-04-01

-temporal analyses by themselves. Thus, the platform also provides a means to analyze issues, such as repeated stops at a particular traffic light, and to communicate the results to other stakeholders, e.g. traffic planners or politicians. For traffic planners, the enviroCar project can also serve as a valuable additional data source for evaluating certain decisions, e.g. changing traffic light sequences. As not only the pure GPS data but also the car sensor data is collected, enviroCar enables to directly relate the traffic data to environmental parameters such as air pollutant emissions and thus to identify, for example, hotspots of CO2 emissions in a street network. Current research activities comprise technical issues, such as implementing scalable solutions for visualizing and analyzing big data sets, on improving estimation methods for fuel consumption and air pollutant emissions, but also include the development of novel spatio-temporal analysis and visualization methods and novel incentives for participation in crowd-sourcing and analyzing geospatial information.

Car seat safety: literature review.

PubMed

Lincoln, Michelle

2005-01-01

After staggering numbers of infants were killed in automotive crashes in the 1970s, the American Academy of Pediatrics (AAP) recommended in 1974 universal use of car seats for all infants. However, positional problems were reported when car seats are used with premature infants less than 37 weeks gestational age as a result of head slouching and its sequelae. In 1990, the AAP responded with another policy statement introducing car seat testing. It recommended that any infant at or under 37 weeks gestational age be observed in a car seat prior to discharge from the hospital. The AAP did not give specific guidelines on type of car seat, length of testing, equipment, or personnel proficiency, however. Few nurseries have standard policies to evaluate car seats, to teach parents about car seats, or to position newborns in them, and not all hospitals actually conduct car seat challenges or have common standards for testing that is performed.

Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients.

PubMed

Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan; Mora-Jensen, Helena; Krogh, Anders; Kohlmann, Alexander; Thiede, Christian; Borregaard, Niels; Bullinger, Lars; Winther, Ole; Theilgaard-Mönch, Kim; Porse, Bo T

2014-02-06

Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.

Physics in a Bouncing Car.

ERIC Educational Resources Information Center

Bartlett, Albert A.

1984-01-01

Defines frame of reference for the analysis of motion in a moving car, discussing the interaction of the car body, the seat springs, and the passenger when the car goes over a bump. Provides a related, but more advanced, problem with the motion of cars involving angular acceleration. (JM)

Perceptual aspects of reproduced sound in car cabin acoustics.

PubMed

Kaplanis, Neofytos; Bech, Søren; Tervo, Sakari; Pätynen, Jukka; Lokki, Tapio; van Waterschoot, Toon; Jensen, Søren Holdt

2017-03-01

An experiment was conducted to determine the perceptual effects of car cabin acoustics on the reproduced sound field. In-car measurements were conducted whilst the cabin's interior was physically modified. The captured sound fields were recreated in the laboratory using a three-dimensional loudspeaker array. A panel of expert assessors followed a rapid sensory analysis protocol, the flash profile, to perceptually characterize and evaluate 12 acoustical conditions of the car cabin using individually elicited attributes. A multivariate analysis revealed the panel's consensus and the identified perceptual constructs. Six perceptual constructs characterize the differences between the acoustical conditions of the cabin, related to bass, ambience, transparency, width and envelopment, brightness, and image focus. The current results indicate the importance of several acoustical properties of a car's interior on the perceived sound qualities. Moreover, they signify the capacity of the applied methodology in assessing spectral and spatial properties of automotive environments in laboratory settings using a time-efficient and flexible protocol.

Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

PubMed Central

2011-01-01

Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

Gasoline-powered series hybrid cars cause lower life cycle carbon emissions than battery cars

NASA Astrophysics Data System (ADS)

Meinrenken, Christoph; Lackner, Klaus S.

2012-02-01

Battery cars powered by grid electricity promise reduced life cycle green house gas (GHG) emissions from the automotive sector. Such scenarios usually point to the much higher emissions from conventional, internal combustion engine cars. However, today's commercially available series hybrid technology achieves the well known efficiency gains in electric drivetrains (regenerative breaking, lack of gearbox) even if the electricity is generated onboard, from conventional fuels. Here, we analyze life cycle GHG emissions for commercially available, state-of the-art plug-in battery cars (e.g. Nissan Leaf) and those of commercially available series hybrid cars (e.g., GM Volt, at same size and performance). Crucially, we find that series hybrid cars driven on (fossil) gasoline cause fewer emissions (126g CO2eq per km) than battery cars driven on current US grid electricity (142g CO2eq per km). We attribute this novel finding to the significant incremental emissions from plug-in battery cars due to losses during grid transmission and battery dis-/charging, and manufacturing larger batteries. We discuss crucial implications for strategic policy decisions towards a low carbon automotive sector as well as relative land intensity when powering cars by biofuel vs. bioelectricity.

Gasoline-powered serial hybrid cars cause lower life cycle carbon emissions than battery cars

NASA Astrophysics Data System (ADS)

Meinrenken, Christoph J.; Lackner, Klaus S.

2011-04-01

Battery cars powered by grid electricity promise reduced life cycle green house gas (GHG) emissions from the automotive sector. Such scenarios usually point to the much higher emissions from conventional, internal combustion engine cars. However, today's commercially available serial hybrid technology achieves the well known efficiency gains from regenerative breaking, lack of gearbox, and light weighting - even if the electricity is generated onboard, from conventional fuels. Here, we analyze emissions for commercially available, state-of the-art battery cars (e.g. Nissan Leaf) and those of commercially available serial hybrid cars (e.g., GM Volt, at same size and performance). Crucially, we find that serial hybrid cars driven on (fossil) gasoline cause fewer life cycle GHG emissions (126g CO2e per km) than battery cars driven on current US grid electricity (142g CO2e per km). We attribute this novel finding to the significant incremental life cycle emissions from battery cars from losses during grid transmission, battery dis-/charging, and larger batteries. We discuss crucial implications for strategic policy decisions towards a low carbon automotive sector as well as relative land intensity when powering cars by biofuel vs. bioelectricity.

Increase of child car seat temperature in cars parked in the outpatient parking lot.

PubMed

Sugimura, Tetsu; Suzue, Junji; Kamada, Makoto; Ozaki, Yukiko; Tananari, Yoshifumi; Maeno, Yasuki; Ito, Shinichi; Nishino, Hiroshi; Kakimoto, Noriko; Yamakawa, Rumi

2011-12-01

A guideline for the safe use of child car seats (CS) was published by the Japan Pediatric Society in 2008. There have been few studies of the increase of temperature of a CS in parked cars. The aim of this study was to determine the change in the temperature of the CS in cars parked in full sun. The temperature of CS was measured during summer (July and August) in 2006, 2007, and 2008. The CS used in this study (n= 50) were for children (≤ 6 years old) who were taken by car to Sugimura Children's Medical Clinic. Temperatures were only measured on sunny days. Measurements were performed from 09.00 to 17.00 hours. Thermochron (Thermochron i-Button: G type, Maxim Integrated Products, CA, USA) was used to measure the temperatures. The maximum temperatures of CS were compared in time at the clinic, taking into consideration seat colors, and car colors. Of the 50 cars, three cars were excluded due to being in the shade while the temperature was measured. A total of 47 cars were used for this study. The temperature of the CS ranged from 38.0 to 65.5°C (47.8 ± 5.8°C). Eighteen CS (38.3%) reached a temperature of 50°C or above. The maximum temperature of the 13.00-15.00-hours group was significantly higher than that of the 09.00-11.00-hours group (P= 0.035). The CS temperatures in the black car group were significantly higher than those of the white car group (P= 0.013). CS may become very hot while a car is parked in sun, especially if the car and the CS are black, so the CS should be cooled before a young child is placed in it. Guardians of small children should be aware of this risk. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Development and Evaluation of an Optimal Human Single-Chain Variable Fragment-Derived BCMA-Targeted CAR T Cell Vector.

PubMed

Smith, Eric L; Staehr, Mette; Masakayan, Reed; Tatake, Ishan J; Purdon, Terence J; Wang, Xiuyan; Wang, Pei; Liu, Hong; Xu, Yiyang; Garrett-Thomson, Sarah C; Almo, Steven C; Riviere, Isabelle; Liu, Cheng; Brentjens, Renier J

2018-06-06

B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered. Despite a narrow range of affinity for BCMA, dramatic differences in CAR T cell expansion were observed between unique scFvs in a repeat antigen stimulation assay. These results were confirmed by screening in a MM xenograft model, where only the top preforming CARs from the repeat antigen stimulation assay eradicated disease and prolonged survival. The results of this screening identified a highly effective CAR T cell therapy with properties, including rapid in vivo expansion (>10,000-fold, day 6), eradication of large tumor burden, and durable protection to tumor re-challenge. We generated a bicistronic construct including a second-generation CAR and a truncated-epithelial growth factor receptor marker. CAR T cell vectors stemming from this work are under clinical investigation. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription*

PubMed Central

Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Lee, Jinhee; Wright, Michael E.

2016-01-01

Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the “AR-interactome.” Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR). A bioanalytical workflow involving streptavidin chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive cytosolic proteins/protein complexes linked to AR activation in prostate tumor cells. Functional studies verified that ligand-sensitive proteins identified in the proteomic screen encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive coatomer protein complex I (COPI) retrograde trafficking complex in vitro. Extensive biochemical and molecular experiments showed that the COPI retrograde complex regulates ligand-mediated AR transcriptional activation, which correlated with the mobilization of the Golgi-localized ARA160 coactivator to the nuclear compartment of prostate tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR

The transcriptional terminator sequences downstream of the covR gene terminate covR/S operon transcription to generate covR monocistronic transcripts in Streptococcus pyogenes.

PubMed

Chiang-Ni, Chuan; Tsou, Chih-Cheng; Lin, Yee-Shin; Chuang, Woei-Jer; Lin, Ming-T; Liu, Ching-Chuan; Wu, Jiunn-Jong

2008-12-31

CovR/S is an important two component regulatory system, which regulates about 15% of the gene expression in Streptococcus pyogenes. The covR/S locus was identified as an operon generating an RNA transcript around 2.5-kb in size. In this study, we found the covR/S operon produced three RNA transcripts (around 2.5-, 1.0-, and 0.8-kb in size). Using RNA transcriptional terminator sequence prediction and transcriptional terminator analysis, we identified two atypical rho-independent terminator sequences downstream of the covR gene and showed these terminator sequences terminate RNA transcription efficiently. These results indicate that covR/S operon generates covR/S transcript and monocistronic covR transcripts.

54. VAL COUNTERWEIGHT CAR DURING CONSTRUCTION SHOWING CAR FRAME, WHEEL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

54. VAL COUNTERWEIGHT CAR DURING CONSTRUCTION SHOWING CAR FRAME, WHEEL ASSEMBLIES AND METAL REINFORCING, December 19, 1947. (Original photograph in possession of Dave Willis, San Diego, California.) - Variable Angle Launcher Complex, Variable Angle Launcher, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ErbB receptors in breast cancer cells.

PubMed

Mina, Marco; Magi, Shigeyuki; Jurman, Giuseppe; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Arner, Erik; Forrest, Alistair R R; Carninci, Piero; Hayashizaki, Yoshihide; Daub, Carsten O; Okada-Hatakeyama, Mariko; Furlanello, Cesare

2015-07-16

The analysis of CAGE (Cap Analysis of Gene Expression) time-course has been proposed by the FANTOM5 Consortium to extend the understanding of the sequence of events facilitating cell state transition at the level of promoter regulation. To identify the most prominent transcriptional regulations induced by growth factors in human breast cancer, we apply here the Complexity Invariant Dynamic Time Warping motif EnRichment (CIDER) analysis approach to the CAGE time-course datasets of MCF-7 cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). We identify a multi-level cascade of regulations rooted by the Serum Response Factor (SRF) transcription factor, connecting the MAPK-mediated transduction of the HRG stimulus to the negative regulation of the MAPK pathway by the members of the DUSP family phosphatases. The finding confirms the known primary role of FOS and FOSL1, members of AP-1 family, in shaping gene expression in response to HRG induction. Moreover, we identify a new potential regulation of DUSP5 and RARA (known to antagonize the transcriptional regulation induced by the estrogen receptors) by the activity of the AP-1 complex, specific to HRG response. The results indicate that a divergence in AP-1 regulation determines cellular changes of breast cancer cells stimulated by ErbB receptors.

Cars, Cycles, and Consumers.

ERIC Educational Resources Information Center

Idleman, Hillis K. Ed.

The purpose of this consumer education module is to provide information and skills, and the ability to raise questions and find answers, while seeking the best automobile or motorcycle buy available for the money. The module may be used for a full or part semester course. The five sections (cars and the consumer, renting and leasing cars, cars and…

New developments in clinical CARS

NASA Astrophysics Data System (ADS)

Weinigel, Martin; Breunig, Hans Georg; Kellner-Höfer, Marcel; Bückle, Rainer; Darvin, Maxim; Lademann, Juergen; König, Karsten

2013-02-01

We combined two-photon fluorescence and coherent anti-Stokes Raman scattering (CARS) imaging in a clinical hybrid multiphoton tomograph for in vivo imaging of human skin. The clinically approved TPEF/CARS system provides simultaneous imaging of endogenous fluorophores and non-fluorescent lipids. The Stokes laser for the two-beam configuration of CARS is based on spectral broadening of femtosecond laser pulses in a photonic crystal fiber (PCF). We report on the highly flexible medical TPEF/CARS tomograph MPTflex®-CARS with an articulated arm and first in vivo measurements on human skin.

Clinical multiphoton and CARS microscopy

NASA Astrophysics Data System (ADS)

Breunig, H. G.; Weinigel, M.; Darvin, M. E.; Lademann, J.; König, K.

2012-03-01

We report on clinical CARS imaging of human skin in vivo with the certified hybrid multiphoton tomograph CARSDermaInspect. The CARS-DermaInspect provides simultaneous imaging of non-fluorescent intradermal lipid and water as well as imaging of two-photon excited fluorescence from intrinsic molecules. Two different excitation schemes for CARS imaging have been realized: In the first setup, a combination of fs oscillator and optical parametric oscillator provided fs-CARS pump and Stokes pulses, respectively. In the second setup a fs oscillator was combined with a photonic crystal fiber which provided a broadband spectrum. A spectral range out of the broadband-spectrum was selected and used for CARS excitation in combination with the residual fs-oscillator output. In both setups, in addition to CARS, single-beam excitation was used for imaging of two-photon excited fluorescence and second harmonic generation signals. Both CARS-excitation systems were successfully used for imaging of lipids inside the skin in vivo.

Scrap car recycling in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, C.H.; Tai, H.S.; Fan, R.K.S.

1997-12-31

The official figure of registered automobiles released by the Ministry of Transportation of Taiwan, R.O.C. as of the end of April 1996, is approximately 4.8 millions. Among them, 18% of the cars are between seven and ten years old and 15% of the cars are old than ten years. The result of this large number of old cars is the problem of abandoned cars on the street of Taiwan. This phenomena not only hinders traffic flow but also undermines the living quality in the cities. To minimize these negative effects, EPA has promulgated a Scrap Motor Vehicles Management Regulation tomore » enforce the scrap car recycling in Taiwan. Under this regulation, a buyer of a new vehicle has to pay the Scrap Motor Vehicle Disposal fee (NT$ 3000, or US$ 110 for a car; and NT$ 700, or US$ 25 for a motorcycle). This paper presents the current status of scrap car recycling in Taiwan.« less

Risks of pedestrian serious injuries and fatalities associated with impact velocities of cars in car-versus-pedestrian accidents in Japan.

PubMed

Matsui, Yasuhiro; Oikawa, Shoko; Ando, Kenichi

2013-11-01

The first purpose of this study is to clarify the relation between the car impact velocity and pedestrian injury severity or mortality risk. We investigated the frequency of serious injuries and fatalities of pedestrians using vehicle-pedestrian accident data from the database of the Institute for Traffic Accident Research and Data Analysis (ITARDA) in Japan. The vehicle types considered are sedans, minivans, and box vans (ordinary automobiles) and light passenger cars and light cargo vans (light automobiles). The results revealed that a 10-km/h reduction in impact velocity could mitigate severe pedestrian injuries in cases involving impact velocities of 40 km/h or more for the five vehicle types analyzed. Specifically, if the impact velocity was 30 km/h or less, the frequency of serious injuries was less than 27% and the frequency of fatalities was less than 5% for the five vehicle types. Therefore, if the collision damage mitigation braking system (CDMBS) that uses a sensor to detect pedestrians can effectively reduce the impact velocity for various vehicle types, pedestrian injuries will be greatly mitigated. The second purpose of this study is to identify the factors that affect injury risk. Impact experiments were conducted in which a sedan impacted against a pedestrian full-scale dummy at 40 km/h and a pedestrian headform impactor was impacted against a road surface. The results indicated that the risk of pedestrian serious injury was significantly affected by multiple impact conditions, such as the pedestrian height, car impact velocity, car frontal shape, and car stiffness in cases where the car impacted the pedestrian's head, the degrees of influence of which were driven by the vehicle impact velocity.

Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smetanina, Mariya A., E-mail: maria.smetanina@gmail.com; Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090; Group of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 8, Novosibirsk 630090

2'-3-dimethyl-4-aminoazobenzene (ortho-aminoazotoluene, OAT) is an azo dye and a rodent carcinogen that has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen. Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT. We found that OAT increases mouse CAR (mCAR) transactivation in a dose-dependent manner. This effect is specific because another closely related azo dye, 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB), did not activate mCAR. Real-time Q-PCR analysis in wild-type C57BL/6 mice revealed that OAT induces the hepaticmore » mRNA expression of the following CAR target genes: Cyp2b10, Cyp2c29, Cyp3a11, Ugt1a1, Mrp4, Mrp2 and c-Myc. CAR-null (Car{sup -/-}) mice showed no increased expression of these genes following OAT treatment, demonstrating that CAR is required for their OAT dependent induction. The OAT-induced CAR-dependent increase of Cyp2b10 and c-Myc expression was confirmed by Western blotting. Immunohistochemistry analysis of wild-type and Car{sup -/-} livers showed that OAT did not acutely induce hepatocyte proliferation, but at much later time points showed an unexpected CAR-dependent proliferative response. These studies demonstrate that mCAR is an OAT xenosensor, and indicate that at least some of the biological effects of this compound are mediated by this nuclear receptor. - Highlights: > The azo dye and mouse carcinogen OAT is a very effective mCAR activator. > OAT increases mCAR transactivation in a dose-dependent manner. > OAT CAR-dependently increases the expression of a specific subset of CAR target genes. > OAT induces an unexpectedly deferred, but CAR-dependent hepatocyte proliferation.« less

Crash protection of stock car racing drivers--application of biomechanical analysis of Indy car crash research.

PubMed

Melvin, John W; Begeman, Paul C; Faller, Ronald K; Sicking, Dean L; McClellan, Scott B; Maynard, Edwin; Donegan, Michael W; Mallott, Annette M; Gideon, Thomas W

2006-11-01

Biomechanical analysis of Indy car crashes using on-board impact recorders (Melvin et al. 1998, Melvin et al. 2001) indicates that Indy car driver protection in high-energy crashes can be achieved in frontal, side, and rear crashes with severities in the range of 100 to 135 G peak deceleration and velocity changes in the range of 50 to 70 mph. These crashes were predominantly single-car impacts with the rigid concrete walls of oval tracks. This impressive level of protection was found to be due to the unique combination of a very supportive and tight-fitting cockpit-seating package, a six-point belt restraint system, and effective head padding with an extremely strong chassis that defines the seat and cockpit of a modern Indy car. In 2000 and 2001, a series of fatal crashes in stock car racing created great concern for improving the crash protection for drivers in those racecars. Unlike the Indy car, the typical racing stock car features a more spacious driver cockpit due to its resemblance to the shape of a passenger car. The typical racing seat used in stock cars did not have the same configuration or support characteristics of the Indy car seat, and five-point belt restraints were used. The tubular steel space frame chassis of a stock car also differs from an Indy car's composite chassis structure in both form and mechanical behavior. This paper describes the application of results of the biomechanical analysis of the Indy car crash studies to the unique requirements of stock car racing driver crash protection. Sled test and full-scale crash test data using both Hybrid III frontal crash anthropomorphic test devices (ATDs) and BioSID side crash ATDs for the purpose of evaluating countermeasures involving restraint systems, seats and head/neck restraints has been instrumental in guiding these developments. In addition, the development of deformable walls for oval tracks (the SAFER Barrier) is described as an adjunct to improved occupant restraint through control

Carboxylic acid reductase enzymes (CARs).

PubMed

Winkler, Margit

2018-04-01

Carboxylate reductases (CARs) are emerging as valuable catalysts for the selective one-step reduction of carboxylic acids to their corresponding aldehydes. The substrate scope of CARs is exceptionally broad and offers potential for their application in diverse synthetic processes. Two major fields of application are the preparation of aldehydes as end products for the flavor and fragrance sector and the integration of CARs in cascade reactions with aldehydes as the key intermediates. The latest applications of CARs are dominated by in vivo cascades and chemo-enzymatic reaction sequences. The challenge to fully exploit product selectivity is discussed. Recent developments in the characterization of CARs are summarized, with a focus on aspects related to the domain architecture and protein sequences of CAR enzymes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying the candidate genes involved in the calyx abscission process of 'Kuerlexiangli' (Pyrus sinkiangensis Yu) by digital transcript abundance measurements.

PubMed

Qi, Xiaoxiao; Wu, Jun; Wang, Lifen; Li, Leiting; Cao, Yufen; Tian, Luming; Dong, Xingguang; Zhang, Shaoling

2013-10-23

'Kuerlexiangli' (Pyrus sinkiangensis Yu), a native pear of Xinjiang, China, is an important agricultural fruit and primary export to the international market. However, fruit with persistent calyxes affect fruit shape and quality. Although several studies have looked into the physiological aspects of the calyx abscission process, the underlying molecular mechanisms remain unknown. In order to better understand the molecular basis of the process of calyx abscission, materials at three critical stages of regulation, with 6000 × Flusilazole plus 300 × PBO treatment (calyx abscising treatment) and 50 mg.L-1GA3 treatment (calyx persisting treatment), were collected and cDNA fragments were sequenced using digital transcript abundance measurements to identify candidate genes. Digital transcript abundance measurements was performed using high-throughput Illumina GAII sequencing on seven samples that were collected at three important stages of the calyx abscission process with chemical agent treatments promoting calyx abscission and persistence. Altogether more than 251,123,845 high quality reads were obtained with approximately 8.0 M raw data for each library. The values of 69.85%-71.90% of clean data in the digital transcript abundance measurements could be mapped to the pear genome database. There were 12,054 differentially expressed genes having Gene Ontology (GO) terms and associating with 251 Kyoto Encyclopedia of Genes and Genomes (KEGG) defined pathways. The differentially expressed genes correlated with calyx abscission were mainly involved in photosynthesis, plant hormone signal transduction, cell wall modification, transcriptional regulation, and carbohydrate metabolism. Furthermore, candidate calyx abscission-specific genes, e.g. Inflorescence deficient in abscission gene, were identified. Quantitative real-time PCR was used to confirm the digital transcript abundance measurements results. We identified candidate genes that showed highly dynamic changes in

Transcriptional Profiling Identifies Functional Interactions of TGFβ and PPARβ/δ Signaling

PubMed Central

Kaddatz, Kerstin; Adhikary, Till; Finkernagel, Florian; Meissner, Wolfgang; Müller-Brüsselbach, Sabine; Müller, Rolf

2010-01-01

Peroxisome proliferator-activated receptors (PPARs) not only play a key role in regulating metabolic pathways but also modulate inflammatory processes, pointing to a functional interaction between PPAR and cytokine signaling pathways. In this study, we show by genome-wide transcriptional profiling that PPARβ/δ and transforming growth factor-β (TGFβ) pathways functionally interact in human myofibroblasts and that a subset of these genes is cooperatively activated by TGFβ and PPARβ/δ. Using the angiopoietin-like 4 (ANGPTL4) gene as a model, we demonstrate that two enhancer regions cooperate to mediate the observed synergistic response. A TGFβ-responsive enhancer located ∼8 kb upstream of the transcriptional start site is regulated by a mechanism involving SMAD3, ETS1, RUNX, and AP-1 transcription factors that interact with multiple contiguous binding sites. A second enhancer (PPAR-E) consisting of three juxtaposed PPAR response elements is located in the third intron ∼3.5 kb downstream of the transcriptional start site. The PPAR-E is strongly activated by all three PPAR subtypes, with a novel type of PPAR response element motif playing a central role. Although the PPAR-E is not regulated by TGFβ, it interacts with SMAD3, ETS1, RUNX2, and AP-1 in vivo, providing a possible mechanistic explanation for the observed synergism. PMID:20595396

Interpreting CARS images of tissue within the C-H-stretching region

NASA Astrophysics Data System (ADS)

Dietzek, Benjamin; Meyer, Tobias; Medyukhina, Anna; Bergner, Norbert; Krafft, Christoph; Romeike, Bernd F. M.; Reichart, Rupert; Kalff, Rolf; Schmitt, Michael; Popp, Jürgen

2014-03-01

Single band coherent anti-Stokes Raman scattering (CARS) microscopy within the CH-stretching region is applied to detect individual cells and nuclei of human brain tissue and brain tumors - an information which allows for histopathologic grading of the tissue. The CARS image contrast within the C-H-stretching region correlated to the tissue composition. Based on the specific application example of identifying nuclei within (coherent) Raman images of neurotissue sections, we shall derive general design parameters for lasers optimally suited to serve in a clinical environment and discuss the potential of recently developed methods to analyze spectrally resolved CARS images and image segmentation algorithms.

49 CFR 215.121 - Defective car body.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Defective car body. 215.121 Section 215.121..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Car Bodies § 215.121 Defective car body. A railroad may not place or continue in service a car, if: (a) Any portion of...

49 CFR 215.121 - Defective car body.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Defective car body. 215.121 Section 215.121..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Car Bodies § 215.121 Defective car body. A railroad may not place or continue in service a car, if: (a) Any portion of...

49 CFR 215.121 - Defective car body.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Defective car body. 215.121 Section 215.121..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Car Bodies § 215.121 Defective car body. A railroad may not place or continue in service a car, if: (a) Any portion of...

49 CFR 215.121 - Defective car body.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Defective car body. 215.121 Section 215.121..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Car Bodies § 215.121 Defective car body. A railroad may not place or continue in service a car, if: (a) Any portion of...

49 CFR 215.121 - Defective car body.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Defective car body. 215.121 Section 215.121..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Car Bodies § 215.121 Defective car body. A railroad may not place or continue in service a car, if: (a) Any portion of...

Car sick.

PubMed

Renner, M G

1988-01-01

The automobile is currently seen as the most desirable mode of transportation. However, this view needs to be changed since the proliferation of the automobile worldwide is leading to the poisoning of the environment and people. In the US the number of passenger cars grew 51% between 1971-86 and in the noncommunist industrialized community that figure is 71%. The gasoline and diesel fuel used to power the overwhelming majority of cars creates a variety of problems. The pollution is estimated to have a hidden cost of US $.80/gallon. Others estimate that the pollution causes 30,000 premature deaths annually just in the US. 75% of the carbon monoxide (CO), 48% of nitrogen oxides (NO2), 13% of particulates (P), and 3% of sulfur (S) emissions come from cars in the countries of the Organization for Economic Cooperation and Development (OECD), which includes the US, Canada, Western Europe, Japan, Australia, and New Zealand. 17% of all worldwide carbon dioxide (CO2) emission comes from the production and use of fossil fuels for cars. The single biggest problem associated with cars is the photochemical smog they create in urban areas. In 1986 75 million Americans lived in areas that failed to meet national air quality standards for CO, P, and ozone (03). The only area of major improvement has been the removal of lead from gasoline. It was known to cause problems from the beginning of its use in the 1920s, but remained for 50 years because of auto and oil company pressure. Ground 03 is estimated by the US government to cost US $4 billion in annual losses, just for corn, wheat, soybeans, and peanuts. Acid rain is the other major problem associated with cars, and its damage is estimated at US $5 billion annually. Both these problems are shortterm, their effects occur immediately; the longterm disadvantage is the build up of CO2 and its contribution to the greenhouse effect. While the US is at the forefront of regulation and many other countries are modeling their emission

Predictors of car smoking rules among smokers in France, Germany and the Netherlands

PubMed Central

Guignard, Romain; Nagelhout, Gera E.; Mons, Ute; Beck, François; van den Putte, Bas; Crone, Mathilde; de Vries, Hein; Hyland, Andrew; Fong, Geoffrey T.

2012-01-01

Background: As exposure to tobacco smoke pollution (TSP) has been identified as a cause of premature death and disease in non-smokers, and studies have demonstrated that smoking in cars produces high levels of TSP, this study will investigate smokers’ rules for smoking in their cars, and predictors of car smoking rules, including potentially modifiable correlates. Methods: Data were drawn from nationally representative samples of current smokers from the International Tobacco Control Policy Evaluation Project surveys in France (2007), Germany (2007), and the Netherlands (2008). Smokers in France and Germany were asked about smoking rules in their cars, and smokers in the Netherlands were asked about smoking rules in cars carrying children. Results: In France and Germany, 59% and 52% of smokers respectively, allowed smoking in their cars. In the Netherlands, 36% of smokers allowed smoking in cars carrying children. Predictors of allowing smoking in cars included: being a daily vs. non-daily smoker, being younger vs. older age, having no (young) children in the home, being a heavier smoker, and allowing smoking in the home. In the Netherlands, smokers who agreed that TSP is dangerous to non-smokers were less likely to allow smoking in cars carrying children. Conclusion: Overall, a sizeable proportion of smokers allowed smoking in their cars across the three countries. Media campaigns with information about the dangers of TSP may increase the adoption of smoke-free cars. These media campaigns could target smokers who are most likely to allow smoking in cars. PMID:22294780

Divergent transcription is associated with promoters of transcriptional regulators

PubMed Central

2013-01-01

Background Divergent transcription is a wide-spread phenomenon in mammals. For instance, short bidirectional transcripts are a hallmark of active promoters, while longer transcripts can be detected antisense from active genes in conditions where the RNA degradation machinery is inhibited. Moreover, many described long non-coding RNAs (lncRNAs) are transcribed antisense from coding gene promoters. However, the general significance of divergent lncRNA/mRNA gene pair transcription is still poorly understood. Here, we used strand-specific RNA-seq with high sequencing depth to thoroughly identify antisense transcripts from coding gene promoters in primary mouse tissues. Results We found that a substantial fraction of coding-gene promoters sustain divergent transcription of long non-coding RNA (lncRNA)/mRNA gene pairs. Strikingly, upstream antisense transcription is significantly associated with genes related to transcriptional regulation and development. Their promoters share several characteristics with those of transcriptional developmental genes, including very large CpG islands, high degree of conservation and epigenetic regulation in ES cells. In-depth analysis revealed a unique GC skew profile at these promoter regions, while the associated coding genes were found to have large first exons, two genomic features that might enforce bidirectional transcription. Finally, genes associated with antisense transcription harbor specific H3K79me2 epigenetic marking and RNA polymerase II enrichment profiles linked to an intensified rate of early transcriptional elongation. Conclusions We concluded that promoters of a class of transcription regulators are characterized by a specialized transcriptional control mechanism, which is directly coupled to relaxed bidirectional transcription. PMID:24365181

Driving CAR T-cells forward.

PubMed

Jackson, Hollie J; Rafiq, Sarwish; Brentjens, Renier J

2016-06-01

The engineered expression of chimeric antigen receptors (CARs) on the surface of T cells enables the redirection of T-cell specificity. Early clinical trials using CAR T cells for the treatment of patients with cancer showed modest results, but the impressive outcomes of several trials of CD19-targeted CAR T cells in the treatment of patients with B-cell malignancies have generated an increased enthusiasm for this approach. Important lessons have been derived from clinical trials of CD19-specific CAR T cells, and ongoing clinical trials are testing CAR designs directed at novel targets involved in haematological and solid malignancies. In this Review, we discuss these trials and present strategies that can increase the antitumour efficacy and safety of CAR T-cell therapy. Given the fast-moving nature of this field, we only discuss studies with direct translational application currently or soon-to-be tested in the clinical setting.

CARS module for multimodal microscopy

NASA Astrophysics Data System (ADS)

Zadoyan, Ruben; Baldacchini, Tommaso; Carter, John; Kuo, Chun-Hung; Ocepek, David

2011-03-01

We describe a stand alone CARS module allowing upgrade of a two-photon microscope with CARS modality. The Stokes beam is generated in a commercially available photonic crystal fiber (PCF) using fraction of the power of femtosecond excitation laser. The output of the fiber is optimized for broadband CARS at Stokes shifts in 2900cm-1 region. The spectral resolution in CARS signal is 50 cm-1. It is achieved by introducing a bandpass filter in the pump beam. The timing between the pump and Stokes pulses is preset inside the module and can be varied. We demonstrate utility of the device on examples of second harmonic, two-photon fluorescence and CARS images of several biological and non-biological samples. We also present results of studies where we used CARS modality to monitor in real time the process of fabrication of microstructures by two-photon polymerization.

Development of an errorable car-following driver model

NASA Astrophysics Data System (ADS)

Yang, H.-H.; Peng, H.

2010-06-01

An errorable car-following driver model is presented in this paper. An errorable driver model is one that emulates human driver's functions and can generate both nominal (error-free), as well as devious (with error) behaviours. This model was developed for evaluation and design of active safety systems. The car-following data used for developing and validating the model were obtained from a large-scale naturalistic driving database. The stochastic car-following behaviour was first analysed and modelled as a random process. Three error-inducing behaviours were then introduced. First, human perceptual limitation was studied and implemented. Distraction due to non-driving tasks was then identified based on the statistical analysis of the driving data. Finally, time delay of human drivers was estimated through a recursive least-square identification process. By including these three error-inducing behaviours, rear-end collisions with the lead vehicle could occur. The simulated crash rate was found to be similar but somewhat higher than that reported in traffic statistics.

Transcriptional dissection of melanoma identifies a high-risk subtype underlying TP53 family genes and epigenome deregulation

PubMed Central

Badal, Brateil; Solovyov, Alexander; Di Cecilia, Serena; Chan, Joseph Minhow; Chang, Li-Wei; Iqbal, Ramiz; Aydin, Iraz T.; Rajan, Geena S.; Chen, Chen; Abbate, Franco; Arora, Kshitij S.; Tanne, Antoine; Gruber, Stephen B.; Johnson, Timothy M.; Fullen, Douglas R.; Phelps, Robert; Bhardwaj, Nina; Bernstein, Emily; Ting, David T.; Brunner, Georg; Schadt, Eric E.; Greenbaum, Benjamin D.; Celebi, Julide Tok

2017-01-01

BACKGROUND. Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS. We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts. RESULTS. Gene expression changes unequivocally discriminated between benign and malignant states, and a dual epigenetic and immune signature emerged defining this transition. To our knowledge, we discovered previously unrecognized melanoma subtypes. A high-risk primary melanoma subset was distinguished by a 122-epigenetic gene signature (“epigenetic” cluster) and TP53 family gene deregulation (TP53, TP63, and TP73). This subtype associated with poor overall survival and showed enrichment of cell cycle genes. Noncoding repetitive element transcripts (LINEs, SINEs, and ERVs) that can result in immunostimulatory signals recapitulating a state of “viral mimicry” were significantly repressed. The high-risk subtype and its poor predictive characteristics were validated in several independent cohorts. Additionally, primary melanomas distinguished by specific immune signatures (“immune” clusters) were identified. CONCLUSION. The TP53 family of genes and genes regulating the epigenetic machinery demonstrate strong prognostic and biological relevance during progression of early disease. Gene expression profiling of protein-coding and -noncoding RNA transcripts may be a better predictor for disease course in melanoma. This study outlines the transcriptional interplay of the cancer cell’s epigenome with the immune milieu with potential for future therapeutic targeting. FUNDING

Inference of Expanded Lrp-Like Feast/Famine Transcription Factor Targets in a Non-Model Organism Using Protein Structure-Based Prediction

PubMed Central

Ashworth, Justin; Plaisier, Christopher L.; Lo, Fang Yin; Reiss, David J.; Baliga, Nitin S.

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer. PMID:25255272

Inference of expanded Lrp-like feast/famine transcription factor targets in a non-model organism using protein structure-based prediction.

PubMed

Ashworth, Justin; Plaisier, Christopher L; Lo, Fang Yin; Reiss, David J; Baliga, Nitin S

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer.

Does information on novel identified autoantibodies contribute to predicting the progression from undifferentiated arthritis to rheumatoid arthritis: a study on anti-CarP antibodies as an example.

PubMed

Boeters, Debbie M; Trouw, Leendert A; van der Helm-van Mil, Annette H M; van Steenbergen, Hanna W

2018-05-03

The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA patients lack both these autoantibodies. Recently, several novel autoantibodies have been identified but their value for the classification of RA patients is unclear. Therefore, we studied the value of novel autoantibodies using the presence of anticarbamylated protein (anti-CarP) antibodies as an example for predicting RA development in patients with undifferentiated arthritis (UA). There were 1352 UA patients included in the Leiden Early Arthritis Clinic (EAC) cohort according to the 1987 criteria. When the 2010 criteria were used, there were 838 UA patients. Of these, we evaluated whether they fulfilled the 1987 or 2010 criteria after 1 year, respectively. Logistic regression analyses were performed with RA as outcome and ACPA, RF, and anti-CarP antibodies as predictors. Analyses were repeated after stratification for ACPA and RF. Thirty-three percent of the 1987-UA patients and 6% of the 2010-UA patients progressed to RA during the first year of follow-up. For the 1987-UA patients, anti-CarP antibodies were associated with progression to RA, an association which remained when a correction was made for the presence of ACPA and RF (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.2-2.4). After stratification for ACPA and RF, anti-CarP antibodies were associated with progression to RA only for ACPA- and RF-negative patients (OR 2.1, 95% CI 1.3-3.7). For the 2010-UA patients, anti-CarP antibodies were associated with progression to RA; however, they were not when a correction was made for the presence of ACPA and RF (OR 0.8, 95% CI 0.3-2.1). Our finding that anti-CarP antibodies have no additional value when RA is defined according to the 2010 criteria might

49 CFR 180.519 - Periodic retest and inspection of tank cars other than single-unit tank car tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Periodic retest and inspection of tank cars other than single-unit tank car tanks. 180.519 Section 180.519 Transportation Other Regulations Relating to... of Tank Cars § 180.519 Periodic retest and inspection of tank cars other than single-unit tank car...

49 CFR 215.203 - Restricted cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

49 CFR 215.203 - Restricted cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

49 CFR 215.203 - Restricted cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

49 CFR 215.203 - Restricted cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

49 CFR 215.203 - Restricted cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

PIV Analysis Comparing Aerodynamic Downforce Devices on Race Car in Water Tunnel

NASA Astrophysics Data System (ADS)

Hellman, Sam; Tkacik, Peter; Uddin, Mesbah; Kelly, Scott

2010-11-01

There have been claims that the rear wing on the NASCAR Car of Tomorrow (COT) race car causes lift in the condition where the car spins during a crash and is traveling backwards down the track at a high rate of speed. When enough lift is generated, the race car can lose control and even fly off of the track surface completely. To address this concern, a new rear spoiler was designed by NASCAR to replace the wing and prevent this dangerous condition. Flow characteristics of both the rear wing and the new spoiler are qualitatively analyzed using particle image velocimetry (PIV). The experiment is done in a continuous flow water tunnel using a simplified 10% scale model COT. Flow structures are identified and compared for both the wing and spoiler. The same conditions are also reviewed when the car is traveling backwards as it might during a crash. The cause of the lift generated by the rear wing when in reverse is shown.

Study concerning the loads over driver's chests in car crashes with cars of the same or different generation

NASA Astrophysics Data System (ADS)

Ispas, N.; Năstăsoiu, M.

2016-08-01

Reducing occupant injuries for cars involves in traffic accidents is a main target of today cars designers. Known as active or passive safety, many technological solutions were developing over the time for an actual better car's occupant safety. In the real world, in traffic accidents are often involved cars from different generations with various safety historical solutions. The main aim of these papers are to quantify the influences over the car driver chest loads in cases of same or different generation of cars involved in side car crashes. Both same and different cars generations were used for the study. Other goal of the paper was the study of in time loads conformity for diver's chests from both cars involved in crash. The paper's experimental results were obtained by support of DSD, Dr. Steffan Datentechnik GmbH - Linz, Austria. The described tests were performed in full test facility of DSD Linz, in “Easter 2015 PC-Crash Seminar”. In all crashes we obtaining results from both dummy placed in impacted and hits car. The novelty of the paper are the comparisons of data set from each of driver (dummy) of two cars involved in each of six experimental crashes. Another novelty of this paper consists in possibilities to analyse the influences of structural historical cars solutions over deformation and loads in cases of traffic accidents involved. Paper's conclusions can be future used for car passive safety improvement.

Driving CAR T-cells forward

PubMed Central

Jackson, Hollie J.; Rafiq, Sarwish; Brentjens, Renier J.

2017-01-01

The engineered expression of chimeric antigen receptors (CARs) on the surface of T cells enables the redirection of T-cell specificity. Early clinical trials using CAR T cells for the treatment of patients with cancer showed modest results, but the impressive outcomes of several trials of CD19-targeted CAR T cells in the treatment of patients with B-cell malignancies have generated an increased enthusiasm for this approach. Important lessons have been derived from clinical trials of CD19-specific CAR T cells, and ongoing clinical trials are testing CAR designs directed at novel targets involved in haematological and solid malignancies. In this Review, we discuss these trials and present strategies that can increase the antitumour efficacy and safety of CAR T-cell therapy. Given the fast-moving nature of this field, we only discuss studies with direct translational application currently or soon-to-be tested in the clinical setting. PMID:27000958

How do CARs work?

PubMed Central

Davila, Marco L.; Brentjens, Renier; Wang, Xiuyan; Rivière, Isabelle; Sadelain, Michel

2012-01-01

Second-generation chimeric antigen receptors (CARs) are powerful tools to redirect antigen-specific T cells independently of HLA-restriction. Recent clinical studies evaluating CD19-targeted T cells in patients with B-cell malignancies demonstrate the potency of CAR-engineered T cells. With results from 28 subjects enrolled by five centers conducting studies in patients with chronic lymphocytic leukemia (CLL) or lymphoma, some insights into the parameters that determine T-cell function and clinical outcome of CAR-based approaches are emerging. These parameters involve CAR design, T-cell production methods, conditioning chemotherapy as well as patient selection. Here, we discuss the potential relevance of these findings and in particular the interplay between the adoptive transfer of T cells and pre-transfer patient conditioning. PMID:23264903

49 CFR 174.615 - Cleaning cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Cleaning cars. 174.615 Section 174.615... Requirements for Division 6.1 (Poisonous) Materials § 174.615 Cleaning cars. (a) [Reserved] (b) After Division 6.1 (poisonous) materials are unloaded from a rail car, that car must be thoroughly cleaned unless...

49 CFR 174.615 - Cleaning cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Cleaning cars. 174.615 Section 174.615... Requirements for Division 6.1 (Poisonous) Materials § 174.615 Cleaning cars. (a) [Reserved] (b) After Division 6.1 (poisonous) materials are unloaded from a rail car, that car must be thoroughly cleaned unless...

49 CFR 174.615 - Cleaning cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Cleaning cars. 174.615 Section 174.615... Requirements for Division 6.1 (Poisonous) Materials § 174.615 Cleaning cars. (a) [Reserved] (b) After Division 6.1 (poisonous) materials are unloaded from a rail car, that car must be thoroughly cleaned unless...

49 CFR 174.615 - Cleaning cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Cleaning cars. 174.615 Section 174.615... Requirements for Division 6.1 (Poisonous) Materials § 174.615 Cleaning cars. (a) [Reserved] (b) After Division 6.1 (poisonous) materials are unloaded from a rail car, that car must be thoroughly cleaned unless...

49 CFR 174.615 - Cleaning cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Cleaning cars. 174.615 Section 174.615... Requirements for Division 6.1 (Poisonous) Materials § 174.615 Cleaning cars. (a) [Reserved] (b) After Division 6.1 (poisonous) materials are unloaded from a rail car, that car must be thoroughly cleaned unless...

Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.

PubMed

Sunkel, Benjamin; Wu, Dayong; Chen, Zhong; Wang, Chiou-Miin; Liu, Xiangtao; Ye, Zhenqing; Horning, Aaron M; Liu, Joseph; Mahalingam, Devalingam; Lopez-Nicora, Horacio; Lin, Chun-Lin; Goodfellow, Paul J; Clinton, Steven K; Jin, Victor X; Chen, Chun-Liang; Huang, Tim H-M; Wang, Qianben

2016-05-19

Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 in androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC) cell lines, primary prostate cancer tissues and circulating tumor cells (CTCs) to investigate their role in defining prostate cancer gene expression profiles. Combining genome-wide binding site and gene expression profiles we define CREB1 as a critical driver of pro-survival, cell cycle and metabolic transcription programs. We show that CREB1 and FoxA1 co-localize and mutually influence each other's binding to define disease-driving transcription profiles associated with advanced prostate cancer. Gene expression analysis in human prostate cancer samples found that CREB1/FoxA1 target gene panels predict prostate cancer recurrence. Finally, we showed that this signaling pathway is sensitive to compounds that inhibit the transcription co-regulatory factor MED1. These findings not only reveal a novel, global transcriptional co-regulatory function of CREB1 and FoxA1, but also suggest CREB1/FoxA1 signaling is a targetable driver of prostate cancer progression and serves as a biomarker of poor clinical outcomes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal

Highlights: •Transcriptome sequencing yielded 223 mill porcine RNA-seq reads, and 59,000 transcribed locations. •Establishment of unique transcription profiles for ten porcine tissues including four brain tissues. •Comparison of transcription profiles at gene, isoform, promoter and transcription start site level. •Highlights a high level of regulation of neuro-related genes at both gene, isoform, and TSS level. •Our results emphasize the pig as a valuable animal model with respect to human biological issues. -- Abstract: The transcriptome is the absolute set of transcripts in a tissue or cell at the time of sampling. In this study RNA-Seq is employed to enable themore » differential analysis of the transcriptome profile for ten porcine tissues in order to evaluate differences between the tissues at the gene and isoform expression level, together with an analysis of variation in transcription start sites, promoter usage, and splicing. Totally, 223 million RNA fragments were sequenced leading to the identification of 59,930 transcribed gene locations and 290,936 transcript variants using Cufflinks with similarity to approximately 13,899 annotated human genes. Pairwise analysis of tissues for differential expression at the gene level showed that the smallest differences were between tissues originating from the porcine brain. Interestingly, the relative level of differential expression at the isoform level did generally not vary between tissue contrasts. Furthermore, analysis of differential promoter usage between tissues, revealed a proportionally higher variation between cerebellum (CBE) versus frontal cortex and cerebellum versus hypothalamus (HYP) than in the remaining comparisons. In addition, the comparison of differential transcription start sites showed that the number of these sites is generally increased in comparisons including hypothalamus in contrast to other pairwise assessments. A comprehensive analysis of one of the tissue contrasts, i

49 CFR 231.6 - Flat cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Flat cars. 231.6 Section 231.6 Transportation... TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.6 Flat cars. (Cars with sides 12 inches or less above the floor may be equipped the same as flat cars.) (a) Hand brakes—(1) Number. Same as specified for...

49 CFR 231.6 - Flat cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Flat cars. 231.6 Section 231.6 Transportation... TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.6 Flat cars. (Cars with sides 12 inches or less above the floor may be equipped the same as flat cars.) (a) Hand brakes—(1) Number. Same as specified for...

49 CFR 231.6 - Flat cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Flat cars. 231.6 Section 231.6 Transportation... TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.6 Flat cars. (Cars with sides 12 inches or less above the floor may be equipped the same as flat cars.) (a) Hand brakes—(1) Number. Same as specified for...

49 CFR 231.6 - Flat cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Flat cars. 231.6 Section 231.6 Transportation... TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.6 Flat cars. (Cars with sides 12 inches or less above the floor may be equipped the same as flat cars.) (a) Hand brakes—(1) Number. Same as specified for...

49 CFR 231.6 - Flat cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Flat cars. 231.6 Section 231.6 Transportation... TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.6 Flat cars. (Cars with sides 12 inches or less above the floor may be equipped the same as flat cars.) (a) Hand brakes—(1) Number. Same as specified for...

Compacted Approach to Reading (CAR): An Intervention Program for At-Risk Beginning Readers.

ERIC Educational Resources Information Center

Gettys, Cynthia M.

A study determined the initial success of the Compacted Approach to Reading (CAR) program as measured at the end of the program's pilot year. Subjects were 21 first graders and 7 second graders in Tennessee identified and recommended by their first and second grade classroom teacher. The CAR program was developed based on concepts observed in the…

Things You "Auto" Know When Buying a Car. Teacher's Guide [and] Student Material.

ERIC Educational Resources Information Center

Bookout, Janet

This unit provides high school students with criteria for deciding to buy a new or used car and selecting a reputable dealer. It is divided into three sections. In the first section students analyze uses and identify car sizes, options, and appearances that are important. The second section describes advantages and disadvantages of new and used…

CAR-T cells are serial killers.

PubMed

Davenport, Alexander J; Jenkins, Misty R; Ritchie, David S; Prince, H Miles; Trapani, Joseph A; Kershaw, Michael H; Darcy, Phillip K; Neeson, Paul J

2015-12-01

Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours.

Myocardin-related transcription factors are required for cardiac development and function

PubMed Central

Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

2016-01-01

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

Art Cars: Transformations of the Mundane

ERIC Educational Resources Information Center

Stienecker, Dawn

2010-01-01

The automobile itself is often understood as an extension of oneself, where individuals may manipulate the interior and exterior of cars and trucks, decorating them through detailing, stickers, custom colors, and so on. Others go further and change their cars into unique works of art called art cars. Such cars break away from the banality of mass…

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer.

PubMed

Kimbung, Siker; Johansson, Ida; Danielsson, Anna; Veerla, Srinivas; Egyhazi Brage, Suzanne; Frostvik Stolt, Marianne; Skoog, Lambert; Carlsson, Lena; Einbeigi, Zakaria; Lidbrink, Elisabet; Linderholm, Barbro; Loman, Niklas; Malmström, Per-Olof; Söderberg, Martin; Walz, Thomas M; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2016-01-01

The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. ©2015 American Association for Cancer Research.

RNAseq versus genome-predicted transcriptomes: a large population of novel transcripts identified in an Illumina-454 Hydra transcriptome.

PubMed

Wenger, Yvan; Galliot, Brigitte

2013-03-25

Evolutionary studies benefit from deep sequencing technologies that generate genomic and transcriptomic sequences from a variety of organisms. Genome sequencing and RNAseq have complementary strengths. In this study, we present the assembly of the most complete Hydra transcriptome to date along with a comparative analysis of the specific features of RNAseq and genome-predicted transcriptomes currently available in the freshwater hydrozoan Hydra vulgaris. To produce an accurate and extensive Hydra transcriptome, we combined Illumina and 454 Titanium reads, giving the primacy to Illumina over 454 reads to correct homopolymer errors. This strategy yielded an RNAseq transcriptome that contains 48'909 unique sequences including splice variants, representing approximately 24'450 distinct genes. Comparative analysis to the available genome-predicted transcriptomes identified 10'597 novel Hydra transcripts that encode 529 evolutionarily-conserved proteins. The annotation of 170 human orthologs points to critical functions in protein biosynthesis, FGF and TOR signaling, vesicle transport, immunity, cell cycle regulation, cell death, mitochondrial metabolism, transcription and chromatin regulation. However, a majority of these novel transcripts encodes short ORFs, at least 767 of them corresponding to pseudogenes. This RNAseq transcriptome also lacks 11'270 predicted transcripts that correspond either to silent genes or to genes expressed below the detection level of this study. We established a simple and powerful strategy to combine Illumina and 454 reads and we produced, with genome assistance, an extensive and accurate Hydra transcriptome. The comparative analysis of the RNAseq transcriptome with genome-predicted transcriptomes lead to the identification of large populations of novel as well as missing transcripts that might reflect Hydra-specific evolutionary events.

49 CFR 1033.1 - Car hire rates.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Car hire rates. 1033.1 Section 1033.1... OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.1 Car hire rates. (a) Definitions applicable to this section: (1) Car. A freight car bearing railroad reporting marks, other than an excluded...

49 CFR 1033.1 - Car hire rates.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Car hire rates. 1033.1 Section 1033.1... OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.1 Car hire rates. (a) Definitions applicable to this section: (1) Car. A freight car bearing railroad reporting marks, other than an excluded...

49 CFR 1033.1 - Car hire rates.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 false Car hire rates. 1033.1 Section 1033.1... OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.1 Car hire rates. (a) Definitions applicable to this section: (1) Car. A freight car bearing railroad reporting marks, other than an excluded...

49 CFR 1033.1 - Car hire rates.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Car hire rates. 1033.1 Section 1033.1... OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.1 Car hire rates. (a) Definitions applicable to this section: (1) Car. A freight car bearing railroad reporting marks, other than an excluded...

49 CFR 1033.1 - Car hire rates.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 false Car hire rates. 1033.1 Section 1033.1... OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.1 Car hire rates. (a) Definitions applicable to this section: (1) Car. A freight car bearing railroad reporting marks, other than an excluded...

49 CFR 238.311 - Single car test.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Single car test. 238.311 Section 238.311... Requirements for Tier I Passenger Equipment § 238.311 Single car test. (a) Except for self-propelled passenger cars, single car tests of all passenger cars and all unpowered vehicles used in passenger trains shall...

49 CFR 238.311 - Single car test.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Single car test. 238.311 Section 238.311... Requirements for Tier I Passenger Equipment § 238.311 Single car test. (a) Except for self-propelled passenger cars, single car tests of all passenger cars and all unpowered vehicles used in passenger trains shall...

49 CFR 238.311 - Single car test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Single car test. 238.311 Section 238.311... Requirements for Tier I Passenger Equipment § 238.311 Single car test. (a) Except for self-propelled passenger cars, single car tests of all passenger cars and all unpowered vehicles used in passenger trains shall...

49 CFR 238.311 - Single car test.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Single car test. 238.311 Section 238.311... Requirements for Tier I Passenger Equipment § 238.311 Single car test. (a) Except for self-propelled passenger cars, single car tests of all passenger cars and all unpowered vehicles used in passenger trains shall...

49 CFR 238.311 - Single car test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Single car test. 238.311 Section 238.311... Requirements for Tier I Passenger Equipment § 238.311 Single car test. (a) Except for self-propelled passenger cars, single car tests of all passenger cars and all unpowered vehicles used in passenger trains shall...

CAR-T cells are serial killers

PubMed Central

Davenport, Alexander J; Jenkins, Misty R; Ritchie, David S; Prince, H Miles; Trapani, Joseph A; Kershaw, Michael H; Darcy, Phillip K; Neeson, Paul J

2015-01-01

Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours. PMID:26587330

Transit car demonstration test program on the roll dynamics unit. Volume 2. Demonstration of a transit car performance test on the roll dynamic unit. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arnold, G.; Nelson, S.; Cooperrider, N.K.

1982-02-11

This report, Volume II, contains the results, conclusions, and recommendations of the first performance test of a transit care on the RDU. This report is limited to performance tests. The objective is to identify advantages and disadvantages of performance testing on the rollers of the RDU as highlighted by the SOAC test. The report involved separate testing, done by TTC personnel, in such traditional performance areas of transit vehicle operation ass traction, acceleration/deceleration, energy consumption, and spin/slide performance. The results of the successful performance test of a transit car on a roller unit is presented and the advantages of thismore » method of testing is discussed. Acceleration, deceleration, spin/slide, and power consumption tests, although of limited scope in comparison to the track tests performed on the same transit car, did show the feasibility of roller testing. It is concluded that the RDU is most suited for developmental testing of transit car systems particularly for power consumption and for cars with non-standard wheel gage. Tests should be of such scope as to justify the cost of car setup on the RDU. The following two test are recommended: (1) a power consumption study for a standard/non-standard gage transit car which investigates methods of reducing power consumption and (2) a non-standard gage full performance test.« less

Evolution of DNA-Binding Sites of a Floral Master Regulatory Transcription Factor

PubMed Central

Muiño, Jose M.; de Bruijn, Suzanne; Pajoro, Alice; Geuten, Koen; Vingron, Martin; Angenent, Gerco C.; Kaufmann, Kerstin

2016-01-01

Flower development is controlled by the action of key regulatory transcription factors of the MADS-domain family. The function of these factors appears to be highly conserved among species based on mutant phenotypes. However, the conservation of their downstream processes is much less well understood, mostly because the evolutionary turnover and variation of their DNA-binding sites (BSs) among plant species have not yet been experimentally determined. Here, we performed comparative ChIP (chromatin immunoprecipitation)-seq experiments of the MADS-domain transcription factor SEPALLATA3 (SEP3) in two closely related Arabidopsis species: Arabidopsis thaliana and A. lyrata which have very similar floral organ morphology. We found that BS conservation is associated with DNA sequence conservation, the presence of the CArG-box BS motif and on the relative position of the BS to its potential target gene. Differences in genome size and structure can explain that SEP3 BSs in A. lyrata can be located more distantly to their potential target genes than their counterparts in A. thaliana. In A. lyrata, we identified transposition as a mechanism to generate novel SEP3 binding locations in the genome. Comparative gene expression analysis shows that the loss/gain of BSs is associated with a change in gene expression. In summary, this study investigates the evolutionary dynamics of DNA BSs of a floral key-regulatory transcription factor and explores factors affecting this phenomenon. PMID:26429922

Car crash and injury among young drivers: contribution of social, circumstantial and car attributes.

PubMed

Laflamme, L; Vaez, M

2007-03-01

The objective of the study was to assess the independent contribution of individual, car and circumstantial features in severe and fatal car crashes involving young drivers. A prospective longitudinal, register-based cohort study was conducted at national level (in Sweden), in which people born in the years 1970-1972 (n = 334070) were followed up for the period 1988-2000 (aged 16-18 years in 1988) for their first two-car crashes leading to severe or fatal injury. Ten variables descriptive of the driver (sociodemographics), the car (safety level) and the crash have been analysed using multiple logistic regressions for male and female drivers separately, compiling crude and adjusted odds ratios with 95% CI. When controlling for other features, none of the variables descriptive of male and female drivers' socio-demographic characteristics impacts significantly on the odds of being severely injured or dying in a car-to-car crash. After adjustment, significant excess risks are observed for speed limits higher than the lowest one, type of crash other than rear end collision and road and light conditions other than favourable (dry and daylight), for both male and female drivers. For males only, cars from all car safety levels have significantly higher odds than those from the safest category. Among male and female young drivers, class differences in the risk of being severely injured in a traffic injury are substantial. Yet, despite this imbalance, crash characteristics (for males and females) and safety level of the vehicle driven (for males) remain the most determinant factors of crash severity. Understanding the social patterning of road traffic injuries is a challenge for public health and it seems that qualitative and quantitative differences in crash exposure offer part of the explanation. Young drivers from all social groups need, however, to be sensitized to the risk factors.

Large and Small Cars in Real-World Crashes -Patterns of Use, Collision Types and Injury Outcomes

PubMed Central

Thomas, Pete; Frampton, Richard

1999-01-01

Previous work examining the effect of vehicle mass has demonstrated the link with occupant injury severity. The principal factor has been related to Newtonian mechanics. This paper analyses data from the UK Co-operative Crash Injury Study and identifies other factors associated with car size. The mass of the car is found to have a predominant effect on injury outcome in frontal collisions only where the effect is seen most in injuries to the head, face and chest. Most fatal casualties in small cars die when in collision with another car in front or side collisions while the key group for large cars is frontal collisions with road-side objects. There are several characteristics of small car occupants that differ from those in large cars including gender, age and vehicle occupancy. New information in the analysis concerns the priorities in casualty reduction between small and large car occupants and the paper argues that vehicle design should take account of this variation to produce vehicles optimised for the complete range of crashes and car occupants.

Modeling the Mousetrap Car

NASA Astrophysics Data System (ADS)

Jumper, William D.

2012-03-01

Many high school and introductory college physics courses make use of mousetrap car projects and competitions as a way of providing an engaging hands-on learning experience incorporating Newton's laws, conversion of potential to kinetic energy, dissipative forces, and rotational mechanics. Presented here is a simple analytical and finite element spreadsheet model for a typical mousetrap car, as shown in Fig. 1. It is hoped that the model will provide students with a tool for designing or modifying the designs of their cars, provide instructors with a means to insure students close the loop between physical principles and an understanding of their car's speed and distance performance, and, third, stimulate in students at an early stage an appreciation for the merits of computer modeling as an aid in understanding and tackling otherwise analytically intractable problems so common in today's professional world.

Integrated expression analysis identifies transcription networks in mouse and human gastric neoplasia.

PubMed

Chen, Zheng; Soutto, Mohammed; Rahman, Bushra; Fazili, Muhammad W; Peng, DunFa; Blanca Piazuelo, Maria; Chen, Heidi; Kay Washington, M; Shyr, Yu; El-Rifai, Wael

2017-07-01

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. The Tff1 knockout (KO) mouse model develops gastric lesions that include low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinomas. In this study, we used Affymetrix microarrays gene expression platforms for analysis of molecular signatures in the mouse stomach [Tff1-KO (LGD) and Tff1 wild-type (normal)] and human gastric cancer tissues and their adjacent normal tissue samples. Combined integrated bioinformatics analysis of mouse and human datasets indicated that 172 genes were consistently deregulated in both human gastric cancer samples and Tff1-KO LGD lesions (P < .05). Using Ingenuity pathway analysis, these genes mapped to important transcription networks that include MYC, STAT3, β-catenin, RELA, NFATC2, HIF1A, and ETS1 in both human and mouse. Further analysis demonstrated activation of FOXM1 and inhibition of TP53 transcription networks in human gastric cancers but not in Tff1-KO LGD lesions. Using real-time RT-PCR, we validated the deregulated expression of several genes (VCAM1, BGN, CLDN2, COL1A1, COL1A2, COL3A1, EpCAM, IFITM1, MMP9, MMP12, MMP14, PDGFRB, PLAU, and TIMP1) that map to altered transcription networks in both mouse and human gastric neoplasia. Our study demonstrates significant similarities in deregulated transcription networks in human gastric cancer and gastric tumorigenesis in the Tff1-KO mouse model. The data also suggest that activation of MYC, STAT3, RELA, and β-catenin transcription networks could be an early molecular step in gastric carcinogenesis. © 2017 Wiley Periodicals, Inc.

Method to determine transcriptional regulation pathways in organisms

DOEpatents

Gardner, Timothy S.; Collins, James J.; Hayete, Boris; Faith, Jeremiah

2012-11-06

The invention relates to computer-implemented methods and systems for identifying regulatory relationships between expressed regulating polypeptides and targets of the regulatory activities of such regulating polypeptides. More specifically, the invention provides a new method for identifying regulatory dependencies between biochemical species in a cell. In particular embodiments, provided are computer-implemented methods for identifying a regulatory interaction between a transcription factor and a gene target of the transcription factor, or between a transcription factor and a set of gene targets of the transcription factor. Further provided are genome-scale methods for predicting regulatory interactions between a set of transcription factors and a corresponding set of transcriptional target substrates thereof.

AAP Updates Recommendations on Car Seats

MedlinePlus

... Size Email Print Share AAP Updates Recommendations on Car Seats Page Content Article Body Children should ride ... of approved car safety seats. Healthy Children Radio: Car Seat Safety Dennis Durbin, MD, FAAP, lead author ...

Car surfing: case studies of a growing dangerous phenomenon.

PubMed

Clark, Steven; Mangram, Alicia; Dunn, Ernest

2008-03-01

Car surfing is a dangerous new pastime for American youth. Car surfing is an activity that is defined as standing (or lying) on a vehicle while it is being driven. This activity frequently results in severe injuries that often require significant surgical intervention. Despite its destructive nature, however, there are many Internet sites that encourage this behavior and view it as amusing. As a result, car surfing is becoming increasingly popular. We conducted a retrospective chart review of all patients injured as a result of car surfing over the last 4 years at our Urban Level II trauma center. Data collected included Injury Severity Score (ISS), Revised Trauma Score (RTS), age, gender, injury pattern, surgical intervention, and length of stay. Eight car surfers were identified. The average age was 17. The average Revised Trauma Score was 6.8 with an average Injury Severity Score of 16.9. Five patients were admitted to the intensive care unit. Four of these five patients needed to be intubated for ventilatory support. Five of the eight patients had significant intracranial injuries. Two patients had epidural hematomas that required evacuation. Two other patients had subdural hematomas that were treated nonoperatively, and one patient had a subarachnoid hemorrhage that was also treated nonoperatively. Four of the eight patients required surgical intervention. There were no deaths in this study. Car surfing leads to severe injuries that can result in significant morbidity. American youth have access to Internet sites that project this activity as an acceptable behavior. Five of our eight patients had a significant intracranial injury. Trauma surgeons need to be more aware of this injury phenomenon.

5' diversity of human hepatic PXR (NR1I2) transcripts and identification of the major transcription initiation site.

PubMed

Kurose, Kouichi; Koyano, Satoru; Ikeda, Shinobu; Tohkin, Masahiro; Hasegawa, Ryuichi; Sawada, Jun-Ichi

2005-05-01

The human pregnane X receptor (PXR) is a crucial regulator of the genes encoding several major cytochrome P450 enzymes and transporters, such as CYP3A4 and MDR1, but its own transcriptional regulation remains unclear. To elucidate the transcriptional mechanisms of human PXR gene, we first endeavored to identify the transcription initiation site of human PXR using 5'-RACE. Five types of 5'-variable transcripts (a, b, c, d, and e) with common exon 2 sequence were found, and comparison of these sequences with the genomic sequence suggested that their 5' diversity is derived from initiation by alternative promoters and alternative splicing. None of the exons found in our study contain any new in-frame coding regions. Newly identified introns IVS-a and IVS-b were found to have CT-AC splice sites that do not follow the GT-AG rule of conventional donor and acceptor splice sites. Of the five types of 5' variable transcripts identified, RT-PCR showed that type-a was the major transcript type. Four transcription initiation sites (A-D) for type-a transcript were identified by 5'-RACE using GeneRacer RACE Ready cDNA (human liver) constructed by the oligo-capping method. Putative TATA boxes were located approximately 30 bp upstream from the transcriptional start sites of the major transcript (C) and the longest minor transcript (A) expressed in the human liver. These results indicate that the initiation of transcription of human PXR is more complex than previously reported.

CAR and PXR-dependent transcriptional changes in the mouse liver after exposure to propiconazole

EPA Science Inventory

Exposure to the conazoles propiconazole and triadimefon but not myclobutanilled to tumors in mice after 2 years. Transcript profiling studies in the livers ofwild-type mice after short-term exposure to the conazoles revealed signatures indicating the involvement ofthe nuclear rec...

Colour blindness in everyday life and car driving.

PubMed

Tagarelli, Antonio; Piro, Anna; Tagarelli, Giuseppe; Lantieri, Pasquale Bruno; Risso, Domenico; Olivieri, Rosario Luciano

2004-08-01

The aim of the present work was to ascertain, through the administration of a psychosocial questionnaire, the difficulties that subjects with defective colour vision experience in carrying out everyday tasks and work, including driving a car with a driver's licence held for no more than 3 years. Subjects with defective colour vision (n = 151) and subjects with normal vision (n = 302) completed a psychosocial questionnaire regarding the difficulties associated with congenital colour vision deficiency in daily life, work and driving a car. Subjects were diagnosed as colour-blind using the Ishihara test. Statistically significant differences between the two samples were found for daily life activities. Subjects with defective colour vision preferred daytime driving. At night, subjects with defective colour vision had difficulty identifying reflectors on the road and the rear signal lights of cars ahead of them. Colour-blind Calabrian subjects admitted to experiencing colour-related difficulties with a wide range of occupational tasks and leisure pursuits. In particular, colour-blind Calabrian subjects preferred daytime driving, and fewer drove regularly, compared to orthochromatics, who were indifferent to night or daytime driving.

RNAseq versus genome-predicted transcriptomes: a large population of novel transcripts identified in an Illumina-454 Hydra transcriptome

PubMed Central

2013-01-01

Background Evolutionary studies benefit from deep sequencing technologies that generate genomic and transcriptomic sequences from a variety of organisms. Genome sequencing and RNAseq have complementary strengths. In this study, we present the assembly of the most complete Hydra transcriptome to date along with a comparative analysis of the specific features of RNAseq and genome-predicted transcriptomes currently available in the freshwater hydrozoan Hydra vulgaris. Results To produce an accurate and extensive Hydra transcriptome, we combined Illumina and 454 Titanium reads, giving the primacy to Illumina over 454 reads to correct homopolymer errors. This strategy yielded an RNAseq transcriptome that contains 48’909 unique sequences including splice variants, representing approximately 24’450 distinct genes. Comparative analysis to the available genome-predicted transcriptomes identified 10’597 novel Hydra transcripts that encode 529 evolutionarily-conserved proteins. The annotation of 170 human orthologs points to critical functions in protein biosynthesis, FGF and TOR signaling, vesicle transport, immunity, cell cycle regulation, cell death, mitochondrial metabolism, transcription and chromatin regulation. However, a majority of these novel transcripts encodes short ORFs, at least 767 of them corresponding to pseudogenes. This RNAseq transcriptome also lacks 11’270 predicted transcripts that correspond either to silent genes or to genes expressed below the detection level of this study. Conclusions We established a simple and powerful strategy to combine Illumina and 454 reads and we produced, with genome assistance, an extensive and accurate Hydra transcriptome. The comparative analysis of the RNAseq transcriptome with genome-predicted transcriptomes lead to the identification of large populations of novel as well as missing transcripts that might reflect Hydra-specific evolutionary events. PMID:23530871

Comparative Transcriptional Analysis of Loquat Fruit Identifies Major Signal Networks Involved in Fruit Development and Ripening Process.

PubMed

Song, Huwei; Zhao, Xiangxiang; Hu, Weicheng; Wang, Xinfeng; Shen, Ting; Yang, Liming

2016-11-04

Loquat ( Eriobotrya japonica Lindl.) is an important non-climacteric fruit and rich in essential nutrients such as minerals and carotenoids. During fruit development and ripening, thousands of the differentially expressed genes (DEGs) from various metabolic pathways cause a series of physiological and biochemical changes. To better understand the underlying mechanism of fruit development, the Solexa/Illumina RNA-seq high-throughput sequencing was used to evaluate the global changes of gene transcription levels. More than 51,610,234 high quality reads from ten runs of fruit development were sequenced and assembled into 48,838 unigenes. Among 3256 DEGs, 2304 unigenes could be annotated to the Gene Ontology database. These DEGs were distributed into 119 pathways described in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A large number of DEGs were involved in carbohydrate metabolism, hormone signaling, and cell-wall degradation. The real-time reverse transcription (qRT)-PCR analyses revealed that several genes related to cell expansion, auxin signaling and ethylene response were differentially expressed during fruit development. Other members of transcription factor families were also identified. There were 952 DEGs considered as novel genes with no annotation in any databases. These unigenes will serve as an invaluable genetic resource for loquat molecular breeding and postharvest storage.

Smoking in cars: knowledge, behaviours and support for smokefree cars legislation among New Zealand smokers and recent quitters.

PubMed

Li, Judy; Nelson, Sarah; Newcombe, Rhiannon; Walton, Darren

2016-08-05

Exposure to second-hand smoke (SHS) poses serious health consequences to non-smokers, and normalises smoking. Currently, there is no legislation restricting smoking in private cars in New Zealand. This paper supplements previous New Zealand studies on exposure to SHS in cars by examining smokers and recent quitters' knowledge and behaviours towards smoking in cars, and their support for two possible smokefree cars policy options. The New Zealand Smoking Monitor is a fortnightly survey that uses a self-refreshing panel approach. The questionnaire contains smoking- and cessation-related questions, including eight non-core questions addressing smoking in homes or cars. These questions were answered by 364 respondents in 2014. Responses were compared by socio-demographic variables and recent quit attempt status. Smoking in cars was common among the respondents in our sample: 63% had recently smoked in a car when they were the only person in it, and 27% had done so when there were other people present. Some groups of respondents exhibited information gaps around the harms (eg, compared with males, females had reduced odds of agreeing with the false statement: "it's OK to smoke inside cars if there are windows open", OR=0.41, 0.21-0.78); however, support for banning smoking in cars if there are children in them was consistently high across different sub-groups (92% overall). Our data show the importance of providing specific information around the danger of smoking in cars, and strategies to enforce a complete smokefree rule in cars. Legislation may be required to further protect children from SHS exposure.

Identifying marker genes in transcription profiling data using a mixture of feature relevance experts.

PubMed

Chow, M L; Moler, E J; Mian, I S

2001-03-08

Transcription profiling experiments permit the expression levels of many genes to be measured simultaneously. Given profiling data from two types of samples, genes that most distinguish the samples (marker genes) are good candidates for subsequent in-depth experimental studies and developing decision support systems for diagnosis, prognosis, and monitoring. This work proposes a mixture of feature relevance experts as a method for identifying marker genes and illustrates the idea using published data from samples labeled as acute lymphoblastic and myeloid leukemia (ALL, AML). A feature relevance expert implements an algorithm that calculates how well a gene distinguishes samples, reorders genes according to this relevance measure, and uses a supervised learning method [here, support vector machines (SVMs)] to determine the generalization performances of different nested gene subsets. The mixture of three feature relevance experts examined implement two existing and one novel feature relevance measures. For each expert, a gene subset consisting of the top 50 genes distinguished ALL from AML samples as completely as all 7,070 genes. The 125 genes at the union of the top 50s are plausible markers for a prototype decision support system. Chromosomal aberration and other data support the prediction that the three genes at the intersection of the top 50s, cystatin C, azurocidin, and adipsin, are good targets for investigating the basic biology of ALL/AML. The same data were employed to identify markers that distinguish samples based on their labels of T cell/B cell, peripheral blood/bone marrow, and male/female. Selenoprotein W may discriminate T cells from B cells. Results from analysis of transcription profiling data from tumor/nontumor colon adenocarcinoma samples support the general utility of the aforementioned approach. Theoretical issues such as choosing SVM kernels and their parameters, training and evaluating feature relevance experts, and the impact of

Parents Smoking in Their Cars With Children Present

PubMed Central

Nabi-Burza, Emara; Regan, Susan; Drehmer, Jeremy; Ossip, Deborah; Rigotti, Nancy; Hipple, Bethany; Dempsey, Janelle; Hall, Nicole; Friebely, Joan; Weiley, Victoria

2012-01-01

OBJECTIVE: To determine prevalence and factors associated with strictly enforced smoke-free car policies among smoking parents. METHODS: As part of a cluster, randomized controlled trial addressing parental smoking, exit interviews were conducted with parents whose children were seen in 10 control pediatric practices. Parents who smoked were asked about smoking behaviors in their car and receipt of smoke-free car advice at the visit. Parents were considered to have a “strictly enforced smoke-free car policy” if they reported having a smoke-free car policy and nobody had smoked in their car within the past 3 months. RESULTS: Of 981 smoking parents, 817 (83%) had a car; of these, 795 parents answered questions about their car smoking policy. Of these 795 parents, 29% reported having a smoke-free car policy, and 24% had a strictly enforced smoke-free car policy. Of the 562 parents without a smoke-free car policy, 48% reported that smoking occurred with children present. Few parents who smoke (12%) were advised to have a smoke-free car. Multivariable logistic regression controlling for parent age, gender, education, and race showed that having a younger child and smoking ≤10 cigarettes per day were associated with having a strictly enforced smoke-free car policy. CONCLUSIONS: The majority of smoking parents exposed their children to tobacco smoke in cars. Coupled with the finding of low rates of pediatricians addressing smoking in cars, this study highlights the need for improved pediatric interventions, public health campaigns, and policies regarding smoke-free car laws to protect children from tobacco smoke. PMID:23147972

Parents smoking in their cars with children present.

PubMed

Nabi-Burza, Emara; Regan, Susan; Drehmer, Jeremy; Ossip, Deborah; Rigotti, Nancy; Hipple, Bethany; Dempsey, Janelle; Hall, Nicole; Friebely, Joan; Weiley, Victoria; Winickoff, Jonathan P

2012-12-01

To determine prevalence and factors associated with strictly enforced smoke-free car policies among smoking parents. As part of a cluster, randomized controlled trial addressing parental smoking, exit interviews were conducted with parents whose children were seen in 10 control pediatric practices. Parents who smoked were asked about smoking behaviors in their car and receipt of smoke-free car advice at the visit. Parents were considered to have a "strictly enforced smoke-free car policy" if they reported having a smoke-free car policy and nobody had smoked in their car within the past 3 months. Of 981 smoking parents, 817 (83%) had a car; of these, 795 parents answered questions about their car smoking policy. Of these 795 parents, 29% reported having a smoke-free car policy, and 24% had a strictly enforced smoke-free car policy. Of the 562 parents without a smoke-free car policy, 48% reported that smoking occurred with children present. Few parents who smoke (12%) were advised to have a smoke-free car. Multivariable logistic regression controlling for parent age, gender, education, and race showed that having a younger child and smoking ≤10 cigarettes per day were associated with having a strictly enforced smoke-free car policy. The majority of smoking parents exposed their children to tobacco smoke in cars. Coupled with the finding of low rates of pediatricians addressing smoking in cars, this study highlights the need for improved pediatric interventions, public health campaigns, and policies regarding smoke-free car laws to protect children from tobacco smoke.

Aerodynamics of Race Cars

NASA Astrophysics Data System (ADS)

Katz, Joseph

2006-01-01

Race car performance depends on elements such as the engine, tires, suspension, road, aerodynamics, and of course the driver. In recent years, however, vehicle aerodynamics gained increased attention, mainly due to the utilization of the negative lift (downforce) principle, yielding several important performance improvements. This review briefly explains the significance of the aerodynamic downforce and how it improves race car performance. After this short introduction various methods to generate downforce such as inverted wings, diffusers, and vortex generators are discussed. Due to the complex geometry of these vehicles, the aerodynamic interaction between the various body components is significant, resulting in vortex flows and lifting surface shapes unlike traditional airplane wings. Typical design tools such as wind tunnel testing, computational fluid dynamics, and track testing, and their relevance to race car development, are discussed as well. In spite of the tremendous progress of these design tools (due to better instrumentation, communication, and computational power), the fluid dynamic phenomenon is still highly nonlinear, and predicting the effect of a particular modification is not always trouble free. Several examples covering a wide range of vehicle shapes (e.g., from stock cars to open-wheel race cars) are presented to demonstrate this nonlinear nature of the flow field.

49 CFR 210.9 - Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars. 210.9 Section 210.9 Transportation Other Regulations... locomotive, rail car, or consist of a locomotive and rail cars. A locomotive, rail car, or consist of a...

49 CFR 210.9 - Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars. 210.9 Section 210.9 Transportation Other Regulations... locomotive, rail car, or consist of a locomotive and rail cars. A locomotive, rail car, or consist of a...

49 CFR 210.9 - Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars. 210.9 Section 210.9 Transportation Other Regulations... locomotive, rail car, or consist of a locomotive and rail cars. A locomotive, rail car, or consist of a...

49 CFR 210.9 - Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars. 210.9 Section 210.9 Transportation Other Regulations... locomotive, rail car, or consist of a locomotive and rail cars. A locomotive, rail car, or consist of a...

49 CFR 210.9 - Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars. 210.9 Section 210.9 Transportation Other Regulations... locomotive, rail car, or consist of a locomotive and rail cars. A locomotive, rail car, or consist of a...

Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription.

PubMed

Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

2015-03-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR(ER)) to restore ER homeostasis. The AAA(+) ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPR(ER) genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA(+) ATPase, as a novel repressor of a subset of UPR(ER) genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPR(ER) genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. © 2015 The Authors.

Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress-induced gene transcription

PubMed Central

Marza, Esther; Taouji, Saïd; Barroso, Kim; Raymond, Anne-Aurélie; Guignard, Léo; Bonneu, Marc; Pallares-Lupon, Néstor; Dupuy, Jean-William; Fernandez-Zapico, Martin E; Rosenbaum, Jean; Palladino, Francesca; Dupuy, Denis; Chevet, Eric

2015-01-01

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPRER) to restore ER homeostasis. The AAA+ ATPase p97/CDC-48 plays key roles in ER stress by promoting both ER protein degradation and transcription of UPRER genes. Although the mechanisms associated with protein degradation are now well established, the molecular events involved in the regulation of gene transcription by p97/CDC-48 remain unclear. Using a reporter-based genome-wide RNAi screen in combination with quantitative proteomic analysis in Caenorhabditis elegans, we have identified RUVB-2, a AAA+ ATPase, as a novel repressor of a subset of UPRER genes. We show that degradation of RUVB-2 by CDC-48 enhances expression of ER stress response genes through an XBP1-dependent mechanism. The functional interplay between CDC-48 and RUVB-2 in controlling transcription of select UPRER genes appears conserved in human cells. Together, these results describe a novel role for p97/CDC-48, whereby its role in protein degradation is integrated with its role in regulating expression of ER stress response genes. PMID:25652260

The kinematic advantage of electric cars

NASA Astrophysics Data System (ADS)

Meyn, Jan-Peter

2015-11-01

Acceleration of a common car with with a turbocharged diesel engine is compared to the same type with an electric motor in terms of kinematics. Starting from a state of rest, the electric car reaches a distant spot earlier than the diesel car, even though the latter has a better specification for engine power and average acceleration from 0 to 100 km h-1. A three phase model of acceleration as a function of time fits the data of the electric car accurately. The first phase is a quadratic growth of acceleration in time. It is shown that the tenfold higher coefficient for the first phase accounts for most of the kinematic advantage of the electric car.

Minimizing the injury potential of deploying airbag interactions with car occupants.

PubMed

Mertz, Harold J; Prasad, Priya; Dalmotas, Dainius

2013-11-01

Minimizing the injury potential of the interactions between deploying airbags and car occupants is the major issue with the design of airbag systems. This concern was identified in 1964 by Carl Clark when he presented the results of human volunteer and dummy testing of the "Airstop" system that was being developed for aircraft. The following is a chronological summary of the actions taken by the car manufacturers, airbag suppliers, SAE and ISO task groups, research institutes and universities, and consumer and government groups to address this issue.

30 CFR 56.19079 - Blocking mine cars.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Blocking mine cars. 56.19079 Section 56.19079... Hoisting Procedures § 56.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

30 CFR 57.19079 - Blocking mine cars.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Blocking mine cars. 57.19079 Section 57.19079... Hoisting Procedures § 57.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

30 CFR 57.19079 - Blocking mine cars.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Blocking mine cars. 57.19079 Section 57.19079... Hoisting Procedures § 57.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

30 CFR 57.19079 - Blocking mine cars.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Blocking mine cars. 57.19079 Section 57.19079... Hoisting Procedures § 57.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

49 CFR 38.109 - Between-car barriers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false Between-car barriers. 38.109 Section 38.109... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Commuter Rail Cars and Systems § 38.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided...

49 CFR 38.109 - Between-car barriers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Between-car barriers. 38.109 Section 38.109... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Commuter Rail Cars and Systems § 38.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided...

30 CFR 56.19079 - Blocking mine cars.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Blocking mine cars. 56.19079 Section 56.19079... Hoisting Procedures § 56.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

49 CFR 38.109 - Between-car barriers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Between-car barriers. 38.109 Section 38.109... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Commuter Rail Cars and Systems § 38.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided...

49 CFR 38.109 - Between-car barriers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Between-car barriers. 38.109 Section 38.109... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Commuter Rail Cars and Systems § 38.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided...

30 CFR 56.19079 - Blocking mine cars.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Blocking mine cars. 56.19079 Section 56.19079... Hoisting Procedures § 56.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

30 CFR 56.19079 - Blocking mine cars.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Blocking mine cars. 56.19079 Section 56.19079... Hoisting Procedures § 56.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

30 CFR 57.19079 - Blocking mine cars.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Blocking mine cars. 57.19079 Section 57.19079... Hoisting Procedures § 57.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

30 CFR 57.19079 - Blocking mine cars.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Blocking mine cars. 57.19079 Section 57.19079... Hoisting Procedures § 57.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

49 CFR 38.109 - Between-car barriers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false Between-car barriers. 38.109 Section 38.109... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Commuter Rail Cars and Systems § 38.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided...

30 CFR 56.19079 - Blocking mine cars.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Blocking mine cars. 56.19079 Section 56.19079... Hoisting Procedures § 56.19079 Blocking mine cars. Where mine cars are hoisted by cage or skip, means for blocking cars shall be provided at all landings and also on the cage. ...

49 CFR 174.57 - Cleaning cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Cleaning cars. 174.57 Section 174.57... and Loading Requirements § 174.57 Cleaning cars. All hazardous material which has leaked from a package in any rail car or on other railroad property must be carefully removed. ...

49 CFR 174.57 - Cleaning cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Cleaning cars. 174.57 Section 174.57... and Loading Requirements § 174.57 Cleaning cars. All hazardous material which has leaked from a package in any rail car or on other railroad property must be carefully removed. ...

49 CFR 174.57 - Cleaning cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Cleaning cars. 174.57 Section 174.57... and Loading Requirements § 174.57 Cleaning cars. All hazardous material which has leaked from a package in any rail car or on other railroad property must be carefully removed. ...

49 CFR 174.57 - Cleaning cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Cleaning cars. 174.57 Section 174.57... and Loading Requirements § 174.57 Cleaning cars. All hazardous material which has leaked from a package in any rail car or on other railroad property must be carefully removed. ...

49 CFR 174.57 - Cleaning cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Cleaning cars. 174.57 Section 174.57... and Loading Requirements § 174.57 Cleaning cars. All hazardous material which has leaked from a package in any rail car or on other railroad property must be carefully removed. ...

Car Builder: Design, Construct and Test Your Own Cars. School Version with Lesson Plans. [CD-ROM].

ERIC Educational Resources Information Center

Highsmith, Joni Bitman

Car Builder is a scientific CD-ROM-based simulation program that lets students design, construct, modify, test, and compare their own cars. Students can design sedans, four-wheel-drive vehicles, vans, sport cars, and hot rods. They may select for aerodynamics, power, and racing ability, or economic and fuel efficiency. It is a program that teaches…

36 CFR 1192.109 - Between-car barriers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Between-car barriers. 1192... Commuter Rail Cars and Systems § 1192.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided, devices or systems shall be...

49 CFR 173.10 - Tank car shipments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Tank car shipments. 173.10 Section 173.10... SHIPMENTS AND PACKAGINGS General § 173.10 Tank car shipments. (a) Tank cars containing any 2.1 material... facilities which have been equipped for piping the liquid from tank cars to permanent storage tanks of...

49 CFR 173.10 - Tank car shipments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Tank car shipments. 173.10 Section 173.10... SHIPMENTS AND PACKAGINGS General § 173.10 Tank car shipments. (a) Tank cars containing any 2.1 material... facilities which have been equipped for piping the liquid from tank cars to permanent storage tanks of...

36 CFR 1192.109 - Between-car barriers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Between-car barriers. 1192... Commuter Rail Cars and Systems § 1192.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided, devices or systems shall be...

49 CFR 173.10 - Tank car shipments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Tank car shipments. 173.10 Section 173.10... SHIPMENTS AND PACKAGINGS General § 173.10 Tank car shipments. (a) Tank cars containing any 2.1 material... facilities which have been equipped for piping the liquid from tank cars to permanent storage tanks of...

49 CFR 173.10 - Tank car shipments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Tank car shipments. 173.10 Section 173.10... SHIPMENTS AND PACKAGINGS General § 173.10 Tank car shipments. (a) Tank cars containing any 2.1 material... facilities which have been equipped for piping the liquid from tank cars to permanent storage tanks of...

36 CFR 1192.109 - Between-car barriers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Between-car barriers. 1192... Commuter Rail Cars and Systems § 1192.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided, devices or systems shall be...

49 CFR 173.10 - Tank car shipments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Tank car shipments. 173.10 Section 173.10... SHIPMENTS AND PACKAGINGS General § 173.10 Tank car shipments. (a) Tank cars containing any 2.1 material... facilities which have been equipped for piping the liquid from tank cars to permanent storage tanks of...

36 CFR 1192.109 - Between-car barriers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Between-car barriers. 1192... Commuter Rail Cars and Systems § 1192.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided, devices or systems shall be...

49 CFR 212.217 - Car inspector.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Car inspector. 212.217 Section 212.217..., DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State Inspection Personnel § 212.217 Car inspector. (a) The car inspector is required, at a minimum, to be able to conduct independent inspections of...

49 CFR 212.217 - Car inspector.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Car inspector. 212.217 Section 212.217..., DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State Inspection Personnel § 212.217 Car inspector. (a) The car inspector is required, at a minimum, to be able to conduct independent inspections of...

49 CFR 212.217 - Car inspector.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Car inspector. 212.217 Section 212.217..., DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State Inspection Personnel § 212.217 Car inspector. (a) The car inspector is required, at a minimum, to be able to conduct independent inspections of...

49 CFR 212.217 - Car inspector.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Car inspector. 212.217 Section 212.217..., DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State Inspection Personnel § 212.217 Car inspector. (a) The car inspector is required, at a minimum, to be able to conduct independent inspections of...

49 CFR 212.217 - Car inspector.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Car inspector. 212.217 Section 212.217..., DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State Inspection Personnel § 212.217 Car inspector. (a) The car inspector is required, at a minimum, to be able to conduct independent inspections of...

49 CFR 179.300 - General specifications applicable to multi-unit tank car tanks designed to be removed from car...

Code of Federal Regulations, 2012 CFR

2012-10-01

... tank car tanks designed to be removed from car structure for filling and emptying (Classes DOT-106A and...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Multi-Unit Tank Car Tanks (Classes DOT-106A and 110AW) § 179.300...

49 CFR 179.300 - General specifications applicable to multi-unit tank car tanks designed to be removed from car...

Code of Federal Regulations, 2011 CFR

2011-10-01

... tank car tanks designed to be removed from car structure for filling and emptying (Classes DOT-106A and...) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Specifications for Multi-Unit Tank Car Tanks (Classes DOT-106A and 110AW) § 179.300...

Getting More Mileage out of Mousetrap Cars

ERIC Educational Resources Information Center

Rutherford, Sandra; Wylo, Bonnie

2004-01-01

Building and racing mousetrap cars is a common activity in many eighth- and ninth-grade physical science classrooms. However, once students have raced their cars, most mousetrap assignments come to an end. In this article, the authors developed a project to help teachers get more mileage out of mousetrap cars. The Mousetrap Car Project addresses…

Dichlorodiphenyltrichloroethane technical mixture regulates cell cycle and apoptosis genes through the activation of CAR and ERα in mouse livers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Pustylnyak, Vladimir O., E-mail: pustylnyak@ngs.ru

Dichlorodiphenyltrichloroethane (DDT) is a widely used organochlorine pesticide and a xenoestrogen that promotes rodent hepatomegaly and tumours. A recent study has shown significant correlation between DDT serum concentration and liver cancer incidence in humans, but the underlying mechanisms remain elusive. We hypothesised that a mixture of DDT isomers could exert effects on the liver through pathways instead of classical ERs. The acute effects of a DDT mixture containing the two major isomers p,p′-DDT (85%) and o,p′-DDT (15%) on CAR and ERα receptors and their cell cycle and apoptosis target genes were studied in mouse livers. ChIP results demonstrated increased CARmore » and ERα recruitment to their specific target gene binding sites in response to the DDT mixture. The results of real-time RT-PCR were consistent with the ChIP data and demonstrated that the DDT was able to activate both CAR and ERα in mouse livers, leading to target gene transcriptional increases including Cyp2b10, Gadd45β, cMyc, Mdm2, Ccnd1, cFos and E2f1. Western blot analysis demonstrated increases in cell cycle progression proteins cMyc, Cyclin D1, CDK4 and E2f1 and anti-apoptosis proteins Mdm2 and Gadd45β. In addition, DDT exposure led to Rb phosphorylation. Increases in cell cycle progression and anti-apoptosis proteins were accompanied by a decrease in p53 content and its transcriptional activity. However, the DDT was unable to stimulate the β-catenin signalling pathway, which can play an important role in hepatocyte proliferation. Thus, our results indicate that DDT treatment may result in cell cycle progression and apoptosis inhibition through CAR- and ERα-mediated gene activation in mouse livers. These findings suggest that the proliferative and anti-apoptotic conditions induced by CAR and ERα activation may be important contributors to the early stages of hepatocarcinogenesis as produced by DDT in rodent livers. - Highlights: • DDT activated both CAR and ERα and their

Video monitoring system for car seat

NASA Technical Reports Server (NTRS)

Elrod, Susan Vinz (Inventor); Dabney, Richard W. (Inventor)

2004-01-01

A video monitoring system for use with a child car seat has video camera(s) mounted in the car seat. The video images are wirelessly transmitted to a remote receiver/display encased in a portable housing that can be removably mounted in the vehicle in which the car seat is installed.

Car Ownership and Welfare-to-Work

ERIC Educational Resources Information Center

Ong, Paul M.

2002-01-01

This study examines the role of car ownership in facilitating employment among recipients under the current welfare-to-work law. Because of a potential problem with simultaneity, the analysis uses predicted car ownership constructed from two instrumental variables, insurance premiums and population density for car ownership. The data come from a…

Structure of adenovirus bound to cellular receptor car

DOEpatents

Freimuth, Paul I.

2004-05-18

Disclosed is a mutant adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have significantly weakened binding affinity for CARD1 relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type. In the method, residues of the adenovirus fiber protein knob domain which are predicted to alter D1 binding when mutated, are identified from the crystal structure coordinates of the AD12knob:CAR-D1 complex. A mutation which alters one or more of the identified residues is introduced into the genome of the adenovirus to generate a mutant adenovirus. Whether or not the mutant produced exhibits altered adenovirus-CAR binding properties is then determined.

49 CFR 180.507 - Qualification of tank cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Qualification of tank cars. 180.507 Section 180... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.507 Qualification of tank cars. (a) Each tank car marked as meeting a “DOT” specification or any other tank car used...

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

PubMed Central

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons. PMID:27698666

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites.

PubMed

Irizarry, Kristopher J L; Bryden, Randall L

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus . Our results provide insight into pigment phenotypes in pythons.

Functional CAR models for large spatially correlated functional datasets.

PubMed

Zhang, Lin; Baladandayuthapani, Veerabhadran; Zhu, Hongxiao; Baggerly, Keith A; Majewski, Tadeusz; Czerniak, Bogdan A; Morris, Jeffrey S

2016-01-01

We develop a functional conditional autoregressive (CAR) model for spatially correlated data for which functions are collected on areal units of a lattice. Our model performs functional response regression while accounting for spatial correlations with potentially nonseparable and nonstationary covariance structure, in both the space and functional domains. We show theoretically that our construction leads to a CAR model at each functional location, with spatial covariance parameters varying and borrowing strength across the functional domain. Using basis transformation strategies, the nonseparable spatial-functional model is computationally scalable to enormous functional datasets, generalizable to different basis functions, and can be used on functions defined on higher dimensional domains such as images. Through simulation studies, we demonstrate that accounting for the spatial correlation in our modeling leads to improved functional regression performance. Applied to a high-throughput spatially correlated copy number dataset, the model identifies genetic markers not identified by comparable methods that ignore spatial correlations.

Stock-car racing makes intuitive physicists

NASA Astrophysics Data System (ADS)

Gwynne, Peter

2008-03-01

Formula One races involve cars festooned with gadgets and complex electronic devices, in which millions of dollars are spent refining a vehicle's aerodynamics and reducing its weight. But in events run by America's National Association of Stock Car Auto Racing (NASCAR), cars hurtle round an oval track at speeds of about 300 km h-1 without the help of the complex sensors that are employed in Formula One cars. To avoid crashing, drivers must make their own adjustments to track conditions, engine problems and the traffic around them.

49 CFR 180.507 - Qualification of tank cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Qualification of tank cars. 180.507 Section 180... MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.507 Qualification of tank cars. (a) Each tank car marked as meeting a “DOT” specification or any other tank car used for the transportation...

49 CFR 180.507 - Qualification of tank cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Qualification of tank cars. 180.507 Section 180... MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.507 Qualification of tank cars. (a) Each tank car marked as meeting a “DOT” specification or any other tank car used for the transportation...

49 CFR 180.507 - Qualification of tank cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Qualification of tank cars. 180.507 Section 180... MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.507 Qualification of tank cars. (a) Each tank car marked as meeting a “DOT” specification or any other tank car used for the transportation...

49 CFR 180.507 - Qualification of tank cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Qualification of tank cars. 180.507 Section 180... MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.507 Qualification of tank cars. (a) Each tank car marked as meeting a “DOT” specification or any other tank car used for the transportation...

Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy.

PubMed

Yeku, Oladapo O; Brentjens, Renier J

2016-04-15

Chimaeric antigen receptor (CAR) T-cells are T-cells that have been genetically modified to express an artificial construct consisting of a synthetic T-cell receptor (TCR) targeted to a predetermined antigen expressed on a tumour. Coupling the T-cell receptor to a CD3ζ signalling domain paved the way for first generation CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies. Optimization with additional signalling domains such as CD28 or 4-1BB in addition to CD3ζ provided T-cell activation signal 2 and further improved the efficacy and persistence of these second generation CAR T-cells. Third generation CAR T-cells which utilize two tandem costimulatory domains have also been reported. In this review, we discuss a different approach to optimization of CAR T-cells. Through additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. The choice of the 'armor' agent is based on knowledge of the tumour microenvironment and the roles of other elements of the innate and adaptive immune system. Although there are several variants of armored CAR T-cells under investigation, here we focus on three unique approaches using interleukin-12 (IL-12), CD40L and 4-1BBL. These agents have been shown to further enhance CAR T-cell efficacy and persistence in the face of a hostile tumour microenvironment via different mechanisms. © 2016 Authors; published by Portland Press Limited.

Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy

PubMed Central

Yeku, Oladapo O.; Brentjens, Renier J.

2017-01-01

Chimaeric antigen receptor (CAR) T-cells are T-cells that have been genetically modified to express an artificial construct consisting of a synthetic T-cell receptor (TCR) targeted to a predetermined antigen expressed on a tumour. Coupling the T-cell receptor to a CD3ζ signalling domain paved the way for first generation CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies. Optimization with additional signalling domains such as CD28 or 4-1BB in addition to CD3ζ provided T-cell activation signal 2 and further improved the efficacy and persistence of these second generation CAR T-cells. Third generation CAR T-cells which utilize two tandem costimulatory domains have also been reported. In this review, we discuss a different approach to optimization of CAR T-cells. Through additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. The choice of the ‘armor’ agent is based on knowledge of the tumour microenvironment and the roles of other elements of the innate and adaptive immune system. Although there are several variants of armored CAR T-cells under investigation, here we focus on three unique approaches using interleukin-12 (IL-12), CD40L and 4-1BBL. These agents have been shown to further enhance CAR T-cell efficacy and persistence in the face of a hostile tumour microenvironment via different mechanisms. PMID:27068948

Greater cerebellar gray matter volume in car drivers: an exploratory voxel-based morphometry study

PubMed Central

Sakai, Hiroyuki; Ando, Takafumi; Sadato, Norihiro; Uchiyama, Yuji

2017-01-01

Previous functional neuroimaging studies have identified multiple brain areas associated with distinct aspects of car driving in simulated traffic environments. Few studies, however, have examined brain morphology associated with everyday car-driving experience in real traffic. Thus, the aim of the current study was to identify gray matter volume differences between drivers and non-drivers. We collected T1-weighted structural brain images from 73 healthy young adults (36 drivers and 37 non-drivers). We performed a whole-brain voxel-based morphometry analysis to examine between-group differences in regional gray matter volume. Compared with non-drivers, drivers showed significantly greater gray matter volume in the left cerebellar hemisphere, which has been associated with cognitive rather than motor functioning. In contrast, we found no brain areas with significantly greater gray matter volume in non-drivers compared with drivers. Our findings indicate that experience with everyday car driving in real traffic is associated with greater gray matter volume in the left cerebellar hemisphere. This brain area may be involved in abilities that are critical for driving a car, but are not commonly or frequently used during other daily activities. PMID:28417971

Greater cerebellar gray matter volume in car drivers: an exploratory voxel-based morphometry study.

PubMed

Sakai, Hiroyuki; Ando, Takafumi; Sadato, Norihiro; Uchiyama, Yuji

2017-04-18

Previous functional neuroimaging studies have identified multiple brain areas associated with distinct aspects of car driving in simulated traffic environments. Few studies, however, have examined brain morphology associated with everyday car-driving experience in real traffic. Thus, the aim of the current study was to identify gray matter volume differences between drivers and non-drivers. We collected T1-weighted structural brain images from 73 healthy young adults (36 drivers and 37 non-drivers). We performed a whole-brain voxel-based morphometry analysis to examine between-group differences in regional gray matter volume. Compared with non-drivers, drivers showed significantly greater gray matter volume in the left cerebellar hemisphere, which has been associated with cognitive rather than motor functioning. In contrast, we found no brain areas with significantly greater gray matter volume in non-drivers compared with drivers. Our findings indicate that experience with everyday car driving in real traffic is associated with greater gray matter volume in the left cerebellar hemisphere. This brain area may be involved in abilities that are critical for driving a car, but are not commonly or frequently used during other daily activities.

Lighting innovations in concept cars

NASA Astrophysics Data System (ADS)

Berlitz, Stephan; Huhn, Wolfgang

2005-02-01

Concept cars have their own styling process. Because of the big media interest they give a big opportunity to bring newest technology with styling ideas to different fairgrounds. The LED technology in the concept cars Audi Pikes Peak, Nuvolari and Le Mans will be explained. Further outlook for the Audi LED strategy starting with LED Daytime Running Lamp will be given. The close work between styling and technical engineers results in those concept cars and further technical innovations based on LED technologies.

49 CFR 174.110 - Car magazine.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Car magazine. 174.110 Section 174.110...) Materials § 174.110 Car magazine. When specially authorized by the carrier, Division 1.1 or 1.2 (explosive) materials in quantity not exceeding 68 kg (150 pounds) may be carried in construction or repair cars if the...

49 CFR 174.110 - Car magazine.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Car magazine. 174.110 Section 174.110...) Materials § 174.110 Car magazine. When specially authorized by the carrier, Division 1.1 or 1.2 (explosive) materials in quantity not exceeding 68 kg (150 pounds) may be carried in construction or repair cars if the...

49 CFR 174.110 - Car magazine.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Car magazine. 174.110 Section 174.110...) Materials § 174.110 Car magazine. When specially authorized by the carrier, Division 1.1 or 1.2 (explosive) materials in quantity not exceeding 68 kg (150 pounds) may be carried in construction or repair cars if the...

49 CFR 174.110 - Car magazine.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Car magazine. 174.110 Section 174.110...) Materials § 174.110 Car magazine. When specially authorized by the carrier, Division 1.1 or 1.2 (explosive) materials in quantity not exceeding 68 kg (150 pounds) may be carried in construction or repair cars if the...

49 CFR 174.110 - Car magazine.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Car magazine. 174.110 Section 174.110...) Materials § 174.110 Car magazine. When specially authorized by the carrier, Division 1.1 or 1.2 (explosive) materials in quantity not exceeding 68 kg (150 pounds) may be carried in construction or repair cars if the...

A single amino acid controls the functional switch of human constitutive androstane receptor (CAR) 1 to the xenobiotic-sensitive splicing variant CAR3.

PubMed

Chen, Tao; Tompkins, Leslie M; Li, Linhao; Li, Haishan; Kim, Gregory; Zheng, Yuxin; Wang, Hongbing

2010-01-01

The constitutive androstane receptor (CAR) is constitutively activated in immortalized cell lines independent of xenobiotic stimuli. This feature of CAR has limited its use as a sensor for xenobiotic-induced expression of drug-metabolizing enzymes. Recent reports, however, reveal that a splicing variant of human CAR (hCAR3), which contains an insertion of five amino acids (APYLT), exhibits low basal but xenobiotic-inducible activities in cell-based reporter assays. Nonetheless, the underlying mechanisms of this functional shift are not well understood. We have now generated chimeric constructs containing various residues of the five amino acids of hCAR3 and examined their response to typical hCAR activators. Our results showed that the retention of alanine (hCAR1+A) alone is sufficient to confer the constitutively activated hCAR1 to the xenobiotic-sensitive hCAR3. It is noteworthy that hCAR1+A was significantly activated by a series of known hCAR activators, and displayed activation superior to that of hCAR3. Moreover, intracellular localization assays revealed that hCAR1+A exhibits nuclear accumulation upon 6-(4-chlorophenyl) imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) treatment in COS1 cells, which differs from the spontaneous nuclear distribution of hCAR1 and the nontranslocatable hCAR3. Mammalian two-hybrid and glutathione S-transferase pull-down assays further demonstrated that hCAR1+A interacts with the coactivator SRC-1 and GRIP-1 at low level before activation, while at significantly enhanced level in the presence of CITCO. Thus, the alanine residue in the insertion of hCAR3 seems in charge of the xenobiotic response of hCAR3 through direct and indirect mechanisms. Activation of hCAR1+A may represent a sensitive avenue for the identification of hCAR activators.

A Single Amino Acid Controls the Functional Switch of Human Constitutive Androstane Receptor (CAR) 1 to the Xenobiotic-Sensitive Splicing Variant CAR3

PubMed Central

Chen, Tao; Tompkins, Leslie M.; Li, Linhao; Li, Haishan; Kim, Gregory; Zheng, Yuxin

2010-01-01

The constitutive androstane receptor (CAR) is constitutively activated in immortalized cell lines independent of xenobiotic stimuli. This feature of CAR has limited its use as a sensor for xenobiotic-induced expression of drug-metabolizing enzymes. Recent reports, however, reveal that a splicing variant of human CAR (hCAR3), which contains an insertion of five amino acids (APYLT), exhibits low basal but xenobiotic-inducible activities in cell-based reporter assays. Nonetheless, the underlying mechanisms of this functional shift are not well understood. We have now generated chimeric constructs containing various residues of the five amino acids of hCAR3 and examined their response to typical hCAR activators. Our results showed that the retention of alanine (hCAR1+A) alone is sufficient to confer the constitutively activated hCAR1 to the xenobiotic-sensitive hCAR3. It is noteworthy that hCAR1+A was significantly activated by a series of known hCAR activators, and displayed activation superior to that of hCAR3. Moreover, intracellular localization assays revealed that hCAR1+A exhibits nuclear accumulation upon 6-(4-chlorophenyl) imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) treatment in COS1 cells, which differs from the spontaneous nuclear distribution of hCAR1 and the nontranslocatable hCAR3. Mammalian two-hybrid and glutathione S-transferase pull-down assays further demonstrated that hCAR1+A interacts with the coactivator SRC-1 and GRIP-1 at low level before activation, while at significantly enhanced level in the presence of CITCO. Thus, the alanine residue in the insertion of hCAR3 seems in charge of the xenobiotic response of hCAR3 through direct and indirect mechanisms. Activation of hCAR1+A may represent a sensitive avenue for the identification of hCAR activators. PMID:19820207

Dual direction blower system powered by solar energy to reduce car cabin temperature in open parking condition

NASA Astrophysics Data System (ADS)

Hamdan, N. S.; Radzi, M. F. M.; Damanhuri, A. A. M.; Mokhtar, S. N.

2017-10-01

El-nino phenomenon that strikes Malaysia with temperature recorded more than 35°C can lead to extreme temperature rise in car cabin up to 80°C. Various problems will arise due to this extreme rising of temperature such as the occupant are vulnerable to heat stroke, emission of benzene gas that can cause cancer due to reaction of high temperature with interior compartments, and damage of compartments in the car. The current solution available to reduce car cabin temperature including tinted of window and portable heat rejection device that are available in the market. As an alternative to reduce car cabin temperature, this project modifies the car’s air conditioning blower motor into dual direction powered by solar energy and identifies its influence to temperature inside the car, parked under scorching sun. By reducing the car cabin temperature up to 10°C which equal to 14% of reduction in the car cabin temperature, this simple proposed system aims to provide comfort to users due to its capability in improving the quality of air and moisture in the car cabin.

The Electric Cars Challenge

ERIC Educational Resources Information Center

Roman, Harry T.

2011-01-01

Over 100 years ago, the great inventor Thomas Edison warned that gasoline cars would pollute the environment and lead to gasoline shortages. He preferred the use of clean electric vehicles. He also put his money where his mouth was and developed an entirely new alkaline storage battery system for his beloved cars, the nickel-iron storage battery.…

Influence maximization in time bounded network identifies transcription factors regulating perturbed pathways

PubMed Central

Jo, Kyuri; Jung, Inuk; Moon, Ji Hwan; Kim, Sun

2016-01-01

Motivation: To understand the dynamic nature of the biological process, it is crucial to identify perturbed pathways in an altered environment and also to infer regulators that trigger the response. Current time-series analysis methods, however, are not powerful enough to identify perturbed pathways and regulators simultaneously. Widely used methods include methods to determine gene sets such as differentially expressed genes or gene clusters and these genes sets need to be further interpreted in terms of biological pathways using other tools. Most pathway analysis methods are not designed for time series data and they do not consider gene-gene influence on the time dimension. Results: In this article, we propose a novel time-series analysis method TimeTP for determining transcription factors (TFs) regulating pathway perturbation, which narrows the focus to perturbed sub-pathways and utilizes the gene regulatory network and protein–protein interaction network to locate TFs triggering the perturbation. TimeTP first identifies perturbed sub-pathways that propagate the expression changes along the time. Starting points of the perturbed sub-pathways are mapped into the network and the most influential TFs are determined by influence maximization technique. The analysis result is visually summarized in TF-Pathway map in time clock. TimeTP was applied to PIK3CA knock-in dataset and found significant sub-pathways and their regulators relevant to the PIP3 signaling pathway. Availability and Implementation: TimeTP is implemented in Python and available at http://biohealth.snu.ac.kr/software/TimeTP/. Supplementary information: Supplementary data are available at Bioinformatics online. Contact: sunkim.bioinfo@snu.ac.kr PMID:27307609

49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Tank cars without side sills and tank cars with... APPLIANCE STANDARDS § 231.8 Tank cars without side sills and tank cars with short side sills and end platforms. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see § 231.1(a)(1...

49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Tank cars without side sills and tank cars with... APPLIANCE STANDARDS § 231.8 Tank cars without side sills and tank cars with short side sills and end platforms. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see § 231.1(a)(1...

49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Tank cars without side sills and tank cars with... APPLIANCE STANDARDS § 231.8 Tank cars without side sills and tank cars with short side sills and end platforms. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see § 231.1(a)(1...

49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Tank cars without side sills and tank cars with... APPLIANCE STANDARDS § 231.8 Tank cars without side sills and tank cars with short side sills and end platforms. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see § 231.1(a)(1...

49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Tank cars without side sills and tank cars with... APPLIANCE STANDARDS § 231.8 Tank cars without side sills and tank cars with short side sills and end platforms. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see § 231.1(a)(1...

Use of seatbelts in cars with automatic belts.

PubMed Central

Williams, A F; Wells, J K; Lund, A K; Teed, N J

1992-01-01

Use of seatbelts in late model cars with automatic or manual belt systems was observed in suburban Washington, DC, Chicago, Los Angeles, and Philadelphia. In cars with automatic two-point belt systems, the use of shoulder belts by drivers was substantially higher than in the same model cars with manual three-point belts. This finding was true in varying degrees whatever the type of automatic belt, including cars with detachable nonmotorized belts, cars with detachable motorized belts, and especially cars with nondetachable motorized belts. Most of these automatic shoulder belts systems include manual lap belts. Use of lap belts was lower in cars with automatic two-point belt systems than in the same model cars with manual three-point belts; precisely how much lower could not be reliably estimated in this survey. Use of shoulder and lap belts was slightly higher in General Motors cars with detachable automatic three-point belts compared with the same model cars with manual three-point belts; in Hondas there was no difference in the rates of use of manual three-point belts and the rates of use of automatic three-point belts. PMID:1561301

Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prokopec, Stephenie D.; Watson, John D.; Lee, Jamie

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male andmore » female C57BL/6 mice to 500 μg/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6 h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144 h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear. - Highlights: • Differences exist between the toxicity phenotypes to TCDD in male and female mice. • TCDD-mediated transcriptomic differences were identified between the sexes. • Resistant female mice displayed a large, early-onset, transcriptomic

49 CFR 232.305 - Single car air brake tests.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Single car air brake tests. 232.305 Section 232... car air brake tests. (a) Single car air brake tests shall be performed by a qualified person in... single car air brake test on a car when: (1) A car has its brakes cut-out or inoperative when removed...

49 CFR 232.305 - Single car air brake tests.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Single car air brake tests. 232.305 Section 232... car air brake tests. (a) Single car air brake tests shall be performed by a qualified person in... single car air brake test on a car when: (1) A car has its brakes cut-out or inoperative when removed...

49 CFR 232.305 - Single car air brake tests.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Single car air brake tests. 232.305 Section 232... car air brake tests. (a) Single car air brake tests shall be performed by a qualified person in... single car air brake test on a car when: (1) A car has its brakes cut-out or inoperative when removed...

Comparative analysis of used car price evaluation models

NASA Astrophysics Data System (ADS)

Chen, Chuancan; Hao, Lulu; Xu, Cong

2017-05-01

An accurate used car price evaluation is a catalyst for the healthy development of used car market. Data mining has been applied to predict used car price in several articles. However, little is studied on the comparison of using different algorithms in used car price estimation. This paper collects more than 100,000 used car dealing records throughout China to do empirical analysis on a thorough comparison of two algorithms: linear regression and random forest. These two algorithms are used to predict used car price in three different models: model for a certain car make, model for a certain car series and universal model. Results show that random forest has a stable but not ideal effect in price evaluation model for a certain car make, but it shows great advantage in the universal model compared with linear regression. This indicates that random forest is an optimal algorithm when handling complex models with a large number of variables and samples, yet it shows no obvious advantage when coping with simple models with less variables.

Is this car looking at you? How anthropomorphism predicts fusiform face area activation when seeing cars.

PubMed

Kühn, Simone; Brick, Timothy R; Müller, Barbara C N; Gallinat, Jürgen

2014-01-01

Anthropomorphism encompasses the attribution of human characteristics to non-living objects. In particular the human tendency to see faces in cars has long been noticed, yet its neural correlates are unknown. We set out to investigate whether the fusiform face area (FFA) is associated with seeing human features in car fronts, or whether, the higher-level theory of mind network (ToM), namely temporoparietal junction (TPJ) and medial prefrontal cortex (MPFC) show a link to anthropomorphism. Twenty participants underwent fMRI scanning during a passive car-front viewing task. We extracted brain activity from FFA, TPJ and MPFC. After the fMRI session participants were asked to spontaneously list adjectives that characterize each car front. Five raters judged the degree to which each adjective can be applied as a characteristic of human beings. By means of linear mixed models we found that the implicit tendency to anthropomorphize individual car fronts predicts FFA, but not TPJ or MPFC activity. The results point to an important role of FFA in the phenomenon of ascribing human attributes to non-living objects. Interestingly, brain regions that have been associated with thinking about beliefs and mental states of others (TPJ, MPFC) do not seem to be related to anthropomorphism of car fronts.

Is This Car Looking at You? How Anthropomorphism Predicts Fusiform Face Area Activation when Seeing Cars

PubMed Central

Kühn, Simone; Brick, Timothy R.; Müller, Barbara C. N.; Gallinat, Jürgen

2014-01-01

Anthropomorphism encompasses the attribution of human characteristics to non-living objects. In particular the human tendency to see faces in cars has long been noticed, yet its neural correlates are unknown. We set out to investigate whether the fusiform face area (FFA) is associated with seeing human features in car fronts, or whether, the higher-level theory of mind network (ToM), namely temporoparietal junction (TPJ) and medial prefrontal cortex (MPFC) show a link to anthropomorphism. Twenty participants underwent fMRI scanning during a passive car-front viewing task. We extracted brain activity from FFA, TPJ and MPFC. After the fMRI session participants were asked to spontaneously list adjectives that characterize each car front. Five raters judged the degree to which each adjective can be applied as a characteristic of human beings. By means of linear mixed models we found that the implicit tendency to anthropomorphize individual car fronts predicts FFA, but not TPJ or MPFC activity. The results point to an important role of FFA in the phenomenon of ascribing human attributes to non-living objects. Interestingly, brain regions that have been associated with thinking about beliefs and mental states of others (TPJ, MPFC) do not seem to be related to anthropomorphism of car fronts. PMID:25517511

49 CFR 172.331 - Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. 172.331 Section 172.331 Transportation Other Regulations... packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. (a) Each person...

49 CFR 172.331 - Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. 172.331 Section 172.331 Transportation Other Regulations... packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. (a) Each person...

49 CFR 172.331 - Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. 172.331 Section 172.331 Transportation Other Regulations... packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. (a) Each person...

49 CFR 172.331 - Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. 172.331 Section 172.331 Transportation Other Regulations... packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. (a) Each person...

49 CFR 172.331 - Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Bulk packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. 172.331 Section 172.331 Transportation Other Regulations... packagings other than portable tanks, cargo tanks, tank cars and multi-unit tank car tanks. (a) Each person...

49 CFR 180.519 - Periodic retest and inspection of tank cars other than single-unit tank car tanks.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Periodic retest and inspection of tank cars other than single-unit tank car tanks. 180.519 Section 180.519 Transportation Other Regulations Relating to... (CONTINUED) CONTINUING QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars...

49 CFR 180.519 - Periodic retest and inspection of tank cars other than single-unit tank car tanks.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Periodic retest and inspection of tank cars other than single-unit tank car tanks. 180.519 Section 180.519 Transportation Other Regulations Relating to... (CONTINUED) CONTINUING QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars...

49 CFR 180.519 - Periodic retest and inspection of tank cars other than single-unit tank car tanks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Periodic retest and inspection of tank cars other than single-unit tank car tanks. 180.519 Section 180.519 Transportation Other Regulations Relating to... (CONTINUED) CONTINUING QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars...

49 CFR 180.519 - Periodic retest and inspection of tank cars other than single-unit tank car tanks.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Periodic retest and inspection of tank cars other than single-unit tank car tanks. 180.519 Section 180.519 Transportation Other Regulations Relating to... (CONTINUED) CONTINUING QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars...

Benefits of magnesium wheels for consumer cars

NASA Astrophysics Data System (ADS)

Frishfelds, Vilnis; Timuhins, Andrejs; Bethers, Uldis

2018-05-01

Advantages and disadvantages of magnesium wheels are considered based on a mechanical model of a car. Magnesium wheels are usually applied to racing cars as they provide slightly better strength/weight ratio than aluminum alloys. Do they provide notable benefits also for the everyday user when the car speeds do not exceed allowed speed limit? Distinct properties of magnesium rims are discussed. Apart from lighter weight of magnesium alloys, they are also good in dissipating the energy of vibrations. The role of energy dissipation in the rim of a wheel is estimated by a quarter car model. Improvements to safety by using the magnesium wheels are considered. Braking distance and responsiveness of the car is studied both with and without using an Anti Blocking System (ABS). Influence of rim weight on various handling parameters of the car is quantitatively tested.

Rear-facing car seat (image)

MedlinePlus

A rear-facing car seat position is recommended for a child who is very young. Extreme injury can occur in an accident because ... child. In a frontal crash a rear-facing car seat is best, because it cradles the head, ...

Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana

PubMed Central

Wu, Yuzhou; Hou, Jiexi; Yu, Fen; Nguyen, Suong T. T.; McCurdy, David W.

2018-01-01

Transfer cells (TCs) play important roles in facilitating enhanced rates of nutrient transport at key apoplasmic/symplasmic junctions along the nutrient acquisition and transport pathways in plants. TCs achieve this capacity by developing elaborate wall ingrowth networks which serve to increase plasma membrane surface area thus increasing the cell's surface area-to-volume ratio to achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma (PP) cells of Arabidopsis leaf veins trans-differentiate to become PP TCs which likely function in a two-step phloem loading mechanism by facilitating unloading of photoassimilates into the apoplasm for subsequent energy-dependent uptake into the sieve element/companion cell (SE/CC) complex. We are using PP TCs in Arabidopsis as a genetic model to identify transcription factors involved in coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo-Schiff propidium iodide-stained tissue revealed different profiles of temporal development of wall ingrowth deposition across maturing cotyledons and juvenile leaves, and a basipetal gradient of deposition across mature adult leaves. RNA-Seq analysis was undertaken to identify differentially expressed genes common to these three different profiles of wall ingrowth deposition. This analysis identified 68 transcription factors up-regulated two-fold or more in at least two of the three experimental comparisons, with six of these transcription factors belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC genes using insertional mutants revealed significant reductions in levels of wall ingrowth deposition, particularly in a double mutant of NAC056 and NAC018, as well as compromised sucrose-dependent root growth, indicating impaired capacity for phloem loading. Collectively, these results support the proposition that Clade III members of the NAC-domain family in Arabidopsis play important roles in regulating wall ingrowth

Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana.

PubMed

Wu, Yuzhou; Hou, Jiexi; Yu, Fen; Nguyen, Suong T T; McCurdy, David W

2018-01-01

Transfer cells (TCs) play important roles in facilitating enhanced rates of nutrient transport at key apoplasmic/symplasmic junctions along the nutrient acquisition and transport pathways in plants. TCs achieve this capacity by developing elaborate wall ingrowth networks which serve to increase plasma membrane surface area thus increasing the cell's surface area-to-volume ratio to achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma (PP) cells of Arabidopsis leaf veins trans -differentiate to become PP TCs which likely function in a two-step phloem loading mechanism by facilitating unloading of photoassimilates into the apoplasm for subsequent energy-dependent uptake into the sieve element/companion cell (SE/CC) complex. We are using PP TCs in Arabidopsis as a genetic model to identify transcription factors involved in coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo-Schiff propidium iodide-stained tissue revealed different profiles of temporal development of wall ingrowth deposition across maturing cotyledons and juvenile leaves, and a basipetal gradient of deposition across mature adult leaves. RNA-Seq analysis was undertaken to identify differentially expressed genes common to these three different profiles of wall ingrowth deposition. This analysis identified 68 transcription factors up-regulated two-fold or more in at least two of the three experimental comparisons, with six of these transcription factors belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC genes using insertional mutants revealed significant reductions in levels of wall ingrowth deposition, particularly in a double mutant of NAC056 and NAC018 , as well as compromised sucrose-dependent root growth, indicating impaired capacity for phloem loading. Collectively, these results support the proposition that Clade III members of the NAC-domain family in Arabidopsis play important roles in regulating wall

The sources, impact and management of car park runoff pollution: a review.

PubMed

Revitt, D Michael; Lundy, Lian; Coulon, Frédéric; Fairley, Martin

2014-12-15

Traffic emissions contribute significantly to the build-up of diffuse pollution loads on urban surfaces with their subsequent mobilisation and direct discharge posing problems for receiving water quality. This review focuses on the impact and mitigation of solids, metals, nutrients and organic pollutants in the runoff deriving from car parks. Variabilities in the discharged pollutant levels and in the potentials for pollutant mitigation complicate an impact assessment of car park runoff. The different available stormwater best management practices and proprietary devices are reported to be capable of reductions of between 20% and almost 100% for both suspended solids and a range of metals. This review contributes to prioritising the treatment options which can achieve the appropriate pollutant reductions whilst conforming to the site requirements of a typical car park. By applying different treatment scenarios to the runoff from a hypothetical car park, it is shown that optimal performance, in terms of ecological benefits for the receiving water, can be achieved using a treatment train incorporating permeable paving and bioretention systems. The review identifies existing research gaps and emphasises the pertinent management practices as well as design issues which are relevant to the mitigation of car park pollution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Driving kids to smoke? Children's reported exposure to smoke in cars and early smoking initiation.

PubMed

Glover, Marewa; Scragg, Robert; Min, Sandar; Kira, Anette; Nosa, Vili; McCool, Judith; Bullen, Chris

2011-11-01

The health risks associated with second hand smoke (SHS) are well-known. However, little is known about exposure to SHS in cars and risk of smoking uptake. This paper investigates the association between pre-adolescents reported exposure to smoking in cars and prevalence of early stage smoking activity. Data from Keeping Kids Smokefree baseline surveys of students were used to investigate smoking status and reported exposure to smoking in cars. Log binomial regression analyses were used to investigate if reported exposure to SHS in cars was associated with smoking prevalence. 83% of 5676 students invited took part. After controlling for all variables reported exposure to smoking in cars and homes were significantly associated with increased risk of initiated smoking (RR 1.87, 95% CI 1.43-2.44, and RR 1.5, 95% CI 1.13-1.97, respectively). Exposure to smoking in cars was substantially and significantly associated with risk of current smoking (RR 3.21, 95% CI 1.45-7.08). Early smoking uptake is associated with students' reported exposure to smoking in cars which confirms the importance of protecting children from SHS. Smoking in cars is under parental control and therefore modifiable. Moreover, children's reports of SHlS exposure offer a simple way of identifying families who can be targeted for tobacco control interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Shopping for a safer car

DOT National Transportation Integrated Search

2010-01-01

This brochure provides some helpful tips on what to look for when shopping for a safer car. Automakers are increasingly advertising the safety features of their cars. The problem is sorting out their claims and zeroing in on the safety features that ...

CARS temperature measurements in the fuel preburner of the Space Shuttle main engine: A feasibility study

NASA Technical Reports Server (NTRS)

Beiting, E. J.; Luthe, J. C.

1983-01-01

This report discusses the feasibility of making temperature profile measurements in the fuel preburner of the main engine of the space shuttle (SSME) using coherent anti-Stokes Raman spectroscopy (CARS). The principal thrust of the work is to identify problems associated with making CARS measurements in high temperature gas phase hydrogen at very high pressures (approx 400 atmospheres). To this end a theoretical study was made of the characteristics of the CAR spectra of H2 as a function of temperature and pressure and the accuracy with which temperatures can be extracted from this spectra. In addition the experimental problems associated with carrying out these measurements on a SSME at NSTL were identified. A conceptual design of a CARS system suitable for this work is included. Many of the results of the calculations made in this report are plotted as a function of temperature. In the course of presenting these results, it was necessary to decide whether the number of density or the pressure should be treated as a fixed parameter.

Eta Car: The Good, the Bad and the Ugly of Nebular and Stellar Confusion

NASA Technical Reports Server (NTRS)

Gull, T.R.; Sonneborn, G.; Jensen, A.G.; Nielsen, K.E.; Vieira Kover, G.; Hillier, D.J.

2008-01-01

Observations in the far-UV provide a unique opportunity to investigate the very massive star Eta Car and its hot binary companion, Eta Car B. Eta Car was observed with FUSE over a large portion of the 5.54 year spectroscopic period before and after the 2003.5 minimum. The observed spectrum is defined by strong stellar wind signatures, primarily from Eta Car A, complicated by the strong absorptions of the ejecta surrounding Eta Car plus interstellar absorption. The Homunculus and Little Homunculus are massive bipolar ejecta historically associable with LBV outbursts in the 1840s and the 1890s and are linked to absorptions at -513 and -146 km/s, respectively. The FUSE spectra are confused by the extended nebulosity and thermal drifting of the FUSE co-pointed instruments. Interpretation is further complicated by two B-stars sufficiently close to h Car to be included most of the time in the large FUSE aperture. Followup observations partially succeeded in obtaining spectra of at least one of these B-stars through the smaller apertures, allowing potential separation of the B-star contributions and h Car. A complete analysis of all available spectra is currently underway. Our ultimate goals are to directly detect the hot secondary star if possible with FUSE and to identify the absorption contributions to the overall spectrum especially of the stellar members and the massive ejecta.

19 CFR 151.26 - Molasses in tank cars.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Molasses in tank cars. 151.26 Section 151.26....26 Molasses in tank cars. When molasses is imported in tank cars, the importer shall file with the... sugars or the character of the molasses in the different cars. ...

49 CFR 215.119 - Defective freight car truck.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Defective freight car truck. 215.119 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.119 Defective freight car truck. A railroad may not place or continue in service a...

19 CFR 151.26 - Molasses in tank cars.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Molasses in tank cars. 151.26 Section 151.26....26 Molasses in tank cars. When molasses is imported in tank cars, the importer shall file with the... sugars or the character of the molasses in the different cars. ...

49 CFR 215.119 - Defective freight car truck.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Defective freight car truck. 215.119 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.119 Defective freight car truck. A railroad may not place or continue in service a...

49 CFR 215.119 - Defective freight car truck.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Defective freight car truck. 215.119 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.119 Defective freight car truck. A railroad may not place or continue in service a...

19 CFR 151.26 - Molasses in tank cars.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Molasses in tank cars. 151.26 Section 151.26....26 Molasses in tank cars. When molasses is imported in tank cars, the importer shall file with the... sugars or the character of the molasses in the different cars. ...

19 CFR 151.26 - Molasses in tank cars.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Molasses in tank cars. 151.26 Section 151.26....26 Molasses in tank cars. When molasses is imported in tank cars, the importer shall file with the... sugars or the character of the molasses in the different cars. ...

49 CFR 215.119 - Defective freight car truck.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Defective freight car truck. 215.119 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.119 Defective freight car truck. A railroad may not place or continue in service a...

49 CFR 215.119 - Defective freight car truck.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Defective freight car truck. 215.119 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Freight Car Components Suspension System § 215.119 Defective freight car truck. A railroad may not place or continue in service a...

19 CFR 151.26 - Molasses in tank cars.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Molasses in tank cars. 151.26 Section 151.26....26 Molasses in tank cars. When molasses is imported in tank cars, the importer shall file with the... sugars or the character of the molasses in the different cars. ...

In vivo hyperspectral CARS and FWM microscopy of carotenoid accumulation in H. Pluvialis

NASA Astrophysics Data System (ADS)

Slepkov, Aaron D.; Barlow, Aaron M.; Ridsdale, Andrew; McGinn, Patrick J.; Stolow, Albert

2014-02-01

Coherent anti-Stokes Raman scattering (CARS) and four-wave-mixing (FWM) microscopy are a related pair of powerful nonlinear optical characterization tools. These techniques often yield strong signals from concentrated samples, but because of their quadratic dependence on concentration, they are not typically employed for imaging or identifying dilute cellular constituents. We report here that, depending on the excitation wavelengths employed, both CARS and degenerate-FWM signals from carotenoid accumulations in alga cysts can be exceptionally large, allowing for low-power imaging of astaxanthin (AXN) deposits in Haematococcus pluvialis microalga. By use of a broadband laser pulse scheme for CARS and FWM, we are able to simultaneously collect strong intrinsic two-photon-excitation fluorescence signals from cellular chlorophyll in vivo. We show that CARS signals from astaxanthin (AXN) samples in vitro strictly follow the expected quadratic dependence on concentration, and we demonstrate the collection of wellresolved CARS spectra in the fingerprint region with sensitivity below 2mM. We suggest that multimodal nonlinear optical microscopy is sufficiently sensitive to AXN and chlorophyll concentrations that it will allow for non-invasive monitoring of carotenogenesis in live H. pluvialis microalgae.

PRIC320, a transcription coactivator, isolated from peroxisome proliferator-binding protein complex.

PubMed

Surapureddi, Sailesh; Viswakarma, Navin; Yu, Songtao; Guo, Dongsheng; Rao, M Sambasiva; Reddy, Janardan K

2006-05-05

Ciprofibrate, a potent peroxisome proliferator, induces pleiotropic responses in liver by activating peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor. Transcriptional regulation by liganded nuclear receptors involves the participation of coregulators that form multiprotein complexes possibly to achieve cell and gene specific transcription. SDS-PAGE and matrix-assisted laser desorption/ionization reflection time-of-flight mass spectrometric analyses of ciprofibrate-binding proteins from liver nuclear extracts obtained using ciprofibrate-Sepharose affinity matrix resulted in the identification of a new high molecular weight nuclear receptor coactivator, which we designated PRIC320. The full-length human cDNA encoding this protein has an open-reading frame that codes for a 320kDa protein containing 2882 amino acids. PRIC320 contains five LXXLL signature motifs that mediate interaction with nuclear receptors. PRIC320 binds avidly to nuclear receptors PPARalpha, CAR, ERalpha, and RXR, but only minimally with PPARgamma. PRIC320 also interacts with transcription cofactors CBP, PRIP, and PBP. Immunoprecipitation-immunoblotting as well as cellular localization studies confirmed the interaction between PPARalpha and PRIC320. PRIC320 acts as a transcription coactivator by stimulating PPARalpha-mediated transcription. We conclude that ciprofibrate, a PPARalpha ligand, binds a multiprotein complex and PRIC320 cloned from this complex functions as a nuclear receptor coactivator.

Identifying modules of coexpressed transcript units and their organization of Saccharopolyspora erythraea from time series gene expression profiles.

PubMed

Chang, Xiao; Liu, Shuai; Yu, Yong-Tao; Li, Yi-Xue; Li, Yuan-Yuan

2010-08-12

The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization. In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs) across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A), and secondary metabolism is induced when the growth is slowed down (phase B). Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery) gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected. This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies on other prokaryotic microorganisms.

49 CFR 215.303 - Stenciling of restricted cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Stenciling of restricted cars. 215.303 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Stenciling § 215.303 Stenciling of restricted cars. (a) Each restricted railroad freight car that is described in § 215.205(a) of...

49 CFR 215.303 - Stenciling of restricted cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Stenciling of restricted cars. 215.303 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Stenciling § 215.303 Stenciling of restricted cars. (a) Each restricted railroad freight car that is described in § 215.205(a) of...

49 CFR 215.303 - Stenciling of restricted cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Stenciling of restricted cars. 215.303 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Stenciling § 215.303 Stenciling of restricted cars. (a) Each restricted railroad freight car that is described in § 215.205(a) of...

49 CFR 215.303 - Stenciling of restricted cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Stenciling of restricted cars. 215.303 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Stenciling § 215.303 Stenciling of restricted cars. (a) Each restricted railroad freight car that is described in § 215.205(a) of...

49 CFR 215.303 - Stenciling of restricted cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Stenciling of restricted cars. 215.303 Section 215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Stenciling § 215.303 Stenciling of restricted cars. (a) Each restricted railroad freight car that is described in § 215.205(a) of...

49 CFR 1033.2 - Car service orders.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 false Car service orders. 1033.2 Section 1033.2 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.2 Car service orders. Emergency...

49 CFR 1033.2 - Car service orders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Car service orders. 1033.2 Section 1033.2 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.2 Car service orders. Emergency...

49 CFR 1033.2 - Car service orders.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 false Car service orders. 1033.2 Section 1033.2 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.2 Car service orders. Emergency...

49 CFR 1033.2 - Car service orders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Car service orders. 1033.2 Section 1033.2 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.2 Car service orders. Emergency...

49 CFR 1033.2 - Car service orders.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Car service orders. 1033.2 Section 1033.2 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.2 Car service orders. Emergency...

Cloning and characterization of an 11S legumin, Car i 4, a major allergen in pecan.

PubMed

Sharma, Girdhari M; Irsigler, Andre; Dhanarajan, Pushparani; Ayuso, Rosalia; Bardina, Luda; Sampson, Hugh A; Roux, Kenneth H; Sathe, Shridhar K

2011-09-14

Among tree nut allergens, pecan allergens remain to be identified and characterized. The objective was to demonstrate the IgE-binding ability of pecan 11S legumin and characterize its sequential IgE-binding epitopes. The 11S legumin gene was amplified from a pecan cDNA library and expressed as a fusion protein in Escherichia coli. The native 11S legumin in pecan extract was identified by mass spectrometry/mass spectrometry (MS/MS). Sequential epitopes were determined by probing the overlapping peptides with three serum pools prepared from different patients' sera. A three-dimensional model was generated using almond legumin as a template and compared with known sequential epitopes on other allergenic tree nut homologues. Of 28 patients tested by dot blot, 16 (57%) bound to 11S legumin, designated Car i 4. MS/MS sequencing of native 11S legumin identified 33 kDa acidic and 20-22 kDa basic subunits. Both pecan and walnut seed protein extracts inhibited IgE binding to recombinant Car i 4, suggesting cross-reactivity with Jug r 4. Sequential epitope mapping results of Car i 4 revealed weak, moderate, and strong reactivity of serum pools against 10, 5, and 4 peptides, respectively. Seven peptides were recognized by all three serum pools, of which two were strongly reactive. The strongly reactive peptides were located in three discrete regions of the Car i 4 acidic subunit sequence (residues 118-132, 208-219, and 238-249). Homology modeling of Car i 4 revealed significant overlapping regions shared in common with other tree nut legumins.

Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis.

PubMed

Liang, Kaiwei; Woodfin, Ashley R; Slaughter, Brian D; Unruh, Jay R; Box, Andrew C; Rickels, Ryan A; Gao, Xin; Haug, Jeffrey S; Jaspersen, Sue L; Shilatifard, Ali

2015-11-05

Although it is established that some general transcription factors are inactivated at mitosis, many details of mitotic transcription inhibition (MTI) and its underlying mechanisms are largely unknown. We have identified mitotic transcriptional activation (MTA) as a key regulatory step to control transcription in mitosis for genes with transcriptionally engaged RNA polymerase II (Pol II) to activate and transcribe until the end of the gene to clear Pol II from mitotic chromatin, followed by global impairment of transcription reinitiation through MTI. Global nascent RNA sequencing and RNA fluorescence in situ hybridization demonstrate the existence of transcriptionally engaged Pol II in early mitosis. Both genetic and chemical inhibition of P-TEFb in mitosis lead to delays in the progression of cell division. Together, our study reveals a mechanism for MTA and MTI whereby transcriptionally engaged Pol II can progress into productive elongation and finish transcription to allow proper cellular division. Copyright © 2015 Elsevier Inc. All rights reserved.

Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

PubMed Central

Cinegaglia, Naiara C.; Andrade, Sonia Cristina S.; Tokar, Tomas; Pinheiro, Maísa; Severino, Fábio E.; Oliveira, Rogério A.; Hasimoto, Erica N.; Cataneo, Daniele C.; Cataneo, Antônio J.M.; Defaveri, Júlio; Souza, Cristiano P.; Marques, Márcia M.C.; Carvalho, Robson F.; Coutinho, Luiz L.; Gross, Jefferson L.; Rogatto, Silvia R.; Lam, Wan L.; Jurisica, Igor; Reis, Patricia P.

2016-01-01

Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma. PMID:27081085

Automated Coal-Mine Shuttle Car

NASA Technical Reports Server (NTRS)

Collins, E. R., Jr.

1984-01-01

Cable-guided car increases efficiency in underground coal mines. Unmanned vehicle contains storage batteries in side panels for driving traction motors located in wheels. Batteries recharged during inactive periods or slid out as unit and replaced by fresh battery bank. Onboard generator charges batteries as car operates.

The phosphorylated C-terminus of cAR1 plays a role in cell-type-specific gene expression and STATa tyrosine phosphorylation.

PubMed

Briscoe, C; Moniakis, J; Kim, J Y; Brown, J M; Hereld, D; Devreotes, P N; Firtel, R A

2001-05-01

cAMP receptors mediate some signaling pathways via coupled heterotrimeric G proteins, while others are G-protein-independent. This latter class includes the activation of the transcription factors GBF and STATa. Within the cellular mounds formed by aggregation of Dictyostelium, micromolar levels of cAMP activate GBF function, thereby inducing the transcription of postaggregative genes and initiating multicellular differentiation. Activation of STATa, a regulator of culmination and ecmB expression, results from cAMP receptor-dependent tyrosine phosphorylation and nuclear localization, also in mound-stage cells. During mound development, the cAMP receptor cAR1 is in a low-affinity state and is phosphorylated on multiple serine residues in its C-terminus. This paper addresses possible roles of cAMP receptor phosphorylation in the cAMP-mediated stimulation of GBF activity, STATa tyrosine phosphorylation, and cell-type-specific gene expression. To accomplish this, we have expressed cAR1 mutants in a strain in which the endogenous cAMP receptors that mediate postaggregative gene expression in vivo are deleted. We then examined the ability of these cells to undergo morphogenesis and induce postaggregative and cell-type-specific gene expression and STATa tyrosine phosphorylation. Analysis of cAR1 mutants in which the C-terminal tail is deleted or the ligand-mediated phosphorylation sites are mutated suggests that the cAR1 C-terminus is not essential for GBF-mediated postaggregative gene expression or STATa tyrosine phosphorylation, but may play a role in regulating cell-type-specific gene expression and morphogenesis. A mutant receptor, in which the C-terminal tail is constitutively phosphorylated, exhibits constitutive activation of STATa tyrosine phosphorylation in pulsed cells in suspension and a significantly impaired ability to induce cell-type-specific gene expression. The constitutively phosphorylated receptor also exerts a partial dominant negative effect on

49 CFR 173.31 - Use of tank cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Use of tank cars. 173.31 Section 173.31... SHIPMENTS AND PACKAGINGS Preparation of Hazardous Materials for Transportation § 173.31 Use of tank cars. (a) General. (1) No person may offer a hazardous material for transportation in a tank car unless the tank car...

49 CFR 173.31 - Use of tank cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Use of tank cars. 173.31 Section 173.31... SHIPMENTS AND PACKAGINGS Preparation of Hazardous Materials for Transportation § 173.31 Use of tank cars. (a) General. (1) No person may offer a hazardous material for transportation in a tank car unless the tank car...

36 CFR § 1192.109 - Between-car barriers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Between-car barriers. § 1192... Commuter Rail Cars and Systems § 1192.109 Between-car barriers. Where vehicles operate in a high-platform, level-boarding mode, and where between-car bellows are not provided, devices or systems shall be...

49 CFR 173.31 - Use of tank cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Use of tank cars. 173.31 Section 173.31... SHIPMENTS AND PACKAGINGS Preparation of Hazardous Materials for Transportation § 173.31 Use of tank cars. (a) General. (1) No person may offer a hazardous material for transportation in a tank car unless the tank car...

49 CFR 173.31 - Use of tank cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Use of tank cars. 173.31 Section 173.31... SHIPMENTS AND PACKAGINGS Preparation of Hazardous Materials for Transportation § 173.31 Use of tank cars. (a) General. (1) No person may offer a hazardous material for transportation in a tank car unless the tank car...

49 CFR 173.31 - Use of tank cars.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Use of tank cars. 173.31 Section 173.31... SHIPMENTS AND PACKAGINGS Preparation of Hazardous Materials for Transportation § 173.31 Use of tank cars. (a) General. (1) No person may offer a hazardous material for transportation in a tank car unless the tank car...

Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital.

PubMed

Schraplau, Anne; Schewe, Bettina; Neuschäfer-Rube, Frank; Ringel, Sebastian; Neuber, Corinna; Kleuser, Burkhard; Püschel, Gerhard P

2015-02-03

Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. Copyright © 2014. Published by Elsevier Ireland Ltd.

CARS microscopy for the monitoring of lipid storage in C. elegans

NASA Astrophysics Data System (ADS)

Enejder, Annika; Brackmann, Christian; Axäng, Claes; Åkeson, Madeleine; Pilon, Marc

2008-02-01

After several years of proof-of-principle measurements and focus on technological development, it is timely to make full use of the capabilities of CARS microscopy within the biosciences. We have here identified an urgent biological problem, to which CARS microscopy provides unique insights and consequently may become a widely accepted experimental procedure. In order to improve present understanding of mechanisms underlying dysfunctional metabolism regulation reported for many of our most wide-spread diseases (obesity, diabetes, cardio-vascular diseases etc.), we have monitored genetic and environmental impacts on cellular lipid storage in the model organism C. elegans in vivo in a full-scale biological study. Important advantages of CARS microscopy could be demonstrated compared to present technology, i.e. fluorescence microscopy of labelled lipid stores. The fluorescence signal varies not only with the presence of lipids, but also with the systemic distribution of the fluorophore and the chemical properties of the surrounding medium. By instead probing high-density regions of CH bonds naturally occurring in the sample, the CARS process was shown to provide a consistent representation of the lipid stores. The increased accumulation of lipid stores in mutants with deficiencies in the insulin and transforming growth factor signalling pathways could hereby be visualized and quantified. Furthermore, spectral CARS microscopy measurements in the C-H bond region of 2780-2930 cm -1 provided the interesting observation that this accumulation comes with a shift in the ordering of the lipids from gel- to liquid phase. The present study illustrates that CARS microscopy has a strong potential to become an important instrument for systemic studies of lipid storage mechanisms in living organisms, providing new insights into the phenomena underlying metabolic disorders.

Landscape pattern and car use: Linking household data with satellite imagery

NASA Astrophysics Data System (ADS)

Keller, R.; Vance, C.

2013-12-01

Landscape pattern has long been hypothesized to influence automobile dependency. Because choices about land development tend to have long-lasting impacts that span over decades, understanding the magnitude of this influence is critical to the design of policies to reduce emissions and other negative externalities associated with car use. Combining household survey data from Germany with satellite imagery and other geo-referenced data sources, we undertake an econometric analysis of the relation between landscape pattern and automobile dependency. Specifically, we employ a two-part model to investigate two dimensions of car use, the discrete decision to own a car and, conditional upon ownership, the continuous decision of how far to drive. Results indicate that landscape pattern, as captured by measures of both land cover (e.g. the extent of open space and landscape diversity) and land use (e.g. the density of regional businesses) are important predictors of car ownership and use. Other policy-relevant variables, such as fuel prices and public transit infrastructure, are also identified as correlates. Based on the magnitude of our estimates, we conclude that carefully considered land development and zoning measures - ones that encourage dense development, diverse land cover and mixed land use - can have beneficial impacts in reducing car dependency that extend far into the future. Key terms: Landscape pattern, Satellite imagery, Germany, Two-part model Figure 1. Distribution of Elasticities of Landscape and Social Effects on German Household Weekly Car Use Results from Two Part Model N = 13,089 (probit) N = 10,987 (OLS)Robust standard errors in parentheses***, **, and *, denotes significance at the 0.01, 0.05, and 0.1 levels

49 CFR 174.67 - Tank car unloading.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Tank car unloading. 174.67 Section 174.67... and Loading Requirements § 174.67 Tank car unloading. For transloading operations, the following rules... least one wheel to prevent movement in any direction. If multiple tank cars are coupled together...

49 CFR 38.85 - Between-car barriers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Between-car barriers. 38.85 Section 38.85... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Light Rail Vehicles and Systems § 38.85 Between-car barriers. Where..., deter or warn individuals from inadvertently stepping off the platform between cars. Appropriate devices...

36 CFR 1192.63 - Between-car barriers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Between-car barriers. 1192.63... Rail Vehicles and Systems § 1192.63 Between-car barriers. (a) Requirement. Suitable devices or systems... between cars. Acceptable solutions include, but are not limited to, pantograph gates, chains, motion...

49 CFR 38.85 - Between-car barriers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false Between-car barriers. 38.85 Section 38.85... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Light Rail Vehicles and Systems § 38.85 Between-car barriers. Where..., deter or warn individuals from inadvertently stepping off the platform between cars. Appropriate devices...

49 CFR 38.85 - Between-car barriers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Between-car barriers. 38.85 Section 38.85... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Light Rail Vehicles and Systems § 38.85 Between-car barriers. Where..., deter or warn individuals from inadvertently stepping off the platform between cars. Appropriate devices...

49 CFR 38.63 - Between-car barriers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Between-car barriers. 38.63 Section 38.63... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Rapid Rail Vehicles and Systems § 38.63 Between-car barriers. (a... inadvertently stepping off the platform between cars. Acceptable solutions include, but are not limited to...

49 CFR 38.63 - Between-car barriers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Between-car barriers. 38.63 Section 38.63... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Rapid Rail Vehicles and Systems § 38.63 Between-car barriers. (a... inadvertently stepping off the platform between cars. Acceptable solutions include, but are not limited to...

36 CFR 1192.63 - Between-car barriers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Between-car barriers. 1192.63... Rail Vehicles and Systems § 1192.63 Between-car barriers. (a) Requirement. Suitable devices or systems... between cars. Acceptable solutions include, but are not limited to, pantograph gates, chains, motion...

49 CFR 174.67 - Tank car unloading.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Tank car unloading. 174.67 Section 174.67... and Loading Requirements § 174.67 Tank car unloading. For transloading operations, the following rules... least one wheel to prevent movement in any direction. If multiple tank cars are coupled together...

36 CFR 1192.63 - Between-car barriers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Between-car barriers. 1192.63... Rail Vehicles and Systems § 1192.63 Between-car barriers. (a) Requirement. Suitable devices or systems... between cars. Acceptable solutions include, but are not limited to, pantograph gates, chains, motion...

49 CFR 38.85 - Between-car barriers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false Between-car barriers. 38.85 Section 38.85... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Light Rail Vehicles and Systems § 38.85 Between-car barriers. Where..., deter or warn individuals from inadvertently stepping off the platform between cars. Appropriate devices...

49 CFR 38.63 - Between-car barriers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Between-car barriers. 38.63 Section 38.63... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Rapid Rail Vehicles and Systems § 38.63 Between-car barriers. (a... inadvertently stepping off the platform between cars. Acceptable solutions include, but are not limited to...

49 CFR 38.85 - Between-car barriers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Between-car barriers. 38.85 Section 38.85... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Light Rail Vehicles and Systems § 38.85 Between-car barriers. Where..., deter or warn individuals from inadvertently stepping off the platform between cars. Appropriate devices...

49 CFR 38.63 - Between-car barriers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false Between-car barriers. 38.63 Section 38.63... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Rapid Rail Vehicles and Systems § 38.63 Between-car barriers. (a... inadvertently stepping off the platform between cars. Acceptable solutions include, but are not limited to...

49 CFR 174.67 - Tank car unloading.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Tank car unloading. 174.67 Section 174.67... and Loading Requirements § 174.67 Tank car unloading. For transloading operations, the following rules... least one wheel to prevent movement in any direction. If multiple tank cars are coupled together...

49 CFR 174.67 - Tank car unloading.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Tank car unloading. 174.67 Section 174.67... and Loading Requirements § 174.67 Tank car unloading. For transloading operations, the following rules... least one wheel to prevent movement in any direction. If multiple tank cars are coupled together...

36 CFR 1192.63 - Between-car barriers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Between-car barriers. 1192.63... Rail Vehicles and Systems § 1192.63 Between-car barriers. (a) Requirement. Suitable devices or systems... between cars. Acceptable solutions include, but are not limited to, pantograph gates, chains, motion...

49 CFR 38.63 - Between-car barriers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 1 2012-10-01 2012-10-01 false Between-car barriers. 38.63 Section 38.63... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Rapid Rail Vehicles and Systems § 38.63 Between-car barriers. (a... inadvertently stepping off the platform between cars. Acceptable solutions include, but are not limited to...

Versatile CAR T-cells for cancer immunotherapy

PubMed Central

Cao, Jingjing; Neelalpu, Sattva S

2018-01-01

Chimeric antigen receptor (CAR) T-cell therapy has been clinically proven to efficiently combat haematological malignancies. However, continuous efforts are required to increase the specificity of CAR T-cells against tumour versus normal tissues, and are essential to improve their antitumour activity in solid tumours. This review summarises the structure of major CAR designs, and strategies to overcome immunosuppressive tumour microenvironment, and reduce toxicities. Along with reviewing currently available techniques that allow the elimination of CAR T-cells after they fulfil their desired functions, using suicide genes, drug elimination strategies are also introduced. A better understanding of the strengths and pitfalls of CAR T-cell therapy will provide fundamental knowledge for the improvement of engineered T-cell therapy in the near future. PMID:29628798

Freedom, Constraint, and Family Responsibility: Teens and Parents Collaboratively Negotiate around the Car, Class, Gender, and Culture

ERIC Educational Resources Information Center

Best, Amy L.

2006-01-01

This article examines kids' talk about cars, exploring what their talk reveals about the dynamics of family life among families with teenagers. Using in depth and focus group interviews with teens, this article identifies how the car serves as cultural object around which parents and kids collaboratively negotiate both kids' autonomy from the…

49 CFR 173.314 - Compressed gases in tank cars and multi-unit tank cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... shield as prescribed in § 179.16(c)(1). (d) Alternative tank car tanks for materials poisonous by... the alternative tank car jacket and head shield. When the jacket and head shield are made from any...., the thickness to be added to the jacket and head shield must be increased by a factor of 1.157...

Intelligent Control Electromagnetic Actuated Continuously Variable Transmission System for Passenger Car

NASA Astrophysics Data System (ADS)

Rahman, Ataur; Sharif, Sazzad; Mohiuddin, AKM; Faris Ismail, Ahmed; Izan, Sany Ihsan

2017-03-01

Continuously variable transmission (CVT) system transmits the engine /battery power to the car driving wheel smoothly and efficiently. Cars with CVT produces some noise and slow acceleration to meet the car power demand on initial start-ups and slow speed. The car noise is produced as a result of CVT adjustment the engine speed with the hydraulic pressure. The current CVT problems incurred due to the slow response of hydraulic pressure and CVT fluid viscosity due to the development of heat.The aim of this study is to develop electromagnetic actuated CVT (EMA-CVT) with intelligent switching controlling system (ICS). The experimental results of ¼ scale EMA shows that it make the acceleration time of the car in 3.5-5 sec which is 40% less than the hydraulic CVT in the market. The EMA develops the electromagnetic force in the ranged of 350 -1200 N for the supply current in the range of 10-15 amp. This study introduced fuzzy intelligent system (FIS) to predict the EMA system dynamic behaviour in order to identify the current control for the EMA actuation during operation of the CVT. It is expecting that the up scale EMA-CVT would reduce the 75% of vehicle power transmission loss by accelerating vehicle in 5 sec and save the IC engine power consumption about 20% which will makes the vehicle energy efficient (EEV) and reduction of green house gas reduction.

36 CFR 1192.85 - Between-car barriers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Between-car barriers. 1192.85... Rail Vehicles and Systems § 1192.85 Between-car barriers. Where vehicles operate in a high-platform... inadvertently stepping off the platform between cars. Appropriate devices include, but are not limited to...

36 CFR 1192.85 - Between-car barriers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Between-car barriers. 1192.85... Rail Vehicles and Systems § 1192.85 Between-car barriers. Where vehicles operate in a high-platform... inadvertently stepping off the platform between cars. Appropriate devices include, but are not limited to...

36 CFR 1192.85 - Between-car barriers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Between-car barriers. 1192.85... Rail Vehicles and Systems § 1192.85 Between-car barriers. Where vehicles operate in a high-platform... inadvertently stepping off the platform between cars. Appropriate devices include, but are not limited to...

36 CFR 1192.85 - Between-car barriers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Between-car barriers. 1192.85... Rail Vehicles and Systems § 1192.85 Between-car barriers. Where vehicles operate in a high-platform... inadvertently stepping off the platform between cars. Appropriate devices include, but are not limited to...

Bone morphogenetic protein-induced MSX1 and MSX2 inhibit myocardin-dependent smooth muscle gene transcription.

PubMed

Hayashi, Ken'ichiro; Nakamura, Seiji; Nishida, Wataru; Sobue, Kenji

2006-12-01

During the onset and progression of atherosclerosis, the vascular smooth muscle cell (VSMC) phenotype changes from differentiated to dedifferentiated, and in some cases, this change is accompanied by osteogenic transition, resulting in vascular calcification. One characteristic of dedifferentiated VSMCs is the down-regulation of smooth muscle cell (SMC) marker gene expression. Bone morphogenetic proteins (BMPs), which are involved in the induction of osteogenic gene expression, are detected in calcified vasculature. In this study, we found that the BMP2-, BMP4-, and BMP6-induced expression of Msx transcription factors (Msx1 and Msx2) preceded the down-regulation of SMC marker expression in cultured differentiated VSMCs. Either Msx1 or Msx2 markedly reduced the myocardin-dependent promoter activities of SMC marker genes (SM22alpha and caldesmon). We further investigated interactions between Msx1 and myocardin/serum response factor (SRF)/CArG-box motif (cis element for SRF) using coimmunoprecipitation, gel-shift, and chromatin immunoprecipitation assays. Our results showed that Msx1 or Msx2 formed a ternary complex with SRF and myocardin and inhibited the binding of SRF or SRF/myocardin to the CArG-box motif, resulting in inhibition of their transcription.

Coal cars - the first three hundred years

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin Robert Karig III

2007-12-15

This is the comprehensive study of the freight cars that conveyed coal across broad swaths of land that had been impassible before the invention of the steam engine. This volume traces the history and evolution of coal cars from their earliest use in England to the construction of major railways for the purpose of coal hauling and the end of the steam era on American railroads. In addition to contextualizing coal cars in the annals of industrial history, the book features extensive design specifications and drawings as well as a complete history of the various safety and mechanical innovations employedmore » on these freight cars. It concludes with a photographic essay illustrating the development of the coal car over its first 300 years of use. 608 photos.« less

A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency

NASA Astrophysics Data System (ADS)

Artyomov, Maxim; Meissner, Alex; Chakraborty, Arup

2010-03-01

Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, pluripotent embryonic stem cells differentiate into diverse cell types that make up the organism (e.g., a human). There has long been an effort to make this process go backward -- i.e., reprogram a differentiated cell (e.g., a skin cell) to pluripotent status. Recently, this has been achieved by transfecting certain transcription factors into differentiated cells. This method does not use embryonic material and promises the development of patient-specific regenerative medicine, but it is inefficient. The mechanisms that make reprogramming rare, or even possible, are poorly understood. We have developed the first computational model of transcription factor-induced reprogramming. Results obtained from the model are consistent with diverse observations, and identify the rare pathways that allow reprogramming to occur. If validated, our model could be further developed to design optimal strategies for reprogramming and shed light on basic questions in biology.

Situations of car-to-pedestrian contact.

PubMed

Matsui, Yasuhiro; Hitosugi, Masahito; Takahashi, Kunio; Doi, Tsutomu

2013-01-01

To reduce the severity of injuries and the number of pedestrian deaths in traffic accidents, active safety devices providing pedestrian detection are considered effective countermeasures. The features of car-to-pedestrian collisions need to be known in detail to develop such safety devices. Because information on real-world accidents is limited, this study investigated near-miss situations captured by drive recorders installed in passenger cars. We showed similarities of the contact situation between near-miss incidents and real-world fatal pedestrian accidents in Japan. We analyzed the near-miss incident data via video capturing pedestrians crossing the road in front of forward-moving cars. Using a video frame captured by a drive recorder, the time to collision (TTC) was calculated from the car velocity and the distance between the car and pedestrian at the moment that the pedestrian initially appeared. The average TTC in the cases where pedestrians were not using a pedestrian crossing was shorter than that in the cases where pedestrians were using a pedestrian crossing. The average TTC in the cases where pedestrians emerged from behind obstructions was shorter than that in the cases where drivers had unobstructed views of the pedestrians. We propose that the specifications of the safety device for pedestrian detection and automatic braking should reflect the severe approach situation for a pedestrian and car including the TTC observed for near-miss incidents.

Pervasive transcription: detecting functional RNAs in bacteria.

PubMed

Lybecker, Meghan; Bilusic, Ivana; Raghavan, Rahul

2014-01-01

Pervasive, or genome-wide, transcription has been reported in all domains of life. In bacteria, most pervasive transcription occurs antisense to protein-coding transcripts, although recently a new class of pervasive RNAs was identified that originates from within annotated genes. Initially considered to be non-functional transcriptional noise, pervasive transcription is increasingly being recognized as important in regulating gene expression. The function of pervasive transcription is an extensively debated question in the field of transcriptomics and regulatory RNA biology. Here, we highlight the most recent contributions addressing the purpose of pervasive transcription in bacteria and discuss their implications.

Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

PubMed

Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

2006-07-01

Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.

Transcript and protein profiling identifies signaling, growth arrest, apoptosis, and NF-κB survival signatures following GNRH receptor activation

PubMed Central

Meyer, Colette; Sims, Andrew H; Morgan, Kevin; Harrison, Beth; Muir, Morwenna; Bai, Jianing; Faratian, Dana; Millar, Robert P; Langdon, Simon P

2013-01-01

GNRH significantly inhibits proliferation of a proportion of cancer cell lines by activating GNRH receptor (GNRHR)-G protein signaling. Therefore, manipulation of GNRHR signaling may have an under-utilized role in treating certain breast and ovarian cancers. However, the precise signaling pathways necessary for the effect and the features of cellular responses remain poorly defined. We used transcriptomic and proteomic profiling approaches to characterize the effects of GNRHR activation in sensitive cells (HEK293-GNRHR, SCL60) in vitro and in vivo, compared to unresponsive HEK293. Analyses of gene expression demonstrated a dynamic response to the GNRH superagonist Triptorelin. Early and mid-phase changes (0.5–1.0 h) comprised mainly transcription factors. Later changes (8–24 h) included a GNRH target gene, CGA, and up- or downregulation of transcripts encoding signaling and cell division machinery. Pathway analysis identified altered MAPK and cell cycle pathways, consistent with occurrence of G2/M arrest and apoptosis. Nuclear factor kappa B (NF-κB) pathway gene transcripts were differentially expressed between control and Triptorelin-treated SCL60 cultures. Reverse-phase protein and phospho-proteomic array analyses profiled responses in cultured cells and SCL60 xenografts in vivo during Triptorelin anti-proliferation. Increased phosphorylated NF-κB (p65) occurred in SCL60 in vitro, and p-NF-κB and IκBϵ were higher in treated xenografts than controls after 4 days Triptorelin. NF-κB inhibition enhanced the anti-proliferative effect of Triptorelin in SCL60 cultures. This study reveals details of pathways interacting with intense GNRHR signaling, identifies potential anti-proliferative target genes, and implicates the NF-κB survival pathway as a node for enhancing GNRH agonist-induced anti-proliferation. PMID:23202794

Occupational Hydrofluoric Acid Injury from Car and Truck Washing--Washington State, 2001-2013.

PubMed

Reeb-Whitaker, Carolyn K; Eckert, Carly M; Anderson, Naomi J; Bonauto, David K

2015-08-21

Exposure to hydrofluoric acid (HF) causes corrosive chemical burns and potentially fatal systemic toxicity. Car and truck wash cleaning products, rust removers, and aluminum brighteners often contain HF because it is efficient in breaking down roadway matter. The death of a truck wash worker from ingestion of an HF-based wash product and 48 occupational HF burn cases associated with car and truck washing in Washington State during 2001-2013 are summarized in this report. Among seven hospitalized workers, two required surgery, and all but one worker returned to the job. Among 48 injured workers, job titles were primarily auto detailer, car wash worker, truck wash worker, and truck driver. Because HF exposure can result in potentially severe health outcomes, efforts to identify less hazardous alternatives to HF-based industrial wash products are warranted.

Widespread anti-sense transcription in apple is correlated with siRNA production and indicates a large potential for transcriptional and/or post-transcriptional control.

PubMed

Celton, Jean-Marc; Gaillard, Sylvain; Bruneau, Maryline; Pelletier, Sandra; Aubourg, Sébastien; Martin-Magniette, Marie-Laure; Navarro, Lionel; Laurens, François; Renou, Jean-Pierre

2014-07-01

Characterizing the transcriptome of eukaryotic organisms is essential for studying gene regulation and its impact on phenotype. The realization that anti-sense (AS) and noncoding RNA transcription is pervasive in many genomes has emphasized our limited understanding of gene transcription and post-transcriptional regulation. Numerous mechanisms including convergent transcription, anti-correlated expression of sense and AS transcripts, and RNAi remain ill-defined. Here, we have combined microarray analysis and high-throughput sequencing of small RNAs (sRNAs) to unravel the complexity of transcriptional and potential post-transcriptional regulation in eight organs of apple (Malus × domestica). The percentage of AS transcript expression is higher than that identified in annual plants such as rice and Arabidopsis thaliana. Furthermore, we show that a majority of AS transcripts are transcribed beyond 3'UTR regions, and may cover a significant portion of the predicted sense transcripts. Finally we demonstrate at a genome-wide scale that anti-sense transcript expression is correlated with the presence of both short (21-23 nt) and long (> 30 nt) siRNAs, and that the sRNA coverage depth varies with the level of AS transcript expression. Our study provides a new insight on the functional role of anti-sense transcripts at the genome-wide level, and a new basis for the understanding of sRNA biogenesis in plants. © 2014 INRA. New Phytologist © 2014 New Phytologist Trust.

Extensive cross-talk and global regulators identified from an analysis of the integrated transcriptional and signaling network in Escherichia coli.

PubMed

Antiqueira, Lucas; Janga, Sarath Chandra; Costa, Luciano da Fontoura

2012-11-01

To understand the regulatory dynamics of transcription factors (TFs) and their interplay with other cellular components we have integrated transcriptional, protein-protein and the allosteric or equivalent interactions which mediate the physiological activity of TFs in Escherichia coli. To study this integrated network we computed a set of network measurements followed by principal component analysis (PCA), investigated the correlations between network structure and dynamics, and carried out a procedure for motif detection. In particular, we show that outliers identified in the integrated network based on their network properties correspond to previously characterized global transcriptional regulators. Furthermore, outliers are highly and widely expressed across conditions, thus supporting their global nature in controlling many genes in the cell. Motifs revealed that TFs not only interact physically with each other but also obtain feedback from signals delivered by signaling proteins supporting the extensive cross-talk between different types of networks. Our analysis can lead to the development of a general framework for detecting and understanding global regulatory factors in regulatory networks and reinforces the importance of integrating multiple types of interactions in underpinning the interrelationships between them.

Children in Hot Cars Result in Fatal Consequences

MedlinePlus

... Cars Result in Fatal Consequences Children in Hot Cars Result in Fatal Consequences Emergency physicians are warning ... it bluntly, leaving your child in a hot car is like leaving your child in a lit ...

A Synthetic Interaction Screen Identifies Factors Selectively Required for Proliferation and TERT Transcription in p53-Deficient Human Cancer Cells

PubMed Central

Park, Sung Mi; Zhu, Lihua J.; Debily, Marie-anne; Kittler, Ellen L. W.; Zapp, Maria L.; Lapointe, David; Gobeil, Stephane; Virbasius, Ching-Man; Green, Michael R.

2012-01-01

Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi)–based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53−) human cancer cells. We find that compared to p53-competent (p53+) human cancer cell lines, diverse p53− human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53− cells, RNAi–mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53− but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53− cancer cells. PMID:23284306

Selected topics in railroad tank car safety. Volume 2 : test plan for accelerated life testing of thermally shielded tank cars

DOT National Transportation Integrated Search

1978-08-01

A test plan for the accelerated life testing of thermally shielded tank cars is described. The test program would be conducted at the DOT Transportation Test Center in Pueblo, Colorado. Eighteen tank cars would be included in the program. Five cars w...

Are all types of expertise created equal? Car experts use different spatial frequency scales for subordinate categorization of cars and faces.

PubMed

Harel, Assaf; Bentin, Shlomo

2013-01-01

A much-debated question in object recognition is whether expertise for faces and expertise for non-face objects utilize common perceptual information. We investigated this issue by assessing the diagnostic information required for different types of expertise. Specifically, we asked whether face categorization and expert car categorization at the subordinate level relies on the same spatial frequency (SF) scales. Fifteen car experts and fifteen novices performed a category verification task with spatially filtered images of faces, cars, and airplanes. Images were categorized based on their basic (e.g. "car") and subordinate level (e.g. "Japanese car") identity. The effect of expertise was not evident when objects were categorized at the basic level. However, when the car experts categorized faces and cars at the subordinate level, the two types of expertise required different kinds of SF information. Subordinate categorization of faces relied on low SFs more than on high SFs, whereas subordinate expert car categorization relied on high SFs more than on low SFs. These findings suggest that expertise in the recognition of objects and faces do not utilize the same type of information. Rather, different types of expertise require different types of diagnostic visual information.

Driving with Intuition: A Preregistered Study about the EEG Anticipation of Simulated Random Car Accidents

PubMed Central

Duma, Gian Marco; Mento, Giovanni; Manari, Tommaso; Martinelli, Massimiliano

2017-01-01

The study of neural pre-stimulus or “anticipatory” activity opened a new window for understanding how the brain actively constructs the forthcoming reality. Usually, experimental paradigms designed to study anticipatory activity make use of stimuli. The purpose of the present study is to expand the study of neural anticipatory activity upon the temporal occurrence of dichotomic, statistically unpredictable (random) stimuli within an ecological experimental paradigm. To this purpose, we used a simplified driving simulation including two possible, randomly-presented trial types: a car crash end trial and a no car crash end trial. Event Related Potentials (ERP) were extracted -3,000 ms before stimulus onset. We identified a fronto-central negativity starting around 1,000 ms before car crash presentation. By contrast, a whole-scalp distributed positivity characterized the anticipatory activity observed before the end of the trial in the no car crash end condition. The present data are in line with the hypothesis that the brain may also anticipate dichotomic, statistically unpredictable stimuli, relaying onto different pre-stimulus ERP activity. Possible integration with car-smart-systems is also suggested. PMID:28103303

Analysis of factors that increase motorcycle rider risk compared to car driver risk.

PubMed

Keall, Michael D; Newstead, Stuart

2012-11-01

As in other parts of the Western world, there is concern in New Zealand about increasing popularity of motorcycles because of potential increases in road trauma. This study sought to identify important factors associated with increased risk for motorcyclists to inform potential policy approaches to reduce motorcyclist injury, such as changes to motorcyclist licensing, training and education. Using data extracted from a register of all New Zealand licensed motor vehicles that were matched to crash data, statistical models were fitted to examine patterns of motorcycle risk in comparison with small cars. These showed generally elevated risks for motorcyclists compared to cars, but particularly elevated risks for motorcycle owners aged in their 20s or who lived in more urbanised settings. In crashes, motorcyclists have little protection from injury, putting the motorcyclist at high risk of injury. When comparing new motorcycles with new cars, the odds of fatal or serious injury to a motorcycle rider involved in an injury crash were almost eight times the odds for a car driver. Copyright © 2011 Elsevier Ltd. All rights reserved.

Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma.

PubMed

Chmielewski, Markus; Hombach, Andreas A; Abken, Hinrich

2014-01-01

Adoptive T-cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody-derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T-cell therapy by modulating the tumor stroma by a CAR T-cell-secreted transgenic cytokine like interleukin-12 (IL-12). The basic process is that CAR T cells, when activated by their CAR, deposit IL-12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine-mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

49 CFR 223.15 - Requirements for existing passenger cars.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built or...

49 CFR 223.15 - Requirements for existing passenger cars.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built or...

49 CFR 223.15 - Requirements for existing passenger cars.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built or...

49 CFR 223.15 - Requirements for existing passenger cars.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built or...

49 CFR 223.15 - Requirements for existing passenger cars.

Code of Federal Regulations, 2013 CFR