Quantifying Intrinsic and Extrinsic Variability in Stochastic Gene Expression Models

PubMed Central

Singh, Abhyudai; Soltani, Mohammad

2013-01-01

Genetically identical cell populations exhibit considerable intercellular variation in the level of a given protein or mRNA. Both intrinsic and extrinsic sources of noise drive this variability in gene expression. More specifically, extrinsic noise is the expression variability that arises from cell-to-cell differences in cell-specific factors such as enzyme levels, cell size and cell cycle stage. In contrast, intrinsic noise is the expression variability that is not accounted for by extrinsic noise, and typically arises from the inherent stochastic nature of biochemical processes. Two-color reporter experiments are employed to decompose expression variability into its intrinsic and extrinsic noise components. Analytical formulas for intrinsic and extrinsic noise are derived for a class of stochastic gene expression models, where variations in cell-specific factors cause fluctuations in model parameters, in particular, transcription and/or translation rate fluctuations. Assuming mRNA production occurs in random bursts, transcription rate is represented by either the burst frequency (how often the bursts occur) or the burst size (number of mRNAs produced in each burst). Our analysis shows that fluctuations in the transcription burst frequency enhance extrinsic noise but do not affect the intrinsic noise. On the contrary, fluctuations in the transcription burst size or mRNA translation rate dramatically increase both intrinsic and extrinsic noise components. Interestingly, simultaneous fluctuations in transcription and translation rates arising from randomness in ATP abundance can decrease intrinsic noise measured in a two-color reporter assay. Finally, we discuss how these formulas can be combined with single-cell gene expression data from two-color reporter experiments for estimating model parameters. PMID:24391934

Quantifying intrinsic and extrinsic variability in stochastic gene expression models.

PubMed

Singh, Abhyudai; Soltani, Mohammad

2013-01-01

Genetically identical cell populations exhibit considerable intercellular variation in the level of a given protein or mRNA. Both intrinsic and extrinsic sources of noise drive this variability in gene expression. More specifically, extrinsic noise is the expression variability that arises from cell-to-cell differences in cell-specific factors such as enzyme levels, cell size and cell cycle stage. In contrast, intrinsic noise is the expression variability that is not accounted for by extrinsic noise, and typically arises from the inherent stochastic nature of biochemical processes. Two-color reporter experiments are employed to decompose expression variability into its intrinsic and extrinsic noise components. Analytical formulas for intrinsic and extrinsic noise are derived for a class of stochastic gene expression models, where variations in cell-specific factors cause fluctuations in model parameters, in particular, transcription and/or translation rate fluctuations. Assuming mRNA production occurs in random bursts, transcription rate is represented by either the burst frequency (how often the bursts occur) or the burst size (number of mRNAs produced in each burst). Our analysis shows that fluctuations in the transcription burst frequency enhance extrinsic noise but do not affect the intrinsic noise. On the contrary, fluctuations in the transcription burst size or mRNA translation rate dramatically increase both intrinsic and extrinsic noise components. Interestingly, simultaneous fluctuations in transcription and translation rates arising from randomness in ATP abundance can decrease intrinsic noise measured in a two-color reporter assay. Finally, we discuss how these formulas can be combined with single-cell gene expression data from two-color reporter experiments for estimating model parameters.

Plankton networks driving carbon export in the oligotrophic ocean

NASA Astrophysics Data System (ADS)

Guidi, L.; Chaffron, S.; Bittner, L.; Eveillard, D.; Raes, J.; Karsenti, E.; Bowler, C.; Gorsky, G.

2016-02-01

The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis that sinks to the deep ocean as particles where it is sequestered. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure and interactions driving the process remain largely uncharacterised. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of the underlying processes. We show that specific plankton communities correlate with carbon export and highlight unexpected and overlooked taxa such as Radiolaria, alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical oligotrophic ocean. Additionally, we show that the relative abundance of just a few bacterial and viral genes can predict most of the variability in carbon export in these regions. Together these results help elucidate ecosystem drivers of the biological carbon pump and present a case study for scaling from genes-to-ecosystems.

Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

PubMed Central

Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

2013-01-01

The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

The promise and peril of CRISPR gene drives: Genetic variation and inbreeding may impede the propagation of gene drives based on the CRISPR genome editing technology.

PubMed

Zentner, Gabriel E; Wade, Michael J

2017-10-01

Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives. © 2017 WILEY Periodicals, Inc.

Meiotic drive impacts expression and evolution of x-linked genes in stalk-eyed flies.

PubMed

Reinhardt, Josephine A; Brand, Cara L; Paczolt, Kimberly A; Johns, Philip M; Baker, Richard H; Wilkinson, Gerald S

2014-01-01

Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (XSR) or a standard X chromosome (XST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that XSR and XST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on XSR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.

Reversible Gene Drive Mechanism Utilizing Trana Inactivating Paramutatlons In Insects (paramutale 0.9)

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

Drocco, Jeffery A.

The paramutate software package Is a tool to calculate the genotyplc and phenotyplc propagation of a gene drive that can be silenced with a homologuus trans-Inactivating panmutatlon, ln dlptera or other species with a slmUar-acttng pl RNA system/Plwi pathway. Method of SolaUon: paramutate uses rults of Mendelian, gene drive (I.e.. stimulated conversion), and maternal Inheritance to compute the propaptlon of a notional gene drive construct and Its trans-lnactlvat1n1 paramutatlon, throu1b a panmlctlc, fixed-size population reproducing In synchronous generations.

Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae

PubMed Central

Roggenkamp, Emily; Giersch, Rachael M.; Schrock, Madison N.; Turnquist, Emily; Halloran, Megan; Finnigan, Gregory C.

2018-01-01

Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g., malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based “gene drive,” allows for the super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive component—Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusions—to modulate drive activity within a population. PMID:29348295

Predictors of Cell Phone Use in Distracted Driving: Extending the Theory of Planned Behavior.

PubMed

Tian, Yan; Robinson, James D

2017-09-01

This study examines the predictors of six distracted driving behaviors, and the survey data partially support Ajzen's (1991) Theory of Planned Behavior (TPB). The data suggest that the attitude variable predicted intention to engage in all six distracted driving behaviors (reading and sending text messages, making and answering cell phone calls, reading/viewing social media, and posting on social media while driving). Extending the model to include past experience and the variable perceived safety of technology yielded an improvement in the prediction of the distraction variables. Specifically, past experience predicted all six distracted driving behaviors, and the variable perceived safety of technology predicted intentions to read/view social media and intention to post on social media while driving. The study provides evidence for the importance of incorporating expanded variables into the original TPB model to predict cell phone use behaviors while driving, and it suggests that it is essential to tailor campaign materials for each specific cell phone use behavior to reduce distracted driving.

Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukii

PubMed Central

Buchman, Anna; Marshall, John M.; Ostrovski, Dennis; Yang, Ting; Akbari, Omar S.

2018-01-01

Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii. We demonstrate that this drive system, based on an engineered maternal “toxin” coupled with a linked embryonic “antidote,” is capable of biasing Mendelian inheritance rates with up to 100% efficiency. However, we find that drive resistance, resulting from naturally occurring genetic variation and associated fitness costs, can be selected for and hinder the spread of such a drive. Despite this, our results suggest that this gene drive could maintain itself at high frequencies in a wild population and spread to fixation if either its fitness costs or toxin resistance were reduced, providing a clear path forward for developing future such systems in this pest. PMID:29666236

FLO1 is a variable green beard gene that drives biofilm-like cooperation in budding yeast

PubMed Central

Smukalla, Scott; Caldara, Marina; Pochet, Nathalie; Beauvais, Anne; Guadagnini, Stephanie; Yan, Chen; Vinces, Marcelo D.; Jansen, An; Prevost, Marie Christine; Latgé, Jean-Paul; Fink, Gerald R.; Foster, Kevin R.; Verstrepen, Kevin J.

2008-01-01

Summary The budding yeast, Saccharomyces cerevisiae, has emerged as an archetype of eukaryotic cell biology. Here we show that S. cerevisiae is also a model for the evolution of cooperative behavior by revisiting flocculation, a self-adherence phenotype lacking in most laboratory strains. Expression of the gene FLO1 in the laboratory strain S288C restores flocculation, an altered physiological state, reminiscent of bacterial biofilms. Flocculation protects the FLO1-expressing cells from multiple stresses, including antimicrobials and ethanol. Furthermore, FLO1+ cells avoid exploitation by non-expressing flo1 cells by self/non-self recognition: FLO1+ cells preferentially stick to one another, regardless of genetic relatedness across the rest of the genome. Flocculation, therefore, is driven by one of a few known “green beard genes”, which direct cooperation towards other carriers of the same gene. Moreover, FLO1 is highly variable among strains both in expression and in sequence, suggesting that flocculation in S. cerevisiae is a dynamic, rapidly-evolving social trait. PMID:19013280

Isolation, characterization, and evaluation of three Citrus sinensis-derived constitutive gene promoters.

PubMed

Erpen, L; Tavano, E C R; Harakava, R; Dutt, M; Grosser, J W; Piedade, S M S; Mendes, B M J; Mourão Filho, F A A

2018-05-23

Regulatory sequences from the citrus constitutive genes cyclophilin (CsCYP), glyceraldehyde-3-phosphate dehydrogenase C2 (CsGAPC2), and elongation factor 1-alpha (CsEF1) were isolated, fused to the uidA gene, and qualitatively and quantitatively evaluated in transgenic sweet orange plants. The 5' upstream region of a gene (the promoter) is the most important component for the initiation and regulation of gene transcription of both native genes and transgenes in plants. The isolation and characterization of gene regulatory sequences are essential to the development of intragenic or cisgenic genetic manipulation strategies, which imply the use of genetic material from the same species or from closely related species. We describe herein the isolation and evaluation of the promoter sequence from three constitutively expressed citrus genes: cyclophilin (CsCYP), glyceraldehyde-3-phosphate dehydrogenase C2 (CsGAPC2), and elongation factor 1-alpha (CsEF1). The functionality of the promoters was confirmed by a histochemical GUS assay in leaves, stems, and roots of stably transformed citrus plants expressing the promoter-uidA construct. Lower uidA mRNA levels were detected when the transgene was under the control of citrus promoters as compared to the expression under the control of the CaMV35S promoter. The association of the uidA gene with the citrus-derived promoters resulted in mRNA levels of up to 60-41.8% of the value obtained with the construct containing CaMV35S driving the uidA gene. Moreover, a lower inter-individual variability in transgene expression was observed amongst the different transgenic lines, where gene constructs containing citrus-derived promoters were used. In silico analysis of the citrus-derived promoter sequences revealed that their activity may be controlled by several putative cis-regulatory elements. These citrus promoters will expand the availability of regulatory sequences for driving gene expression in citrus gene-modification programs.

Can variable frequency drives reduce irrigation costs for rice producers?

USDA-ARS?s Scientific Manuscript database

Variable Frequency Drives (VFD's) allow for variable speed operation of electrical motor drive irrigation pumps and are an emerging technology for agricultural irrigation, primarily for pressurized irrigation systems. They are considered an energy savings device, but less is known about their app...

Continuously-Variable Positive-Mesh Power Transmission

NASA Technical Reports Server (NTRS)

Johnson, J. L.

1982-01-01

Proposed transmission with continuously-variable speed ratio couples two mechanical trigonometric-function generators. Transmission is expected to handle higher loads than conventional variable-pulley drives; and, unlike variable pulley, positive traction through entire drive train with no reliance on friction to transmit power. Able to vary speed continuously through zero and into reverse. Possible applications in instrumentation where drive-train slippage cannot be tolerated.

wtf genes are prolific dual poison-antidote meiotic drivers.

PubMed

Nuckolls, Nicole L; Bravo Núñez, María Angélica; Eickbush, Michael T; Young, Janet M; Lange, Jeffrey J; Yu, Jonathan S; Smith, Gerald R; Jaspersen, Sue L; Malik, Harmit S; Zanders, Sarah E

2017-06-20

Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe . We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes. wtf4 utilizes dual, overlapping transcripts to encode both a gamete-killing poison and an antidote to the poison. To enact drive, all gametes are poisoned, whereas only those that inherit wtf4 are rescued by the antidote. Our work suggests that the wtf multigene family proliferated due to meiotic drive and highlights the power of selfish genes to shape genomes, even while imposing tremendous costs to fertility.

Concerning RNA-guided gene drives for the alteration of wild populations.

PubMed

Esvelt, Kevin M; Smidler, Andrea L; Catteruccia, Flaminia; Church, George M

2014-07-17

Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology.

Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates.

PubMed

Prowse, Thomas A A; Cassey, Phillip; Ross, Joshua V; Pfitzner, Chandran; Wittmann, Talia A; Thomas, Paul

2017-08-16

Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial 'silver bullet' for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that are replicated during meiosis via homologous recombination. However, their efficacy for controlling wild populations is threatened by inherent polymorphic resistance and the creation of resistance alleles via non-homologous end-joining (NHEJ)-mediated DNA repair. We used stochastic individual-based models to identify realistic gene-drive strategies capable of eradicating vertebrate pest populations (mice, rats and rabbits) on islands. One popular strategy, a sex-reversing drive that converts heterozygous females into sterile males, failed to spread and required the ongoing deployment of gene-drive carriers to achieve eradication. Under alternative strategies, multiplexed gRNAs could overcome inherent polymorphic resistance and were required for eradication success even when the probability of NHEJ was low. Strategies causing homozygotic embryonic non-viability or homozygotic female sterility produced high probabilities of eradication and were robust to NHEJ-mediated deletion of the DNA sequence between multiplexed endonuclease recognition sites. The latter two strategies also purged the gene drive when eradication failed, therefore posing lower long-term risk should animals escape beyond target islands. Multiplexing gRNAs will be necessary if this technology is to be useful for insular extirpation attempts; however, precise knowledge of homing rates will be required to design low-risk gene drives with high probabilities of eradication success. © 2017 The Author(s).

Propagating gene expression fronts in a one-dimensional coupled system of artificial cells

NASA Astrophysics Data System (ADS)

Tayar, Alexandra M.; Karzbrun, Eyal; Noireaux, Vincent; Bar-Ziv, Roy H.

2015-12-01

Living systems employ front propagation and spatiotemporal patterns encoded in biochemical reactions for communication, self-organization and computation. Emulating such dynamics in minimal systems is important for understanding physical principles in living cells and in vitro. Here, we report a one-dimensional array of DNA compartments in a silicon chip as a coupled system of artificial cells, offering the means to implement reaction-diffusion dynamics by integrated genetic circuits and chip geometry. Using a bistable circuit we programmed a front of protein synthesis propagating in the array as a cascade of signal amplification and short-range diffusion. The front velocity is maximal at a saddle-node bifurcation from a bistable regime with travelling fronts to a monostable regime that is spatially homogeneous. Near the bifurcation the system exhibits large variability between compartments, providing a possible mechanism for population diversity. This demonstrates that on-chip integrated gene circuits are dynamical systems driving spatiotemporal patterns, cellular variability and symmetry breaking.

wtf genes are prolific dual poison-antidote meiotic drivers

PubMed Central

Nuckolls, Nicole L; Bravo Núñez, María Angélica; Eickbush, Michael T; Young, Janet M; Lange, Jeffrey J; Yu, Jonathan S; Smith, Gerald R; Jaspersen, Sue L; Malik, Harmit S; Zanders, Sarah E

2017-01-01

Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, we demonstrate a complex landscape of meiotic drive genes on chromosome 3 of the fission yeasts Schizosaccharomyces kambucha and S. pombe. We identify S. kambucha wtf4 as one of these genes that acts to kill gametes (known as spores in yeast) that do not inherit the gene from heterozygotes. wtf4 utilizes dual, overlapping transcripts to encode both a gamete-killing poison and an antidote to the poison. To enact drive, all gametes are poisoned, whereas only those that inherit wtf4 are rescued by the antidote. Our work suggests that the wtf multigene family proliferated due to meiotic drive and highlights the power of selfish genes to shape genomes, even while imposing tremendous costs to fertility. DOI: http://dx.doi.org/10.7554/eLife.26033.001 PMID:28631612

Concerning RNA-guided gene drives for the alteration of wild populations

PubMed Central

Esvelt, Kevin M; Smidler, Andrea L; Catteruccia, Flaminia; Church, George M

2014-01-01

Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology. DOI: http://dx.doi.org/10.7554/eLife.03401.001 PMID:25035423

Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?

PubMed Central

Macias, Vanessa M.; Ohm, Johanna R.; Rasgon, Jason L.

2017-01-01

Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease. PMID:28869513

Fgf8 expression in the Tbx1 domain causes skeletal abnormalities and modifies the aortic arch but not the outflow tract phenotype of Tbx1 mutants

PubMed Central

Vitelli, Francesca; Zhang, Zhen; Huynh, Tuong; Sobotka, Angela; Mupo, Annalisa; Baldini, Antonio

2007-01-01

Fgf8 and Tbx1 have been shown to interact in patterning the aortic arch, and both genes are required in formation and growth of the outflow tract of the heart. However, the nature of the interaction of the two genes is unclear. We have utilized a novel Tbx1Fgf8 allele which drives Fgf8 expression in Tbx1-positive cells and an inducible Cre-LoxP recombination system to address the role of Fgf8 in Tbx1 positive cells in modulating cardiovascular development. Results support a requirement of Fgf8 in Tbx1 expressing cells to finely control patterning of the aortic arch and great arteries specifically during the pharyngeal arch artery remodeling process and indicate that the endoderm is the most likely site of this interaction. Furthermore, our data suggest that Fgf8 and Tbx1 play independent roles in regulating outflow tract development. This finding is clinically relevant since TBX1 is the candidate for DGS/VCFS, characterized clinically by variable expressivity and reduced penetrance of cardiovascular defects; Fgf8 gene variants may provide molecular clues to this variability. PMID:16696966

A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings.

PubMed

Sonuga-Barke, Edmund J S; Kumsta, Robert; Schlotz, Wolff; Lasky-Su, Jessica; Marco, Rafaela; Miranda, Ana; Mulas, Fernando; Oades, Robert D; Banaschewski, Tobias; Mueller, Ueli; Andreou, Penny; Christiansen, Hanna; Gabriels, Isabel; Uebel, Henrik; Kuntsi, Jonna; Franke, Barbara; Buitelaar, Jan; Ebstein, Richard; Gill, Michael; Anney, Richard; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph; Steinhausen, Hans Christoph; Asherson, Philip; Faraone, Stephen V

2011-08-01

Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes. Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene. There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms. The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs.

PubMed

Gonen, Serap; Jenko, Janez; Gorjanc, Gregor; Mileham, Alan J; Whitelaw, C Bruce A; Hickey, John M

2017-01-04

This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance [Formula: see text], rate of change in inbreeding ([Formula: see text]), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding.

Alcohol-impaired driving: average quantity consumed and frequency of drinking do matter.

PubMed

Birdsall, William C; Reed, Beth Glover; Huq, Syeda S; Wheeler, Laura; Rush, Sarah

2012-01-01

The objective of this article is to estimate and validate a logistic model of alcohol-impaired driving using previously ignored alcohol consumption behaviors, other risky behaviors, and demographic characteristics as independent variables. The determinants of impaired driving are estimated using the US Centers for Disease Control and Prevention's (CDC) Behavioral Risk Factor Surveillance System (BRFSS) surveys. Variables used in a logistic model to explain alcohol-impaired driving are not only standard sociodemographic variables and bingeing but also frequency of drinking and average quantity consumed, as well as other risky behaviors. We use interactions to understand how being female and being young affect impaired driving. Having estimated our model using the 1997 survey, we validated our model using the BRFSS data for 1999. Drinking 9 or more times in the past month doubled the odds of impaired driving. The greater average consumption of alcohol per session, the greater the odds of driving impaired, especially for persons in the highest quartile of alcohol consumed. Bingeing has the greatest effect on impaired driving. Seat belt use is the one risky behavior found to be related to such driving. Sociodemographic effects are consistent with earlier research. Being young (18-30) interacts with two of the alcohol consumption variables and being a woman interacts with always wearing a seat belt. Our model was robust in the validation analysis. All 3 dimensions of drinking behavior are important determinants of alcohol-impaired driving, including frequency and average quantity consumed. Including these factors in regressions improves the estimates of the effects of all variables.

Driven to extinction? The ethics of eradicating mosquitoes with gene-drive technologies.

PubMed

Pugh, Jonathan

2016-09-01

Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in 'gene-drive' technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the 'sanctity of life' in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Intra-tumor heterogeneity of cancer cells and its implications for cancer treatment

PubMed Central

Sun, Xiao-xiao; Yu, Qiang

2015-01-01

Recent studies have revealed extensive genetic and non-genetic variation across different geographical regions of a tumor or throughout different stages of tumor progression, which is referred to as intra-tumor heterogeneity. Several causes contribute to this phenomenon, including genomic instability, epigenetic alteration, plastic gene expression, signal transduction, and microenvironmental differences. These variables may affect key signaling pathways that regulate cancer cell growth, drive phenotypic diversity, and pose challenges to cancer treatment. Understanding the mechanisms underlying this heterogeneity will support the development of effective therapeutic strategies. PMID:26388155

Considerations when using variable frequency drive technology for pond aquculture

USDA-ARS?s Scientific Manuscript database

Some farmers have decided to use variable frequency drives (VFDs) to control pump speed and water flow rate to reduce operational cost and costs associated with repairs and maintenance. Mixed performance issues with VFDs and electric motors have been reported. Examples include frequent drive failure...

Aging increases cell-to-cell transcriptional variability upon immune stimulation.

PubMed

Martinez-Jimenez, Celia Pilar; Eling, Nils; Chen, Hung-Chang; Vallejos, Catalina A; Kolodziejczyk, Aleksandra A; Connor, Frances; Stojic, Lovorka; Rayner, Timothy F; Stubbington, Michael J T; Teichmann, Sarah A; de la Roche, Maike; Marioni, John C; Odom, Duncan T

2017-03-31

Aging is characterized by progressive loss of physiological and cellular functions, but the molecular basis of this decline remains unclear. We explored how aging affects transcriptional dynamics using single-cell RNA sequencing of unstimulated and stimulated naïve and effector memory CD4 + T cells from young and old mice from two divergent species. In young animals, immunological activation drives a conserved transcriptomic switch, resulting in tightly controlled gene expression characterized by a strong up-regulation of a core activation program, coupled with a decrease in cell-to-cell variability. Aging perturbed the activation of this core program and increased expression heterogeneity across populations of cells in both species. These discoveries suggest that increased cell-to-cell transcriptional variability will be a hallmark feature of aging across most, if not all, mammalian tissues. Copyright © 2017, American Association for the Advancement of Science.

Deconstructing transcriptional heterogeneity in pluripotent stem cells

PubMed Central

Shalek, Alex K.; Satija, Rahul; DaleyKeyser, AJay; Li, Hu; Zhang, Jin; Pardee, Keith; Gennert, David; Trombetta, John J.; Ferrante, Thomas C.; Regev, Aviv; Daley, George Q.; Collins, James J.

2014-01-01

SUMMARY Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates, but the regulatory circuits specifying these states and enabling transitions between them are not well understood. We set out to characterize transcriptional heterogeneity in PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signaling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signaling pathways and chromatin regulators. Strikingly, either removal of mature miRNAs or pharmacologic blockage of signaling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal, and a distinct chromatin state, an effect mediated by opposing miRNA families acting on the c-myc / Lin28 / let-7 axis. These data illuminate the nature of transcriptional heterogeneity in PSCs. PMID:25471879

Identification of germline transcriptional regulatory elements in Aedes aegypti.

PubMed

Akbari, Omar S; Papathanos, Philippos A; Sandler, Jeremy E; Kennedy, Katie; Hay, Bruce A

2014-02-04

The mosquito Aedes aegypti is the principal vector for the yellow fever and dengue viruses, and is also responsible for recent outbreaks of the alphavirus chikungunya. Vector control strategies utilizing engineered gene drive systems are being developed as a means of replacing wild, pathogen transmitting mosquitoes with individuals refractory to disease transmission, or bringing about population suppression. Several of these systems, including Medea, UD(MEL), and site-specific nucleases, which can be used to drive genes into populations or bring about population suppression, utilize transcriptional regulatory elements that drive germline-specific expression. Here we report the identification of multiple regulatory elements able to drive gene expression specifically in the female germline, or in the male and female germline, in the mosquito Aedes aegypti. These elements can also be used as tools with which to probe the roles of specific genes in germline function and in the early embryo, through overexpression or RNA interference.

Developing standard operating procedures for gene drive research in disease vector mosquitoes.

PubMed

Adelman, Zach N; Pledger, David; Myles, Kevin M

2017-12-01

Numerous arthropod species represent potential targets for gene-drive-based population suppression or replacement, including those that transmit diseases, damage crops, or act as deleterious invasive species. Containment measures for gene drive research in arthropods have been discussed in the literature, but the importance of developing safe and effective standard operating procedures (SOPs) for these types of experiments has not been adequately addressed. Concisely written SOPs link safe work practices, containment measures, institutional training, and research-specific protocols. Here we discuss information to be considered by principal investigators, biosafety officers, and institutional biosafety committees as they work together to develop SOPs for experiments involving gene drive in arthropods, and describe various courses of action that can be used to maintain the effectiveness of SOPs through evaluation and revision. The information provided herein will be especially useful to investigators and regulatory personnel who may lack extensive experience working with arthropods under containment conditions.

Identification of germline transcriptional regulatory elements in Aedes aegypti

NASA Astrophysics Data System (ADS)

Akbari, Omar S.; Papathanos, Philippos A.; Sandler, Jeremy E.; Kennedy, Katie; Hay, Bruce A.

2014-02-01

The mosquito Aedes aegypti is the principal vector for the yellow fever and dengue viruses, and is also responsible for recent outbreaks of the alphavirus chikungunya. Vector control strategies utilizing engineered gene drive systems are being developed as a means of replacing wild, pathogen transmitting mosquitoes with individuals refractory to disease transmission, or bringing about population suppression. Several of these systems, including Medea, UDMEL, and site-specific nucleases, which can be used to drive genes into populations or bring about population suppression, utilize transcriptional regulatory elements that drive germline-specific expression. Here we report the identification of multiple regulatory elements able to drive gene expression specifically in the female germline, or in the male and female germline, in the mosquito Aedes aegypti. These elements can also be used as tools with which to probe the roles of specific genes in germline function and in the early embryo, through overexpression or RNA interference.

Chapter 18: Variable Frequency Drive Evaluation Protocol. The Uniform Methods Project: Methods for Determining Energy Efficiency Savings for Specific Measures

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

Romberger, Jeff

An adjustable-speed drive (ASD) includes all devices that vary the speed of a rotating load, including those that vary the motor speed and linkage devices that allow constant motor speed while varying the load speed. The Variable Frequency Drive Evaluation Protocol presented here addresses evaluation issues for variable-frequency drives (VFDs) installed on commercial and industrial motor-driven centrifugal fans and pumps for which torque varies with speed. Constant torque load applications, such as those for positive displacement pumps, are not covered by this protocol.

Plankton networks driving carbon export in the oligotrophic ocean

PubMed Central

Larhlimi, Abdelhalim; Roux, Simon; Darzi, Youssef; Audic, Stephane; Berline, Léo; Brum, Jennifer; Coelho, Luis Pedro; Espinoza, Julio Cesar Ignacio; Malviya, Shruti; Sunagawa, Shinichi; Dimier, Céline; Kandels-Lewis, Stefanie; Picheral, Marc; Poulain, Julie; Searson, Sarah; Stemmann, Lars; Not, Fabrice; Hingamp, Pascal; Speich, Sabrina; Follows, Mick; Karp-Boss, Lee; Boss, Emmanuel; Ogata, Hiroyuki; Pesant, Stephane; Weissenbach, Jean; Wincker, Patrick; Acinas, Silvia G.; Bork, Peer; de Vargas, Colomban; Iudicone, Daniele; Sullivan, Matthew B.; Raes, Jeroen; Karsenti, Eric; Bowler, Chris; Gorsky, Gabriel

2015-01-01

The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis, exported through sinking particles, and finally sequestered in the deep ocean. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure driving the process remains largely uncharacterised. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of carbon export in the oligotrophic ocean. We show that specific plankton communities, from the surface and deep chlorophyll maximum, correlate with carbon export at 150 m and highlight unexpected taxa such as Radiolaria, alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical, nutrient-depleted, oligotrophic ocean. Additionally, we show that the relative abundance of just a few bacterial and viral genes can predict most of the variability in carbon export in these regions. PMID:26863193

Plankton networks driving carbon export in the oligotrophic ocean

NASA Astrophysics Data System (ADS)

2016-04-01

The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis, exported through sinking particles, and finally sequestered in the deep ocean. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure driving the process remains largely uncharacterized. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of carbon export in the oligotrophic ocean. We show that specific plankton communities, from the surface and deep chlorophyll maximum, correlate with carbon export at 150 m and highlight unexpected taxa such as Radiolaria and alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical, nutrient-depleted, oligotrophic ocean. Additionally, we show that the relative abundance of a few bacterial and viral genes can predict a significant fraction of the variability in carbon export in these regions.

Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila; a theoretical exploration of Medea-dependent population suppression.

PubMed

Akbari, Omar S; Chen, Chun-Hong; Marshall, John M; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A

2014-12-19

Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.

Identification of driving network of cellular differentiation from single sample time course gene expression data

NASA Astrophysics Data System (ADS)

Chen, Ye; Wolanyk, Nathaniel; Ilker, Tunc; Gao, Shouguo; Wang, Xujing

Methods developed based on bifurcation theory have demonstrated their potential in driving network identification for complex human diseases, including the work by Chen, et al. Recently bifurcation theory has been successfully applied to model cellular differentiation. However, there one often faces a technical challenge in driving network prediction: time course cellular differentiation study often only contains one sample at each time point, while driving network prediction typically require multiple samples at each time point to infer the variation and interaction structures of candidate genes for the driving network. In this study, we investigate several methods to identify both the critical time point and the driving network through examination of how each time point affects the autocorrelation and phase locking. We apply these methods to a high-throughput sequencing (RNA-Seq) dataset of 42 subsets of thymocytes and mature peripheral T cells at multiple time points during their differentiation (GSE48138 from GEO). We compare the predicted driving genes with known transcription regulators of cellular differentiation. We will discuss the advantages and limitations of our proposed methods, as well as potential further improvements of our methods.

Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group†.

PubMed

James, Stephanie; Collins, Frank H; Welkhoff, Philip A; Emerson, Claudia; Godfray, H Charles J; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W; Mbogo, Charles M; Okumu, Fredros O; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A; Tountas, Karen H; Touré, Yeya T

2018-06-01

Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes , focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes.

Pathway to Deployment of Gene Drive Mosquitoes as a Potential Biocontrol Tool for Elimination of Malaria in Sub-Saharan Africa: Recommendations of a Scientific Working Group†

PubMed Central

James, Stephanie; Collins, Frank H.; Welkhoff, Philip A.; Emerson, Claudia; Godfray, H. Charles J.; Gottlieb, Michael; Greenwood, Brian; Lindsay, Steve W.; Mbogo, Charles M.; Okumu, Fredros O.; Quemada, Hector; Savadogo, Moussa; Singh, Jerome A.; Tountas, Karen H.; Touré, Yeya T.

2018-01-01

Abstract. Gene drive technology offers the promise for a high-impact, cost-effective, and durable method to control malaria transmission that would make a significant contribution to elimination. Gene drive systems, such as those based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein, have the potential to spread beneficial traits through interbreeding populations of malaria mosquitoes. However, the characteristics of this technology have raised concerns that necessitate careful consideration of the product development pathway. A multidisciplinary working group considered the implications of low-threshold gene drive systems on the development pathway described in the World Health Organization Guidance Framework for testing genetically modified (GM) mosquitoes, focusing on reduction of malaria transmission by Anopheles gambiae s.l. mosquitoes in Africa as a case study. The group developed recommendations for the safe and ethical testing of gene drive mosquitoes, drawing on prior experience with other vector control tools, GM organisms, and biocontrol agents. These recommendations are organized according to a testing plan that seeks to maximize safety by incrementally increasing the degree of human and environmental exposure to the investigational product. As with biocontrol agents, emphasis is placed on safety evaluation at the end of physically confined laboratory testing as a major decision point for whether to enter field testing. Progression through the testing pathway is based on fulfillment of safety and efficacy criteria, and is subject to regulatory and ethical approvals, as well as social acceptance. The working group identified several resources that were considered important to support responsible field testing of gene drive mosquitoes. PMID:29882508

Development of real-world driving cycles and estimation of emission factors for in-use light-duty gasoline vehicles in urban areas.

PubMed

Hwa, Mei-Yin; Yu, Tai-Yi

2014-07-01

This investigation adopts vehicle tracking manner to establish real-world driving patterns and estimates emission factors with dynamometers with 23 traffic-driving variables for 384 in-use light-duty passenger vehicles during non-rush hour. Adequate numbers of driving variables were decided with factor analysis and cluster analysis. The dynamometer tests were performed on FTP75 cycle and five local driving cycles derived from real-world speed profiles. Results presented that local driving cycles and FTP75 cycle were completely different in driving characteristic parameters of typical driving cycles and emission factors. The highest values of emission factor ratios of local driving cycle and FTP75 cycle for CO, NMHC, NO x , CH4, and CO2 were 1.38, 1.65, 1.58, 1.39, and 1.14, respectively.

Social Bond Theory and Drunk Driving in a Sample of College Students

ERIC Educational Resources Information Center

Durkin, Keith F.; Wolfe, Scott E.; May, Ross W.

2007-01-01

This paper reports the finding from a study that examined the relationship between social bond variables and drunk driving in a sample of university students. A questionnaire containing indicators representing social bond variables, as well as a measure of drunk driving was administered to a sample of 1459 college students. The results of this…

Variable-Reluctance Motor For Electric Vehicles

NASA Technical Reports Server (NTRS)

Lang, Jeffrey H.

1987-01-01

Report describes research on variable-reluctance electric-motor drive for eventual use in electric-vehicle propulsion. Primary design and performance criteria were torque and power output per unit mass of motor, cost, and drive efficiency. For each criterion, optimized drive design developed, and designs unified to yield single electric-vehicle drive. Scaled-down motor performed as expected. Prototype of paraplegic lift operated by toggle switch and joystick. Lift plugs into household electrical outlet for recharging when not in use.

A multimodal dataset for various forms of distracted driving

PubMed Central

Taamneh, Salah; Tsiamyrtzis, Panagiotis; Dcosta, Malcolm; Buddharaju, Pradeep; Khatri, Ashik; Manser, Michael; Ferris, Thomas; Wunderlich, Robert; Pavlidis, Ioannis

2017-01-01

We describe a multimodal dataset acquired in a controlled experiment on a driving simulator. The set includes data for n=68 volunteers that drove the same highway under four different conditions: No distraction, cognitive distraction, emotional distraction, and sensorimotor distraction. The experiment closed with a special driving session, where all subjects experienced a startle stimulus in the form of unintended acceleration—half of them under a mixed distraction, and the other half in the absence of a distraction. During the experimental drives key response variables and several explanatory variables were continuously recorded. The response variables included speed, acceleration, brake force, steering, and lane position signals, while the explanatory variables included perinasal electrodermal activity (EDA), palm EDA, heart rate, breathing rate, and facial expression signals; biographical and psychometric covariates as well as eye tracking data were also obtained. This dataset enables research into driving behaviors under neatly abstracted distracting stressors, which account for many car crashes. The set can also be used in physiological channel benchmarking and multispectral face recognition. PMID:28809848

Pan Genome of the Phytoplankton Emiliania Underpins its Global Distribution

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

Read, Betsy A.; Kegel, Jessica; Klute, Mary J.

2012-06-18

Coccolithophores have influenced the global climate for over 200 million years1. These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems2. They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering themvisible fromspace3.Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO 2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO 2 production or uptake, sequestration and export to the deepmore » ocean4. Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate thatE. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.« less

Pan genome of the phytoplankton Emiliania underpins its global distribution.

PubMed

Read, Betsy A; Kegel, Jessica; Klute, Mary J; Kuo, Alan; Lefebvre, Stephane C; Maumus, Florian; Mayer, Christoph; Miller, John; Monier, Adam; Salamov, Asaf; Young, Jeremy; Aguilar, Maria; Claverie, Jean-Michel; Frickenhaus, Stephan; Gonzalez, Karina; Herman, Emily K; Lin, Yao-Cheng; Napier, Johnathan; Ogata, Hiroyuki; Sarno, Analissa F; Shmutz, Jeremy; Schroeder, Declan; de Vargas, Colomban; Verret, Frederic; von Dassow, Peter; Valentin, Klaus; Van de Peer, Yves; Wheeler, Glen; Dacks, Joel B; Delwiche, Charles F; Dyhrman, Sonya T; Glöckner, Gernot; John, Uwe; Richards, Thomas; Worden, Alexandra Z; Zhang, Xiaoyu; Grigoriev, Igor V

2013-07-11

Coccolithophores have influenced the global climate for over 200 million years. These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems. They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space. Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean. Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.

Low reproductive isolation and highly variable levels of gene flow reveal limited progress towards speciation between European river and brook lampreys.

PubMed

Rougemont, Q; Gaigher, A; Lasne, E; Côte, J; Coke, M; Besnard, A-L; Launey, S; Evanno, G

2015-12-01

Ecologically based divergent selection is a factor that could drive reproductive isolation even in the presence of gene flow. Population pairs arrayed along a continuum of divergence provide a good opportunity to address this issue. Here, we used a combination of mating trials, experimental crosses and population genetic analyses to investigate the evolution of reproductive isolation between two closely related species of lampreys with distinct life histories. We used microsatellite markers to genotype over 1000 individuals of the migratory parasitic river lamprey (Lampetra fluviatilis) and freshwater-resident nonparasitic brook lamprey (Lampetra planeri) distributed in 10 sympatric and parapatric population pairs in France. Mating trials, parentage analyses and artificial fertilizations demonstrated a low level of reproductive isolation between species even though size-assortative mating may contribute to isolation. Most parapatric population pairs were strongly differentiated due to the joint effects of geographic distance and barriers to migration. In contrast, we found variable levels of gene flow between sympatric populations ranging from panmixia to moderate differentiation, which indicates a gradient of divergence with some population pairs that may correspond to alternative morphs or ecotypes of a single species and others that remain partially isolated. Ecologically based divergent selection may explain these variable levels of divergence among sympatric population pairs, but incomplete genome swamping following secondary contact could have also played a role. Overall, this study illustrates how highly differentiated phenotypes can be maintained despite high levels of gene flow that limit the progress towards speciation. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

The drive for muscularity in men: media influences and objectification theory.

PubMed

Daniel, Samantha; Bridges, Sara K

2010-01-01

Presently, objectification theory has yielded mixed results when utilized to explain body image concerns in men. An online survey assessing internalization of media ideals, self-objectification, body surveillance, body shame, the drive for muscularity, and body mass index (BMI) was completed by 244 predominantly college-aged males. Path analyses were used to investigate relationships among these variables where it was hypothesized that objectification variables would mediate the relationship between internalization of media ideals and the drive for muscularity. Internalization of media ideals was the strongest predictor of the drive for muscularity, followed by BMI, though variables of objectification theory had no impact on the drive for muscularity contrary to hypotheses. The results suggest that objectification theory may not be applicable to men as it is currently measured. Copyright 2009 Elsevier Ltd. All rights reserved.

Novel Synthetic Medea selfish genetic elements drive population replacement in Drosophila, and a theoretical exploration of Medea-dependent population suppression

PubMed Central

Akbari, Omar S.; Chen, Chun-Hong; Marshall, John M.; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A.

2013-01-01

Insects act as vectors for diseases of plants, animals and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression. PMID:23654248

Does a threat appeal moderate reckless driving? A terror management theory perspective.

PubMed

Ben-Ari, O T; Florian, V; Mikulincer, M

2000-01-01

A series of two studies examined the effects of threat appeals on reckless driving from a terror management theory perspective. In both studies, all the participants (N = 109) reported on the relevance of driving to their self-esteem, and, then, half of them were exposed to a road trauma film and the remaining to a neutral film. In Study 1, the dependent variable was the self-report of intentions to drive recklessly in hypothetical scenarios. In Study 2, the dependent variable was actual behavior (driving speed) in a driving simulator. Findings indicated that a road trauma film led to less reported intentions of reckless driving, but to higher driving speed than a neutral film. These effects were only found among participants who perceived driving as relevant to their self-esteem. The discussion emphasized the self-enhancing mechanisms proposed by the terror management theory.

Minireview: Genetic basis of heterogeneity and severity in sickle cell disease

PubMed Central

Habara, Alawi

2016-01-01

Sickle cell disease, a common single gene disorder, has a complex pathophysiology that at its root is initiated by the polymerization of deoxy sickle hemoglobin. Sickle vasoocclusion and hemolytic anemia drive the development of disease complications. In this review, we focus on the genetic modifiers of disease heterogeneity. The phenotypic heterogeneity of disease is only partially explained by genetic variability of fetal hemoglobin gene expression and co-inheritance of α thalassemia. Given the complexity of pathophysiology, many different definitions of severity are possible complicating a full understanding of its genetic foundation. The pathophysiological complexity and the interlocking nature of the biological processes underpinning disease severity are becoming better understood. Nevertheless, useful genetic signatures of severity, regardless of how this is defined, are insufficiently developed to be used for treatment decisions and for counseling. PMID:26936084

Phoning while driving I: a review of epidemiological, psychological, behavioural and physiological studies.

PubMed

Collet, C; Guillot, A; Petit, C

2010-05-01

The impact of cell (mobile) phone use on driving performance has been widely questioned for 20 years. This paper reviews the literature to evaluate the extent to which phoning may impact behaviour with a risk to affect safety. After analysing epidemiological studies that give an overview of cell phone use, this paper examines the experimental results and focuses on variables showing that driving is impacted by holding a mobile-phone conversation. Information processing (e.g. reaction time and detection rate of cues related to driving information) and variables associated with vehicle control (e.g. lane-keeping, headway and vehicle speed) seem the most relevant. Although less studied than behavioural indices, physiological data give information about the supplementary potential strain that the driver may undergo under dual-task conditions. This first part of the review highlights common findings, questionable results and differences among studies, which originate from specific experimental designs with particular dependent variables, i.e. self-report, behavioural and physiological indicators. Finally, how drivers try to compensate for the additional load brought by phone use is described. STATEMENT OF RELEVANCE: The two papers review the influence of mobile-phone use on driving performance. While there is ample evidence that this dual task is likely to increase the risk of car crash, the review analyses the variables eliciting detrimental conditions and, conversely, those that may preserve acceptable conditions for safety, close to usual driving. The decision of answering or initiating a cell phone call while driving depends upon the complex interaction among several variables, including driving conditions and driver's own characteristics. In addition, this decision remains under driver's awareness of being able or not to manage the two tasks simultaneously.

Factors Driving Potential Ammonia Oxidation in Canadian Arctic Ecosystems: Does Spatial Scale Matter?

PubMed Central

Banerjee, Samiran

2012-01-01

Ammonia oxidation is a major process in nitrogen cycling, and it plays a key role in nitrogen limited soil ecosystems such as those in the arctic. Although mm-scale spatial dependency of ammonia oxidizers has been investigated, little is known about the field-scale spatial dependency of aerobic ammonia oxidation processes and ammonia-oxidizing archaeal and bacterial communities, particularly in arctic soils. The purpose of this study was to explore the drivers of ammonia oxidation at the field scale in cryosols (soils with permafrost within 1 m of the surface). We measured aerobic ammonia oxidation potential (both autotrophic and heterotrophic) and functional gene abundance (bacterial amoA and archaeal amoA) in 279 soil samples collected from three arctic ecosystems. The variability associated with quantifying genes was substantially less than the spatial variability observed in these soils, suggesting that molecular methods can be used reliably evaluate spatial dependency in arctic ecosystems. Ammonia-oxidizing archaeal and bacterial communities and aerobic ammonia oxidation were spatially autocorrelated. Gene abundances were spatially structured within 4 m, whereas biochemical processes were structured within 40 m. Ammonia oxidation was driven at small scales (<1m) by moisture and total organic carbon, whereas gene abundance and other edaphic factors drove ammonia oxidation at medium (1 to 10 m) and large (10 to 100 m) scales. In these arctic soils heterotrophs contributed between 29 and 47% of total ammonia oxidation potential. The spatial scale for aerobic ammonia oxidation genes differed from potential ammonia oxidation, suggesting that in arctic ecosystems edaphic, rather than genetic, factors are an important control on ammonia oxidation. PMID:22081570

Chronotype-dependent circadian rhythmicity of driving safety.

PubMed

Del Rio-Bermudez, Carlos; Diaz-Piedra, Carolina; Catena, Andrés; Buela-Casal, Gualberto; Di Stasi, Leandro Luigi

2014-05-01

Among the factors associated with driving safety, sleep-related variables constitute a leading cause of road accidents. Circadian fluctuations of driver's somnolence has been previously linked to road safety. However, the role of chronotype in this relationship has been poorly investigated. Thus, the aim of the present work was to address whether driving performance is influenced by circadian patterns, in turn modulated by the driver's chronotype and the time of day (i.e. synchrony effect). We assessed 47 healthy young adults with specific chronotypes in several simulated driving sessions, both in the morning and in the evening. We collected driving performance data, along with self-reported levels of activation prior to each driving session and other sleep-related variables. Participants drove less safely when testing times took place outside their optimal time of day, as determined by their chronotype and confirmed by self-reported levels of activation. These differences were more pronounced in the morning, when morning types shown a better driving performance. Our results suggest that chronotype plays an important role as a modulator of the relationship between the time of day and driving safety. Therefore, it is necessary to acknowledge this variable in theoretical models of driving behavior, and for the improvement of occupational accidents prevention programs.

Safe and Efficient Gene Therapy for Pyruvate Kinase Deficiency.

PubMed

Garcia-Gomez, Maria; Calabria, Andrea; Garcia-Bravo, Maria; Benedicenti, Fabrizio; Kosinski, Penelope; López-Manzaneda, Sergio; Hill, Collin; Del Mar Mañu-Pereira, María; Martín, Miguel A; Orman, Israel; Vives-Corrons, Joan-LLuis; Kung, Charles; Schambach, Axel; Jin, Shengfang; Bueren, Juan A; Montini, Eugenio; Navarro, Susana; Segovia, Jose C

2016-08-01

Pyruvate kinase deficiency (PKD) is a monogenic metabolic disease caused by mutations in the PKLR gene that leads to hemolytic anemia of variable symptomatology and that can be fatal during the neonatal period. PKD recessive inheritance trait and its curative treatment by allogeneic bone marrow transplantation provide an ideal scenario for developing gene therapy approaches. Here, we provide a preclinical gene therapy for PKD based on a lentiviral vector harboring the hPGK eukaryotic promoter that drives the expression of the PKLR cDNA. This therapeutic vector was used to transduce mouse PKD hematopoietic stem cells (HSCs) that were subsequently transplanted into myeloablated PKD mice. Ectopic RPK expression normalized the erythroid compartment correcting the hematological phenotype and reverting organ pathology. Metabolomic studies demonstrated functional correction of the glycolytic pathway in RBCs derived from genetically corrected PKD HSCs, with no metabolic disturbances in leukocytes. The analysis of the lentiviral insertion sites in the genome of transplanted hematopoietic cells demonstrated no evidence of genotoxicity in any of the transplanted animals. Overall, our results underscore the therapeutic potential of the hPGK-coRPK lentiviral vector and provide high expectations toward the gene therapy of PKD and other erythroid metabolic genetic disorders.

Examining the influence of aggressive driving behavior on driver injury severity in traffic crashes.

PubMed

Paleti, Rajesh; Eluru, Naveen; Bhat, Chandra R

2010-11-01

In this paper, we capture the moderating effect of aggressive driving behavior while assessing the influence of a comprehensive set of variables on injury severity. In doing so, we are able to account for the indirect effects of variables on injury severity through their influence on aggressive driving behavior, as well as the direct effect of variables on injury severity. The methodology used in the paper to accommodate the moderating effect of aggressive driving behavior takes the form of two models--one for aggressive driving and another for injury severity. These are appropriately linked to obtain the indirect and direct effects of variables. The data for estimation is obtained from the National Motor Vehicle Crash Causation Study (NMVCCS). From an empirical standpoint, we consider a fine age categorization until 20 years of age when examining age effects on aggressive driving behavior and injury severity. There are several important results from the empirical analysis undertaken in the current paper based on post-crash data collection on aggressive behavior participation just prior to the crash and injury severity sustained in a crash. Young drivers (especially novice drivers between 16 and 17 years of age), drivers who are not wearing seat belt, under the influence of alcohol, not having a valid license, and driving a pick-up are found to be most likely to behave aggressively. Situational, vehicle, and roadway factors such as young drivers traveling with young passengers, young drivers driving an SUV or a pick-up truck, driving during the morning rush hour, and driving on roads with high speed limits are also found to trigger aggressive driving behavior. In terms of vehicle occupants, the safest situation from a driver injury standpoint is when there are two or more passengers in the vehicle, at least one of whom is above the age of 20 years. These and many other results are discussed, along with implications of the result for graduated driving licensing (GDL) programs. 2010 Elsevier Ltd. All rights reserved.

Driving performance changes of middle-aged experienced taxi drivers due to distraction tasks during unexpected situations.

PubMed

Kim, Hyung-Sik; Choi, Mi-Hyun; Choi, Jin-Seung; Kim, Hyun-Joo; Hong, Sang-Pyo; Jun, Jae-Hoon; Tack, Gye-Rae; Kim, Boseong; Min, Ung-Chan; Lim, Dae-Woon; Chung, Soon-Cheol

2013-10-01

This study investigated the effects of distraction taskssuch as sending a text message with a cellphone and searching navigation with car navigation system-on the driving performance of 29 highly experienced taxi drivers in their 50s. All participants were instructed to drive using a driving simulator for 2 min. while maintaining a constant distance from the vehicle in front and a constant speed. Participants drove without any distractions for the first minute. For an additional minute, they performed Driving Only or performed a task while driving (Driving + Sending Text Message or Driving + Searching Navigation). An unexpected situation, in which the participant had to stop abruptly due to a sudden stop of the preceding vehicle, occurred during this period. Driving performance during the unexpected situation was evaluated by car control variables, medial-lateral coefficient of variation and brake time, and by motion variables such as the jerk-cost function. Compared to Driving Only, jerk-cost function, medial-lateral coefficient of variation, and brake time increased during Driving + Sending Text Message or Driving + Searching Navigation.

Testing and Contrasting Road Safety Education, Deterrence, and Social Capital Theories: A Sociological Approach to the Understanding of Male Drink-Driving in Chile's Metropolitan Region.

PubMed

Nazif, José Ignacio

2011-01-01

Three theories offer different explanations to the understanding of male drink-driving. In order to test road safety education, deterrence, and social capital theories, logistic regression analysis was applied to predict respondents' statements of having or not having engaged in actual drink-driving (DD). Variable for road safety education theory was whether a driver had graduated from a professional driving school or not. Deterrence theory was operationalized with a variable of whether a driver had been issued a traffic ticket or not. Social capital theory was operationalized with two variables, having children or not and having religion identification or not. Since both variables 'years of formal education' and 'years of driving experience' have been reported to be correlated to alcohol consumption and DD respectively, these were introduced as controls. In order to assess the significance of each variable statistically, Wald tests were applied in seven models. Results indicate on the one hand that road safety education variable is not statistically significant; and on the other, deterrence theory variable and social capital theory variable 'having children' were both statistically significant at the level of .01. Findings are discussed in reference to Chile's context. Data were taken from the "Road Users Attitudes and Behaviors towards Traffic Safety" survey from the National Commission of Road Safety of the Government of Chile (2005). The sample size was reported to be 2,118 (N of male drivers was 396). This survey was representative of Chile's Metropolitan Region road users' population.

Testing and Contrasting Road Safety Education, Deterrence, and Social Capital Theories: A Sociological Approach to the Understanding of Male Drink-Driving in Chile’s Metropolitan Region

PubMed Central

Nazif, José Ignacio

2011-01-01

Three theories offer different explanations to the understanding of male drink-driving. In order to test road safety education, deterrence, and social capital theories, logistic regression analysis was applied to predict respondents’ statements of having or not having engaged in actual drink-driving (DD). Variable for road safety education theory was whether a driver had graduated from a professional driving school or not. Deterrence theory was operationalized with a variable of whether a driver had been issued a traffic ticket or not. Social capital theory was operationalized with two variables, having children or not and having religion identification or not. Since both variables ‘years of formal education’ and ‘years of driving experience’ have been reported to be correlated to alcohol consumption and DD respectively, these were introduced as controls. In order to assess the significance of each variable statistically, Wald tests were applied in seven models. Results indicate on the one hand that road safety education variable is not statistically significant; and on the other, deterrence theory variable and social capital theory variable ‘having children’ were both statistically significant at the level of .01. Findings are discussed in reference to Chile’s context. Data were taken from the “Road Users Attitudes and Behaviors towards Traffic Safety” survey from the National Commission of Road Safety of the Government of Chile (2005). The sample size was reported to be 2,118 (N of male drivers was 396). This survey was representative of Chile’s Metropolitan Region road users' population. PMID:22105406

Origin, evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster.

PubMed

Brand, Cara L; Larracuente, Amanda M; Presgraves, Daven C

2015-05-01

Meiotic drive elements are a special class of evolutionarily "selfish genes" that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran-GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Metatranscriptome sequence analysis reveals diel periodicity of microbial community gene expression in the ocean's interior

NASA Astrophysics Data System (ADS)

Vislova, A.; Aylward, F.; Sosa, O.; DeLong, E.

2016-02-01

Previous work has revealed diel periodicity of gene expression in key metabolic pathways in both autotrophic and heterotrophic microbes in the surface ocean. In this study, we investigated patterns of diel periodicity of gene expression in depth profiles (25, 75, 125 and 250 meters). We postulated that microbial diel transcriptional signals would be increasingly dampened with depth, and that the timing of peak expression of specific transcripts would be shifted in time between depths, in accordance with depth-dependent diel light variability. Bacterioplankton were sampled from four depths every four hours at station ALOHA (22° 45' N 158° W) over 2 days. RNA was extracted from cells preserved on filters, converted to cDNA, and sequenced on the Illumina platform. Surprisingly, harmonic regression analysis revealed an increasing proportion of genes with diel periodic expression patterns with increasing depth between 25- 125 meters. At 250 meters, the proportion of genes exhibiting diel expression patterns decreased an order of magnitude compared to the photic zone. Community composition, functional gene categories, and diel patterns of gene expression were significantly different between the photic zone and 250 meter samples. The signals driving diel periodic gene expression in microbes at 250 meters is under further investigation. These data are now beginning provide a better understanding of the tempo and mode of microbial dynamics among specific taxa, throughout the ocean's interior.

Moderating effects of social engagement on driving cessation in older women.

PubMed

Pachana, Nancy A; Leung, Janni K; Gardiner, Paul A; McLaughlin, Deirdre

2016-08-01

Driving cessation in later life is associated with depression. This study examines if social support can buffer the negative effects of driving cessation on older women's mental health. Participants were drawn from the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health (ALSWH) and included 4,075 older women (aged 76-87 years) who drove at baseline, following them for three years to assess driving cessation. The outcome variable was mental health, measured by the mental health index (MHI) of the SF-36. The explanatory variables were social support factors, including social interaction, whether the women were living alone or with others, and engagement in social activities. Control variables included age, country of birth, area of residence, ability to manage on income, marital status, and general health. Main effect results showed that poor mental health was predicted by driving cessation, low levels of social interaction, and non-engagement in social activities. There was a significant interaction effect of driving status by social activities engagement on mental health. Women who remained active in their engagement of social activities were able to maintain a good level of mental health despite driving cessation. Engagement and participation in social activities can help older women who stopped driving maintain a good level of mental health.

A CRISPR Cas9-based gene drive platform for genetic interaction analysis in Candida albicans

PubMed Central

Shapiro, Rebecca S.; Chavez, Alejandro; Porter, Caroline B. M.; Hamblin, Meagan; Kaas, Christian S.; DiCarlo, James E.; Zeng, Guisheng; Xu, Xiaoli; Revtovich, Alexey V.; Kirienko, Natalia V.; Wang, Yue; Church, George M.; Collins, James J.

2018-01-01

Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR-Cas9-based ‘gene drive array’ (GDA) platform to facilitate efficient genetic analysis in C. albicans. In our system, a modified DNA donor molecule acts as a selfish genetic element, replaces the targeted site, and propagates to replace additional wild-type loci. Using mating-competent C. albicans haploids, each carrying a different gene drive disabling a gene of interest, we are able to create diploid strains that are homozygous double-deletion mutants. We generate double-gene deletion libraries to demonstrate this technology, targeting antifungal efflux and biofilm adhesion factors. We screen these libraries to identify virulence regulators and determine how genetic networks shift under diverse conditions. This platform transforms our ability to perform genetic interaction analysis in C. albicans and is readily extended to other fungal pathogens. PMID:29062088

Holoprosencephaly: signalling interactions between the brain and the face, the environment and the genes, and the phenotypic variability in animal models and humans

PubMed Central

Graf, Daniel; Marcucio, Ralph

2014-01-01

Holoprosencephaly (HPE) is the most common developmental defect of the forebrain characterized by inadequate or absent midline division of the forebrain into cerebral hemispheres, with concomitant midline facial defects in the majority of cases. Understanding the pathogenesis of HPE requires knowledge of the relationship between the developing brain and the facial structures during embryogenesis. A number of signalling pathways control and coordinate the development of the brain and face, including Sonic hedgehog (SHH), Bone Morphogenetic Protein (BMP), Fibroblast Growth Factor (FGF), and Nodal signalling. Mutations in these pathways have been identified in animal models of HPE and human patients. Due to incomplete penetrance and variable expressivity of HPE, patients carrying defined mutations may not manifest the disease at all, or have a spectrum of defects. It is currently unknown what drives manifestation of HPE in genetically at risk individuals, but it has been speculated that other gene mutations and environmental factors may combine as cumulative insults. HPE can be diagnosed in utero by a high-resolution prenatal ultrasound or a fetal magnetic resonance imaging, sometimes in combination with molecular testing from chorionic villi or amniotic fluid sampling. Currently, there are no effective preventive methods for HPE. Better understanding of the mechanisms of gene-environment interactions in HPE would provide avenues for such interventions. PMID:25339593

Effects of the Contextual Variables of Racing Games on Risky Driving Behavior.

PubMed

Deng, Mingming; Chan, Alan H S; Wu, Feng; Liu, Shulin

2017-08-01

This research conducted experimental studies to investigate the effects of the contextual variables of racing games on risky driving behavior. Three experiments were conducted. In Experiment 1, the effect of racing game violence on the driving-related risk-taking inclination of racing game players was examined. Experiment 2 investigated the impact of the competitiveness of racing games on risk-taking inclination, and Experiment 3 investigated the impact of the rewarded/punitive characteristics of racing games on the risk-taking inclination of racing game players. The Vienna Risk-Taking Test was used to measure risk-taking inclination of participants. The game violence, competitiveness, and the reward characteristics of racing games, all had significant impacts in increasing risky driving behavior. The punitive characteristics of racing games had a significant effect, which decreases risky driving behavior. The contextual variables of game violence, competitiveness, and rewarded/punitive characteristics of racing games investigated in this study were all shown to influence the risk-taking inclination of game players, which increased risky driving behavior. This study provides a useful reference for the classification and graded management of racing games.

Transcription termination factor Rho and microbial phenotypic heterogeneity.

PubMed

Bidnenko, Elena; Bidnenko, Vladimir

2018-06-01

Populations of genetically identical microorganisms exhibit high degree of cell-to-cell phenotypic diversity even when grown in uniform environmental conditions. Heterogeneity is a genetically determined trait, which ensures bacterial adaptation and survival in the ever changing environmental conditions. Fluctuations in gene expression (noise) at the level of transcription initiation largely contribute to cell-to-cell variability within population. Not surprisingly, the analyses of the mechanisms driving phenotypic heterogeneity are mainly focused on the activity of promoters and transcriptional factors. Less attention is currently given to a role of intrinsic and factor-dependent transcription terminators. Here, we discuss recent advances in understanding the regulatory role of the multi-functional transcription termination factor Rho, the major inhibitor of pervasive transcription in bacteria and the emerging global regulator of gene expression. We propose that termination activity of Rho might be among the mechanisms by which cells manage the intensity of transcriptional noise, thus affecting population heterogeneity.

Modeling Driving Performance Using In-Vehicle Speech Data From a Naturalistic Driving Study.

PubMed

Kuo, Jonny; Charlton, Judith L; Koppel, Sjaan; Rudin-Brown, Christina M; Cross, Suzanne

2016-09-01

We aimed to (a) describe the development and application of an automated approach for processing in-vehicle speech data from a naturalistic driving study (NDS), (b) examine the influence of child passenger presence on driving performance, and (c) model this relationship using in-vehicle speech data. Parent drivers frequently engage in child-related secondary behaviors, but the impact on driving performance is unknown. Applying automated speech-processing techniques to NDS audio data would facilitate the analysis of in-vehicle driver-child interactions and their influence on driving performance. Speech activity detection and speaker diarization algorithms were applied to audio data from a Melbourne-based NDS involving 42 families. Multilevel models were developed to evaluate the effect of speech activity and the presence of child passengers on driving performance. Speech activity was significantly associated with velocity and steering angle variability. Child passenger presence alone was not associated with changes in driving performance. However, speech activity in the presence of two child passengers was associated with the most variability in driving performance. The effects of in-vehicle speech on driving performance in the presence of child passengers appear to be heterogeneous, and multiple factors may need to be considered in evaluating their impact. This goal can potentially be achieved within large-scale NDS through the automated processing of observational data, including speech. Speech-processing algorithms enable new perspectives on driving performance to be gained from existing NDS data, and variables that were once labor-intensive to process can be readily utilized in future research. © 2016, Human Factors and Ergonomics Society.

Variable-pulse-shape pulsed-power accelerator

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

Stoltzfus, Brian S.; Austin, Kevin; Hutsel, Brian Thomas

A variable-pulse-shape pulsed-power accelerator is driven by a large number of independent LC drive circuits. Each LC circuit drives one or more coaxial transmission lines that deliver the circuit's output power to several water-insulated radial transmission lines that are connected in parallel at small radius by a water-insulated post-hole convolute. The accelerator can be impedance matched throughout. The coaxial transmission lines are sufficiently long to transit-time isolate the LC drive circuits from the water-insulated transmission lines, which allows each LC drive circuit to be operated without being affected by the other circuits. This enables the creation of any power pulsemore » that can be mathematically described as a time-shifted linear combination of the pulses of the individual LC drive circuits. Therefore, the output power of the convolute can provide a variable pulse shape to a load that can be used for magnetically driven, quasi-isentropic compression experiments and other applications.« less

A BAC-bacterial recombination method to generate physically linked multiple gene reporter DNA constructs.

PubMed

Maye, Peter; Stover, Mary Louise; Liu, Yaling; Rowe, David W; Gong, Shiaochin; Lichtler, Alexander C

2009-03-13

Reporter gene mice are valuable animal models for biological research providing a gene expression readout that can contribute to cellular characterization within the context of a developmental process. With the advancement of bacterial recombination techniques to engineer reporter gene constructs from BAC genomic clones and the generation of optically distinguishable fluorescent protein reporter genes, there is an unprecedented capability to engineer more informative transgenic reporter mouse models relative to what has been traditionally available. We demonstrate here our first effort on the development of a three stage bacterial recombination strategy to physically link multiple genes together with their respective fluorescent protein (FP) reporters in one DNA fragment. This strategy uses bacterial recombination techniques to: (1) subclone genes of interest into BAC linking vectors, (2) insert desired reporter genes into respective genes and (3) link different gene-reporters together. As proof of concept, we have generated a single DNA fragment containing the genes Trap, Dmp1, and Ibsp driving the expression of ECFP, mCherry, and Topaz FP reporter genes, respectively. Using this DNA construct, we have successfully generated transgenic reporter mice that retain two to three gene readouts. The three stage methodology to link multiple genes with their respective fluorescent protein reporter works with reasonable efficiency. Moreover, gene linkage allows for their common chromosomal integration into a single locus. However, the testing of this multi-reporter DNA construct by transgenesis does suggest that the linkage of two different genes together, despite their large size, can still create a positional effect. We believe that gene choice, genomic DNA fragment size and the presence of endogenous insulator elements are critical variables.

An analysis of crash likelihood : age versus driving experience

DOT National Transportation Integrated Search

1995-05-01

The study was designed to determine the crash likelihood of drivers in Michigan as a function of two independent variables: driver age and driving experience. The age variable had eight levels (18, 19, 20, 21, 22, 23, 24, and 25 years old) and the ex...

Recurrent selection on the Winters sex-ratio genes in Drosophila simulans.

PubMed

Kingan, Sarah B; Garrigan, Daniel; Hartl, Daniel L

2010-01-01

Selfish genes, such as meiotic drive elements, propagate themselves through a population without increasing the fitness of host organisms. X-linked (or Y-linked) meiotic drive elements reduce the transmission of the Y (X) chromosome and skew progeny and population sex ratios, leading to intense conflict among genomic compartments. Drosophila simulans is unusual in having a least three distinct systems of X chromosome meiotic drive. Here, we characterize naturally occurring genetic variation at the Winters sex-ratio driver (Distorter on the X or Dox), its progenitor gene (Mother of Dox or MDox), and its suppressor gene (Not Much Yang or Nmy), which have been previously mapped and characterized. We survey three North American populations as well as 13 globally distributed strains and present molecular polymorphism data at the three loci. We find that all three genes show signatures of selection in North America, judging from levels of polymorphism and skews in the site-frequency spectrum. These signatures likely result from the biased transmission of the driver and selection on the suppressor for the maintenance of equal sex ratios. Coalescent modeling indicates that the timing of selection is more recent than the age of the alleles, suggesting that the driver and suppressor are coevolving under an evolutionary "arms race." None of the Winters sex-ratio genes are fixed in D. simulans, and at all loci we find ancestral alleles, which lack the gene insertions and exhibit high levels of nucleotide polymorphism compared to the derived alleles. In addition, we find several "null" alleles that have mutations on the derived Dox background, which result in loss of drive function. We discuss the possible causes of the maintenance of presence-absence polymorphism in the Winters sex-ratio genes.

A meta-analysis of the effects of texting on driving.

PubMed

Caird, Jeff K; Johnston, Kate A; Willness, Chelsea R; Asbridge, Mark; Steel, Piers

2014-10-01

Text messaging while driving is considered dangerous and known to produce injuries and fatalities. However, the effects of text messaging on driving performance have not been synthesized or summarily estimated. All available experimental studies that measured the effects of text messaging on driving were identified through database searches using variants of "driving" and "texting" without restriction on year of publication through March 2014. Of the 1476 abstracts reviewed, 82 met general inclusion criteria. Of these, 28 studies were found to sufficiently compare reading or typing text messages while driving with a control or baseline condition. Independent variables (text-messaging tasks) were coded as typing, reading, or a combination of both. Dependent variables included eye movements, stimulus detection, reaction time, collisions, lane positioning, speed and headway. Statistics were extracted from studies to compute effect sizes (rc). A total sample of 977 participants from 28 experimental studies yielded 234 effect size estimates of the relationships among independent and dependent variables. Typing and reading text messages while driving adversely affected eye movements, stimulus detection, reaction time, collisions, lane positioning, speed and headway. Typing text messages alone produced similar decrements as typing and reading, whereas reading alone had smaller decrements over fewer dependent variables. Typing and reading text messages affects drivers' capability to adequately direct attention to the roadway, respond to important traffic events, control a vehicle within a lane and maintain speed and headway. This meta-analysis provides convergent evidence that texting compromises the safety of the driver, passengers and other road users. Combined efforts, including legislation, enforcement, blocking technologies, parent modeling, social media, social norms and education, will be required to prevent continued deaths and injuries from texting and driving. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Energy conservation strategy in Hydraulic Power Packs using Variable Frequency Drive IOP Conference Series: Materials Science and Engineering

NASA Astrophysics Data System (ADS)

Ramesh, S.; Ashok, S. Denis; Nagaraj, Shanmukha; Reddy, M. Lohith Kumar; Naulakha, Niranjan Kumar; Adithyakumar, C. R.

2018-02-01

At present, energy consumption is to such an extent that if the same trend goes on then in the future at some point of time, the energy sources will all be exploited. Energy conservation in a hydraulic power pack refers to the reduction in the energy consumed by the power pack. Many experiments have been conducted to reduce the energy consumption and one of those methods is by introducing a variable frequency drive. The main objective of the present work is to reduce the energy consumed by the hydraulic power pack using variable frequency drive. Variable Frequency drive is used to vary the speed of the motor by receiving electrical signals from the pressure switch which acts as the feedback system. Using this concept, the speed of the motor can be varied between the specified limits. In the present work, a basic hydraulic power pack and a variable frequency drive based hydraulic power pack were designed and compared both of them with the results obtained. The comparison was based on the power consumed, rise in temperature, noise levels, and flow of oil through pressure relief valve, total oil flow during loading cycle. By comparing both the circuits, it is found that for the proposed system, consumption of power reduces by 78.4% and is as powerful as the present system.

Bacterial community assembly in activated sludge: mapping beta diversity across environmental variables.

PubMed

Isazadeh, Siavash; Jauffur, Shameem; Frigon, Dominic

2016-12-01

Effect of ecological variables on community assembly of heterotrophic bacteria at eight full-scale and two pilot-scale activated sludge wastewater treatment plants (AS-WWTPs) were explored by pyrosequencing of 16S rRNA gene amplicons. In total, 39 samples covering a range of abiotic factors spread over space and time were analyzed. A core bacterial community of 24 families detected in at least six of the eight AS-WWTPs was defined. In addition to the core families, plant-specific families (observed at <50% AS-WWTPs) were found to be also important in the community structure. Observed beta diversity was partitioned with respect to ecological variables. Specifically, the following variables were considered: influent wastewater characteristics, season (winter vs. summer), process operations (conventional, oxidation ditch, and sequence batch reactor), reactor sizes (pilot-scale vs. full-scale reactors), chemical stresses defined by ozonation of return activated sludge, interannual variation, and geographical locations. Among the assessed variables, influent wastewater characteristics and geographical locations contributed more in explaining the differences between AS-WWTP bacterial communities with a maximum of approximately 26% of the observed variations. Partitioning of beta diversity is necessary to interpret the inherent variability in microbial community assembly and identify the driving forces at play in engineered microbial ecosystem. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

22. VAL, VIEW OF PROJECTILE LOADING DECK LOOKING NORTHEAST TOWARD ...

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

22. VAL, VIEW OF PROJECTILE LOADING DECK LOOKING NORTHEAST TOWARD TOP OF CONCRETE 'A' FRAME STRUCTURE SHOWING DRIVE CABLES, DRIVE GEAR, BOTTOM OF CAMERA TOWER AND 'CROWS NEST' CONTROL ROOM. - Variable Angle Launcher Complex, Variable Angle Launcher, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

Contributions of physical and cognitive impairments to self-reported driving difficulty in chronic whiplash-associated disorders.

PubMed

Takasaki, Hiroshi; Treleaven, Julia; Johnston, Venerina; Jull, Gwendolen

2013-08-15

Cross-sectional. To conduct a preliminary analysis of the physical, cognitive, and psychological domains contributing to self-reported driving difficulty after adjusting for neck pain, dizziness, and relevant demographics in chronic whiplash-associated disorders (WAD) using hierarchical regression modeling. Pain is a risk factor for car crashes, and dizziness may affect fitness to drive. Both symptoms are common in chronic WAD and difficulty driving is a common complaint in this group. Chronic WAD is often accompanied by physical, cognitive, and psychological impairments. These impairments may contribute to self-reported driving difficulty beyond neck pain, dizziness, and relevant demographics. Forty individuals with chronic WAD participated. Dependent variables were the magnitude of self-reported driving difficulty assessed in the strategic, tactical, and operational levels of the Neck Pain Driving Index. Three models were developed to assess the contributions of independent variables (physical, cognitive, and psychological domains) to each of the 3 dependent variables after adjusting for neck pain intensity, dizziness, and driving demographics. The measures included were: physical domain-range and maximum speed of head rotation, performances during gaze stability, eye-head coordination, and visual dependency tests; cognitive domain-self-reported cognitive symptoms including fatigue and the trail making tests; and psychological domain-general stress, traumatic stress, depression, and fear of neck movements and driving. Symptom duration was relevant to driving difficulty in the strategic and tactical levels. The cognitive domain increased statistical power to estimate the strategic and operational levels (P < 0.1) beyond other contributors. The physical domain increased statistical power to estimate the tactical level (P < 0.1) beyond other contributors. Physical and cognitive impairments independently contributed to self-reported driving difficulty in chronic WAD beyond neck pain, dizziness, and symptom duration. 3.

Defining the limits of physiological plasticity: how gene expression can assess and predict the consequences of ocean change

PubMed Central

Evans, Tyler G.; Hofmann, Gretchen E.

2012-01-01

Anthropogenic stressors, such as climate change, are driving fundamental shifts in the abiotic characteristics of marine ecosystems. As the environmental aspects of our world's oceans deviate from evolved norms, of major concern is whether extant marine species possess the capacity to cope with such rapid change. In what many scientists consider the post-genomic era, tools that exploit the availability of DNA sequence information are being increasingly recognized as relevant to questions surrounding ocean change and marine conservation. In this review, we highlight the application of high-throughput gene-expression profiling, primarily transcriptomics, to the field of marine conservation physiology. Through the use of case studies, we illustrate how gene expression can be used to standardize metrics of sub-lethal stress, track organism condition in natural environments and bypass phylogenetic barriers that hinder the application of other physiological techniques to conservation. When coupled with fine-scale monitoring of environmental variables, gene-expression profiling provides a powerful approach to conservation capable of informing diverse issues related to ocean change, from coral bleaching to the spread of invasive species. Integrating novel approaches capable of improving existing conservation strategies, including gene-expression profiling, will be critical to ensuring the ecological and economic health of the global ocean. PMID:22566679

Dosage changes of a segment at 17p13.1 lead to intellectual disability and microcephaly as a result of complex genetic interaction of multiple genes.

PubMed

Carvalho, Claudia M B; Vasanth, Shivakumar; Shinawi, Marwan; Russell, Chad; Ramocki, Melissa B; Brown, Chester W; Graakjaer, Jesper; Skytte, Anne-Bine; Vianna-Morgante, Angela M; Krepischi, Ana C V; Patel, Gayle S; Immken, LaDonna; Aleck, Kyrieckos; Lim, Cynthia; Cheung, Sau Wai; Rosenberg, Carla; Katsanis, Nicholas; Lupski, James R

2014-11-06

The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A review of precipitation and temperature control on seedling emergence and establishment for ponderosa and lodgepole pine forest regeneration

USGS Publications Warehouse

Petrie, Matthew; Wildeman, A.M.; Bradford, John B.; Hubbard, R.M.; Lauenroth, W.K.

2016-01-01

The persistence of ponderosa pine and lodgepole pine forests in the 21st century depends to a large extent on how seedling emergence and establishment are influenced by driving climate and environmental variables, which largely govern forest regeneration. We surveyed the literature, and identified 96 publications that reported data on dependent variables of seedling emergence and/or establishment and one or more independent variables of air temperature, soil temperature, precipitation and moisture availability. Our review suggests that seedling emergence and establishment for both species is highest at intermediate temperatures (20 to 25 °C), and higher precipitation and higher moisture availability support a higher percentage of seedling emergence and establishment at daily, monthly and annual timescales. We found that ponderosa pine seedlings may be more sensitive to temperature fluctuations whereas lodgepole pine seedlings may be more sensitive to moisture fluctuations. In a changing climate, increasing temperatures and declining moisture availability may hinder forest persistence by limiting seedling processes. Yet, only 23 studies in our review investigated the effects of driving climate and environmental variables directly. Furthermore, 74 studies occurred in a laboratory or greenhouse, which do not often replicate the conditions experienced by tree seedlings in a field setting. It is therefore difficult to provide strong conclusions on how sensitive emergence and establishment in ponderosa and lodgepole pine are to these specific driving variables, or to investigate their potential aggregate effects. Thus, the effects of many driving variables on seedling processes remain largely inconclusive. Our review stresses the need for additional field and laboratory studies to better elucidate the effects of driving climate and environmental variables on seedling emergence and establishment for ponderosa and lodgepole pine.

Contributors to young drivers' driving styles - A comparison between Israel and Queensland.

PubMed

Skvirsky, Vera; Ben-Ari, Orit Taubman; Greenbury, Timothy J; Prato, Carlo G

2017-12-01

Among the numerous factors that contribute to young novice drivers' driving styles, personality characteristics, sociodemographic variables, family atmosphere, and friends' norms are known to have an important impact. However, cross-cultural comparisons are relatively rare in the safety literature concerning young drivers. This study aimed at comparing young drivers from Israel and Queensland (Australia) and examining the contribution of personality, sociodemographic, family and friends' aspects to their driving styles (reckless and careless; hostile and angry; anxious; patient and careful). More specifically, this study examined the associations between young drivers' driving style and their perceptions of separation-individuation, the family climate for road safety, and the safe driving climate among friends. We also examined sociodemographic and driving history variables such as gender, the marital status of parents, and personal exposure to traffic crashes. The study consisted of two samples of male and female young drivers (age 17-22) from Israel (n=160) and Queensland (n=160), who completed a set of valid and reliable self-report questionnaires. Findings indicate that in general, maladaptive driving styles are associated with lower family tendency to engage in promoting road safety, higher pressure and costs of driving with peers, and unhealthier separation-individuation aspects. The opposite is observed for the patient and careful driving style that relates to higher engagement of the family in road safety, lower pressure from friends, and healthier separation-individuation. Some differences were found regarding specific styles between the two samples. In addition, women scored lower than men in the reckless and careless style, and higher (in the Israeli sample) in the anxious as well as the patient and careful styles. Overall, similarities in the associations between the study variables in the samples exceed the differences, and the importance of examining variables on multi-levels when referring to young drivers' driving styles, is confirmed. The findings attest to the universal utility of the MDSI, together with the understanding that only a wider examination of personal and environmental contributors enables true insights into the complex behavior of driving among young drivers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes

PubMed Central

Moorthy, Sakthi D.; Davidson, Scott; Shchuka, Virlana M.; Singh, Gurdeep; Malek-Gilani, Nakisa; Langroudi, Lida; Martchenko, Alexandre; So, Vincent; Macpherson, Neil N.; Mitchell, Jennifer A.

2017-01-01

Transcriptional enhancers are critical for maintaining cell-type–specific gene expression and driving cell fate changes during development. Highly transcribed genes are often associated with a cluster of individual enhancers such as those found in locus control regions. Recently, these have been termed stretch enhancers or super-enhancers, which have been predicted to regulate critical cell identity genes. We employed a CRISPR/Cas9-mediated deletion approach to study the function of several enhancer clusters (ECs) and isolated enhancers in mouse embryonic stem (ES) cells. Our results reveal that the effect of deleting ECs, also classified as ES cell super-enhancers, is highly variable, resulting in target gene expression reductions ranging from 12% to as much as 92%. Partial deletions of these ECs which removed only one enhancer or a subcluster of enhancers revealed partially redundant control of the regulated gene by multiple enhancers within the larger cluster. Many highly transcribed genes in ES cells are not associated with a super-enhancer; furthermore, super-enhancer predictions ignore 81% of the potentially active regulatory elements predicted by cobinding of five or more pluripotency-associated transcription factors. Deletion of these additional enhancer regions revealed their robust regulatory role in gene transcription. In addition, select super-enhancers and enhancers were identified that regulated clusters of paralogous genes. We conclude that, whereas robust transcriptional output can be achieved by an isolated enhancer, clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes. PMID:27895109

Age and inconsistency in driving performance.

PubMed

Bunce, David; Young, Mark S; Blane, Alison; Khugputh, Priya

2012-11-01

Research in cognitive neuropsychology suggests that investigation of the within-person variability, or inconsistency, of cognitive performance may provide valuable insights into ageing mental processes. It is rare though, for this interest in intraindividual variability to extend to everyday activities. As this may provide important information about driving behaviour, we therefore assessed age differences in driving inconsistency in younger (n=24, M age=21.29 years) and older (n=21, M age=71.24 years) persons who drove in residential, urban and motorway conditions in a fully immersive driving simulator. In measures of headway (maintaining a safe distance to a preceding vehicle) and lateral lane position, older drivers exhibited significantly greater performance inconsistency, and this was particularly marked in the faster motorway condition. Older drivers also recorded greater perceived mental demands associated with driving, and greater within-person variability across a range of cognitive measures. The findings suggest that age-related deficits in attentional and executive control may affect the consistency of driving performance in older persons. Discussion considers interventions to introduce in-vehicle systems to help maintain attention in older drivers, and to intervene when safety-critical boundaries are exceeded. Copyright © 2012 Elsevier Ltd. All rights reserved.

Potential determinants of drink driving in young adults.

PubMed

González-Iglesias, Beatriz; Gómez-Fraguela, José António; Sobral, Jorge

2015-01-01

The main purposes of this study were to examine the usefulness of the variables of the theory of planned behavior (viz. attitudes, social norms, and self-efficacy) and to explore the relationship between optimism bias and drink driving in young adults. In addition, we explored gender differences in drink driving with provision for the effect of variables such as driving frequency and alcohol consumption. Data were collected via a questionnaire administered to 274 drivers (59.9% females) aged 18-30 years (24.36 ± 2.96). The results obtained with provision for driving frequency revealed substantial differences in driving behaviors between genders. Thus, males were more prone to drink driving, perceived less disapproval by their significant others (parents and peers), and felt less able to avoid drinking-and-driving situations. In addition, they self-reported more frequent alcohol consumption and driving under the influence. The results also confirm the significance of peers' subjective norms and attitudes to drink driving in males. Overconfidence in their own driving skills for driving drunk and perceived behavioral control were found to be significant predictors for drink driving in females. Optimism bias also played a slightly significant role in predicting drink driving but only in females. The important practical implications of these results with a view to designing effective interventions to prevent the risks associated with drink driving in the young population are discussed. Interventions should focus on young people's perceptions of group norms and promoting cautionary driving choices and alternatives to drink driving.

PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina

PubMed Central

Hickmott, Jack W; Chen, Chih-yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

2016-01-01

Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia. PMID:27556059

PAX6 MiniPromoters drive restricted expression from rAAV in the adult mouse retina.

PubMed

Hickmott, Jack W; Chen, Chih-Yu; Arenillas, David J; Korecki, Andrea J; Lam, Siu Ling; Molday, Laurie L; Bonaguro, Russell J; Zhou, Michelle; Chou, Alice Y; Mathelier, Anthony; Boye, Sanford L; Hauswirth, William W; Molday, Robert S; Wasserman, Wyeth W; Simpson, Elizabeth M

2016-01-01

Current gene therapies predominantly use small, strong, and readily available ubiquitous promoters. However, as the field matures, the availability of small, cell-specific promoters would be greatly beneficial. Here we design seven small promoters from the human paired box 6 (PAX6) gene and test them in the adult mouse retina using recombinant adeno-associated virus. We chose the retina due to previous successes in gene therapy for blindness, and the PAX6 gene since it is: well studied; known to be driven by discrete regulatory regions; expressed in therapeutically interesting retinal cell types; and mutated in the vision-loss disorder aniridia, which is in need of improved therapy. At the PAX6 locus, 31 regulatory regions were bioinformatically predicted, and nine regulatory regions were constructed into seven MiniPromoters. Driving Emerald GFP, these MiniPromoters were packaged into recombinant adeno-associated virus, and injected intravitreally into postnatal day 14 mice. Four MiniPromoters drove consistent retinal expression in the adult mouse, driving expression in combinations of cell-types that endogenously express Pax6: ganglion, amacrine, horizontal, and Müller glia. Two PAX6-MiniPromoters drive expression in three of the four cell types that express PAX6 in the adult mouse retina. Combined, they capture all four cell types, making them potential tools for research, and PAX6-gene therapy for aniridia.

Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: Implications for the microbial “pan-genome”

PubMed Central

Tettelin, Hervé; Masignani, Vega; Cieslewicz, Michael J.; Donati, Claudio; Medini, Duccio; Ward, Naomi L.; Angiuoli, Samuel V.; Crabtree, Jonathan; Jones, Amanda L.; Durkin, A. Scott; DeBoy, Robert T.; Davidsen, Tanja M.; Mora, Marirosa; Scarselli, Maria; Margarit y Ros, Immaculada; Peterson, Jeremy D.; Hauser, Christopher R.; Sundaram, Jaideep P.; Nelson, William C.; Madupu, Ramana; Brinkac, Lauren M.; Dodson, Robert J.; Rosovitz, Mary J.; Sullivan, Steven A.; Daugherty, Sean C.; Haft, Daniel H.; Selengut, Jeremy; Gwinn, Michelle L.; Zhou, Liwei; Zafar, Nikhat; Khouri, Hoda; Radune, Diana; Dimitrov, George; Watkins, Kisha; O'Connor, Kevin J. B.; Smith, Shannon; Utterback, Teresa R.; White, Owen; Rubens, Craig E.; Grandi, Guido; Madoff, Lawrence C.; Kasper, Dennis L.; Telford, John L.; Wessels, Michael R.; Rappuoli, Rino; Fraser, Claire M.

2005-01-01

The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for ≈80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes. PMID:16172379

Initial testing of a variable-stroke Stirling engine

NASA Technical Reports Server (NTRS)

Thieme, L. G.

1985-01-01

In support of the U.S. Department of Energy's Stirling Engine Highway Vehicle Systems Program, NASA Lewis Research Center is evaluating variable-stroke control for Stirling engines. The engine being tested is the Advenco Stirling engine; this engine was manufactured by Philips Research Laboratories of the Netherlands and uses a variable-angle swash-plate drive to achieve variable stroke operation. The engine is described, initial steady-state test data taken at Lewis are presented, a major drive system failure and subsequent modifications are described. Computer simulation results are presented to show potential part-load efficiency gains with variable-stroke control.

Adaptive Genetic Divergence along Narrow Environmental Gradients in Four Stream Insects

PubMed Central

Watanabe, Kozo; Kazama, So; Omura, Tatsuo; Monaghan, Michael T.

2014-01-01

A central question linking ecology with evolutionary biology is how environmental heterogeneity can drive adaptive genetic divergence among populations. We examined adaptive divergence of four stream insects from six adjacent catchments in Japan by combining field measures of habitat and resource components with genome scans of non-neutral Amplified Fragment Length Polymorphism (AFLP) loci. Neutral genetic variation was used to measure gene flow and non-neutral genetic variation was used to test for adaptive divergence. We identified the environmental characteristics contributing to divergence by comparing genetic distances at non-neutral loci between sites with Euclidean distances for each of 15 environmental variables. Comparisons were made using partial Mantel tests to control for geographic distance. In all four species, we found strong evidence for non-neutral divergence along environmental gradients at between 6 and 21 loci per species. The relative contribution of these environmental variables to each species' ecological niche was quantified as the specialization index, S, based on ecological data. In each species, the variable most significantly correlated with genetic distance at non-neutral loci was the same variable along which each species was most narrowly distributed (i.e., highest S). These were gradients of elevation (two species), chlorophyll-a, and ammonia-nitrogen. This adaptive divergence occurred in the face of ongoing gene flow (F st = 0.01–0.04), indicating that selection was strong enough to overcome homogenization at the landscape scale. Our results suggest that adaptive divergence is pronounced, occurs along different environmental gradients for different species, and may consistently occur along the narrowest components of species' niche. PMID:24681871

The Effects of Blood Alcohol Levels on Driving Variables in a High-Risk Population: Objective and Subjective Measures.

ERIC Educational Resources Information Center

Cox, Daniel J.; And Others

1995-01-01

Assessed high-risk individuals' subjective awareness of legal intoxication and ability to drive, and objectively quantified their blood alcohol levels and driving performance. While subjects were able to recognize legal intoxication, one-third of the subjects were still willing to drive after becoming intoxicated beyond the legal limit to drive.…

High-risk driving attitudes and everyday driving violations of car and racing enthusiasts in Ontario, Canada.

PubMed

Yildirim-Yenier, Zümrüt; Vingilis, Evelyn; Wiesenthal, David L; Mann, Robert E; Seeley, Jane

2015-01-01

Attitudes and individual difference variables of car and racing enthusiasts regarding high-risk behaviors of street racing and stunt driving have recently been investigated. Positive attitudes toward high-risk driving, personality variables such as driver thrill seeking, and other self-reported risky driving acts were associated with these behaviors. However, probable relationships among high-risk driving tendencies, everyday driving behaviors, and negative road safety outcomes have remained largely unexamined. This study aimed to investigate the associations among car and racing enthusiasts' high-risk driving attitudes, self-reported everyday driving violations (i.e., ordinary and aggressive violations), and self-reported negative outcomes (i.e., collisions and driving offense citations). A web-based survey was conducted with members and visitors of car club and racing websites in Ontario, Canada. Data were obtained from 366 participants. The questionnaire included 4 attitude measures-(1) attitudes toward new penalties for Ontario's Street Racers, Stunt and Aggressive Drivers Legislation; (2) attitudes toward new offenses of stunt driving under the same legislation; (3) general attitudes toward street racing and stunt driving; (4) comparison of street racing with other risky driving behaviors-self-reported driving violations (i.e., ordinary and aggressive violations); self-reported collisions and offense citations; and background and driving questions (e.g., age, driving frequency). Results revealed that attitudes toward stunt driving offenses negatively and general attitudes toward street racing and stunt driving positively predicted ordinary violations, which, in turn, predicted offense citations. Moreover, general attitudes toward street racing and stunt driving positively predicted aggressive violations, which, in turn, predicted offense citations. The findings indicate that positive high-risk driving attitudes may be transferring to driving violations in everyday traffic, which mediates driving offense citations.

Elucidation of major contributors involved in nitrogen removal and transcription level of nitrogen-cycling genes in activated sludge from WWTPs

NASA Astrophysics Data System (ADS)

Che, You; Liang, Peixin; Gong, Ting; Cao, Xiangyu; Zhao, Ying; Yang, Chao; Song, Cunjiang

2017-03-01

We investigated nitrogen-cycle bacterial communities in activated sludge from 8 municipal wastewater treatment plants (WWTPs). Redundancy analyses (RDA) showed that temperature was the most significant driving force in shaping microbial community structure, followed by influent NH4+ and total nitrogen (TN). The diversity of ammonia oxidizing and nitrite reducing bacteria were investigated by the construction of amoA, nirS and nirK gene clone libraries. Phylogenetic analysis indicated that Thauera and Mesorhizobium were the predominant nitrite reducing bacteria, and Nitrosomonas was the only detected ammonia oxidizing bacteria in all samples. Quantification of transcription level of nirS and nirK genes indicated that nirS-type nitrite reducing bacteria played the dominant roles in nitrite reduction process. Transcription level of nirS gene positively correlated with influent NH4+ and TN significantly, whereas inversely linked with hydraulic retention time. Temperature had a strong positive correlation to transcription level of amoA gene. Overall, this study deepened our understanding of the major types of ammonia oxidizing and nitrite reducing bacteria in activated sludge of municipal WWTPs. The relationship between transcription level of nitrogen-cycle genes and operational or environmental variables of WWTPs revealed in this work could provide guidance for optimization of operating parameters and improving the performance of nitrogen removal.

63. VIEW LOOKING DOWN VAL LAUNCHING SLAB SHOWING DRIVE GEARS, ...

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

63. VIEW LOOKING DOWN VAL LAUNCHING SLAB SHOWING DRIVE GEARS, CABLES, LAUNCHER RAILS, PROJECTILE CAR AND SUPPORT CARRIAGE, April 8, 1948. (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

Design and dynamic simulation of a fixed pitch 56 kW wind turbine drive train with a continuously variable transmission

NASA Technical Reports Server (NTRS)

Gallo, C.; Kasuba, R.; Pintz, A.; Spring, J.

1986-01-01

The dynamic analysis of a horizontal axis fixed pitch wind turbine generator (WTG) rated at 56 kW is discussed. A mechanical Continuously Variable Transmission (CVT) was incorporated in the drive train to provide variable speed operation capability. One goal of the dynamic analysis was to determine if variable speed operation, by means of a mechanical CVT, is capable of capturing the transient power in the WTG/wind environment. Another goal was to determine the extent of power regulation possible with CVT operation.

Relationships between thrill seeking, speeding attitudes, and driving violations among a sample of motorsports spectators and drivers.

PubMed

Yıldırım-Yenier, Zümrüt; Vingilis, Evelyn; Wiesenthal, David L; Mann, Robert E; Seeley, Jane

2016-01-01

Motor racing includes high speed driving and risky maneuvers and can result in negative outcomes for both spectators and drivers. Interest in motorsports is also associated with risky driving attitudes and behaviors on public roads as well as with individual difference variables, such as sensation seeking. However, whether the links between motorsports involvement and risky driving tendencies differ for spectators and drivers has remained mainly unexamined. The aim of this study was to investigate the relationships between thrill seeking, attitudes toward speeding, and self-reported driving violations among a sample of motorsports spectators and drivers. A web-based survey was conducted and sampled 408 members and visitors of car club and racing websites in Ontario, Canada. The questionnaire included measures of (i) motorsports involvement, (ii) thrill seeking (Driver Thrill Seeking Scale), (iii) attitudes (Attitudes toward Speed Limits on Roadways and Competitive Attitudes toward Driving Scale); (iv) self-reported driving violations (adapted from Driver Behaviour Questionnaire), and (v) background variables. Path analysis was performed to test the relationships among the variables. For both spectators and drivers, thrill seeking directly predicted driving violations; competitive attitudes toward driving further mediated this relationship. Attitudes toward speed limits, however, mediated the relationship between thrill seeking and violations only for drivers. We observed significant relationships among individual difference measures, motorsports involvement, speeding attitudes and violations that may inform road safety interventions, including differences in the relationships among thrill seeking, speeding attitudes, and violations for motorsports spectators and drivers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural equation model analysis for the evaluation of overall driving performance: A driving simulator study focusing on driver distraction.

PubMed

Papantoniou, Panagiotis

2018-04-03

The present research relies on 2 main objectives. The first is to investigate whether latent model analysis through a structural equation model can be implemented on driving simulator data in order to define an unobserved driving performance variable. Subsequently, the second objective is to investigate and quantify the effect of several risk factors including distraction sources, driver characteristics, and road and traffic environment on the overall driving performance and not in independent driving performance measures. For the scope of the present research, 95 participants from all age groups were asked to drive under different types of distraction (conversation with passenger, cell phone use) in urban and rural road environments with low and high traffic volume in a driving simulator experiment. Then, in the framework of the statistical analysis, a correlation table is presented investigating any of a broad class of statistical relationships between driving simulator measures and a structural equation model is developed in which overall driving performance is estimated as a latent variable based on several individual driving simulator measures. Results confirm the suitability of the structural equation model and indicate that the selection of the specific performance measures that define overall performance should be guided by a rule of representativeness between the selected variables. Moreover, results indicate that conversation with the passenger was not found to have a statistically significant effect, indicating that drivers do not change their performance while conversing with a passenger compared to undistracted driving. On the other hand, results support the hypothesis that cell phone use has a negative effect on driving performance. Furthermore, regarding driver characteristics, age, gender, and experience all have a significant effect on driving performance, indicating that driver-related characteristics play the most crucial role in overall driving performance. The findings of this study allow a new approach to the investigation of driving behavior in driving simulator experiments and in general. By the successful implementation of the structural equation model, driving behavior can be assessed in terms of overall performance and not through individual performance measures, which allows an important scientific step forward from piecemeal analyses to a sound combined analysis of the interrelationship between several risk factors and overall driving performance.

Hostility, driving anger, and dangerous driving: the emerging role of hemispheric preference.

PubMed

Gidron, Yori; Gaygısız, Esma; Lajunen, Timo

2014-12-01

Various studies have implicated psychosocial variables (e.g., hostility) in risk of dangerous driving and traffic accidents. However, whether these variables are related to more basic neurobiological factors, and whether such associations have implications for the modification of psychosocial risk factors in the context of driving, have not been examined in depth. This study examined the relationship between hemispheric preference (HP), hostility and self-reported dangerous driving, and the ability to affect driving anger via hemisphere activating cognitive exercises (HACE). In Study 1, 254 Turkish students completed questionnaires of hostility, HP and driving behavior. In Study 2, we conducted a "proof of concept" experimental study, and tested effects of left, right and neutral HACE on driving anger, by exposing N=650 Turkish students to written scenarios including either logical (left hemisphere), visuo-spatial (right hemisphere) or "mild doses" of both types of contents (control). In Study 1, left-HP was associated with higher hostility and with more dangerous driving, and hostility mediated the relationship between L-HP and reported driving behavior. In Study 2, only right-HACE led to immediate significant reductions in self-reported driving anger. Left-HP is related to hostility and to dangerous driving, and it may be possible to partly reduce driving anger by right-HACE. Future studies must replicate these findings with objective measures, more enduring interventions and longer follow-ups. Copyright © 2014. Published by Elsevier Ltd.

The reaction times of drivers aged 20 to 80 during a divided attention driving.

PubMed

Svetina, Matija

2016-11-16

Many studies addressing age-related changes in driving performance focus on comparing young vs. older drivers, which might lead to the biased conclusion that driving performance decreases only after the age of 65. The main aim of the study was to show that changes in driving performance are progressive throughout the adult years. A sample of 351 drivers aged 20 to 80 was assessed for their reaction times while driving between road cones. The drivers were exposed to 2 conditions varying according to task complexity. In single task conditions, the drivers performed a full stopping maneuver at a given signal; in dual task conditions, the drivers were distracted before the signal for stopping maneuver was triggered. Reaction times were compared across conditions and age groups. The results showed that both reaction times and variability of driving performance increased progressively between the ages of 20 and 80. The increase in both reaction times and variability was greater in the complex task condition. The high-performing quarter of elderly drivers performed equally well or better than younger drivers did. The data clearly supported the claim that driving performance changes steadily across age groups: both mean reaction time and interindividual variability progressively increase with age. In addition, a significant group of older drivers was identified who did not show the expected age-related decrease in performance. The findings have important implications, suggesting that in relation to driving, aging is a progressive phenomenon and may lead to variety of driving performance; age-related studies of driving performance should put more emphasis on investigating changes across the whole driver age range rather than only comparing younger and older drivers.

Genetics Home Reference: androgen insensitivity syndrome

MedlinePlus

... particular ethnic groups? Genetic Changes Mutations in the AR gene cause androgen insensitivity syndrome . This gene provides ... hair growth and sex drive. Mutations in the AR gene prevent androgen receptors from working properly, which ...

Study on the application of permanent magnet synchronous motors in underground belt conveyors

NASA Astrophysics Data System (ADS)

Ma, S. H.

2017-12-01

This paper analyzes and compares the advantages and disadvantages of several kinds of drive devices of belt conveyors from the angle of energy saving, and summarizes the application advantages and using problems of permanent magnet motor variable frequency drive system in belt conveyors. An example is given to demonstrate the energy saving effect of this system compared with other driving methods. This paper points out the application prospect of permanent magnet motor variable frequency drive system on belt conveyors and other large mining machines in coal mine. This paper is aimed to provide the design direction for the designer and the choice basis for the user on belt conveyor.

Variable speed induction motor operation from a 20-kHz power bus

NASA Technical Reports Server (NTRS)

Hansen, Irving G.

1989-01-01

Induction motors are recognized for their simple rugged construction. To date, however, their application to variable speed or servo drives was hampered by limitations on their control. Induction motor drives tend to be complex and to display troublesome low speed characteristics due in part to nonsinusoidal driving voltages. A technique was developed which involves direct synthesis of sinusoidal driving voltages from a high frequency power bus and independent control of frequency and voltages. Separation of frequency and voltage allows independent control of rotor and stator flux, full four quadrant operation, and instantaneous torque control. Recent test results, current status of the technology, and proposed aerospace applications will be discussed.

Variable speed induction motor operation from a 20-kHz power bus

NASA Technical Reports Server (NTRS)

Hansen, Irving G.

1989-01-01

Induction motors are recognized for their simple rugged construction to date, however, their application to variable speed or servo drives has been hampered by limitations on their control. Induction motor drives tend to be complex and to display troublesome low speed characteristics due in part to nonsinusoidal driving voltages. A technique was developed which involves direct synthesis of sinusoidal driving voltages from a high frequency power bus and independent control of frequency and voltages. Separation offrequency and voltage allows independent control of rotor and stator flux, full four-quadrant operation, and instantaneous torque control. Recent test results, current status of the technology, and proposed aerospace applications will be discussed.

Modelling and control algorithms of the cross conveyors line with multiengine variable speed drives

NASA Astrophysics Data System (ADS)

Cheremushkina, M. S.; Baburin, S. V.

2017-02-01

The paper deals with the actual problem of developing the control algorithm that meets the technical requirements of the mine belt conveyors, and enables energy and resource savings taking into account a random sort of traffic. The most effective method of solution of these tasks is the construction of control systems with the use of variable speed drives for asynchronous motors. The authors designed the mathematical model of the system ‘variable speed multiengine drive - conveyor - control system of conveyors’ that takes into account the dynamic processes occurring in the elements of the transport system, provides an assessment of the energy efficiency of application the developed algorithms, which allows one to reduce the dynamic overload in the belt to 15-20%.

Impact of distraction on the driving performance of adolescents with and without attention-deficit/hyperactivity disorder.

PubMed

Narad, Megan; Garner, Annie A; Brassell, Anne A; Saxby, Dyani; Antonini, Tanya N; O'Brien, Kathleen M; Tamm, Leanne; Matthews, Gerald; Epstein, Jeffery N

2013-10-01

This study extends the literature regarding attention-deficit/hyperactivity disorder (ADHD)-related driving impairments to a newly licensed, adolescent population. To investigate the combined risks of adolescence, ADHD, and distracted driving (cell phone conversation and text messaging) on driving performance. Adolescents aged 16 to 17 years with (n = 28) and without (n = 33) ADHD engaged in a simulated drive under 3 conditions (no distraction, cell phone conversation, and texting). During each condition, one unexpected event (eg, another car suddenly merging into driver's lane) was introduced. Cell phone conversation, texting, and no distraction while driving. Self-report of driving history, average speed, standard deviation of speed, standard deviation of lateral position, and braking reaction time during driving simulation. Adolescents with ADHD reported fewer months of driving experience and a higher proportion of driving violations than control subjects. After controlling for months of driving history, adolescents with ADHD demonstrated more variability in speed and lane position than control subjects. There were no group differences for braking reaction time. Furthermore, texting negatively impacted the driving performance of all participants as evidenced by increased variability in speed and lane position. To our knowledge, this study is one of the first to investigate distracted driving in adolescents with ADHD and adds to a growing body of literature documenting that individuals with ADHD are at increased risk for negative driving outcomes. Furthermore, texting significantly impairs the driving performance of all adolescents and increases existing driving-related impairment in adolescents with ADHD, highlighting the need for education and enforcement of regulations against texting for this age group.

Modeling of Autovariator Operation as Power Components Adjuster in Adaptive Machine Drives

NASA Astrophysics Data System (ADS)

Balakin, P. D.; Belkov, V. N.; Shtripling, L. O.

2018-01-01

Full application of the available power and stationary mode preservation for the power station (engine) operation of the transport machine under the conditions of variable external loading, are topical issues. The issues solution is possible by means of mechanical drives with the autovaried rate transfer function and nonholonomic constraint of the main driving mediums. Additional to the main motion, controlled motion of the driving mediums is formed by a variable part of the transformed power flow and is implemented by the integrated control loop, functioning only on the basis of the laws of motion. The mathematical model of the mechanical autovariator operation is developed using Gibbs function, acceleration energy; the study results are presented; on their basis, the design calculations of the autovariator driving mediums and constraints, including its automatic control loop, are possible.

Genetics Home Reference: spinal and bulbar muscular atrophy

MedlinePlus

... from a particular type of mutation in the AR gene. This gene provides instructions for making a ... as regulating hair growth and sex drive. The AR gene mutation that causes spinal and bulbar muscular ...

Genomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals novel recurrent driver mutations

PubMed Central

Spinella, Jean-François; Cassart, Pauline; Richer, Chantal; Saillour, Virginie; Ouimet, Manon; Langlois, Sylvie; St-Onge, Pascal; Sontag, Thomas; Healy, Jasmine; Minden, Mark D.; Sinnett, Daniel

2016-01-01

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with variable prognosis. It represents 15% of diagnosed pediatric ALL cases and has a threefold higher incidence among males. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Using an integrative approach combining genomic and transcriptomic data, we molecularly characterized 30 pediatric T-ALLs and identified common recurrent T-ALL targets such as FBXW7, JAK1, JAK3, PHF6, KDM6A and NOTCH1 as well as novel candidate T-ALL driver mutations including the p.R35L missense mutation in splicesome factor U2AF1 found in 3 patients and loss of function mutations in the X-linked tumor suppressor genes MED12 (frameshit mutation p.V167fs, splice site mutation g.chrX:70339329T>C, missense mutation p.R1989H) and USP9X (nonsense mutation p.Q117*). In vitro functional studies further supported the putative role of these novel T-ALL genes in driving transformation. U2AF1 p.R35L was shown to induce aberrant splicing of downstream target genes, and shRNA knockdown of MED12 and USP9X was shown to confer resistance to apoptosis following T-ALL relevant chemotherapy drug treatment in Jurkat leukemia cells. Interestingly, nearly 60% of novel candidate driver events were identified among immature T-ALL cases, highlighting the underlying genomic complexity of pediatric T-ALL, and the need for larger integrative studies to decipher the mechanisms that contribute to its various subtypes and provide opportunities to refine patient stratification and treatment. PMID:27602765

Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world.

PubMed

Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

2013-01-01

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem.

Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world

PubMed Central

Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

2013-01-01

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem. PMID:23404545

nanos-Driven expression of piggyBac transposase induces mobilization of a synthetic autonomous transposon in the malaria vector mosquito, Anopheles stephensi.

PubMed

Macias, Vanessa M; Jimenez, Alyssa J; Burini-Kojin, Bianca; Pledger, David; Jasinskiene, Nijole; Phong, Celine Hien; Chu, Karen; Fazekas, Aniko; Martin, Kelcie; Marinotti, Osvaldo; James, Anthony A

2017-08-01

Transposons are a class of selfish DNA elements that can mobilize within a genome. If mobilization is accompanied by an increase in copy number (replicative transposition), the transposon may sweep through a population until it is fixed in all of its interbreeding members. This introgression has been proposed as the basis for drive systems to move genes with desirable phenotypes into target species. One such application would be to use them to move a gene conferring resistance to malaria parasites throughout a population of vector mosquitos. We assessed the feasibility of using the piggyBac transposon as a gene-drive mechanism to distribute anti-malarial transgenes in populations of the malaria vector, Anopheles stephensi. We designed synthetic gene constructs that express the piggyBac transposase in the female germline using the control DNA of the An. stephensi nanos orthologous gene linked to marker genes to monitor inheritance. Two remobilization events were observed with a frequency of one every 23 generations, a rate far below what would be useful to drive anti-pathogen transgenes into wild mosquito populations. We discuss the possibility of optimizing this system and the impetus to do so. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pleistocene glacial cycles drive isolation, gene flow and speciation in the high-elevation Andes.

PubMed

Nevado, Bruno; Contreras-Ortiz, Natalia; Hughes, Colin; Filatov, Dmitry A

2018-06-04

Mountain ranges are amongst the most species-rich habitats, with many large and rapid evolutionary radiations. The tempo and mode of diversification in these systems are key unanswered questions in evolutionary biology. Here we study the Andean Lupinus radiation to understand the processes driving very rapid diversification in montane systems. We use genomic and transcriptomic data of multiple species and populations, and apply phylogenomic and demographic analyses to test whether diversification proceeded without interspecific gene flow - as expected if Andean orogeny and geographic isolation were the main drivers of diversification - or if diversification was accompanied by gene flow, in which case other processes were probably involved. We uncover several episodes of gene flow between species, including very recent events likely to have been prompted by changes in habitat connectivity during Pleistocene glacial cycles. Furthermore, we find that gene flow between species was heterogeneously distributed across the genome. We argue that exceptionally fast diversification of Andean Lupinus was partly a result of Late Pleistocene glacial cycles, with associated cycles of expansion and contraction driving geographic isolation or secondary contact of species. Furthermore, heterogeneous gene flow across the genome suggests a role for selection and ecological speciation in rapid diversification in this system. © 2018 The Authors New Phytologist © 2018 New Phytologist Trust.

The early stages of duplicate gene evolution

PubMed Central

Moore, Richard C.; Purugganan, Michael D.

2003-01-01

Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8–20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes. PMID:14671323

The impact of dissociation on transposon-mediated disease control strategies.

PubMed

Marshall, John M

2008-03-01

Vector-borne diseases such as malaria and dengue fever continue to be a major health concern through much of the world. The emergence of chloroquine-resistant strains of malaria and insecticide-resistant mosquitoes emphasize the need for novel methods of disease control. Recently, there has been much interest in the use of transposable elements to drive resistance genes into vector populations as a means of disease control. One concern that must be addressed before a release is performed is the potential loss of linkage between a transposable element and a resistance gene. Transposable elements such as P and hobo have been shown to produce internal deletion derivatives at a significant rate, and there is concern that a similar process could lead to loss of the resistance gene from the drive system following a transgenic release. Additionally, transposable elements such as Himar1 have been shown to transpose significantly more frequently when free of exogenous DNA. Here, we show that any transposon-mediated gene drive strategy must have an exceptionally low rate of dissociation if it is to be effective. Additionally, the resistance gene must confer a large selective advantage to the vector to surmount the effects of a moderate dissociation rate and transpositional handicap.

Assessing climate impacts

PubMed Central

Wohl, Ellen E.; Pulwarty, Roger S.; Zhang, Jian Yun

2000-01-01

Assessing climate impacts involves identifying sources and characteristics of climate variability, and mitigating potential negative impacts of that variability. Associated research focuses on climate driving mechanisms, biosphere–hydrosphere responses and mediation, and human responses. Examples of climate impacts come from 1998 flooding in the Yangtze River Basin and hurricanes in the Caribbean and Central America. Although we have limited understanding of the fundamental driving-response interactions associated with climate variability, increasingly powerful measurement and modeling techniques make assessing climate impacts a rapidly developing frontier of science. PMID:11027321

Using collective variables to drive molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Fiorin, Giacomo; Klein, Michael L.; Hénin, Jérôme

2013-12-01

A software framework is introduced that facilitates the application of biasing algorithms to collective variables of the type commonly employed to drive massively parallel molecular dynamics (MD) simulations. The modular framework that is presented enables one to combine existing collective variables into new ones, and combine any chosen collective variable with available biasing methods. The latter include the classic time-dependent biases referred to as steered MD and targeted MD, the temperature-accelerated MD algorithm, as well as the adaptive free-energy biases called metadynamics and adaptive biasing force. The present modular software is extensible, and portable between commonly used MD simulation engines.

Analysis of a Temperature-Controlled Exhaust Thermoelectric Generator During a Driving Cycle

NASA Astrophysics Data System (ADS)

Brito, F. P.; Alves, A.; Pires, J. M.; Martins, L. B.; Martins, J.; Oliveira, J.; Teixeira, J.; Goncalves, L. M.; Hall, M. J.

2016-03-01

Thermoelectric generators can be used in automotive exhaust energy recovery. As car engines operate under wide variable loads, it is a challenge to design a system for operating efficiently under these variable conditions. This means being able to avoid excessive thermal dilution under low engine loads and being able to operate under high load, high temperature events without the need to deflect the exhaust gases with bypass systems. The authors have previously proposed a thermoelectric generator (TEG) concept with temperature control based on the operating principle of the variable conductance heat pipe/thermosiphon. This strategy allows the TEG modules’ hot face to work under constant, optimized temperature. The variable engine load will only affect the number of modules exposed to the heat source, not the heat transfer temperature. This prevents module overheating under high engine loads and avoids thermal dilution under low engine loads. The present work assesses the merit of the aforementioned approach by analysing the generator output during driving cycles simulated with an energy model of a light vehicle. For the baseline evaporator and condenser configuration, the driving cycle averaged electrical power outputs were approximately 320 W and 550 W for the type-approval Worldwide harmonized light vehicles test procedure Class 3 driving cycle and for a real-world highway driving cycle, respectively.

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy

PubMed Central

Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N.; D’Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F.; Zeviani, Massimo; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A.; Tancredi, Andrea; Mancini, Massimiliano; d’Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro

2014-01-01

Leber’s hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber’s hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber’s hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. PMID:24369379

Features of electric drive sucker rod pumps for oil production

NASA Astrophysics Data System (ADS)

Gizatullin, F. A.; Khakimyanov, M. I.; Khusainov, F. F.

2018-01-01

This article is about modes of operation of electric drives of downhole sucker rod pumps. Downhole oil production processes are very energy intensive. Oil fields contain many oil wells; many of them operate in inefficient modes with significant additional losses. Authors propose technical solutions to improve energy performance of a pump unit drives: counterweight balancing, reducing of electric motor power, replacing induction motors with permanent magnet motors, replacing balancer drives with chain drives, using of variable frequency drives.

Driving Comparisons Between Young Adults with Autism Spectrum Disorder and Typical Development.

PubMed

Patrick, Kristina E; Hurewitz, Felicia; McCurdy, Mark D; Agate, Frederic Taylor; Daly, Brian P; Tarazi, Reem A; Chute, Douglas L; Schultheis, Maria T

2018-05-18

Many individuals with autism spectrum disorder (ASD) are reluctant to pursue driving because of concerns about their ability to drive safely. This study aimed to assess differences in simulated driving performance in young adults with ASD and typical development, examining relationships between driving performance and the level of experience (none, driver's permit, licensed) across increasingly difficult driving environments. Participants included 50 English-speaking young adults (16-26 years old) with ASD matched for sex, age, and licensure with 50 typically-developing (TD) peers. Participants completed a structured driving assessment using a virtual-reality simulator that included increasingly complex environmental demands. Differences in mean speed and speed and lane variability by diagnostic group and driving experience were analyzed using multilevel linear modeling. Young adults with ASD demonstrated increased variability in speed and lane positioning compared with controls, even during low demand tasks. When driving demands became more complex, group differences were moderated by driving experience such that licensed drivers with ASD drove similarly to TD licensed drivers for most tasks, whereas unlicensed drivers with ASD had more difficulty with speed and lane management than TD drivers. Findings suggest that young adults with ASD may have more difficulty with basic driving skills than peers, particularly in the early stages of driver training. Increased difficulty compared with peers increases as driving demands become more complex, suggesting that individuals with ASD may benefit from a slow and gradual approach to driver training. Future studies should evaluate predictors of driving performance, on-road driving, and ASD-specific driving interventions.

Confinement of gene drive systems to local populations: A comparative analysis

PubMed Central

Marshall, John M.; Hay, Bruce A.

2011-01-01

Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered synthetic drive systems have provided encouragement for this strategy; but at the same time have been greeted with caution over the concern that transgenes may spread into countries and communities without their consent. Consequently, there is also interest in gene drive systems that, while strong enough to bring about local population replacement, are unable to establish themselves beyond a partially-isolated release site, at least during the testing phase. Here, we develop simple deterministic and stochastic models to compare the confinement properties of a variety of gene drive systems. Our results highlight several systems with desirable features for confinement – a high migration rate required to become established in neighboring populations, and low-frequency persistence in neighboring populations for moderate migration rates. Single-allele underdominance and single-locus engineered underdominance have the strongest confinement properties, but are difficult to engineer and require a high introduction frequency, respectively. Toxin-antidote systems such as Semele, Merea and two-locus engineered underdominance show promising confinement properties and require lower introduction frequencies. Killer-rescue is self-limiting in time, but is able to disperse to significant levels in neighboring populations. We discuss the significance of these results in the context of a phased release of transgenic mosquitoes, and the need for characterization of local ecology prior to a release. PMID:22094363

The Impact of Distraction on the Driving Performance of Adolescents with and without Attention Deficit Hyperactivity Disorder

PubMed Central

Narad, Megan; Garner, Annie A.; Brassell, Anne A.; Saxby, Dyani; Antonini, Tanya N.; O'Brien, Kathleen M.; Tamm, Leanne; Matthews, Gerald; Epstein, Jeffery N.

2013-01-01

Importance This study extends the literature regarding Attention-Deficit/Hyperactivity Disorder (ADHD) related driving impairments to a newly-licensed, adolescent population. Objective To investigate the combined risks of adolescence, ADHD, and distracted driving (cell phone conversation and text messaging) on driving performance. Design Adolescents with and without ADHD engaged in a simulated drive under three conditions (no distraction, cell phone conversation, texting). During each condition, one unexpected event (e.g., car suddenly merging into driver's lane) was introduced. Setting Driving simulator. Participants Adolescents aged 16–17 with ADHD (n=28) and controls (n=33). Interventions/Main Exposures Cell phone conversation, texting, and no distraction while driving. Outcome Measures Self-report of driving history; Average speed, standard deviation of speed, standard deviation of lateral position, braking reaction time during driving simulation. Results Adolescents with ADHD reported fewer months of driving experience and a higher proportion of driving violations than controls. After controlling for months of driving history, adolescents with ADHD demonstrated more variability in speed and lane position than controls. There were no group differences for braking reaction time. Further, texting negatively impacted the driving performance of all participants as evidenced by increased variability in speed and lane position. Conclusions This study, one of the first to investigate distracted driving in adolescents with ADHD, adds to a growing body of literature documenting that individuals with ADHD are at increased risk for negative driving outcomes. Furthermore, texting significantly impairs the driving performance of all adolescents and increases existing driving-related impairment in adolescents with ADHD, highlighting the need for education and enforcement of regulations against texting for this age group. PMID:23939758

Poor mental health status and aggression are associated with poor driving behavior among male traffic offenders

PubMed Central

Abdoli, Nasrin; Farnia, Vahid; Delavar, Ali; Esmaeili, Alirez; Dortaj, Fariborz; Farrokhi, Noorali; Karami, Majid; Shakeri, Jalal; Holsboer-Trachsler, Edith; Brand, Serge

2015-01-01

Background In Iran, traffic accidents and deaths from traffic accidents are among the highest in the world, and generally driver behavior rather than either technical failures or environmental conditions are responsible for traffic accidents. In the present study, we explored the extent to which aggressive traits, health status, and sociodemographic variables explain driving behavior among Iranian male traffic offenders. Method A total of 443 male driving offenders (mean age: M =31.40 years, standard deviation =9.56) from Kermanshah (Iran) took part in the study. Participants completed a questionnaire booklet covering sociodemographic variables, traits of aggression, health status, and driving behavior. Results Poor health status, such as symptoms of depression, anxiety, insomnia, and social dysfunction, and also higher levels of trait aggression explained poor driving behavior. Multiple regressions indicated that poor health status, but not aggression, independently predicted poor driving behavior. Conclusion Results suggest that health status concerns are associated with poor driving behavior. Prevention and intervention might therefore focus on drivers reporting poor mental health status. PMID:26316753

Identifying driver characteristics influencing overtaking crashes.

PubMed

Mohaymany, Afshin Shariat; Kashani, Ali Tavakoli; Ranjbari, Andishe

2010-08-01

To identify the most important driver characteristics influencing crash-causing overtaking maneuvers on 2-lane, 2-way rural roads of Iran. Based on the crash data for rural roads of Iran over 3 years from 2006 to 2008, the classification and regression tree (CART) method combined with the quasi-induced exposure concept was applied for 4 independent variables and one target variable of "driver status" with 2 classes of at fault and not at fault. The independent variables were vehicle type, driver's age, driving license, and driving experience of the driver-the latter 2 driver characteristics are relatively new in traffic safety studies. According to the data set, 16,809 drivers were involved in 2-lane, 2-way rural roads overtaking crashes. The analysis revealed that drivers who are younger than 28 years old, whose driving license is type 2--a common driving license that is for driving with passenger car and light vehicles--and whose driving experience is less than 2 years are most probably responsible for overtaking crashes. It was indicated that vehicle type is the most important factor associated with drivers being responsible for the crashes. The results also revealed that younger drivers (18-28 years) are most likely to be at fault in overtaking crashes. Therefore, enforcement and education should be more concentrated on this age group. Due to the incompliant nature of this group, changing the type and amount of traffic fines is essential for more preventing objectives. The research also found 2 relatively new factors of driving license and driving experience to have considerable effects on drivers being at fault, such that type 2 licensed drivers are more responsible compared to type 1 (a driving license for driving with all motor vehicles, which has some age and experience requirements) licensed drivers or drivers with a special license (a driving license with special vehicle types). Moreover, drivers with less than 2 years' driving experience are more responsible for these kind of crashes; thus prohibiting new drivers from driving on rural roads for new drivers seems substantial.

Variability of sea surface height and circulation in the North Atlantic: Forcing mechanisms and linkages

NASA Astrophysics Data System (ADS)

Wang, Zeliang; Lu, Youyu; Dupont, Frederic; W. Loder, John; Hannah, Charles; G. Wright, Daniel

2015-03-01

Simulations with a coarse-resolution global ocean model during 1958-2004 are analyzed to understand the inter-annual and decadal variability of the North Atlantic. Analyses of Empirical Orthogonal Functions (EOFs) suggest relationships among basin-scale variations of sea surface height (SSH) and depth-integrated circulation, and the winter North Atlantic Oscillation (NAO) or the East Atlantic Pattern (EAP) indices. The linkages between the atmospheric indices and ocean variables are shown to be related to the different roles played by surface momentum and heat fluxes in driving ocean variability. In the subpolar region, variations of the gyre strength, SSH in the central Labrador Sea and the NAO index are highly correlated. Surface heat flux is important in driving variations of SSH and circulation in the upper ocean and decadal variations of the Atlantic Meridional Overturning Circulation (AMOC). Surface momentum flux drives a significant barotropic component of flow and makes a noticeable contribution to the AMOC. In the subtropical region, momentum flux plays a dominant role in driving variations of the gyre circulation and AMOC; there is a strong correlation between gyre strength and SSH at Bermuda.

The multidimensional driving style inventory a decade later: Review of the literature and re-evaluation of the scale.

PubMed

Taubman-Ben-Ari, Orit; Skvirsky, Vera

2016-08-01

The Multidimensional Driving Style Inventory (MDSI; Taubman - Ben-Ari, Mikulincer, & Gillath, 2004a), a self-report questionnaire assessing four broad driving styles, has been in use for the last ten years. During that time, numerous studies have explored the associations between the MDSI factors and sociodemographic and driving-related variables. The current paper employs two large data sets to summarize the accumulated knowledge, examining MDSI factors in samples of young drivers aged 17-21 (Study 1, n=1436) and older drivers aged 22-84 (Study 2, n=3409). Findings indicate that driving-related indicators are coherently and systematically related to the four driving styles in the expected directions, revalidating the structure of the MDSI. The results also help clarify the relationships between the driving styles and variables such as gender, ethnicity, car ownership, age, and experience, and suggest that driving styles are largely unaffected by sociodemographic characteristics, except for gender and ethnicity, and appear to represent a relatively stable and universal trait. The two studies highlight the validity and reliability of the MDSI, attesting to its practical value as a tool for purposes of research, evaluation, and intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch

PubMed Central

Day, Nancy F; Kimball, Todd Haswell; Aamodt, Caitlin M; Heston, Jonathan B; Hilliard, Austin T; Xiao, Xinshu; White, Stephanie A

2018-01-01

Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans. PMID:29360038

Evolutionary origins of a novel host plant detoxification gene in butterflies.

PubMed

Fischer, Hanna M; Wheat, Christopher W; Heckel, David G; Vogel, Heiko

2008-05-01

Chemical interactions between plants and their insect herbivores provide an excellent opportunity to study the evolution of species interactions on a molecular level. Here, we investigate the molecular evolutionary events that gave rise to a novel detoxifying enzyme (nitrile-specifier protein [NSP]) in the butterfly family Pieridae, previously identified as a coevolutionary key innovation. By generating and sequencing expressed sequence tags, genomic libraries, and screening databases we found NSP to be a member of an insect-specific gene family, which we characterized and named the NSP-like gene family. Members consist of variable tandem repeats, are gut expressed, and are found across Insecta evolving in a dynamic, ongoing birth-death process. In the Lepidoptera, multiple copies of single-domain major allergen genes are present and originate via tandem duplications. Multiple domain genes are found solely within the brassicaceous-feeding Pieridae butterflies, one of them being NSP and another called major allergen (MA). Analyses suggest that NSP and its paralog MA have a unique single-domain evolutionary origin, being formed by intragenic domain duplication followed by tandem whole-gene duplication. Duplicates subsequently experienced a period of relaxed constraint followed by an increase in constraint, perhaps after neofunctionalization. NSP and its ortholog MA are still experiencing high rates of change, reflecting a dynamic evolution consistent with the known role of NSP in plant-insect interactions. Our results provide direct evidence to the hypothesis that gene duplication is one of the driving forces for speciation and adaptation, showing that both within- and whole-gene tandem duplications are a powerful force underlying evolutionary adaptation.

Assessing drivers' response during automated driver support system failures with non-driving tasks.

PubMed

Shen, Sijun; Neyens, David M

2017-06-01

With the increase in automated driver support systems, drivers are shifting from operating their vehicles to supervising their automation. As a result, it is important to understand how drivers interact with these automated systems and evaluate their effect on driver responses to safety critical events. This study aimed to identify how drivers responded when experiencing a safety critical event in automated vehicles while also engaged in non-driving tasks. In total 48 participants were included in this driving simulator study with two levels of automated driving: (a) driving with no automation and (b) driving with adaptive cruise control (ACC) and lane keeping (LK) systems engaged; and also two levels of a non-driving task (a) watching a movie or (b) no non-driving task. In addition to driving performance measures, non-driving task performance and the mean glance duration for the non-driving task were compared between the two levels of automated driving. Drivers using the automated systems responded worse than those manually driving in terms of reaction time, lane departure duration, and maximum steering wheel angle to an induced lane departure event. These results also found that non-driving tasks further impaired driver responses to a safety critical event in the automated system condition. In the automated driving condition, driver responses to the safety critical events were slower, especially when engaged in a non-driving task. Traditional driver performance variables may not necessarily effectively and accurately evaluate driver responses to events when supervising autonomous vehicle systems. Thus, it is important to develop and use appropriate variables to quantify drivers' performance under these conditions. Copyright © 2017 Elsevier Ltd and National Safety Council. All rights reserved.

A State-by-State Analysis of Laws Dealing With Driving Under the Influence of Drugs

DOT National Transportation Integrated Search

2009-12-01

This study reviewed each State statute regarding drug-impaired driving as of December 2008. There : is a high degree of variability across the States in the ways they approach drug-impaired driving. : Current laws in many States contain provisions ma...

Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

PubMed Central

Rangel, Roberto; Lee, Song-Choon; Hon-Kim Ban, Kenneth; Guzman-Rojas, Liliana; Mann, Michael B.; Newberg, Justin Y.; McNoe, Leslie A.; Selvanesan, Luxmanan; Ward, Jerrold M.; Rust, Alistair G.; Chin, Kuan-Yew; Black, Michael A.; Jenkins, Nancy A.; Copeland, Neal G.

2016-01-01

Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1. Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC. PMID:27849608

Simulated driving and brain imaging: combining behavior, brain activity, and virtual reality.

PubMed

Carvalho, Kara N; Pearlson, Godfrey D; Astur, Robert S; Calhoun, Vince D

2006-01-01

Virtual reality in the form of simulated driving is a useful tool for studying the brain. Various clinical questions can be addressed, including both the role of alcohol as a modulator of brain function and regional brain activation related to elements of driving. We reviewed a study of the neural correlates of alcohol intoxication through the use of a simulated-driving paradigm and wished to demonstrate the utility of recording continuous-driving behavior through a new study using a programmable driving simulator developed at our center. Functional magnetic resonance imaging data was collected from subjects while operating a driving simulator. Independent component analysis (ICA) was used to analyze the data. Specific brain regions modulated by alcohol, and relationships between behavior, brain function, and alcohol blood levels were examined with aggregate behavioral measures. Fifteen driving epochs taken from two subjects while also recording continuously recorded driving variables were analyzed with ICA. Preliminary findings reveal that four independent components correlate with various aspects of behavior. An increase in braking while driving was found to increase activation in motor areas, while cerebellar areas showed signal increases during steering maintenance, yet signal decreases during steering changes. Additional components and significant findings are further outlined. In summary, continuous behavioral variables conjoined with ICA may offer new insight into the neural correlates of complex human behavior.

Speciation within Columnea section Angustiflora (Gesneriaceae): islands, pollinators and climate.

PubMed

Schulte, Lacie J; Clark, John L; Novak, Stephen J; Jeffries, Shandra K; Smith, James F

2015-03-01

Despite many advances in evolutionary biology, understanding the proximate mechanisms that lead to speciation for many taxonomic groups remains elusive. Phylogenetic analyses provide a means to generate well-supported estimates of species relationships. Understanding how genetic isolation (restricted gene flow) occurred in the past requires not only a well-supported molecular phylogenetic analysis, but also an understanding of when character states that define species may have changed. In this study, phylogenetic trees resolve species level relationships for fourteen of the fifteen species within Columnea section Angustiflorae (Gesneriaceae). The distributions of sister species pairs are compared and ancestral character states are reconstructed using Bayesian stochastic mapping. Climate variables were also assessed and shifts in ancestral climate conditions were mapped using SEEVA. The relationships between morphological character states and climate variables were assessed with correlation analyses. These results indicate that species in section Angustiflorae have likely diverged as a result of allopatric, parapatric, and sympatric speciation, with both biotic and abiotic forces driving morphological and phenological divergence. Copyright © 2015 Elsevier Inc. All rights reserved.

Antibody repertoire diversification through VH gene replacement in mice cloned from an IgA plasma cell.

PubMed

Kumar, Rashmi; Bach, Martina P; Mainoldi, Federica; Maruya, Mikako; Kishigami, Satoshi; Jumaa, Hassan; Wakayama, Teruhiko; Kanagawa, Osami; Fagarasan, Sidonia; Casola, Stefano

2015-02-03

In mammals, VDJ recombination is responsible for the establishment of a highly diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy (H) chain variable (V) gene rearrangement is thought to prevent further recombination at the IgH locus. Here, we describe VHQ52(NT); Vκgr32(NT) Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma cell. In VHQ52(NT) mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In VHQ52(NT) animals, over 20% of mature B cells disrupted the single productive, nonautoimmune IgH rearrangement through VH replacement and exchanged it with a highly diversified pool of IgH specificities. VH replacement occurred in early pro-B cells, was independent of pre-B-cell receptor signaling, and involved predominantly one adjacent VH germ-line gene. VH replacement was also identified in 5% of peripheral B cells of mice inheriting a different productive VH rearrangement expressed in the form of an IgM H chain. In summary, editing of a productive IgH rearrangement through VH replacement can account for up to 20% of the IgH repertoire expressed by mature B cells.

Genome-nuclear lamina interactions: from cell populations to single cells.

PubMed

Yáñez-Cuna, J Omar; van Steensel, Bas

2017-04-01

Lamina-associated domains (LADs) are large genomic regions that interact with the nuclear lamina (NL) and help to guide the spatial folding of chromosomes in the interphase nucleus. LADs have been linked to gene repression and other functions. Recent studies have begun to uncover some of the molecular players that drive LAD-NL interactions. A picture emerges in which DNA sequence, chromatin components and nuclear lamina proteins play an important role. Complementary to this, imaging and single-cell genomics approaches have revealed that some LAD-NL interactions are variable from cell to cell, while others are very stable. Understanding LADs can provide a unique perspective into the general process of genome organization. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

PubMed

Yang, Lun; Price, Elvin T; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

2013-01-01

Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

Stimulation of Respiratory Motor Output and Ventilation in a Murine Model of Pompe Disease by Ampakines.

PubMed

ElMallah, Mai K; Pagliardini, Silvia; Turner, Sara M; Cerreta, Anthony J; Falk, Darin J; Byrne, Barry J; Greer, John J; Fuller, David D

2015-09-01

Pompe disease results from a mutation in the acid α-glucosidase gene leading to lysosomal glycogen accumulation. Respiratory insufficiency is common, and the current U.S. Food and Drug Administration-approved treatment, enzyme replacement, has limited effectiveness. Ampakines are drugs that enhance α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses and can increase respiratory motor drive. Recent work indicates that respiratory motor drive can be blunted in Pompe disease, and thus pharmacologic stimulation of breathing may be beneficial. Using a murine Pompe model with the most severe clinical genotype (the Gaa(-/-) mouse), our primary objective was to test the hypothesis that ampakines can stimulate respiratory motor output and increase ventilation. Our second objective was to confirm that neuropathology was present in Pompe mouse medullary respiratory control neurons. The impact of ampakine CX717 on breathing was determined via phrenic and hypoglossal nerve recordings in anesthetized mice and whole-body plethysmography in unanesthetized mice. The medulla was examined using standard histological methods coupled with immunochemical markers of respiratory control neurons. Ampakine CX717 robustly increased phrenic and hypoglossal inspiratory bursting and reduced respiratory cycle variability in anesthetized Pompe mice, and it increased inspiratory tidal volume in unanesthetized Pompe mice. CX717 did not significantly alter these variables in wild-type mice. Medullary respiratory neurons showed extensive histopathology in Pompe mice. Ampakines stimulate respiratory neuromotor output and ventilation in Pompe mice, and therefore they have potential as an adjunctive therapy in Pompe disease.

Large-scale maps of variable infection efficiencies in aquatic Bacteroidetes phage-host model systems: Variable phage-host infection interactions

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

Holmfeldt, Karin; Solonenko, Natalie; Howard-Varona, Cristina

Microbes drive ecosystem functioning and their viruses modulate these impacts through mortality, gene transfer and metabolic reprogramming. Despite the importance of virus-host interactions and likely variable infection efficiencies of individual phages across hosts, such variability is seldom quantified. In this paper, we quantify infection efficiencies of 38 phages against 19 host strains in aquatic Cellulophaga (Bacteroidetes) phage-host model systems. Binary data revealed that some phages infected only one strain while others infected 17, whereas quantitative data revealed that efficiency of infection could vary 10 orders of magnitude, even among phages within one population. This provides a baseline for understanding andmore » modeling intrapopulation host range variation. Genera specific host ranges were also informative. For example, the Cellulophaga Microviridae, showed a markedly broader intra-species host range than previously observed in Escherichia coli systems. Further, one phage genus, Cba41, was examined to investigate nonheritable changes in plating efficiency and burst size that depended on which host strain it most recently infected. While consistent with host modification of phage DNA, no differences in nucleotide sequence or DNA modifications were detected, leaving the observation repeatable, but the mechanism unresolved. Overall, this study highlights the importance of quantitatively considering replication variations in studies of phage-host interactions.« less

Large-scale maps of variable infection efficiencies in aquatic Bacteroidetes phage-host model systems: Variable phage-host infection interactions

DOE PAGES

Holmfeldt, Karin; Solonenko, Natalie; Howard-Varona, Cristina; ...

2016-06-28

Microbes drive ecosystem functioning and their viruses modulate these impacts through mortality, gene transfer and metabolic reprogramming. Despite the importance of virus-host interactions and likely variable infection efficiencies of individual phages across hosts, such variability is seldom quantified. In this paper, we quantify infection efficiencies of 38 phages against 19 host strains in aquatic Cellulophaga (Bacteroidetes) phage-host model systems. Binary data revealed that some phages infected only one strain while others infected 17, whereas quantitative data revealed that efficiency of infection could vary 10 orders of magnitude, even among phages within one population. This provides a baseline for understanding andmore » modeling intrapopulation host range variation. Genera specific host ranges were also informative. For example, the Cellulophaga Microviridae, showed a markedly broader intra-species host range than previously observed in Escherichia coli systems. Further, one phage genus, Cba41, was examined to investigate nonheritable changes in plating efficiency and burst size that depended on which host strain it most recently infected. While consistent with host modification of phage DNA, no differences in nucleotide sequence or DNA modifications were detected, leaving the observation repeatable, but the mechanism unresolved. Overall, this study highlights the importance of quantitatively considering replication variations in studies of phage-host interactions.« less

Glaucoma and quality of life: fall and driving risk.

PubMed

Montana, Cynthia L; Bhorade, Anjali M

2018-03-01

Numerous population-based studies suggest that glaucoma is an independent risk factor for falling and motor vehicle collisions, particularly for older adults. These adverse events lead to increased healthcare expenditures and decreased quality of life. Current research priorities, therefore, include identifying factors that predispose glaucoma patients to falling and unsafe driving, and developing screening strategies and targeted rehabilitation. The purpose of this article is to review recent studies that address these priorities. Studies continue to support that glaucoma patients, particularly those with advanced disease, have an increased risk of falling or unsafe driving. Risk factors, however, remain variable and include severity and location of visual field defects, contrast sensitivity, and performance on divided attention tasks. Such variability is likely because of the multifactorial nature of ambulating and driving and compensatory strategies used by patients. Falls and unsafe driving remain a serious public health issue for older adults with glaucoma. Ambulation and driving are complex tasks and there is no consensus yet, regarding the best methods for risk stratification and targeted interventions to increase safety. Therefore, comprehensive and individualized assessments are recommended to most effectively evaluate a patient's risk for falling or unsafe driving.

Mobile phone use while driving: a hybrid modeling approach.

PubMed

Márquez, Luis; Cantillo, Víctor; Arellana, Julián

2015-05-01

The analysis of the effects that mobile phone use produces while driving is a topic of great interest for the scientific community. There is consensus that using a mobile phone while driving increases the risk of exposure to traffic accidents. The purpose of this research is to evaluate the drivers' behavior when they decide whether or not to use a mobile phone while driving. For that, a hybrid modeling approach that integrates a choice model with the latent variable "risk perception" was used. It was found that workers and individuals with the highest education level are more prone to use a mobile phone while driving than others. Also, "risk perception" is higher among individuals who have been previously fined and people who have been in an accident or almost been in an accident. It was also found that the tendency to use mobile phones while driving increases when the traffic speed reduces, but it decreases when the fine increases. Even though the urgency of the phone call is the most important explanatory variable in the choice model, the cost of the fine is an important attribute in order to control mobile phone use while driving. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drowsiness detection using heart rate variability.

PubMed

Vicente, José; Laguna, Pablo; Bartra, Ariadna; Bailón, Raquel

2016-06-01

It is estimated that 10-30 % of road fatalities are related to drowsy driving. Driver's drowsiness detection based on biological and vehicle signals is being studied in preventive car safety. Autonomous nervous system activity, which can be measured noninvasively from the heart rate variability (HRV) signal obtained from surface electrocardiogram, presents alterations during stress, extreme fatigue and drowsiness episodes. We hypothesized that these alterations manifest on HRV and thus could be used to detect driver's drowsiness. We analyzed three driving databases in which drivers presented different sleep-deprivation levels, and in which each driving minute was annotated as drowsy or awake. We developed two different drowsiness detectors based on HRV. While the drowsiness episodes detector assessed each minute of driving as "awake" or "drowsy" with seven HRV derived features (positive predictive value 0.96, sensitivity 0.59, specificity 0.98 on 3475 min of driving), the sleep-deprivation detector discerned if a driver was suitable for driving or not, at driving onset, as function of his sleep-deprivation state. Sleep-deprivation state was estimated from the first three minutes of driving using only one HRV feature (positive predictive value 0.80, sensitivity 0.62, specificity 0.88 on 30 drivers). Incorporating drowsiness assessment based on HRV signal may add significant improvements to existing car safety systems.

Drive system for the retraction/extension of variable diameter rotor systems

NASA Technical Reports Server (NTRS)

Gmirya, Yuriy (Inventor)

2003-01-01

A drive system for a variable diameter rotor (VDR) system includes a plurality of rotor blade assemblies with inner and outer rotor blade segments. The outer blade segment being telescopically mounted to the inner blade segment. The VDR retraction/extension system includes a drive housing mounted at the root of each blade. The housing supports a spool assembly, a harmonic gear set and an electric motor. The spool assembly includes a pair of counter rotating spools each of which drive a respective cable which extends through the interior of the inboard rotor blade section and around a pulley mounted to the outboard rotor blade section. In operation, the electric motor drives the harmonic gear set which rotates the counter rotating spools. Rotation of the spools causes the cables to be wound onto or off their respective spool consequently effecting retraction/extension of the pulley and the attached outboard rotor blade section relative the inboard rotor blade section. As each blade drive system is independently driven by a separate electrical motor, each independent VDR blade assembly is independently positionable.

[Role of some psycho-physiological factors on driving safety].

PubMed

Bergomi, M; Vivoli, G; Rovesti, S; Bussetti, P; Ferrari, A; Vivoli, R

2010-01-01

Within a research project on the role played by human factors on road accidents, the aim of the present study is to evaluate, in young adults, the relationships between driver behaviour and personality factors as well as to assess the neuroendocrine correlates of psychological and behavioural factors investigated. Another aim is to estimate in what measure the performance levels are affected by demographic, psychological and chronobiological variables. It has been found a positive relation between highway code violations, extroversion trait of personality and Sensation Seeking scores, so confirming that this component of personality can affect risky behaviour. Furthermore the subjects more oriented to morningness chronotype were found to be prone to adopt safe driving behaviour. Regarding the relations of the neuroendocrine parameters and driving behaviour a positive correlation was observed between dopamine levels and frequency of driving violations while a negative relationship was found between adrenaline levels and frequency of driving errors. In conclusion the identification of psycho-physiological variables related to driving risky behaviour might be a useful instrument to design traffic safety programs tailored to high risk subjects.

Quiet Clean Short-haul Experimental Engine (QCSEE): Hamilton Standard cam/harmonic drive variable pitch fan actuation system detail design report

NASA Technical Reports Server (NTRS)

1976-01-01

A variable pitch fan actuation system was designed which incorporates a remote nacelle-mounted blade angle regulator. The regulator drives a rotating fan-mounted mechanical actuator through a flexible shaft and differential gear train. The actuator incorporates a high ratio harmonic drive attached to a multitrack spherical cam which changes blade pitch through individual cam follower arms attached to each blade trunnion. Detail design parameters of the actuation system are presented. These include the following: design philosophies, operating limits, mechanical, hydraulic and thermal characteristics, mechanical efficiencies, materials, weights, lubrication, stress analyses, reliability and failure analyses.

Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive' hypothesis.

PubMed

Chatterjee, Aniruddha; Lagisz, Malgorzata; Rodger, Euan J; Zhen, Li; Stockwell, Peter A; Duncan, Elizabeth J; Horsfield, Julia A; Jeyakani, Justin; Mathavan, Sinnakaruppan; Ozaki, Yuichi; Nakagawa, Shinichi

2016-09-30

The sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain. Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis. Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time. Copyright © 2016 Elsevier B.V. All rights reserved.

Four quadrant control of induction motors

NASA Technical Reports Server (NTRS)

Hansen, Irving G.

1991-01-01

Induction motors are the nation's workhorse, being the motor of choice in most applications due to their simple rugged construction. It has been estimated that 14 to 27 percent of the country's total electricity use could be saved with adjustable speed drives. Until now, induction motors have not been suited well for variable speed or servo-drives, due to the inherent complexity, size, and inefficiency of their variable speed controls. Work at NASA Lewis Research Center on field oriented control of induction motors using pulse population modulation method holds the promise for the desired drive electronics. The system allows for a variable voltage to frequency ratio which enables the user to operate the motor at maximum efficiency, while having independent control of both the speed and torque of an induction motor in all four quadrants of the speed torque map. Multiple horsepower machine drives were demonstrated, and work is on-going to develop a 20 hp average, 40 hp peak class of machine. The pulse population technique, results to date, and projections for implementation of this existing new motor control technology are discussed.

Testing the effects of safety climate and disruptive children behavior on school bus drivers performance: A multilevel model.

PubMed

Zohar, Dov; Lee, Jin

2016-10-01

The study was designed to test a multilevel path model whose variables exert opposing effects on school bus drivers' performance. Whereas departmental safety climate was expected to improve driving safety, the opposite was true for in-vehicle disruptive children behavior. The driving safety path in this model consists of increasing risk-taking practices starting with safety shortcuts leading to rule violations and to near-miss events. The study used a sample of 474 school bus drivers in rural areas, driving children to school and school-related activities. Newly developed scales for measuring predictor, mediator and outcome variables were validated with video data taken from inner and outer cameras, which were installed in 29 buses. Results partially supported the model by indicating that group-level safety climate and individual-level children distraction exerted opposite effects on the driving safety path. Furthermore, as hypothesized, children disruption moderated the strength of the safety rule violation-near miss relationship, resulting in greater strength under high disruptiveness. At the same time, the hypothesized interaction between the two predictor variables was not supported. Theoretical and practical implications for studying safety climate in general and distracted driving in particular for professional drivers are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selection and geographic isolation influence hummingbird speciation: genetic, acoustic and morphological divergence in the wedge-tailed sabrewing (Campylopterus curvipennis).

PubMed

González, Clementina; Ornelas, Juan Francisco; Gutiérrez-Rodríguez, Carla

2011-02-08

Mesoamerica is one of the most threatened biodiversity hotspots in the world, yet we are far from understanding the geologic history and the processes driving population divergence and speciation for most endemic taxa. In species with highly differentiated populations selective and/or neutral factors can induce rapid changes to traits involved in mate choice, promoting reproductive isolation between allopatric populations that can eventually lead to speciation. We present the results of genetic differentiation, and explore drift and selection effects in promoting acoustic and morphological divergence among populations of Campylopterus curvipennis, a lekking hummingbird with an extraordinary vocal variability across Mesoamerica. Analyses of two mitochondrial genes and ten microsatellite loci genotyped for 160 individuals revealed the presence of three lineages with no contemporary gene flow: C. c. curvipennis, C. c. excellens, and C. c. pampa disjunctly distributed in the Sierra Madre Oriental, the Tuxtlas region and the Yucatan Peninsula, respectively. Sequence mtDNA and microsatellite data were congruent with two diversification events: an old vicariance event at the Isthmus of Tehuantepec (c. 1.4 Ma), and a more recent Pleistocene split, isolating populations in the Tuxtlas region. Hummingbirds of the excellens group were larger, and those of the pampa group had shorter bills, and lineages that have been isolated the longest shared fewer syllables and differed in spectral and temporal traits of a shared syllable. Coalescent simulations showed that fixation of song types has occurred faster than expected under neutrality but the null hypothesis that morphological divergence resulted from drift was not rejected. Our phylogeographic analyses uncovered the presence of three Mesoamerican wedge-tailed sabrewing lineages, which diverged at different time scales. These results highlight the importance of the Isthmus of Tehuantepec and more recent Pleistocene climatic events in driving isolation and population divergence. Coalescent analyses of the evolution of phenotypic traits suggest that selection is driving song evolution in wedge-tailed sabrewings but drift could not be rejected as a possibility for morphological divergence.

Driving Performance on the Descending Limb of Blood Alcohol Concentration (BAC) in Undergraduate Students: A Pilot Study

PubMed Central

Silvey, Dustin; Behm, David; Albert, Wayne J.

2015-01-01

Young drivers are overrepresented in collisions resulting in fatalities. It is not uncommon for young drivers to socially binge drink and decide to drive a vehicle a few hours after consumption. To better understand the risks that may be associated with this behaviour, the present study has examined the effects of a social drinking bout followed by a simulated drive in undergraduate students on the descending limb of their BAC (blood alcohol concentration) curve. Two groups of eight undergraduate students (n = 16) took part in this study. Participants in the alcohol group were assessed before drinking, then at moderate and low BAC as well as 24 hours post-acute consumption. This group consumed an average of 5.3 ± 1.4 (mean ± SD) drinks in an hour in a social context and were then submitted to a driving and a predicted crash risk assessment. The control group was assessed at the same time points without alcohol intake or social context.; at 8 a.m., noon, 3 p.m. and 8 a.m. the next morning. These multiple time points were used to measure any potential learning effects from the assessment tools (i.e. driving simulator and useful field of view test (UFOV)). Diminished driving performance at moderate BAC was observed with no increases in predicted crash risk. Moderate correlations between driving variables were observed. No association exists between driving variables and UFOV variables. The control group improved measures of selective attention after the third asessement. No learning effect was observed from multiple sessions with the driving simulator. Our results show that a moderate BAC, although legal, increases the risky behaviour. Effects of alcohol expectancy could have been displayed by the experimental group. UFOV measures and predicted crash risk categories were not sentitive enough to predict crash risk for young drivers, even when intoxicated. PMID:25723618

Driving performance on the descending limb of blood alcohol concentration (BAC) in undergraduate students: a pilot study.

PubMed

Tremblay, Mathieu; Gallant, François; Lavallière, Martin; Chiasson, Martine; Silvey, Dustin; Behm, David; Albert, Wayne J; Johnson, Michel J

2015-01-01

Young drivers are overrepresented in collisions resulting in fatalities. It is not uncommon for young drivers to socially binge drink and decide to drive a vehicle a few hours after consumption. To better understand the risks that may be associated with this behaviour, the present study has examined the effects of a social drinking bout followed by a simulated drive in undergraduate students on the descending limb of their BAC (blood alcohol concentration) curve. Two groups of eight undergraduate students (n = 16) took part in this study. Participants in the alcohol group were assessed before drinking, then at moderate and low BAC as well as 24 hours post-acute consumption. This group consumed an average of 5.3 ± 1.4 (mean ± SD) drinks in an hour in a social context and were then submitted to a driving and a predicted crash risk assessment. The control group was assessed at the same time points without alcohol intake or social context.; at 8 a.m., noon, 3 p.m. and 8 a.m. the next morning. These multiple time points were used to measure any potential learning effects from the assessment tools (i.e. driving simulator and useful field of view test (UFOV)). Diminished driving performance at moderate BAC was observed with no increases in predicted crash risk. Moderate correlations between driving variables were observed. No association exists between driving variables and UFOV variables. The control group improved measures of selective attention after the third assessment. No learning effect was observed from multiple sessions with the driving simulator. Our results show that a moderate BAC, although legal, increases the risky behaviour. Effects of alcohol expectancy could have been displayed by the experimental group. UFOV measures and predicted crash risk categories were not sensitive enough to predict crash risk for young drivers, even when intoxicated.

Conditions for success of engineered underdominance gene drive systems.

PubMed

Edgington, Matthew P; Alphey, Luke S

2017-10-07

Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually suppressing lethals. In such a system two genetic constructs are introduced, each possessing a lethal element and a suppressor of the lethal at the other locus. Specifically, we formulate and analyse a population genetics model of this system to assess when different combinations of release strategies (i.e. single or multiple releases of both sexes or males only) and genetic systems (i.e. bisex lethal or female-specific lethal elements and different strengths of suppressors) will give population replacement or fail to do so. We anticipate that results presented here will inform the future design of engineered underdominance gene drive systems as well as providing a point of reference regarding release strategies for those looking to test such a system. Our discussion is framed in the context of genetic control of insect vectors of disease. One of several serious threats in this context are Aedes aegypti mosquitoes as they are the primary vectors of dengue viruses. However, results are also applicable to Ae. aegypti as vectors of Zika, yellow fever and chikungunya viruses and also to the control of a number of other insect species and thereby of insect-vectored pathogens. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Preliminary report of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) score.

PubMed

Baskin-Bey, Edwina S; Stewart, Charmaine A; Mitchell, Mary M; Bida, John P; Rosenthal, Theodore J; Nyberg, Scott L

2008-01-01

Audiovisual simulations of real-life driving (ie, driving simulators) have been used to assess neurologic dysfunction in a variety of medical applications. However, the use of simulated driving to assess neurologic impairment in the setting of liver disease (ie, hepatic encephalopathy) is limited. The aim of this analysis was to develop a scoring system based on simulated driving performance to assess mild cognitive impairment in cirrhotic patients with hepatic encephalopathy. This preliminary analysis was conducted as part of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) pilot study. Cirrhotic volunteers initially underwent a battery of neuropsychological tests to identify those cirrhotic patients with mild cognitive impairment. Performance during an audiovisually simulated course of on-road driving was then compared between mildly impaired cirrhotic patients and healthy volunteers. A scoring system was developed to quantify the likelihood of cognitive impairment on the basis of data from the simulated on-road driving. Mildly impaired cirrhotic patients performed below the level of healthy volunteers on the driving simulator. Univariate logistic regression and correlation models indicated that several driving simulator variables were significant predictors of cognitive impairment. Five variables (run time, total map performance, number of collisions, visual divided attention response, and average lane position) were incorporated into a quantitative model, the HEADS scoring system. The HEADS score (0-9 points) showed a strong correlation with cognitive impairment as measured by area under the receiver-operator curve (.89). The HEADS system appears to be a promising new tool for the assessment of mild hepatic encephalopathy.

Identifying driving gene clusters in complex diseases through critical transition theory

NASA Astrophysics Data System (ADS)

Wolanyk, Nathaniel; Wang, Xujing; Hessner, Martin; Gao, Shouguo; Chen, Ye; Jia, Shuang

A novel approach of looking at the human body using critical transition theory has yielded positive results: clusters of genes that act in tandem to drive complex disease progression. This cluster of genes can be thought of as the first part of a large genetic force that pushes the body from a curable, but sick, point to an incurable diseased point through a catastrophic bifurcation. The data analyzed is time course microarray blood assay data of 7 high risk individuals for Type 1 Diabetes who progressed into a clinical onset, with an additional larger study requested to be presented at the conference. The normalized data is 25,000 genes strong, which were narrowed down based on statistical metrics, and finally a machine learning algorithm using critical transition metrics found the driving network. This approach was created to be repeatable across multiple complex diseases with only progression time course data needed so that it would be applicable to identifying when an individual is at risk of developing a complex disease. Thusly, preventative measures can be enacted, and in the longer term, offers a possible solution to prevent all Type 1 Diabetes.

Trends in non-stationary signal processing techniques applied to vibration analysis of wind turbine drive train - A contemporary survey

NASA Astrophysics Data System (ADS)

Uma Maheswari, R.; Umamaheswari, R.

2017-02-01

Condition Monitoring System (CMS) substantiates potential economic benefits and enables prognostic maintenance in wind turbine-generator failure prevention. Vibration Monitoring and Analysis is a powerful tool in drive train CMS, which enables the early detection of impending failure/damage. In variable speed drives such as wind turbine-generator drive trains, the vibration signal acquired is of non-stationary and non-linear. The traditional stationary signal processing techniques are inefficient to diagnose the machine faults in time varying conditions. The current research trend in CMS for drive-train focuses on developing/improving non-linear, non-stationary feature extraction and fault classification algorithms to improve fault detection/prediction sensitivity and selectivity and thereby reducing the misdetection and false alarm rates. In literature, review of stationary signal processing algorithms employed in vibration analysis is done at great extent. In this paper, an attempt is made to review the recent research advances in non-linear non-stationary signal processing algorithms particularly suited for variable speed wind turbines.

Extreme Events in China under Climate Change: Uncertainty and related impacts (CSSP-FOREX)

NASA Astrophysics Data System (ADS)

Leckebusch, Gregor C.; Befort, Daniel J.; Hodges, Kevin I.

2016-04-01

Suitable adaptation strategies or the timely initiation of related mitigation efforts in East Asia will strongly depend on robust and comprehensive information about future near-term as well as long-term potential changes in the climate system. Therefore, understanding the driving mechanisms associated with the East Asian climate is of major importance. The FOREX project (Fostering Regional Decision Making by the Assessment of Uncertainties of Future Regional Extremes and their Linkage to Global Climate System Variability for China and East Asia) focuses on the investigation of extreme wind and rainfall related events over Eastern Asia and their possible future changes. Here, analyses focus on the link between local extreme events and their driving weather systems. This includes the coupling between local rainfall extremes and tropical cyclones, the Meiyu frontal system, extra-tropical teleconnections and monsoonal activity. Furthermore, the relation between these driving weather systems and large-scale variability modes, e.g. NAO, PDO, ENSO is analysed. Thus, beside analysing future changes of local extreme events, the temporal variability of their driving weather systems and related large-scale variability modes will be assessed in current CMIP5 global model simulations to obtain more robust results. Beyond an overview of FOREX itself, first results regarding the link between local extremes and their steering weather systems based on observational and reanalysis data are shown. Special focus is laid on the contribution of monsoonal activity, tropical cyclones and the Meiyu frontal system on the inter-annual variability of the East Asian summer rainfall.

NIH scientists map gene changes driving tumors in common pediatric soft-tissue cancer

Cancer.gov

Scientists have mapped the genetic changes that drive tumors in rhabdomyosarcoma, a pediatric soft-tissue cancer, and found that the disease is characterized by two distinct genotypes. The genetic alterations identified in this malignancy could be useful

Genetic Variation in Taste Sensitivity to Sugars in Drosophila melanogaster.

PubMed

Uchizono, Shun; Tanimura, Teiichi

2017-05-01

Taste sensitivity plays a major role in controlling feeding behavior, and alterations in feeding habit induced by changes in taste sensitivity can drive speciation. We investigated variability in taste preferences in wild-derived inbred lines from the Drosophila melanogaster Genetic Reference Panel. Preferences for different sugars, which are essential nutrients for fruit flies, were assessed using two-choice preference tests that paired glucose with fructose, sucrose, or trehalose. The two-choice tests revealed that individual lines have differential and widely variable sugar preferences, and that sugar taste sensitivity is polygenic in the inbred population tested. We focused on 2 strains that exhibited opposing preferences for glucose and fructose, and performed proboscis extension reflex tests and electrophysiological recordings on taste sensilla upon exposure to fructose and glucose. The results indicated that taste sensitivity to fructose is dimorphic between the 2 lines. Genetic analysis showed that high sensitivity to fructose is autosomal dominant over low sensitivity, and that multiple loci on chromosomes 2 and 3 influence sensitivity. Further genetic complementation tests for fructose sensitivity on putative gustatory receptor (Gr) genes for sugars suggested that the Gr64a-Gr64f locus, not the fructose receptor gene Gr43a, might contribute to the dimorphic sensitivity to fructose between the 2 lines. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Safe Driving Climate among Friends (SDCaF): A new scale.

PubMed

Guggenheim, Noga; Taubman-Ben-Ari, Orit

2018-01-01

Reckless driving among young people, especially young men, is a major cause of injury and fatalities the world over. Like other aspects of this age group, young drivers' driving behaviors and norms are influenced by the accepted social discourse of their peers. Yet despite extensive existing knowledge on young drivers, very few studies have dealt specifically with their characteristic friendship relations. This lacuna in the literature may reflect the absence of specific research tools for examining driving with friends. To fill this gap, we conducted a series of studies with 706 young drivers (aged 17-24) of both sexes aimed at developing and validating a multidimensional scale designed to examine the effect of the social relations of adolescents and young adults on their driving. Entitled Safe Driving Climate among Friends (SDCaF), the final scale consists of 19 items, which tap four dimensions of driving with friends: friends' pressure; social costs of driving with friends; communication with friends about driving; and shared commitment to safe driving. The validity of the scale was established by examining associations between its four dimensions and various variables of personality, friendship, and driving. The findings indicate good reliability and validity, with the three variables of resistance to peer influence, self-disclosure, and personal responsibility for safe driving yielding positive associations with the SDCaF dimensions communication and shared commitment to safe driving, and negative associations with the dimensions friends' pressure and social costs. General tendency to respond to social pressure was positively associated with the dimensions of friends' pressure and social costs, and negatively associated with shared commitment to safe driving. Gender differences were also found, with men scoring higher than women on friends' pressure, and lower than women on shared commitment to safe driving. The SDCaF can serve as a research tool, as well as a diagnostic instrument for detecting susceptibility to reckless driving among young drivers, thereby aiding in the design of targeted educational and intervention programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evolving gene regulation networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system

PubMed Central

Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L.

2014-01-01

Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs, their localized patterning into remarkably different cell types aggregated into variably sized parts of the central nervous system begin to emerge. Insights at the cellular and molecular level begin to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early and not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system. PMID:25416504

Evolving gene regulatory networks into cellular networks guiding adaptive behavior: an outline how single cells could have evolved into a centralized neurosensory system.

PubMed

Fritzsch, Bernd; Jahan, Israt; Pan, Ning; Elliott, Karen L

2015-01-01

Understanding the evolution of the neurosensory system of man, able to reflect on its own origin, is one of the major goals of comparative neurobiology. Details of the origin of neurosensory cells, their aggregation into central nervous systems and associated sensory organs and their localized patterning leading to remarkably different cell types aggregated into variably sized parts of the central nervous system have begun to emerge. Insights at the cellular and molecular level have begun to shed some light on the evolution of neurosensory cells, partially covered in this review. Molecular evidence suggests that high mobility group (HMG) proteins of pre-metazoans evolved into the definitive Sox [SRY (sex determining region Y)-box] genes used for neurosensory precursor specification in metazoans. Likewise, pre-metazoan basic helix-loop-helix (bHLH) genes evolved in metazoans into the group A bHLH genes dedicated to neurosensory differentiation in bilaterians. Available evidence suggests that the Sox and bHLH genes evolved a cross-regulatory network able to synchronize expansion of precursor populations and their subsequent differentiation into novel parts of the brain or sensory organs. Molecular evidence suggests metazoans evolved patterning gene networks early, which were not dedicated to neuronal development. Only later in evolution were these patterning gene networks tied into the increasing complexity of diffusible factors, many of which were already present in pre-metazoans, to drive local patterning events. It appears that the evolving molecular basis of neurosensory cell development may have led, in interaction with differentially expressed patterning genes, to local network modifications guiding unique specializations of neurosensory cells into sensory organs and various areas of the central nervous system.

The Measurement and Comparison of Variables Related to Driver and Highway Safety Between Educable Mentally Retarded and Normal High School Age Students in Pennsylvania. Final Report.

ERIC Educational Resources Information Center

Bologa, James F.; And Others

The study was conducted to measure variables related to safe driving and to designate factors predictive of success in driving safety of educable mentally retarded (EMR) students as compared to normal students. Subjects were 349 EMR and 443 intellectually normal students (ages 16-20), who were evaluated in the following areas: visual acuity,…

Variable-frequency synchronous motor drives for electric vehicles

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

Chalmers, B.J.; Musaba, L.; Gosden, D.F.

1996-07-01

The performance capability envelope of a variable-frequency, permanent-magnet synchronous motor drive with field weakening is dependent upon the product of maximum current and direct-axis inductance. To obtain a performance characteristic suitable for a typical electric vehicle drive, in which short-term increase of current is applied, it is necessary to design an optimum value of direct-axis inductance. The paper presents an analysis of a hybrid motor design which uses a two-part rotor construction comprising a surface-magnet part and an axially laminated reluctance part. This arrangement combines the properties of all other types of synchronous motor and offers a greater choice ofmore » design variables. It is shown that the desired form of performance may be achieved when the high-inductance axis of the reluctance part is arranged to lead the magnet axis by 90{degree} (elec.).« less

Variable-frequency synchronous motor drives for electric vehicles

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

Chalmers, B.J.; Musaba, L.; Gosden, D.F.

1995-12-31

The performance capability envelope of a variable-frequency, permanent-magnet synchronous motor drive with field weakening is dependent upon the product of maximum current and direct-axis inductance. To obtain a performance characteristic suitable for a typical electric vehicle drive, in which short-term increase of current is applied, it is necessary to design an optimum value of direct-axis inductance. The paper presents an analysis of a hybrid motor design which uses a two-part rotor construction comprising a surface-magnet part and an axially-laminated reluctance part. This arrangement combines the properties of all other types of synchronous motor and offers a greater choice of designmore » variables. It is shown that the desired form of performance may be achieved when the high-inductance axis of the reluctance part is arranged to lead the magnet axis by 90{degree} (elec.).« less

Axial force and efficiency tests of fixed center variable speed belt drive

NASA Technical Reports Server (NTRS)

Bents, D. J.

1981-01-01

An investigation of how the axial force varies with the centerline force at different speed ratios, speeds, and loads, and how the drive's transmission efficiency is affected by these related forces is described. The tests, intended to provide a preliminary performance and controls characterization for a variable speed belt drive continuously variable transmission (CVT), consisted of the design and construction of an experimental test rig geometrically similar to the CVT, and operation of that rig at selected speed ratios and power levels. Data are presented which show: how axial forces exerted on the driver and driven sheaves vary with the centerline force at constant values of speed ratio, speed, and output power; how the transmission efficiency varies with centerline force and how it is also a function of the V belt coefficient; and the axial forces on both sheaves as normalized functions of the traction coefficient.

Molecular population genetics of X-linked genes in Drosophila pseudoobscura.

PubMed Central

Kovacevic, M; Schaeffer, S W

2000-01-01

This article presents a nucleotide sequence analysis of 500 bp determined in each of five X-linked genes, runt, sisterlessA, period, esterase 5, and Heat-shock protein 83, in 40 Drosophila pseudoobscura strains collected from two populations. Estimates of the neutral migration parameter for the five loci show that gene flow among D. pseudoobscura populations is sufficient to homogenize inversion frequencies across the range of the species. Nucleotide diversity at each locus fails to reject a neutral model of molecular evolution. The sample of 40 chromosomes included six Sex-ratio inversions, a series of three nonoverlapping inversions that are associated with a strong meiotic drive phenotype. The selection driven by the Sex-ratio meiotic drive element has not fixed variation across the X chromosome of D. pseudoobscura because, while significant linkage disequilibrium was observed within the sisterlessA, period, and esterase 5 genes, we did not find evidence for nonrandom association among loci. The Sex-ratio chromosome was estimated to be 25,000 years old based on the decomposition of linkage disequilibrium between esterase 5 and Heat-shock protein 83 or 1 million years old based on the net divergence of esterase 5 between Standard and Sex-ratio chromosomes. Genetic diversity was depressed within esterase 5 within Sex-ratio chromosomes, while the four other genes failed to show a reduction in heterozygosity in the Sex-ratio background. The reduced heterogeneity in esterase 5 is due either to its location near one of the Sex-ratio inversion breakpoints or that it is closely linked to a gene or genes responsible for the Sex-ratio meiotic drive system. PMID:10978282

Wire-Guide Manipulator For Automated Welding

NASA Technical Reports Server (NTRS)

Morris, Tim; White, Kevin; Gordon, Steve; Emerich, Dave; Richardson, Dave; Faulkner, Mike; Stafford, Dave; Mccutcheon, Kim; Neal, Ken; Milly, Pete

1994-01-01

Compact motor drive positions guide for welding filler wire. Drive part of automated wire feeder in partly or fully automated welding system. Drive unit contains three parallel subunits. Rotations of lead screws in three subunits coordinated to obtain desired motions in three degrees of freedom. Suitable for both variable-polarity plasma arc welding and gas/tungsten arc welding.

Statistical algorithms improve accuracy of gene fusion detection

PubMed Central

Hsieh, Gillian; Bierman, Rob; Szabo, Linda; Lee, Alex Gia; Freeman, Donald E.; Watson, Nathaniel; Sweet-Cordero, E. Alejandro

2017-01-01

Abstract Gene fusions are known to play critical roles in tumor pathogenesis. Yet, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. In this paper, we present a new statistical algorithm, MACHETE (Mismatched Alignment CHimEra Tracking Engine), which achieves highly sensitive and specific detection of gene fusions from RNA-Seq data, including the highest Positive Predictive Value (PPV) compared to the current state-of-the-art, as assessed in simulated data. We show that the best performing published algorithms either find large numbers of fusions in negative control data or suffer from low sensitivity detecting known driving fusions in gold standard settings, such as EWSR1-FLI1. As proof of principle that MACHETE discovers novel gene fusions with high accuracy in vivo, we mined public data to discover and subsequently PCR validate novel gene fusions missed by other algorithms in the ovarian cancer cell line OVCAR3. These results highlight the gains in accuracy achieved by introducing statistical models into fusion detection, and pave the way for unbiased discovery of potentially driving and druggable gene fusions in primary tumors. PMID:28541529

A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila.

PubMed

Chen, Chun-Hong; Huang, Haixia; Ward, Catherine M; Su, Jessica T; Schaeffer, Lorian V; Guo, Ming; Hay, Bruce A

2007-04-27

One proposed strategy for controlling the transmission of insect-borne pathogens uses a drive mechanism to ensure the rapid spread of transgenes conferring disease refractoriness throughout wild populations. Here, we report the creation of maternal-effect selfish genetic elements in Drosophila that drive population replacement and are resistant to recombination-mediated dissociation of drive and disease refractoriness functions. These selfish elements use microRNA-mediated silencing of a maternally expressed gene essential for embryogenesis, which is coupled with early zygotic expression of a rescuing transgene.

A post-gene silencing bioinformatics protocol for plant-defence gene validation and underlying process identification: case study of the Arabidopsis thaliana NPR1.

PubMed

Yocgo, Rosita E; Geza, Ephifania; Chimusa, Emile R; Mazandu, Gaston K

2017-11-23

Advances in forward and reverse genetic techniques have enabled the discovery and identification of several plant defence genes based on quantifiable disease phenotypes in mutant populations. Existing models for testing the effect of gene inactivation or genes causing these phenotypes do not take into account eventual uncertainty of these datasets and potential noise inherent in the biological experiment used, which may mask downstream analysis and limit the use of these datasets. Moreover, elucidating biological mechanisms driving the induced disease resistance and influencing these observable disease phenotypes has never been systematically tackled, eliciting the need for an efficient model to characterize completely the gene target under consideration. We developed a post-gene silencing bioinformatics (post-GSB) protocol which accounts for potential biases related to the disease phenotype datasets in assessing the contribution of the gene target to the plant defence response. The post-GSB protocol uses Gene Ontology semantic similarity and pathway dataset to generate enriched process regulatory network based on the functional degeneracy of the plant proteome to help understand the induced plant defence response. We applied this protocol to investigate the effect of the NPR1 gene silencing to changes in Arabidopsis thaliana plants following Pseudomonas syringae pathovar tomato strain DC3000 infection. Results indicated that the presence of a functionally active NPR1 reduced the plant's susceptibility to the infection, with about 99% of variability in Pseudomonas spore growth between npr1 mutant and wild-type samples. Moreover, the post-GSB protocol has revealed the coordinate action of target-associated genes and pathways through an enriched process regulatory network, summarizing the potential target-based induced disease resistance mechanism. This protocol can improve the characterization of the gene target and, potentially, elucidate induced defence response by more effectively utilizing available phenotype information and plant proteome functional knowledge.

The relationship of drive for muscularity to sociocultural factors, self-esteem, physical attributes gender role, and social comparison in middle school boys.

PubMed

Smolak, Linda; Stein, Jonathan A

2006-06-01

This study examines the relationship of three sociocultural factors-media influence, peer teasing, and parent teasing/comments and three potential moderator variables-self-esteem, social comparison, and endorsement of male strength and athleticism-to drive for muscularity in middle school boys. There were 287 seventh and eighth grade boys who completed a questionnaire measuring these variables as well as body mass index (BMI) and pubertal status. Results indicated that media influence and male physical attributes endorsement were particularly important correlates of drive for muscularity. These findings have implications for programs designed to prevent body dissatisfaction among adolescent boys.

Environmental characteristics drive variation in Amazonian understorey bird assemblages

PubMed Central

Magnusson, William E.; Anderson, Marti J.; Schlegel, Martin; Pe’er, Guy; Henle, Klaus

2017-01-01

Tropical bird assemblages display patterns of high alpha and beta diversity and, as tropical birds exhibit strong habitat specificity, their spatial distributions are generally assumed to be driven primarily by environmental heterogeneity and interspecific interactions. However, spatial distributions of some Amazonian forest birds are also often restricted by large rivers and other large-scale topographic features, suggesting that dispersal limitation may also play a role in driving species’ turnover. In this study, we evaluated the effects of environmental characteristics, topographic and spatial variables on variation in local assemblage structure and diversity of birds in an old-growth forest in central Amazonia. Birds were mist-netted in 72 plots distributed systematically across a 10,000 ha reserve in each of three years. Alpha diversity remained stable through time, but species composition changed. Spatial variation in bird-assemblage structure was significantly related to environmental and topographic variables but not strongly related to spatial variables. At a broad scale, we found bird assemblages to be significantly distinct between two watersheds that are divided by a central ridgeline. We did not detect an effect of the ridgeline per se in driving these patterns, indicating that most birds are able to fly across it, and that differences in assemblage structure between watersheds may be due to unmeasured environmental variables or unique combinations of measured variables. Our study indicates that complex geography and landscape features can act together with environmental variables to drive changes in the diversity and composition of tropical bird assemblages at local scales, but highlights that we still know very little about what makes different parts of tropical forest suitable for different species. PMID:28225774

Effects of central nervous system drugs on driving: speed variability versus standard deviation of lateral position as outcome measure of the on-the-road driving test.

PubMed

Verster, Joris C; Roth, Thomas

2014-01-01

The on-the-road driving test in normal traffic is used to examine the impact of drugs on driving performance. This paper compares the sensitivity of standard deviation of lateral position (SDLP) and SD speed in detecting driving impairment. A literature search was conducted to identify studies applying the on-the-road driving test, examining the effects of anxiolytics, antidepressants, antihistamines, and hypnotics. The proportion of comparisons (treatment versus placebo) where a significant impairment was detected with SDLP and SD speed was compared. About 40% of 53 relevant papers did not report data on SD speed and/or SDLP. After placebo administration, the correlation between SDLP and SD speed was significant but did not explain much variance (r = 0.253, p = 0.0001). A significant correlation was found between ΔSDLP and ΔSD speed (treatment-placebo), explaining 48% of variance. When using SDLP as outcome measure, 67 significant treatment-placebo comparisons were found. Only 17 (25.4%) were significant when SD speed was used as outcome measure. Alternatively, for five treatment-placebo comparisons, a significant difference was found for SD speed but not for SDLP. Standard deviation of lateral position is a more sensitive outcome measure to detect driving impairment than speed variability.

Naturalistic conversation improves daytime motorway driving performance under a benzodiazepine: a randomised, crossover, double-blind, placebo-controlled study.

PubMed

Moták, Ladislav; Bayssac, Laëtitia; Taillard, Jacques; Sagaspe, Patricia; Huet, Nathalie; Terrier, Patrice; Philip, Pierre; Daurat, Agnès

2014-06-01

The adverse effects of benzodiazepines on driving are widely recognised. The aims of this study were both to determine the impact of naturalistic conversation on the driving ability of drivers under a benzodiazepine, and to measure the accuracy of drivers' assessments of the joint effects of the benzodiazepine and conversation. Sixteen healthy male participants (29.69 ± 3.30 years) underwent a randomised, crossover, double-blind, placebo-controlled study with the benzodiazepine lorazepam (2mg). They drove 200 km (125 miles) on a motorway in the morning. We measured two driving ability-related variables (i.e., lane-keeping performance), and collected a set of self-assessed variables (i.e., self-assessment of driving performance) during two 10-min sequences of interest (no conversation vs. conversation). An analysis of variance revealed an interaction whereby lane-keeping performance under lorazepam was worse in the no-conversation condition than in the conversation condition. No such difference was detected under placebo. Pearson's correlation coefficients revealed that self-assessments were (i) not at all predictive of lane-keeping when performed before the drive, but (ii) moderately predictive of lane-keeping performance when performed during or after the drive. We conclude that conversation with a passenger may contribute to safer lane-keeping when driving under a benzodiazepine. Moreover, a degree of awareness may be attained after some experience of driving under the influence of this type of medication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multiswitching compound antisynchronization of four chaotic systems

NASA Astrophysics Data System (ADS)

Khan, Ayub; Khattar, Dinesh; Prajapati, Nitish

2017-12-01

Based on three drive-one response system, in this article, the authors investigate a novel synchronization scheme for a class of chaotic systems. The new scheme, multiswitching compound antisynchronization (MSCoAS), is a notable extension of the earlier multiswitching schemes concerning only one drive-one response system model. The concept of multiswitching synchronization is extended to compound synchronization scheme such that the state variables of three drive systems antisynchronize with different state variables of the response system, simultaneously. The study involving multiswitching of three drive systems and one response system is first of its kind. Various switched modified function projective antisynchronization schemes are obtained as special cases of MSCoAS, for a suitable choice of scaling factors. Using suitable controllers and Lyapunov stability theory, sufficient condition is obtained to achieve MSCoAS between four chaotic systems and the corresponding theoretical proof is given. Numerical simulations are performed using Lorenz system in MATLAB to demonstrate the validity of the presented method.

Forgiveness and Consideration of Future Consequences in Aggressive Driving

PubMed Central

Moore, Michael; Dahlen, Eric R.

2008-01-01

Most research on aggressive driving has focused on identifying aspects of driver personality which will exacerbate it (e.g., sensation seeking, impulsiveness, driving anger, etc.). The present study was designed to examine two theoretically relevant but previously unexplored personality factors predicted to reduce the risk of aggressive driving: trait forgiveness and consideration of future consequences. The utility of these variables in predicting aggressive driving and driving anger expression was evaluated among 316 college student volunteers. Hierarchical multiple regressions permitted an analysis of the incremental validity of these constructs beyond respondent gender, age, miles driven per week, and driving anger. Both forgiveness and consideration of future consequences contributed to the prediction of aggressive driving and driving anger expression, independent of driving anger. Research on aggressive driving may be enhanced by greater attention to adaptive, potentially risk-reducing traits. Moreover, forgiveness and consideration of future consequences may have implications for accident prevention. PMID:18760093

CYP76M7 Is an ent-Cassadiene C11α-Hydroxylase Defining a Second Multifunctional Diterpenoid Biosynthetic Gene Cluster in Rice[W][OA

PubMed Central

Swaminathan, Sivakumar; Morrone, Dana; Wang, Qiang; Fulton, D. Bruce; Peters, Reuben J.

2009-01-01

Biosynthetic gene clusters are common in microbial organisms, but rare in plants, raising questions regarding the evolutionary forces that drive their assembly in multicellular eukaryotes. Here, we characterize the biochemical function of a rice (Oryza sativa) cytochrome P450 monooxygenase, CYP76M7, which seems to act in the production of antifungal phytocassanes and defines a second diterpenoid biosynthetic gene cluster in rice. This cluster is uniquely multifunctional, containing enzymatic genes involved in the production of two distinct sets of phytoalexins, the antifungal phytocassanes and antibacterial oryzalides/oryzadiones, with the corresponding genes being subject to distinct transcriptional regulation. The lack of uniform coregulation of the genes within this multifunctional cluster suggests that this was not a primary driving force in its assembly. However, the cluster is dedicated to specialized metabolism, as all genes in the cluster are involved in phytoalexin metabolism. We hypothesize that this dedication to specialized metabolism led to the assembly of the corresponding biosynthetic gene cluster. Consistent with this hypothesis, molecular phylogenetic comparison demonstrates that the two rice diterpenoid biosynthetic gene clusters have undergone independent elaboration to their present-day forms, indicating continued evolutionary pressure for coclustering of enzymatic genes encoding components of related biosynthetic pathways. PMID:19825834

Effect of promoter driving selectable marker on corn transformation.

PubMed

Prakash, N Shiva; Prasad, V; Chidambram, Thillai P; Cherian, Shoba; Jayaprakash, T L; Dasgupta, Santanu; Wang, Qi; Mann, Michael T; Spencer, T Michael; Boddupalli, Raghava S

2008-08-01

Identification of an appropriate selection agent and its corresponding selectable marker gene is one of the first steps in establishing a transformation protocol for a given plant species. As the promoter controls expression level of the genes, the promoter driving the selectable marker gene can affect transformation. However, investigations into the direct effect of promoters driving selectable marker on transformation are lacking in the literature though many reports of relative strengths of promoters driving reporter genes like GUS or CAT or GFP are available. In the present study, we have compared rice Actin1 and CaMV.35S (commonly used promoters in monocotyledonous plant transformation) promoters driving nptII for their effectiveness in paromomycin selection of transgenic corn events. To enable statistically meaningful analysis of the results, a large sample size of nearly 5,000 immature embryos (explants) was employed producing approximately 1,250 independent events from each of the two constructs in four independent experiments. The rate of appearance of resistant calli and percentage of resistant calli recovered was higher with P-Os.Actin1/nptII/nos3' as compared to P-CaMV.35S/nptII/nos3' in all four experiments. There was no appreciable difference either in the frequency of plant regeneration or in the morphological characteristics of plants recovered from the two constructs. Although the escape rate trended lower with P-Os.Actin1 as compared to P-CaMV.35S, the recovery of low copy events was significantly higher with P-CaMV.35S. The higher transformation frequency with P-Os.Actin1 could be related to the strength of this promoter as compared to P-CaMV.35S in the explants and/or calli. Based on these results, we infer that the promoter driving the selectable marker is an important factor to be considered while establishing a high throughput transformation protocol as it could not only influence the transformation frequency but also the copy number of the transgene in the recovered transgenics.

Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles.

PubMed

Nagamori, Akira; Laine, Christopher M; Valero-Cuevas, Francisco J

2018-01-01

Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,'common drive'), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary 'isometric' force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease.

Distracted Driving in Teens With and Without Attention-Deficit/Hyperactivity Disorder.

PubMed

Stavrinos, Despina; Garner, Annie A; Franklin, Crystal A; Johnson, Haley D; Welburn, Sharon C; Griffin, Russell; Underhill, Andrea T; Fine, Philip R

2015-01-01

This study is among the first to examine the effect of talking on a cell phone or text messaging while driving in teens with and without attention deficit/hyperactivity disorder (ADHD). Teens (average age 17years) with a diagnosis of ADHD (N=16) were matched with typically developing controls (N=18). All participants operated a driving simulator while (1) conversing on a cell phone, (2) text messaging, and (3) with no distraction during a baseline condition. Six indicators of driving performance were recorded: (a) time to complete the drive; (b) lane deviations; (c) variability in lane position (i.e., root mean square [RMS]); (d) reaction time; (e) motor vehicle collisions; and, (f) speed fluctuation. Significantly greater variation in lane position occurred in the texting task compared to no task and the cell phone task. While texting, in particular, teens with ADHD took significantly less time to complete the scenario. No significant main effects of group were found. Generally, those with ADHD did not differ in regard to driving performance, when compared to controls, with the exception of one outcome: time to complete scenario. These findings suggest that distracted driving impairs driving performance of teen drivers, regardless of ADHD status. Texting while driving had the greatest negative impact on driving performance, particularly with regard to variability in lane position (i.e., RMS). This study sheds light on key issues regarding injury prevention, with the intent of providing pediatric care providers with the knowledge to inform teen drivers of risks associated with distracted driving which will ultimately result in reduced rates of motor vehicle crashes and concomitant injuries. Published by Elsevier Inc.

Distracted Driving in Teens with and without Attention-Deficit/Hyperactivity Disorder

PubMed Central

Stavrinos, Despina; Garner, Annie A.; Franklin, Crystal A.; Johnson, Haley D.; Welburn, Sharon C.; Griffin, Russell; Underhill, Andrea T.; Fine, Philip R.

2015-01-01

Objective This study is among the first to examine the effect of talking on a cell phone or text messaging while driving in teens with and without Attention Deficit/Hyperactivity Disorder (ADHD). Method Teens (average age 17 years) with a diagnosis of ADHD (N=16) were matched with typically developing controls (N=18). All participants operated a driving simulator while (1) conversing on a cell phone, (2) text messaging, and (3) with no distraction during a baseline condition. Six indicators of driving performance were recorded: (a) time to complete the drive; (b) lane deviations; (c) variability in lane position (i.e., Root Mean Square [RMS]); (d) reaction time; (e) motor vehicle collisions; and, (f) speed fluctuation. Results Significantly greater variation in lane position occurred in the texting task compared to no task and the cell phone task. While texting, in particular, teens with ADHD took significantly less time to complete the scenario. No significant main effects of group were found. Conclusions Generally, those with ADHD did not differ in regard to driving performance, when compared to controls, with the exception of one outcome: time to complete scenario. These findings suggest that distracted driving impairs driving performance of teen drivers, regardless of ADHD status. Texting while driving had the greatest negative impact on driving performance, particularly with regard to variability in lane position (i.e., RMS). This study sheds light on key issues regarding injury prevention, with the intent of providing pediatric care providers with the knowledge to inform teen drivers of risks associated with distracted driving which will ultimately result in reduced rates of motor vehicle crashes and concomitant injuries. PMID:26049214

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

PubMed Central

Moriarity, Branden S; Otto, George M; Rahrmann, Eric P; Rathe, Susan K; Wolf, Natalie K; Weg, Madison T; Manlove, Luke A; LaRue, Rebecca S; Temiz, Nuri A; Molyneux, Sam D; Choi, Kwangmin; Holly, Kevin J; Sarver, Aaron L; Scott, Milcah C; Forster, Colleen L; Modiano, Jaime F; Khanna, Chand; Hewitt, Stephen M; Khokha, Rama; Yang, Yi; Gorlick, Richard; Dyer, Michael A; Largaespada, David A

2016-01-01

Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma. PMID:25961939

The evolution of sensory divergence in the context of limited gene flow in the bumblebee bat

PubMed Central

Puechmaille, Sébastien J.; Gouilh, Meriadeg Ar; Piyapan, Piyathip; Yokubol, Medhi; Mie, Khin Mie; Bates, Paul J.; Satasook, Chutamas; Nwe, Tin; Bu, Si Si Hla; Mackie, Iain J.; Petit, Eric J.; Teeling, Emma C.

2011-01-01

The sensory drive theory of speciation predicts that populations of the same species inhabiting different environments can differ in sensory traits, and that this sensory difference can ultimately drive speciation. However, even in the best-known examples of sensory ecology driven speciation, it is uncertain whether the variation in sensory traits is the cause or the consequence of a reduction in levels of gene flow. Here we show strong genetic differentiation, no gene flow and large echolocation differences between the allopatric Myanmar and Thai populations of the world's smallest mammal, Craseonycteris thonglongyai, and suggest that geographic isolation most likely preceded sensory divergence. Within the geographically continuous Thai population, we show that geographic distance has a primary role in limiting gene flow rather than echolocation divergence. In line with sensory-driven speciation models, we suggest that in C. thonglongyai, limited gene flow creates the suitable conditions that favour the evolution of sensory divergence via local adaptation. PMID:22146392

Does Talking on a Cell Phone, With a Passenger, or Dialing Affect Driving Performance? An Updated Systematic Review and Meta-Analysis of Experimental Studies.

PubMed

Caird, Jeff K; Simmons, Sarah M; Wiley, Katelyn; Johnston, Kate A; Horrey, William J

2018-02-01

Objective An up-to-date meta-analysis of experimental research on talking and driving is needed to provide a comprehensive, empirical, and credible basis for policy, legislation, countermeasures, and future research. Background The effects of cell, mobile, and smart phone use on driving safety continues to be a contentious societal issue. Method All available studies that measured the effects of cell phone use on driving were identified through a variety of search methods and databases. A total of 93 studies containing 106 experiments met the inclusion criteria. Coded independent variables included conversation target (handheld, hands-free, and passenger), setting (laboratory, simulation, or on road), and conversation type (natural, cognitive task, and dialing). Coded dependent variables included reaction time, stimulus detection, lane positioning, speed, headway, eye movements, and collisions. Results The overall sample had 4,382 participants, with driver ages ranging from 14 to 84 years ( M = 25.5, SD = 5.2). Conversation on a handheld or hands-free phone resulted in performance costs when compared with baseline driving for reaction time, stimulus detection, and collisions. Passenger conversation had a similar pattern of effect sizes. Dialing while driving had large performance costs for many variables. Conclusion This meta-analysis found that cell phone and passenger conversation produced moderate performance costs. Drivers minimally compensated while conversing on a cell phone by increasing headway or reducing speed. A number of additional meta-analytic questions are discussed. Application The results can be used to guide legislation, policy, countermeasures, and future research.

Orthogonal control of expression mean and variance by epigenetic features at different genomic loci

DOE PAGES

Dey, Siddharth S.; Foley, Jonathan E.; Limsirichai, Prajit; ...

2015-05-05

While gene expression noise has been shown to drive dramatic phenotypic variations, the molecular basis for this variability in mammalian systems is not well understood. Gene expression has been shown to be regulated by promoter architecture and the associated chromatin environment. However, the exact contribution of these two factors in regulating expression noise has not been explored. Using a dual-reporter lentiviral model system, we deconvolved the influence of the promoter sequence to systematically study the contribution of the chromatin environment at different genomic locations in regulating expression noise. By integrating a large-scale analysis to quantify mRNA levels by smFISH andmore » protein levels by flow cytometry in single cells, we found that mean expression and noise are uncorrelated across genomic locations. Furthermore, we showed that this independence could be explained by the orthogonal control of mean expression by the transcript burst size and noise by the burst frequency. Finally, we showed that genomic locations displaying higher expression noise are associated with more repressed chromatin, thereby indicating the contribution of the chromatin environment in regulating expression noise.« less

Careful with That Axe, Gene, Genome Perturbation after a PEG-Mediated Protoplast Transformation in Fusarium verticillioides.

PubMed

Scala, Valeria; Grottoli, Alessandro; Aiese Cigliano, Riccardo; Anzar, Irantzu; Beccaccioli, Marzia; Fanelli, Corrado; Dall'Asta, Chiara; Battilani, Paola; Reverberi, Massimo; Sanseverino, Walter

2017-05-31

Fusarium verticillioides causes ear rot disease in maize and its contamination with fumonisins, mycotoxins harmful for humans and livestock. Lipids, and their oxidized forms, may drive the fate of this disease. In a previous study, we have explored the role of oxylipins in this interaction by deleting by standard transformation procedures a linoleate diol synthase-coding gene, lds1 , in F. verticillioides . A profound phenotypic diversity in the mutants generated has prompted us to investigate more deeply the whole genome of two lds1 -deleted strains. Bioinformatics analyses pinpoint significant differences in the genome sequences emerged between the wild type and the lds1 -mutants further than those trivially attributable to the deletion of the lds1 locus, such as single nucleotide polymorphisms, small deletion/insertion polymorphisms and structural variations. Results suggest that the effect of a (theoretically) punctual transformation event might have enhanced the natural mechanisms of genomic variability and that transformation practices, commonly used in the reverse genetics of fungi, may potentially be responsible for unexpected, stochastic and henceforth off-target rearrangements throughout the genome.

Careful with That Axe, Gene, Genome Perturbation after a PEG-Mediated Protoplast Transformation in Fusarium verticillioides

PubMed Central

Scala, Valeria; Grottoli, Alessandro; Aiese Cigliano, Riccardo; Anzar, Irantzu; Beccaccioli, Marzia; Fanelli, Corrado; Dall’Asta, Chiara; Battilani, Paola; Reverberi, Massimo; Sanseverino, Walter

2017-01-01

Fusarium verticillioides causes ear rot disease in maize and its contamination with fumonisins, mycotoxins harmful for humans and livestock. Lipids, and their oxidized forms, may drive the fate of this disease. In a previous study, we have explored the role of oxylipins in this interaction by deleting by standard transformation procedures a linoleate diol synthase-coding gene, lds1, in F. verticillioides. A profound phenotypic diversity in the mutants generated has prompted us to investigate more deeply the whole genome of two lds1-deleted strains. Bioinformatics analyses pinpoint significant differences in the genome sequences emerged between the wild type and the lds1-mutants further than those trivially attributable to the deletion of the lds1 locus, such as single nucleotide polymorphisms, small deletion/insertion polymorphisms and structural variations. Results suggest that the effect of a (theoretically) punctual transformation event might have enhanced the natural mechanisms of genomic variability and that transformation practices, commonly used in the reverse genetics of fungi, may potentially be responsible for unexpected, stochastic and henceforth off-target rearrangements throughout the genome. PMID:28561789

Gene duplication and fragment recombination drive functional diversification of a superfamily of cytoplasmic effectors in Phytophthora sojae.

PubMed

Shen, Danyu; Liu, Tingli; Ye, Wenwu; Liu, Li; Liu, Peihan; Wu, Yuren; Wang, Yuanchao; Dou, Daolong

2013-01-01

Phytophthora and other oomycetes secrete a large number of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling and necrosis inducing proteins (CRN), or Crinkler. Here, we first investigated the evolutionary patterns and mechanisms of CRN effectors in Phytophthora sojae and compared them to two other Phytophthora species. The genes encoding CRN effectors could be divided into 45 orthologous gene groups (OGG), and most OGGs unequally distributed in the three species, in which each underwent large number of gene gains or losses, indicating that the CRN genes expanded after species evolution in Phytophthora and evolved through pathoadaptation. The 134 expanded genes in P. sojae encoded family proteins including 82 functional genes and expressed at higher levels while the other 68 genes encoding orphan proteins were less expressed and contained 50 pseudogenes. Furthermore, we demonstrated that most expanded genes underwent gene duplication or/and fragment recombination. Three different mechanisms that drove gene duplication or recombination were identified. Finally, the expanded CRN effectors exhibited varying pathogenic functions, including induction of programmed cell death (PCD) and suppression of PCD through PAMP-triggered immunity or/and effector-triggered immunity. Overall, these results suggest that gene duplication and fragment recombination may be two mechanisms that drive the expansion and neofunctionalization of the CRN family in P. sojae, which aids in understanding the roles of CRN effectors within each oomycete pathogen.

Cognitive, sensory and physical factors enabling driving safety in older adults.

PubMed

Anstey, Kaarin J; Wood, Joanne; Lord, Stephen; Walker, Janine G

2005-01-01

We reviewed literature on cognitive, sensory, motor and physical factors associated with safe driving and crash risk in older adults with the goal of developing a model of factors enabling safe driving behaviour. Thirteen empirical studies reporting associations between cognitive, sensory, motor and physical factors and either self-reported crashes, state crash records or on-road driving measures were identified. Measures of attention, reaction time, memory, executive function, mental status, visual function, and physical function variables were associated with driving outcome measures. Self-monitoring was also identified as a factor that may moderate observed effects by influencing driving behavior. We propose that three enabling factors (cognition, sensory function and physical function/medical conditions) predict driving ability, but that accurate self-monitoring of these enabling factors is required for safe driving behaviour.

Climate variability drives population cycling and synchrony

Treesearch

Lars Y. Pomara; Benjamin Zuckerberg

2017-01-01

Aim There is mounting concern that climate change will lead to the collapse of cyclic population dynamics, yet the influence of climate variability on population cycling remains poorly understood. We hypothesized that variability in survival and fecundity, driven by climate variability at different points in the life cycle, scales up from...

Multiroller traction drive speed reducer: Evaluation for automotive gas turbine engine

NASA Technical Reports Server (NTRS)

Rohn, D. A.; Anderson, N. E.; Loewenthal, S. H.

1982-01-01

Tests were conducted on a nominal 14:1 fixed-ratio Nasvytis multiroller traction drive retrofitted as the speed reducer in an automotive gas turbine engine. Power turbine speeds of 45,000 rpm and a drive output power of 102 kW (137 hp) were reached. The drive operated under both variable roller loading (proportional to torque) and fixed roller loading (automatic loading mechanism locked). The drive operated smoothly and efficiently as the engine speed reducer. Engine specific fuel consumption with the traction speed reducer was comparable to that with the original helical gearset.

Functional conservation between rodents and chicken of regulatory sequences driving skeletal muscle gene expression in transgenic chickens

PubMed Central

2010-01-01

Background Regulatory elements that control expression of specific genes during development have been shown in many cases to contain functionally-conserved modules that can be transferred between species and direct gene expression in a comparable developmental pattern. An example of such a module has been identified at the rat myosin light chain (MLC) 1/3 locus, which has been well characterised in transgenic mouse studies. This locus contains two promoters encoding two alternatively spliced isoforms of alkali myosin light chain. These promoters are differentially regulated during development through the activity of two enhancer elements. The MLC3 promoter alone has been shown to confer expression of a reporter gene in skeletal and cardiac muscle in transgenic mice and the addition of the downstream MLC enhancer increased expression levels in skeletal muscle. We asked whether this regulatory module, sufficient for striated muscle gene expression in the mouse, would drive expression in similar domains in the chicken. Results We have observed that a conserved downstream MLC enhancer is present in the chicken MLC locus. We found that the rat MLC1/3 regulatory elements were transcriptionally active in chick skeletal muscle primary cultures. We observed that a single copy lentiviral insert containing this regulatory cassette was able to drive expression of a lacZ reporter gene in the fast-fibres of skeletal muscle in chicken in three independent transgenic chicken lines in a pattern similar to the endogenous MLC locus. Reporter gene expression in cardiac muscle tissues was not observed for any of these lines. Conclusions From these results we conclude that skeletal expression from this regulatory module is conserved in a genomic context between rodents and chickens. This transgenic module will be useful in future investigations of muscle development in avian species. PMID:20184756

Transposon mutagenesis identifies genes and cellular processes driving epithelial-mesenchymal transition in hepatocellular carcinoma

PubMed Central

Kodama, Takahiro; Newberg, Justin Y.; Kodama, Michiko; Rangel, Roberto; Yoshihara, Kosuke; Tien, Jean C.; Parsons, Pamela H.; Wu, Hao; Finegold, Milton J.; Copeland, Neal G.; Jenkins, Nancy A.

2016-01-01

Epithelial-mesenchymal transition (EMT) is thought to contribute to metastasis and chemoresistance in patients with hepatocellular carcinoma (HCC), leading to their poor prognosis. The genes driving EMT in HCC are not yet fully understood, however. Here, we show that mobilization of Sleeping Beauty (SB) transposons in immortalized mouse hepatoblasts induces mesenchymal liver tumors on transplantation to nude mice. These tumors show significant down-regulation of epithelial markers, along with up-regulation of mesenchymal markers and EMT-related transcription factors (EMT-TFs). Sequencing of transposon insertion sites from tumors identified 233 candidate cancer genes (CCGs) that were enriched for genes and cellular processes driving EMT. Subsequent trunk driver analysis identified 23 CCGs that are predicted to function early in tumorigenesis and whose mutation or alteration in patients with HCC is correlated with poor patient survival. Validation of the top trunk drivers identified in the screen, including MET (MET proto-oncogene, receptor tyrosine kinase), GRB2-associated binding protein 1 (GAB1), HECT, UBA, and WWE domain containing 1 (HUWE1), lysine-specific demethylase 6A (KDM6A), and protein-tyrosine phosphatase, nonreceptor-type 12 (PTPN12), showed that deregulation of these genes activates an EMT program in human HCC cells that enhances tumor cell migration. Finally, deregulation of these genes in human HCC was found to confer sorafenib resistance through apoptotic tolerance and reduced proliferation, consistent with recent studies showing that EMT contributes to the chemoresistance of tumor cells. Our unique cell-based transposon mutagenesis screen appears to be an excellent resource for discovering genes involved in EMT in human HCC and potentially for identifying new drug targets. PMID:27247392

Assessing the driving performance of older adult drivers: on-road versus simulated driving.

PubMed

Lee, Hoe C; Cameron, Don; Lee, Andy H

2003-09-01

To validate a laboratory-based driving simulator in measuring on-road driving performance, 129 older adult drivers were assessed with both the simulator and an on-road test. The driving performance of the participants was gauged by appropriate and reliable age-specific assessment criteria, which were found to be negatively correlated with age. Using principal component analysis, two performance indices were developed from the criteria to represent the overall performance in simulated driving and the on-road assessment. There was significant positive association between the two indices, with the simulated driving performance index explaining over two-thirds of the variability of the on-road driving performance index, after adjustment for age and gender of the drivers. The results supported the validity of the driving simulator and it is a safer and more economical method than the on-road testing to assess the driving performance of older adult drivers.

Nitrous oxide emissions and denitrification rates: A blueprint for smart management and remediation of agricultural landscapes.

NASA Astrophysics Data System (ADS)

Tomasek, A.; Hondzo, M.; Kozarek, J. L.

2015-12-01

Anthropogenic activities have greatly altered the global nitrogen cycle, especially in the agriculturally dominated Midwest, with severe consequences on human and aquatic health. Complete microbial denitrification can be viewed as a nitrogen sink, converting soluble nitrate into inert nitrogen gas. This research aims to quantify and correlate the driving parameters in microbial denitrification and explore the relationship to the abundance of denitrifying genes and the microbial communities at these sites. Denitrifying genes for each step in the denitrification process have been quantified. Data from a field site in Southern Minnesota has been collected throughout the season for two years enabling investigation into the temporal variability of denitrification. Data was collected at two cross-sections across the channel to determine the effect of bank location and moisture content on denitrification. Data were collected in an experimental basin in the summer of 2015 to determine the effect of flooding and benthic organic matter content and quality on microbial denitrification and nitrous oxide production. Four sediment types were investigated in three different flood regimes. After each raising or lowering of the water level, soil cores were taken to determine soil characteristics, the potential denitrification using the denitrification enzyme activity method, nitrous oxide production using a static core method, and the denitrifying gene abundance. Chambers were also deployed over each soil amendment in each flood regime to determine the nitrous oxide production over time. Results from these studies will convey a more complete explanation of denitrification and nitrous oxide production under varying environmental conditions. By determining the driving parameters for microbial denitrification, denitrification hot spots and hot moments can be created and enhanced. One potential consequence of increased denitrification is the possibility of incomplete denitrification resulting in the release of nitrous oxide, a greenhouse gas with 300 times the warming potential of carbon dioxide. The investigation of nitrous oxide emissions and correlation to denitrification rates will facilitate smart management and remediation efforts of agricultural landscapes.

Driving towards ecotechnologies.

PubMed

Najjar, Devora A; Normandin, Avery M; Strait, Elizabeth A; Esvelt, Kevin M

2017-12-01

The prospect of using genetic methods to target vector, parasite, and reservoir species offers tremendous potential benefits to public health, but the use of genome editing to alter the shared environment will require special attention to public perception and community governance in order to benefit the world. Public skepticism combined with the media scrutiny of gene drive systems could easily derail unpopular projects entirely, especially given the potential for trade barriers to be raised against countries that employ self-propagating gene drives. Hence, open and community-guided development of thoughtfully chosen applications is not only the most ethical approach, but also the most likely to overcome the economic, social, and diplomatic barriers. Here we review current and past attempts to alter ecosystems using biological methods, identify key determinants of social acceptance, and chart a stepwise path for developers towards safe and widely supported use.

Bioluminescence-based system for rapid detection of natural transformation.

PubMed

Santala, Ville; Karp, Matti; Santala, Suvi

2016-07-01

Horizontal gene transfer plays a significant role in bacterial evolution and has major clinical importance. Thus, it is vital to understand the mechanisms and kinetics of genetic transformations. Natural transformation is the driving mechanism for horizontal gene transfer in diverse genera of bacteria. Our study introduces a simple and rapid method for the investigation of natural transformation. This highly sensitive system allows the detection of a transformation event directly from a bacterial population without any separation step or selection of cells. The system is based on the bacterial luciferase operon from Photorhabdus luminescens The studied molecular tools consist of the functional modules luxCDE and luxAB, which involve a replicative plasmid and an integrative gene cassette. A well-established host for bacterial genetic investigations, Acinetobacter baylyi ADP1, is used as the model bacterium. We show that natural transformation followed by homologous recombination or plasmid recircularization can be readily detected in both actively growing and static biofilm-like cultures, including very rare transformation events. The system allows the detection of natural transformation within 1 h of introducing sample DNA into the culture. The introduced method provides a convenient means to study the kinetics of natural transformation under variable conditions and perturbations. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Statistical Models for Predicting Automobile Driving Postures for Men and Women Including Effects of Age.

PubMed

Park, Jangwoon; Ebert, Sheila M; Reed, Matthew P; Hallman, Jason J

2016-03-01

Previously published statistical models of driving posture have been effective for vehicle design but have not taken into account the effects of age. The present study developed new statistical models for predicting driving posture. Driving postures of 90 U.S. drivers with a wide range of age and body size were measured in laboratory mockup in nine package conditions. Posture-prediction models for female and male drivers were separately developed by employing a stepwise regression technique using age, body dimensions, vehicle package conditions, and two-way interactions, among other variables. Driving posture was significantly associated with age, and the effects of other variables depended on age. A set of posture-prediction models is presented for women and men. The results are compared with a previously developed model. The present study is the first study of driver posture to include a large cohort of older drivers and the first to report a significant effect of age. The posture-prediction models can be used to position computational human models or crash-test dummies for vehicle design and assessment. © 2015, Human Factors and Ergonomics Society.

Effects of age and the use of hands-free cellular phones on driving behavior and task performance.

PubMed

Liu, Yung-Ching; Ou, Yang-Kun

2011-12-01

This study used a driving simulator to investigate the effect of using a Bluetooth hands-free cellular phone earpiece on the driving behavior of two age groups. Forty-eight participants (24 aged 20-26 and 24 aged 65-73) were examined to assess their performance on the following divided-attention tasks under 2 driving load conditions (high and low): (1) attempting to maintain the speed limit and (2) using a cellular phone while driving. The length of the call conversation (long vs. short) and the conversational content (complex vs. simple) were manipulated as within-subject independent variables. The driving behavior of the participants, their task reaction times and accuracy, and subjective ratings were collected as dependent variables. The results indicate that under low driving loads, short talk times, and simple conversational content, the driving behavior of the participants showed low variance in the vehicle's mean speed. In contrast, complex conversation had a significantly negative impact on driving behavior. Notably, under a low driving load, motorists' driving behaviors, measured in lateral acceleration, caused significantly smaller variance in complex conversations compared to no call and simple conversations. The use of a hands-free cellular phone affected the performance (acceleration, lane deviation, reaction time, and accuracy) of older drivers significantly more than younger drivers. While performing divided attention tasks, the accuracy of the older drivers was 66.3 percent and that of the younger drivers was 96.3 percent. Although this study did not find a clear impact of cellular phone use on the driving behavior of younger drivers, their divided-attention task reaction times and accuracy were better under no-call than calling conditions. This study indicates that the use of hands-free cellular phones could significantly affect the safety of driving among the older and present risks, although lesser, for younger drivers.

Prevention of traffic accidents: the assessment of perceptual-motor alterations before obtaining a driving license. A longitudinal study of the first years of driving.

PubMed

Martín, Fermina Sánchez; Estévez, M Angeles Quiroga

2005-03-01

A longitudinal study was designed with two objectives: first, to provide a wide cognitive, personality and social description of new drivers before they started to drive cars. Second, to examine the relationship between cognitive and other characteristics drivers had before obtaining their driving license and the number and type of accidents they were involved in during the first years as drivers. The longitudinal study started in 1997 and ended in 2002. The first assessment was made up of 241 individuals at the time they enrolled on the driving course. The follow-up evaluation in the year 2002 was carried out on 144 components of the initial sample after five years driving. Age, gender and education level were matched to represent the population of Spain. Participants were assessed with the Bender Test for visual-motor ability, the B101 Test for practical intelligence, the B19 Test for visual-motor bi-manual coordination, and the TKK-1108 for speed anticipation. Personality was also evaluated with the Rorschach test and the PSY (Psychological Assessment Questionnaire). Five years later, a new examination of all those variables was made as well as a structured interview with each participant in order to collect data relating to significant life events during that time, driving habits, opinions in relation to certain traffic rules and information on accidents, incidents and/or sanctions. Serious and/or minor accidents are concentrated on a few drivers. Accidentality is not related to gender or age, but educational level is related to serious accidents. The number of accidents (severe or minor ones) cannot be predicted if considered as a continuous variable, but it is possible if considered as a discrete variable. In this case two different cognitive profiles account for the number and type of accidents. The number and type of accidents during their first years of driving are related to the cognitive profiles of drivers assessed before they obtained their driving license.

Mate choice theory and the mode of selection in sexual populations.

PubMed

Carson, Hampton L

2003-05-27

Indirect new data imply that mate and/or gamete choice are major selective forces driving genetic change in sexual populations. The system dictates nonrandom mating, an evolutionary process requiring both revised genetic theory and new data on heritability of characters underlying Darwinian fitness. Successfully reproducing individuals represent rare selections from among vigorous, competing survivors of preadult natural selection. Nonrandom mating has correlated demographic effects: reduced effective population size, inbreeding, low gene flow, and emphasis on deme structure. Characters involved in choice behavior at reproduction appear based on quantitative trait loci. This variability serves selection for fitness within the population, having only an incidental relationship to the origin of genetically based reproductive isolation between populations. The claim that extensive hybridization experiments with Drosophila indicate that selection favors a gradual progression of "isolating mechanisms" is flawed, because intra-group random mating is assumed. Over deep time, local sexual populations are strong, independent genetic systems that use rich fields of variable polygenic components of fitness. The sexual reproduction system thus particularizes, in small subspecific populations, the genetic basis of the grand adaptive sweep of selective evolutionary change, much as Darwin proposed.

Effects of personality on risky driving behavior and accident involvement for Chinese drivers.

PubMed

Yang, Jiaoyan; Du, Feng; Qu, Weina; Gong, Zhun; Sun, Xianghong

2013-01-01

Motor vehicle accidents are the leading cause of injury-related fatalities in China and pose the most serious threat to driving safety. Driver personality is considered as an effective predictor for risky driving behavior and accident liability. Previous studies have focused on the relationship between personality and risky driving behavior, but only a few of them have explored the effects of personality variables on accident involvement. In addition, few studies have examined the effects of personality on Chinese drivers' risky driving and accident involvement. The present study aimed to examine the effects of personality variables on Chinese drivers' unsafe driving behaviors and accident involvement. Two hundred and twenty-four Chinese drivers aged 20 to 50 were required to complete questionnaires assessing their personality traits (anger, sensation-seeking, altruism, and normlessness), risky driving behaviors (aggressive violations, ordinary violations), and accident involvement (all accidents, serious accidents, at-fault accidents). Multivariate regression analyses, adjusting for gender, age, and overall mileage, were conducted to identify the personality traits related to risky driving behaviors and accident involvement. Participants' personality traits were found to be significantly correlated with both risky driving behavior and accident involvement. Specifically, the traits of anger and normlessness were effective predictors for aggressive violations. The traits of anger, sensation-seeking, normlessness, and altruism were effective predictors for ordinary violations. Moreover, altruism and normlessness were significant predictors for the total number of accidents participants had during the past 3 years. Consistent with previous studies, the present study revealed that personality traits play an important role in predicting Chinese drivers' risky driving behaviors. In addition, Chinese drivers' personality characteristics were also associated with accident involvement.

Speed control: cogs and gears that drive the circadian clock.

PubMed

Zheng, Xiangzhong; Sehgal, Amita

2012-09-01

In most organisms, an intrinsic circadian (~24-h) timekeeping system drives rhythms of physiology and behavior. Within cells that contain a circadian clock, specific transcriptional activators and repressors reciprocally regulate each other to generate a basic molecular oscillator. A mismatch of the period generated by this oscillator with the external environment creates circadian disruption, which can have adverse effects on neural function. Although several clock genes have been extensively characterized, a fundamental question remains: how do these genes work together to generate a ~24-h period? Period-altering mutations in clock genes can affect any of multiple regulated steps in the molecular oscillator. In this review, we examine the regulatory mechanisms that contribute to setting the pace of the circadian oscillator. Copyright © 2012 Elsevier Ltd. All rights reserved.

The role of effort in moderating the anxiety-performance relationship: Testing the prediction of processing efficiency theory in simulated rally driving.

PubMed

Wilson, Mark; Smith, Nickolas C; Chattington, Mark; Ford, Mike; Marple-Horvat, Dilwyn E

2006-11-01

We tested some of the key predictions of processing efficiency theory using a simulated rally driving task. Two groups of participants were classified as either dispositionally high or low anxious based on trait anxiety scores and trained on a simulated driving task. Participants then raced individually on two similar courses under counterbalanced experimental conditions designed to manipulate the level of anxiety experienced. The effort exerted on the driving tasks was assessed though self-report (RSME), psychophysiological measures (pupil dilation) and visual gaze data. Efficiency was measured in terms of efficiency of visual processing (search rate) and driving control (variability of wheel and accelerator pedal) indices. Driving performance was measured as the time taken to complete the course. As predicted, increased anxiety had a negative effect on processing efficiency as indexed by the self-report, pupillary response and variability of gaze data. Predicted differences due to dispositional levels of anxiety were also found in the driving control and effort data. Although both groups of drivers performed worse under the threatening condition, the performance of the high trait anxious individuals was affected to a greater extent by the anxiety manipulation than the performance of the low trait anxious drivers. The findings suggest that processing efficiency theory holds promise as a theoretical framework for examining the relationship between anxiety and performance in sport.

Driving Safety after Spinal Surgery: A Systematic Review

PubMed Central

Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-01-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving. PMID:28443178

Driving Safety after Spinal Surgery: A Systematic Review.

PubMed

Alhammoud, Abduljabbar; Alkhalili, Kenan; Hannallah, Jack; Ibeche, Bashar; Bajammal, Sohail; Baco, Abdul Moeen

2017-04-01

This study aimed to assess driving reaction times (DRTs) after spinal surgery to establish a timeframe for safe resumption of driving by the patient postoperatively. The MEDLINE and Google Scholar databases were analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement for clinical studies that investigated changes in DRTs following cervical and lumbar spinal surgery. Changes in DRTs and patients' clinical presentation, pathology, anatomical level affected, number of spinal levels involved, type of intervention, pain level, and driving skills were assessed. The literature search identified 12 studies that investigated postoperative DRTs. Six studies met the inclusion criteria; five studies assessed changes in DRT after lumbar spine surgery and two studies after cervical spina surgery. The spinal procedures were selective nerve root block, anterior cervical discectomy and fusion, and lumbar fusion and/ordecompression. DRTs exhibited variable responses to spinal surgery and depended on the patients' clinical presentation, spinal level involved, and type of procedure performed. The evidence regarding the patients' ability to resume safe driving after spinal surgery is scarce. Normalization of DRT or a return of DRT to pre-spinal intervention level is a widely accepted indicator for safe driving, with variable levels of statistical significance owing to multiple confounding factors. Considerations of the type of spinal intervention, pain level, opioid consumption, and cognitive function should be factored in the assessment of a patient's ability to safely resume driving.

Mechanisms driving variability in the ocean forcing of Pine Island Glacier

PubMed Central

Webber, Benjamin G. M.; Heywood, Karen J.; Stevens, David P.; Dutrieux, Pierre; Abrahamsen, E. Povl; Jenkins, Adrian; Jacobs, Stanley S.; Ha, Ho Kyung; Lee, Sang Hoon; Kim, Tae Wan

2017-01-01

Pine Island Glacier (PIG) terminates in a rapidly melting ice shelf, and ocean circulation and temperature are implicated in the retreat and growing contribution to sea level rise of PIG and nearby glaciers. However, the variability of the ocean forcing of PIG has been poorly constrained due to a lack of multi-year observations. Here we show, using a unique record close to the Pine Island Ice Shelf (PIIS), that there is considerable oceanic variability at seasonal and interannual timescales, including a pronounced cold period from October 2011 to May 2013. This variability can be largely explained by two processes: cumulative ocean surface heat fluxes and sea ice formation close to PIIS; and interannual reversals in ocean currents and associated heat transport within Pine Island Bay, driven by a combination of local and remote forcing. Local atmospheric forcing therefore plays an important role in driving oceanic variability close to PIIS. PMID:28211473

Searching for a Spore killer: A meiotic drive element in Neurospora fungi

USDA-ARS?s Scientific Manuscript database

Mendelian inheritance predicts that different alleles of the same gene will have an equal chance of being transmitted to the next generation. However, meiotic drive is a phenomenon where certain alleles evolve the ability to bias transmission in their own favor. In this study we are investigating a ...

Identification of a set of genes showing regionally enriched expression in the mouse brain

PubMed Central

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa LC; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven JM

2008-01-01

Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression. PMID:18625066

Identification of a set of genes showing regionally enriched expression in the mouse brain.

PubMed

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa L C; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven J M

2008-07-14

The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

Driving habits and risk exposure in older drivers: lessons learned from the implementation of a self-regulation curriculum.

PubMed

Jones, Vanya C; Cho, Juhee; Abendschoen-Milani, Jackie; Gielen, Andrea

2011-10-01

This article describes the development and pilot testing of Seniors on the MOVE (Mature Operators Vehicular Education), a safe driving education program for older adults. The study aims are to describe driving experiences and habits of a community sample of older drivers and to determine whether the program reduces their driving risk exposures. A 2-group randomized design was used. Fifty-eight participants with an average age of 70 were randomly assigned to the MOVE program or a no treatment control group. MOVE is a 4-session program designed to help older drivers better understand and utilize self-regulation skills for safer driving. Baseline and 4-week follow-up questionnaires were completed by both groups, after which the control group received the MOVE program. In the total sample, 14 percent reported having ever been in a traffic crash where someone was injured, and 10 percent reported having received a traffic citation in the past 6 months. Almost one half of the sample (47%) reported thinking about reducing the amount of driving done at night. Nearly one third were thinking about reducing the amount of driving done in unfamiliar places (32%) and the number of miles driven each week (30%). Participants reported most frequently driving between 2 to 10 miles from home, on local roadways, and between 9:00 am and 4:00 pm. Based on responses to items that measured such driving habits, a risk exposure score was created by combining driving exposure variables. Participants were categorized into lower and higher driving risk exposure groups at baseline and follow-up. There were no statistical differences in changes in higher or lower risk driving exposure variables when comparing the 2 groups. Although the impact of this program on reported driving behaviors yielded null results, descriptions of older drivers' habits and plans are informative. Because many participants were thinking about making changes to their driving habits, and many already had, the need for more effective self-regulation driving safety programs to help with this process is clear.

Biasogram: Visualization of Confounding Technical Bias in Gene Expression Data

PubMed Central

Krzystanek, Marcin; Szallasi, Zoltan; Eklund, Aron C.

2013-01-01

Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may have been driven by a confounding technical variable. This approach can be used as a quality control step to identify data sets that are likely to yield false positive results. PMID:23613961

That's close enough--a threshold effect of time headway on the experience of risk, task difficulty, effort, and comfort.

PubMed

Lewis-Evans, Ben; De Waard, Dick; Brookhuis, Karel A

2010-11-01

Subjective impressions of task difficulty, risk, effort, and comfort are key variables of several theories of driver behaviour. A point of difference between many of these theories is not only the importance of these variables, but also whether they are continuously present and monitored or only experienced by individuals at certain critical points in the driving task. Both a threshold relationship and evidence of constant monitoring of risk and task difficulty have been found for speed choice. In light of these conflicting findings this study seeks to examine a different part of the driving task, the choice of time headway. Participants (N=40, aged 19 to 30) drove in a simulator behind a vehicle travelling at 50 km/h at set time headways ranging from 0.5 seconds to 4.0 seconds. After each drive ratings of task difficulty, risk, comfort, and effort were collected. In addition participants were asked to drive at the time headway they preferred. In order to assess familiarity participants also drove on both the left and right hand side of the road and the role of driving experience was also examined. The results show support for a threshold awareness of task difficulty, risk, effort, and comfort in relation to time headway. Participant's ratings of these variables tended to be low or nil at large time headways, but then around the 2.0 second mark began to noticeably increase. Feelings of task difficulty, risk, and effort were also found to be highly correlated with each other. No effect of driving experience or side of the road was found. 2010 Elsevier Ltd. All rights reserved.

Lengths of Orthologous Prokaryotic Proteins Are Affected by Evolutionary Factors

PubMed Central

Tatarinova, Tatiana; Dien Bard, Jennifer; Cohen, Irit

2015-01-01

Proteins of the same functional family (for example, kinases) may have significantly different lengths. It is an open question whether such variation in length is random or it appears as a response to some unknown evolutionary driving factors. The main purpose of this paper is to demonstrate existence of factors affecting prokaryotic gene lengths. We believe that the ranking of genomes according to lengths of their genes, followed by the calculation of coefficients of association between genome rank and genome property, is a reasonable approach in revealing such evolutionary driving factors. As we demonstrated earlier, our chosen approach, Bubble-sort, combines stability, accuracy, and computational efficiency as compared to other ranking methods. Application of Bubble Sort to the set of 1390 prokaryotic genomes confirmed that genes of Archaeal species are generally shorter than Bacterial ones. We observed that gene lengths are affected by various factors: within each domain, different phyla have preferences for short or long genes; thermophiles tend to have shorter genes than the soil-dwellers; halophiles tend to have longer genes. We also found that species with overrepresentation of cytosines and guanines in the third position of the codon (GC3 content) tend to have longer genes than species with low GC3 content. PMID:26114113

Lengths of Orthologous Prokaryotic Proteins Are Affected by Evolutionary Factors.

PubMed

Tatarinova, Tatiana; Salih, Bilal; Dien Bard, Jennifer; Cohen, Irit; Bolshoy, Alexander

2015-01-01

Proteins of the same functional family (for example, kinases) may have significantly different lengths. It is an open question whether such variation in length is random or it appears as a response to some unknown evolutionary driving factors. The main purpose of this paper is to demonstrate existence of factors affecting prokaryotic gene lengths. We believe that the ranking of genomes according to lengths of their genes, followed by the calculation of coefficients of association between genome rank and genome property, is a reasonable approach in revealing such evolutionary driving factors. As we demonstrated earlier, our chosen approach, Bubble-sort, combines stability, accuracy, and computational efficiency as compared to other ranking methods. Application of Bubble Sort to the set of 1390 prokaryotic genomes confirmed that genes of Archaeal species are generally shorter than Bacterial ones. We observed that gene lengths are affected by various factors: within each domain, different phyla have preferences for short or long genes; thermophiles tend to have shorter genes than the soil-dwellers; halophiles tend to have longer genes. We also found that species with overrepresentation of cytosines and guanines in the third position of the codon (GC3 content) tend to have longer genes than species with low GC3 content.

Soil environment is a key driver of adaptation in Medicago truncatula: new insights from landscape genomics.

PubMed

Guerrero, Jimena; Andrello, Marco; Burgarella, Concetta; Manel, Stephanie

2018-07-01

Spatial differences in environmental selective pressures interact with the genomes of organisms, ultimately leading to local adaptation. Landscape genomics is an emergent research area that uncovers genome-environment associations, thus allowing researchers to identify candidate loci for adaptation to specific environmental variables. In the present study, we used latent factor mixed models (LFMMs) and Moran spectral outlier detection/randomization (MSOD-MSR) to identify candidate loci for adaptation to 10 environmental variables (climatic, soil and atmospheric) among 43 515 single nucleotide polymorphisms (SNPs) from 202 accessions of the model legume Medicago truncatula. Soil variables were associated with a large number of candidate loci identified through both LFMMs and MSOD-MSR. Genes tagged by candidate loci associated with drought and salinity are involved in the response to biotic and abiotic stresses, while those tagged by candidates associated with soil nitrogen and atmospheric nitrogen, participate in the legume-rhizobia symbiosis. Candidate SNPs identified through both LFMMs and MSOD-MSR explained up to 56% of variance in flowering traits. Our findings highlight the importance of soil in driving adaptation in the system and elucidate the basis of evolutionary potential of M. truncatula to respond to global climate change and anthropogenic disruption of the nitrogen cycle. © 2018 The Authors New Phytologist © 2018 New Phytologist Trust.

The effects of text messaging on young drivers.

PubMed

Hosking, Simon G; Young, Kristie L; Regan, Michael A

2009-08-01

This study investigated the effects of using a cell phone to retrieve and send text messages on the driving performance of young novice drivers. Young drivers are particularly susceptible to driver distraction and have an increased risk of distraction-related crashes. Distractions from in-vehicle devices, particularly, those that require manual input, are known to cause decrements in driving performance. Twenty young novice drivers used a cell phone to retrieve and send text messages while driving a simulator. The amount of time that drivers spent not looking at the road when text messaging was up to approximately 400% greater than that recorded in baseline (notext-messaging) conditions. Furthermore, drivers' variability in lane position increased up to approximately 50%, and missed lane changes increased 140%. There was also an increase of up to approximately 150% in drivers' variability in following distances to lead vehicles. Previous research has shown that the risk of crashing while dialing a handheld device, such as when text messaging and driving, is more than double that of conversing on a cell phone. The present study has identified the detrimental effects of text messaging on driving performance that may underlie such increased crash risk. More effective road safety measures are needed to prevent and mitigate the adverse effects on driving performance of using cell phones to retrieve and send text messages.

The selfish Segregation Distorter gene complex of Drosophila melanogaster.

PubMed

Larracuente, Amanda M; Presgraves, Daven C

2012-09-01

Segregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD(+) spermatids so that SD/SD(+) males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily "selfish," enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci--the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)--and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd-RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd-RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.

Genomic context drives transcription of insertion sequences in the bacterial endosymbiont Wolbachia wVulC.

PubMed

Cerveau, Nicolas; Gilbert, Clément; Liu, Chao; Garrett, Roger A; Grève, Pierre; Bouchon, Didier; Cordaux, Richard

2015-06-10

Transposable elements (TEs) are DNA pieces that are present in almost all the living world at variable genomic density. Due to their mobility and density, TEs are involved in a large array of genomic modifications. In eukaryotes, TE expression has been studied in detail in several species. In prokaryotes, studies of IS expression are generally linked to particular copies that induce a modification of neighboring gene expression. Here we investigated global patterns of IS transcription in the Alphaproteobacterial endosymbiont Wolbachia wVulC, using both RT-PCR and bioinformatic analyses. We detected several transcriptional promoters in all IS groups. Nevertheless, only one of the potentially functional IS groups possesses a promoter located upstream of the transposase gene, that could lead up to the production of a functional protein. We found that the majority of IS groups are expressed whatever their functional status. RT-PCR analyses indicate that the transcription of two IS groups lacking internal promoters upstream of the transposase start codon may be driven by the genomic environment. We confirmed this observation with the transcription analysis of individual copies of one IS group. These results suggest that the genomic environment is important for IS expression and it could explain, at least partly, copy number variability of the various IS groups present in the wVulC genome and, more generally, in bacterial genomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Prioritizing individual genetic variants after kernel machine testing using variable selection.

PubMed

He, Qianchuan; Cai, Tianxi; Liu, Yang; Zhao, Ni; Harmon, Quaker E; Almli, Lynn M; Binder, Elisabeth B; Engel, Stephanie M; Ressler, Kerry J; Conneely, Karen N; Lin, Xihong; Wu, Michael C

2016-12-01

Kernel machine learning methods, such as the SNP-set kernel association test (SKAT), have been widely used to test associations between traits and genetic polymorphisms. In contrast to traditional single-SNP analysis methods, these methods are designed to examine the joint effect of a set of related SNPs (such as a group of SNPs within a gene or a pathway) and are able to identify sets of SNPs that are associated with the trait of interest. However, as with many multi-SNP testing approaches, kernel machine testing can draw conclusion only at the SNP-set level, and does not directly inform on which one(s) of the identified SNP set is actually driving the associations. A recently proposed procedure, KerNel Iterative Feature Extraction (KNIFE), provides a general framework for incorporating variable selection into kernel machine methods. In this article, we focus on quantitative traits and relatively common SNPs, and adapt the KNIFE procedure to genetic association studies and propose an approach to identify driver SNPs after the application of SKAT to gene set analysis. Our approach accommodates several kernels that are widely used in SNP analysis, such as the linear kernel and the Identity by State (IBS) kernel. The proposed approach provides practically useful utilities to prioritize SNPs, and fills the gap between SNP set analysis and biological functional studies. Both simulation studies and real data application are used to demonstrate the proposed approach. © 2016 WILEY PERIODICALS, INC.

Origins of extrinsic variability in eukaryotic gene expression

NASA Astrophysics Data System (ADS)

Volfson, Dmitri; Marciniak, Jennifer; Blake, William J.; Ostroff, Natalie; Tsimring, Lev S.; Hasty, Jeff

2006-02-01

Variable gene expression within a clonal population of cells has been implicated in a number of important processes including mutation and evolution, determination of cell fates and the development of genetic disease. Recent studies have demonstrated that a significant component of expression variability arises from extrinsic factors thought to influence multiple genes simultaneously, yet the biological origins of this extrinsic variability have received little attention. Here we combine computational modelling with fluorescence data generated from multiple promoter-gene inserts in Saccharomyces cerevisiae to identify two major sources of extrinsic variability. One unavoidable source arising from the coupling of gene expression with population dynamics leads to a ubiquitous lower limit for expression variability. A second source, which is modelled as originating from a common upstream transcription factor, exemplifies how regulatory networks can convert noise in upstream regulator expression into extrinsic noise at the output of a target gene. Our results highlight the importance of the interplay of gene regulatory networks with population heterogeneity for understanding the origins of cellular diversity.

Origins of extrinsic variability in eukaryotic gene expression

NASA Astrophysics Data System (ADS)

Volfson, Dmitri; Marciniak, Jennifer; Blake, William J.; Ostroff, Natalie; Tsimring, Lev S.; Hasty, Jeff

2006-03-01

Variable gene expression within a clonal population of cells has been implicated in a number of important processes including mutation and evolution, determination of cell fates and the development of genetic disease. Recent studies have demonstrated that a significant component of expression variability arises from extrinsic factors thought to influence multiple genes in concert, yet the biological origins of this extrinsic variability have received little attention. Here we combine computational modeling with fluorescence data generated from multiple promoter-gene inserts in Saccharomyces cerevisiae to identify two major sources of extrinsic variability. One unavoidable source arising from the coupling of gene expression with population dynamics leads to a ubiquitous noise floor in expression variability. A second source which is modeled as originating from a common upstream transcription factor exemplifies how regulatory networks can convert noise in upstream regulator expression into extrinsic noise at the output of a target gene. Our results highlight the importance of the interplay of gene regulatory networks with population heterogeneity for understanding the origins of cellular diversity.

Diverse Cis-Regulatory Mechanisms Contribute to Expression Evolution of Tandem Gene Duplicates

PubMed Central

Baudouin-Gonzalez, Luís; Santos, Marília A; Tempesta, Camille; Sucena, Élio; Roch, Fernando; Tanaka, Kohtaro

2017-01-01

Abstract Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. We have directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 Ma. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, we show that they diverged from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. Our analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. We argue that our findings will encourage studying cis-regulatory evolution at the whole-locus level to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression. PMID:28961967

Emotional abilities as predictors of risky driving behavior among a cohort of middle aged drivers.

PubMed

Arnau-Sabatés, Laura; Sala-Roca, Josefina; Jariot-Garcia, Mercè

2012-03-01

The aim of this study is to analyze the relationship between emotional abilities and the influence of this relationship on self reported drivers' risky attitudes. The risky driving attitudes and emotional abilities of 177 future driving instructors were measured. The results demonstrate that risky attitudes correlate negatively with emotional abilities. Regression analysis showed that adaptability and interpersonal abilities explained the differences observed in the global risk attitude index. There were some differences in the specific risk factors. The variability observed in the speed and distraction and fatigue factors could also be explained by interpersonal and adaptability abilities. Nevertheless the tendency to take risks was explained by stress management and also interpersonal components. Emotional abilities have the weakest relation with alcohol and drugs factor, and in this case the variability observed was explained by the adaptability component. The results obtained highlight the importance take off including emotional abilities in prevention programs to reduce risky driving behaviors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Expression and Sequence Evolution of Aromatase cyp19a1 and Other Sexual Development Genes in East African Cichlid Fishes

PubMed Central

Böhne, Astrid; Heule, Corina; Boileau, Nicolas; Salzburger, Walter

2013-01-01

Sex determination mechanisms are highly variable across teleost fishes and sexual development is often plastic. Nevertheless, downstream factors establishing the two sexes are presumably conserved. Here, we study sequence evolution and gene expression of core genes of sexual development in a prime model system in evolutionary biology, the East African cichlid fishes. Using the available five cichlid genomes, we test for signs of positive selection in 28 genes including duplicates from the teleost whole-genome duplication, and examine the expression of these candidate genes in three cichlid species. We then focus on a particularly striking case, the A- and B-copies of the aromatase cyp19a1, and detect different evolutionary trajectories: cyp19a1A evolved under strong positive selection, whereas cyp19a1B remained conserved at the protein level, yet is subject to regulatory changes at its transcription start sites. Importantly, we find shifts in gene expression in both copies. Cyp19a1 is considered the most conserved ovary-factor in vertebrates, and in all teleosts investigated so far, cyp19a1A and cyp19a1B are expressed in ovaries and the brain, respectively. This is not the case in cichlids, where we find new expression patterns in two derived lineages: the A-copy gained a novel testis-function in the Ectodine lineage, whereas the B-copy is overexpressed in the testis of the speciest-richest cichlid group, the Haplochromini. This suggests that even key factors of sexual development, including the sex steroid pathway, are not conserved in fish, supporting the idea that flexibility in sexual determination and differentiation may be a driving force of speciation. PMID:23883521

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU.

PubMed

Depienne, Christel; Nava, Caroline; Keren, Boris; Heide, Solveig; Rastetter, Agnès; Passemard, Sandrine; Chantot-Bastaraud, Sandra; Moutard, Marie-Laure; Agrawal, Pankaj B; VanNoy, Grace; Stoler, Joan M; Amor, David J; Billette de Villemeur, Thierry; Doummar, Diane; Alby, Caroline; Cormier-Daire, Valérie; Garel, Catherine; Marzin, Pauline; Scheidecker, Sophie; de Saint-Martin, Anne; Hirsch, Edouard; Korff, Christian; Bottani, Armand; Faivre, Laurence; Verloes, Alain; Orzechowski, Christine; Burglen, Lydie; Leheup, Bruno; Roume, Joelle; Andrieux, Joris; Sheth, Frenny; Datar, Chaitanya; Parker, Michael J; Pasquier, Laurent; Odent, Sylvie; Naudion, Sophie; Delrue, Marie-Ange; Le Caignec, Cédric; Vincent, Marie; Isidor, Bertrand; Renaldo, Florence; Stewart, Fiona; Toutain, Annick; Koehler, Udo; Häckl, Birgit; von Stülpnagel, Celina; Kluger, Gerhard; Møller, Rikke S; Pal, Deb; Jonson, Tord; Soller, Maria; Verbeek, Nienke E; van Haelst, Mieke M; de Kovel, Carolien; Koeleman, Bobby; Monroe, Glen; van Haaften, Gijs; Attié-Bitach, Tania; Boutaud, Lucile; Héron, Delphine; Mignot, Cyril

2017-04-01

Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.

Peer Passenger Norms and Pressure: Experimental Effects on Simulated Driving Among Teenage Males.

PubMed

Bingham, C Raymond; Simons-Morton, Bruce G; Pradhan, Anuj K; Li, Kaigang; Almani, Farideh; Falk, Emily B; Shope, Jean T; Buckley, Lisa; Ouimet, Marie Claude; Albert, Paul S

2016-08-01

Serious crashes are more likely when teenage drivers have teenage passengers. One likely source of this increased risk is social influences on driving performance. This driving simulator study experimentally tested the effects of peer influence (i.e., risk-accepting compared to risk-averse peer norms reinforced by pressure) on the driving risk behavior (i.e., risky driving behavior and inattention to hazards) of male teenagers. It was hypothesized that peer presence would result in greater driving risk behavior (i.e., increased driving risk and reduced latent hazard anticipation), and that the effect would be greater when the peer was risk-accepting. Fifty-three 16- and 17-year-old male participants holding a provisional U.S., State of Michigan driver license were randomized to either a risk-accepting or risk-averse condition. Each participant operated a driving simulator while alone and separately with a confederate peer passenger. The simulator world included scenarios designed to elicit variation in driving risk behavior with a teen passenger present in the vehicle. Significant interactions of passenger presence (passenger present vs. alone) by risk condition (risk-accepting vs. risk-averse) were observed for variables measuring: failure to stop at yellow light intersections (Incident Rate Ratio (IRR)=2.16; 95% Confidence Interval [95CI]=1.06, 4.43); higher probability of overtaking (IRR=10.17; 95CI=1.43, 73.35); shorter left turn latency (IRR=0.43; 95CI=0.31,0.60); and, failure to stop at an intersection with an occluded stop sign (IRR=7.90; 95CI=2.06,30.35). In all cases, greater risky driving by participants was more likely with a risk-accepting passenger versus a risk-averse passenger present and a risk-accepting passenger present versus driving alone. Exposure of male teenagers to a risk-accepting confederate peer passenger who applied peer influence increased simulated risky driving behavior compared with exposure to a risk-averse confederate peer passenger or driving alone. These results are consistent with the contention that variability in teenage risky driving is in part explained by social influences.

Peer Passenger Norms and Pressure: Experimental Effects on Simulated Driving Among Teenage Males

PubMed Central

Bingham, C. Raymond; Simons-Morton, Bruce G.; Pradhan, Anuj K.; Li, Kaigang; Almani, Farideh; Falk, Emily B.; Shope, Jean T.; Buckley, Lisa; Ouimet, Marie Claude; Albert, Paul S.

2016-01-01

Objective Serious crashes are more likely when teenage drivers have teenage passengers. One likely source of this increased risk is social influences on driving performance. This driving simulator study experimentally tested the effects of peer influence (i.e., risk-accepting compared to risk-averse peer norms reinforced by pressure) on the driving risk behavior (i.e., risky driving behavior and inattention to hazards) of male teenagers. It was hypothesized that peer presence would result in greater driving risk behavior (i.e., increased driving risk and reduced latent hazard anticipation), and that the effect would be greater when the peer was risk-accepting. Methods Fifty-three 16- and 17-year-old male participants holding a provisional U.S., State of Michigan driver license were randomized to either a risk-accepting or risk-averse condition. Each participant operated a driving simulator while alone and separately with a confederate peer passenger. The simulator world included scenarios designed to elicit variation in driving risk behavior with a teen passenger present in the vehicle. Results Significant interactions of passenger presence (passenger present vs. alone) by risk condition (risk-accepting vs. risk-averse) were observed for variables measuring: failure to stop at yellow light intersections (Incident Rate Ratio (IRR)=2.16; 95% Confidence Interval [95CI]=1.06, 4.43); higher probability of overtaking (IRR=10.17; 95CI=1.43, 73.35); shorter left turn latency (IRR=0.43; 95CI=0.31,0.60); and, failure to stop at an intersection with an occluded stop sign (IRR=7.90; 95CI=2.06,30.35). In all cases, greater risky driving by participants was more likely with a risk-accepting passenger versus a risk-averse passenger present and a risk-accepting passenger present versus driving alone. Conclusions Exposure of male teenagers to a risk-accepting confederate peer passenger who applied peer influence increased simulated risky driving behavior compared with exposure to a risk-averse confederate peer passenger or driving alone. These results are consistent with the contention that variability in teenage risky driving is in part explained by social influences. PMID:27818610

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

Martel, Peter M.; Norris Cotton Cancer Center, Dartmouth Medical School; Bingham, Chad M.

Most breast cancers exhibit brisk lipogenesis, and require it for growth. S14 is a lipogenesis-related nuclear protein that is overexpressed in most breast cancers. Sterol response element-binding protein-1c (SREBP-1c) is required for induction of lipogenesis-related genes, including S14 and fatty acid synthase (FAS), in hepatocytes, and correlation of SREBP-1c and FAS expression suggested that SREBP-1c drives lipogenesis in tumors as well. We directly tested the hypothesis that SREBP-1c drives S14 expression and mediates lipogenic effects of progestin in T47D breast cancer cells. Dominant-negative SREBP-1c inhibited induction of S14 and FAS mRNAs by progestin, while active SREBP-1c induced without hormone andmore » superinduced in its presence. Changes in S14 mRNA were reflected in protein levels. A lag time and lack of progestin response elements indicated that S14 and FAS gene activation by progestin is indirect. Knockdown of S14 reduced, whereas overexpression stimulated, T47D cell growth, while nonlipogenic MCF10a mammary epithelial cells were not growth-inhibited. These data directly demonstrate that SREBP-1c drives S14 gene expression in breast cancer cells, and progestin magnifies that effect via an indirect mechanism. This supports the prediction, based on S14 gene amplification and overexpression in breast tumors, that S14 augments breast cancer cell growth and survival.« less

SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells.

PubMed

Liang, Yang; Tebaldi, Toma; Rejeski, Kai; Joshi, Poorval; Stefani, Giovanni; Taylor, Ashley; Song, Yuanbin; Vasic, Radovan; Maziarz, Jamie; Balasubramanian, Kunthavai; Ardasheva, Anastasia; Ding, Alicia; Quattrone, Alessandro; Halene, Stephanie

2018-06-01

Recurrent mutations in the splicing factor SRSF2 are associated with poor clinical outcomes in myelodysplastic syndromes (MDS). Their high frequency suggests these mutations drive oncogenesis, yet the molecular explanation for this process is unclear. SRSF2 mutations could directly affect pre-mRNA splicing of a vital gene product; alternatively, a whole network of gene products could be affected. Here we determine how SRSF2 mutations globally affect RNA binding and splicing in vivo using HITS-CLIP. Remarkably, the majority of differential binding events do not translate into alternative splicing of exons with SRSF2 P95H binding sites. Alternative splice alterations appear to be dominated by indirect effects. Importantly, SRSF2 P95H targets are enriched in RNA processing and splicing genes, including several members of the hnRNP and SR families of proteins, suggesting a "splicing-cascade" phenotype wherein mutation of a single splicing factor leads to widespread modifications in multiple RNA processing and splicing proteins. We show that splice alteration of HNRNPA2B1, a splicing factor differentially bound and spliced by SRSF2 P95H , impairs hematopoietic differentiation in vivo. Our data suggests a model whereby the recurrent mutations in splicing factors set off a cascade of gene regulatory events that together affect hematopoiesis and drive cancer.

Gene expression profiling of MYC-driven tumor signatures in porcine liver stem cells by transcriptome sequencing

USDA-ARS?s Scientific Manuscript database

It is now well-established that cancer stem cells (CSCs) drive tumor growth and that the cancer gene, c-Myc, plays a critical role in converting cells to CSCs. However, little is known about the genes that are induced and regulated by c-Myc to generate tumors, and, in particular, tumors of the live...

INDUCTION OF GENE EXPRESSION IN SHEEPSHEAD MINNOWS (CYPRINODON VARIEGATUS) TREATED WITH 17B-ESTRADIOL, DIETHYLSTILBESTROL, OR ETHINYLESTRADIOL: THE USE OF MRNA FINGERPRINTS AS AN INDICATOR OF GENE REGULATION

EPA Science Inventory

The recent interest in hormonally active environmental contaminants has sparked a drive to find sensitive methods to measure their effects on wildlife. A molecular-based assay has been developed to measure the induction of gene expression in sheepshead minnows (Cyprinodon variega...

Modeling the safety impacts of driving hours and rest breaks on truck drivers considering time-dependent covariates.

PubMed

Chen, Chen; Xie, Yuanchang

2014-12-01

Driving hours and rest breaks are closely related to driver fatigue, which is a major contributor to truck crashes. This study investigates the effects of driving hours and rest breaks on commercial truck driver safety. A discrete-time logistic regression model is used to evaluate the crash odds ratios of driving hours and rest breaks. Driving time is divided into 11 one hour intervals. These intervals and rest breaks are modeled as dummy variables. In addition, a Cox proportional hazards regression model with time-dependent covariates is used to assess the transient effects of rest breaks, which consists of a fixed effect and a variable effect. Data collected from two national truckload carriers in 2009 and 2010 are used. The discrete-time logistic regression result indicates that only the crash odds ratio of the 11th driving hour is statistically significant. Taking one, two, and three rest breaks can reduce drivers' crash odds by 68%, 83%, and 85%, respectively, compared to drivers who did not take any rest breaks. The Cox regression result shows clear transient effects for rest breaks. It also suggests that drivers may need some time to adjust themselves to normal driving tasks after a rest break. Overall, the third rest break's safety benefit is very limited based on the results of both models. The findings of this research can help policy makers better understand the impact of driving time and rest breaks and develop more effective rules to improve commercial truck safety. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Interactive risk analysis on crash injury severity at a mountainous freeway with tunnel groups in China.

PubMed

Huang, Helai; Peng, Yunying; Wang, Jie; Luo, Qizhang; Li, Xiang

2018-02-01

Traffic safety of freeways has attracted major concerns, especially for a mountainous freeway affected by adverse terrain conditions, constrained roadway geometry and complicated driving environments. On the basis of a comprehensive dataset collected from a mountainous freeway with a length of 61km but gathering 12 tunnels, this study seeks to examining the interactive effect of mountainous freeway alignment, driving behaviors, vehicle characteristics and environmental factors on crash severity. A classification and regression tree (CART) model is employed as it can deal with high-order interactions between explanatory variables. Results show that the driving behavior is the most important determinant for injury severity of mountainous freeway crashes, followed by the crash time, grade, curve radius and vehicle type. These variables, interacted with the factors of season and crash location, may largely account for the likelihood of high risk events which may result in severe crashes. Events associated with a notably higher probability of severe crashes include coach drivers involved in improper lane changing and other improper actions, drivers involved in speeding during afternoon or evening, drivers involved in speeding along large curve and straight segment during morning, noon or night, and drivers involved in fatigue while passing along the downgrade. Safety interventions to prevent severe crashes at the mountainous freeway include hierarchical supervision in terms of hazardous driving events, enhanced enforcement for speeding and fatigue driving, deployment of advanced driving assistance systems for fatigue driving warning, and cumulative driving time monitoring for long-distance-travel freight vehicles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer. | Office of Cancer Genomics

Cancer.gov

Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in TCGA datasets.

Modeling Gene-Wise Dependencies Improves the Identification of Drug Response Biomarkers in Cancer Studies | Office of Cancer Genomics

Cancer.gov

Recent advances in biomedical and sequencing technologies have revealed the genomic landscape of common forms of human cancer in unprecedented detail. Of the genes that drive tumorigenesis when altered, for most cancers it is believed that there exist a small number of “mountains” (genes altered at high frequencies across the population), and a much larger number of “hills” (much less frequently altered genes).

Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria

PubMed Central

Adler, Carolyn E; Seidel, Chris W; McKinney, Sean A; Sánchez Alvarado, Alejandro

2014-01-01

Planarian flatworms regenerate every organ after amputation. Adult pluripotent stem cells drive this ability, but how injury activates and directs stem cells into the appropriate lineages is unclear. Here we describe a single-organ regeneration assay in which ejection of the planarian pharynx is selectively induced by brief exposure of animals to sodium azide. To identify genes required for pharynx regeneration, we performed an RNAi screen of 356 genes upregulated after amputation, using successful feeding as a proxy for regeneration. We found that knockdown of 20 genes caused a wide range of regeneration phenotypes and that RNAi of the forkhead transcription factor FoxA, which is expressed in a subpopulation of stem cells, specifically inhibited regrowth of the pharynx. Selective amputation of the pharynx therefore permits the identification of genes required for organ-specific regeneration and suggests an ancient function for FoxA-dependent transcriptional programs in driving regeneration. DOI: http://dx.doi.org/10.7554/eLife.02238.001 PMID:24737865

Load capacity improvements in nucleic acid based systems using partially open feedback control.

PubMed

Kulkarni, Vishwesh; Kharisov, Evgeny; Hovakimyan, Naira; Kim, Jongmin

2014-08-15

Synthetic biology is facilitating novel methods and components to build in vivo and in vitro circuits to better understand and re-engineer biological networks. Recently, Kim and Winfree have synthesized a remarkably elegant network of transcriptional oscillators in vitro using a modular architecture of synthetic gene analogues and a few enzymes that, in turn, could be used to drive a variety of downstream circuits and nanodevices. However, these oscillators are sensitive to initial conditions and downstream load processes. Furthermore, the oscillations are not sustained since the inherently closed design suffers from enzyme deactivation, NTP fuel exhaustion, and waste product build up. In this paper, we show that a partially open architecture in which an [Symbol: see text]1 adaptive controller, implemented inside an in silico computer that resides outside the wet-lab apparatus, can ensure sustained tunable oscillations in two specific designs of the Kim-Winfree oscillator networks. We consider two broad cases of operation: (1) the oscillator network operating in isolation and (2) the oscillator network driving a DNA tweezer subject to a variable load. In both scenarios, our simulation results show a significant improvement in the tunability and robustness of these oscillator networks. Our approach can be easily adopted to improve the loading capacity of a wide range of synthetic biological devices.

Chaotic dynamics and diffusion in a piecewise linear equation

NASA Astrophysics Data System (ADS)

Shahrear, Pabel; Glass, Leon; Edwards, Rod

2015-03-01

Genetic interactions are often modeled by logical networks in which time is discrete and all gene activity states update simultaneously. However, there is no synchronizing clock in organisms. An alternative model assumes that the logical network is preserved and plays a key role in driving the dynamics in piecewise nonlinear differential equations. We examine dynamics in a particular 4-dimensional equation of this class. In the equation, two of the variables form a negative feedback loop that drives a second negative feedback loop. By modifying the original equations by eliminating exponential decay, we generate a modified system that is amenable to detailed analysis. In the modified system, we can determine in detail the Poincaré (return) map on a cross section to the flow. By analyzing the eigenvalues of the map for the different trajectories, we are able to show that except for a set of measure 0, the flow must necessarily have an eigenvalue greater than 1 and hence there is sensitive dependence on initial conditions. Further, there is an irregular oscillation whose amplitude is described by a diffusive process that is well-modeled by the Irwin-Hall distribution. There is a large class of other piecewise-linear networks that might be analyzed using similar methods. The analysis gives insight into possible origins of chaotic dynamics in periodically forced dynamical systems.

Classification of driving workload affected by highway alignment conditions based on classification and regression tree algorithm.

PubMed

Hu, Jiangbi; Wang, Ronghua

2018-02-17

Guaranteeing a safe and comfortable driving workload can contribute to reducing traffic injuries. In order to provide safe and comfortable threshold values, this study attempted to classify driving workload from the aspects of human factors mainly affected by highway geometric conditions and to determine the thresholds of different workload classifications. This article stated a hypothesis that the values of driver workload change within a certain range. Driving workload scales were stated based on a comprehensive literature review. Through comparative analysis of different psychophysiological measures, heart rate variability (HRV) was chosen as the representative measure for quantifying driving workload by field experiments. Seventy-two participants (36 car drivers and 36 large truck drivers) and 6 highways with different geometric designs were selected to conduct field experiments. A wearable wireless dynamic multiparameter physiological detector (KF-2) was employed to detect physiological data that were simultaneously correlated to the speed changes recorded by a Global Positioning System (GPS) (testing time, driving speeds, running track, and distance). Through performing statistical analyses, including the distribution of HRV during the flat, straight segments and P-P plots of modified HRV, a driving workload calculation model was proposed. Integrating driving workload scales with values, the threshold of each scale of driving workload was determined by classification and regression tree (CART) algorithms. The driving workload calculation model was suitable for driving speeds in the range of 40 to 120 km/h. The experimental data of 72 participants revealed that driving workload had a significant effect on modified HRV, revealing a change in driving speed. When the driving speed was between 100 and 120 km/h, drivers showed an apparent increase in the corresponding modified HRV. The threshold value of the normal driving workload K was between -0.0011 and 0.056 for a car driver and between -0.00086 and 0.067 for a truck driver. Heart rate variability was a direct and effective index for measuring driving workload despite being affected by multiple highway alignment elements. The driving workload model and the thresholds of driving workload classifications can be used to evaluate the quality of highway geometric design. A higher quality of highway geometric design could keep driving workload within a safer and more comfortable range. This study provided insight into reducing traffic injuries from the perspective of disciplinary integration of highway engineering and human factor engineering.

Continuing to drive while sleepy: the influence of sleepiness countermeasures, motivation for driving sleepy, and risk perception.

PubMed

Watling, Christopher N; Armstrong, Kerry A; Obst, Patricia L; Smith, Simon S

2014-12-01

Driver sleepiness is a major contributor to road crashes. The current study sought to examine the association between perceptions of effectiveness of six sleepiness countermeasures and their relationship with self-reports of continuing to drive while sleepy among 309 drivers after controlling for the influence of age, sex, motivation for driving sleepy, and risk perception of sleepy driving. The results demonstrate that the variables of age, sex, motivation, and risk perception were significantly associated with self-reports of continuing to drive while sleepy and only one countermeasure was associated with self-reports of continuing to drive while sleepy. Further, it was found that age differences in self-reports of continuing to drive while sleepy was mediated by participants' motivation and risk perception. These findings highlight modifiable factors that could be focused on with interventions that seek to modify drivers' attitudes and behaviours of driving while sleepy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Origami Wheel Transformer: A Variable-Diameter Wheel Drive Robot Using an Origami Structure.

PubMed

Lee, Dae-Young; Kim, Sa-Reum; Kim, Ji-Suk; Park, Jae-Jun; Cho, Kyu-Jin

2017-06-01

A wheel drive mechanism is simple, stable, and efficient, but its mobility in unstructured terrain is seriously limited. Using a deformable wheel is one of the ways to increase the mobility of a wheel drive robot. By changing the radius of its wheels, the robot becomes able to pass over not only high steps but also narrow gaps. In this article, we propose a novel design for a variable-diameter wheel using an origami-based soft robotics design approach. By simply folding a patterned sheet into a wheel shape, a variable-diameter wheel was built without requiring lots of mechanical parts and a complex assembly process. The wheel's diameter can change from 30 to 68 mm, and it is light in weight at about 9.7 g. Although composed of soft materials (fabrics and films), the wheel can bear more than 400 times its weight. The robot was able to change the wheel's radius in response to terrain conditions, allowing it to pass over a 50-mm gap when the wheel is shrunk and a 50-mm step when the wheel is enlarged.

General hybrid projective complete dislocated synchronization with non-derivative and derivative coupling based on parameter identification in several chaotic and hyperchaotic systems

NASA Astrophysics Data System (ADS)

Sun, Jun-Wei; Shen, Yi; Zhang, Guo-Dong; Wang, Yan-Feng; Cui, Guang-Zhao

2013-04-01

According to the Lyapunov stability theorem, a new general hybrid projective complete dislocated synchronization scheme with non-derivative and derivative coupling based on parameter identification is proposed under the framework of drive-response systems. Every state variable of the response system equals the summation of the hybrid drive systems in the previous hybrid synchronization. However, every state variable of the drive system equals the summation of the hybrid response systems while evolving with time in our method. Complete synchronization, hybrid dislocated synchronization, projective synchronization, non-derivative and derivative coupling, and parameter identification are included as its special item. The Lorenz chaotic system, Rössler chaotic system, memristor chaotic oscillator system, and hyperchaotic Lü system are discussed to show the effectiveness of the proposed methods.

Research on Power Loss of Continuously Variable Transmission Based on Driving Cycles

NASA Astrophysics Data System (ADS)

Fu, Bing; Zhou, Yunshan; Cao, Chenglong; Li, Quan; Zhang, Feitie

2018-01-01

In order to further enhance the fuel economy of vehicles with continuously variable transmission (CVT), a CVT power loss model under dynamic condition is established based on the power loss model of each transmission component and the vehicle dynamic model. With driving cycles 10-15, NEDC and US06 as input, the distribution of CVT power loss and the influence of the main losses to vehicle fuel economy are analysed. The results show that the variation loss, oil pump loss and torque converter loss are the main losses of CVT power loss under driving cycles, and the metal belt and oil pump have relatively larger fuel saving potential. At low speed reducing the pump loss is more effective to fuel saving, while at high speed reducing the variation loss is more effective.

Distracted driving in elderly and middle-aged drivers.

PubMed

Thompson, Kelsey R; Johnson, Amy M; Emerson, Jamie L; Dawson, Jeffrey D; Boer, Erwin R; Rizzo, Matthew

2012-03-01

Automobile driving is a safety-critical real-world example of multitasking. A variety of roadway and in-vehicle distracter tasks create information processing loads that compete for the neural resources needed to drive safely. Drivers with mind and brain aging may be particularly susceptible to distraction due to waning cognitive resources and control over attention. This study examined distracted driving performance in an instrumented vehicle (IV) in 86 elderly (mean=72.5 years, SD=5.0 years) and 51 middle-aged drivers (mean=53.7 years, SD=9.3 year) under a concurrent auditory-verbal processing load created by the Paced Auditory Serial Addition Task (PASAT). Compared to baseline (no-task) driving performance, distraction was associated with reduced steering control in both groups, with middle-aged drivers showing a greater increase in steering variability. The elderly drove slower and showed decreased speed variability during distraction compared to middle-aged drivers. They also tended to "freeze up", spending significantly more time holding the gas pedal steady, another tactic that may mitigate time pressured integration and control of information, thereby freeing mental resources to maintain situation awareness. While 39% of elderly and 43% of middle-aged drivers committed significantly more driving safety errors during distraction, 28% and 18%, respectively, actually improved, compatible with allocation of attention resources to safety critical tasks under a cognitive load. Copyright © 2011 Elsevier Ltd. All rights reserved.

Distracted Driving in Elderly and Middle-Aged Drivers

PubMed Central

Thompson, Kelsey R.; Johnson, Amy M.; Emerson, Jamie L.; Dawson, Jeffrey D.; Boer, Erwin R.

2011-01-01

Automobile driving is a safety-critical real-world example of multitasking. A variety of roadway and in-vehicle distracter tasks create information processing loads that compete for the neural resources needed to drive safely. Drivers with mind and brain aging may be particularly susceptible to distraction due to waning cognitive resources and control over attention. This study examined distracted driving performance in an instrumented vehicle (IV) in 86 elderly (mean = 72.5 years, SD = 5.0 years) and 51 middle-aged drivers (mean = 53.7 years, SD = 9.3 year) under a concurrent auditory-verbal processing load created by the Paced Auditory Serial Addition Task (PASAT). Compared to baseline (no-task) driving performance, distraction was associated with reduced steering control in both groups, with middle-aged drivers showing a greater increase in steering variability. The elderly drove slower and showed decreased speed variability during distraction compared to middle-aged drivers. They also tended to “freeze up”, spending significantly more time holding the gas pedal steady, another tactic that may mitigate time pressured integration and control of information, thereby freeing mental resources to maintain situation awareness. While 39% of elderly and 43% of middle-aged drivers committed significantly more driving safety errors during distraction, 28% and 18%, respectively, actually improved, compatible with allocation of attention resources to safety critical tasks under a cognitive load. PMID:22269561

The drive-wise project: driving simulator training increases real driving performance in healthy older drivers

PubMed Central

Casutt, Gianclaudio; Theill, Nathan; Martin, Mike; Keller, Martin; Jäncke, Lutz

2014-01-01

Background: Age-related cognitive decline is often associated with unsafe driving behavior. We hypothesized that 10 active training sessions in a driving simulator increase cognitive and on-road driving performance. In addition, driving simulator training should outperform cognitive training. Methods: Ninety-one healthy active drivers (62–87 years) were randomly assigned to one of three groups: (1) a driving simulator training group, (2) an attention training group (vigilance and selective attention), or (3) a control group. The main outcome variables were on-road driving and cognitive performance. Seventy-seven participants (85%) completed the training and were included in the analyses. Training gains were analyzed using a multiple regression analysis with planned orthogonal comparisons. Results: The driving simulator-training group showed an improvement in on-road driving performance compared to the attention-training group. In addition, both training groups increased cognitive performance compared to the control group. Conclusion: Driving simulator training offers the potential to enhance driving skills in older drivers. Compared to the attention training, the simulator training seems to be a more powerful program for increasing older drivers' safety on the road. PMID:24860497

Some interactions among driver, vehicle, and roadway variables in normal driving

NASA Technical Reports Server (NTRS)

Ritchie, M. L.; Howard, J. M.; Myers, W. D.

1972-01-01

Effects of road and vehicle conditions, visual warning signs, direction of turns, night time, and skill on automobile driver performance are studied in several experiments. Considered criteria are variability in speed and acceleration.

Range expansion through fragmented landscapes under a variable climate

PubMed Central

Bennie, Jonathan; Hodgson, Jenny A; Lawson, Callum R; Holloway, Crispin TR; Roy, David B; Brereton, Tom; Thomas, Chris D; Wilson, Robert J

2013-01-01

Ecological responses to climate change may depend on complex patterns of variability in weather and local microclimate that overlay global increases in mean temperature. Here, we show that high-resolution temporal and spatial variability in temperature drives the dynamics of range expansion for an exemplar species, the butterfly Hesperia comma. Using fine-resolution (5 m) models of vegetation surface microclimate, we estimate the thermal suitability of 906 habitat patches at the species' range margin for 27 years. Population and metapopulation models that incorporate this dynamic microclimate surface improve predictions of observed annual changes to population density and patch occupancy dynamics during the species' range expansion from 1982 to 2009. Our findings reveal how fine-scale, short-term environmental variability drives rates and patterns of range expansion through spatially localised, intermittent episodes of expansion and contraction. Incorporating dynamic microclimates can thus improve models of species range shifts at spatial and temporal scales relevant to conservation interventions. PMID:23701124

NEK1 genetic variability in a Belgian cohort of ALS and ALS-FTD patients.

PubMed

Nguyen, Hung Phuoc; Van Mossevelde, Sara; Dillen, Lubina; De Bleecker, Jan L; Moisse, Matthieu; Van Damme, Philip; Van Broeckhoven, Christine; van der Zee, Julie

2018-01-01

We evaluated the genetic impact of the amyotrophic lateral sclerosis (ALS) risk gene never in mitosis gene a-related kinase 1 (NEK1) in a Belgian cohort of 278 patients with ALS (n = 245) or ALS with frontotemporal dementia (ALS-FTD, n = 33) and 609 control individuals. We identified 2 ALS patients carrying a loss-of-function (LOF) mutation, p.Leu854Tyrfs*2 and p.Tyr871Valfs*17, that was absent in the control group. A third LOF variant p.Ser1036* was present in 2 sibs with familial ALS but also in an unrelated control person. Missense variants were common in both patients (3.6%) and controls (3.0%). The missense variant, p.Arg261His, which was previously associated with ALS risk, was detected with a minor allele frequency of 0.90% in patients compared to 0.33% in controls. Taken together, NEK1 LOF variants accounted for 1.1% of patients, although interpretation of pathogenicity and penetrance is complicated by the observation of occasional LOF variants in unaffected individuals (0.16%). Furthermore, enrichment of additional ALS gene mutations was observed in NEK1 carriers, suggestive of a "second hit" model were NEK1 variants may modify disease presentation of driving mutations. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Transcriptomics Profiling of Alzheimer’s Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs

PubMed Central

Magistri, Marco; Velmeshev, Dmitry; Makhmutova, Madina; Faghihi, Mohammad Ali

2015-01-01

Abstract The underlying genetic variations of late-onset Alzheimer’s disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD pathological process. Transcriptome profiling using deep sequencing technology offers insight into common altered pathways regardless of underpinning genetic or epigenetic factors and thus represents an ideal tool to investigate molecular mechanisms related to the pathophysiology of LOAD. We performed directional RNA sequencing on high quality RNA samples extracted from hippocampi of LOAD and age-matched controls. We further validated our data using qRT-PCR on a larger set of postmortem brain tissues, confirming downregulation of the gene encoding substance P (TAC1) and upregulation of the gene encoding the plasminogen activator inhibitor-1 (SERPINE1). Pathway analysis indicates dysregulation in neural communication, cerebral vasculature, and amyloid-β clearance. Beside protein coding genes, we identified several annotated and non-annotated long noncoding RNAs that are differentially expressed in LOAD brain tissues, three of them are activity-dependent regulated and one is induced by Aβ1 - 42 exposure of human neural cells. Our data provide a comprehensive list of transcriptomics alterations in LOAD hippocampi and warrant holistic approach including both coding and non-coding RNAs in functional studies aimed to understand the pathophysiology of LOAD. PMID:26402107

Impact of Distracted Driving on Safety and Traffic Flow

PubMed Central

Stavrinos, Despina; Jones, Jennifer L.; Garner, Annie A.; Griffin, Russell; Franklin, Crystal A.; Ball, David; Welburn, Sharon C.; Ball, Karlene K.; Sisiopiku, Virginia P.; Fine, Philip R.

2015-01-01

Studies have documented a link between distracted driving and diminished safety; however, an association between distracted driving and traffic congestion has not been investigated in depth. The present study examined the behavior of teens and young adults operating a driving simulator while engaged in various distractions (i.e., cell phone, texting, and undistracted) and driving conditions (i.e., free flow, stable flow, and oversaturation). Seventy five participants 16 to 25 years of age (split into 2 groups: novice drivers and young adults) drove a STISIM simulator three times, each time with one of three randomly presented distractions. Each drive was designed to represent daytime scenery on a 4 lane divided roadway and included three equal roadway portions representing Levels of Service (LOS) A, C, and E as defined in the 2000 Highway Capacity Manual. Participants also completed questionnaires documenting demographics and driving history. Both safety and traffic flow related driving outcomes were considered. A Repeated Measures Multivariate Analysis of Variance was employed to analyze continuous outcome variables and a Generalized Estimate Equation (GEE) poisson model was used to analyze count variables. Results revealed that, in general more lane deviations and crashes occurred during texting. Distraction (in most cases, text messaging) had a significantly negative impact on traffic flow, such that participants exhibited greater fluctuation in speed, changed lanes significantly fewer times, and took longer to complete the scenario. In turn, more simulated vehicles passed the participant drivers while they were texting or talking on a cell phone than while undistracted. The results indicate that distracted driving, particularly texting, may lead to reduced safety and traffic flow, thus having a negative impact on traffic operations. No significant differences were detected between age groups, suggesting that all drivers, regardless of age, may drive in a manner that impacts safety and traffic flow negatively when distracted. PMID:23465745

Impact of distracted driving on safety and traffic flow.

PubMed

Stavrinos, Despina; Jones, Jennifer L; Garner, Annie A; Griffin, Russell; Franklin, Crystal A; Ball, David; Welburn, Sharon C; Ball, Karlene K; Sisiopiku, Virginia P; Fine, Philip R

2013-12-01

Studies have documented a link between distracted driving and diminished safety; however, an association between distracted driving and traffic congestion has not been investigated in depth. The present study examined the behavior of teens and young adults operating a driving simulator while engaged in various distractions (i.e., cell phone, texting, and undistracted) and driving conditions (i.e., free flow, stable flow, and oversaturation). Seventy five participants 16-25 years of age (split into 2 groups: novice drivers and young adults) drove a STISIM simulator three times, each time with one of three randomly presented distractions. Each drive was designed to represent daytime scenery on a 4 lane divided roadway and included three equal roadway portions representing Levels of Service (LOS) A, C, and E as defined in the 2000 Highway Capacity Manual. Participants also completed questionnaires documenting demographics and driving history. Both safety and traffic flow related driving outcomes were considered. A Repeated Measures Multivariate Analysis of Variance was employed to analyze continuous outcome variables and a Generalized Estimate Equation (GEE) Poisson model was used to analyze count variables. Results revealed that, in general more lane deviations and crashes occurred during texting. Distraction (in most cases, text messaging) had a significantly negative impact on traffic flow, such that participants exhibited greater fluctuation in speed, changed lanes significantly fewer times, and took longer to complete the scenario. In turn, more simulated vehicles passed the participant drivers while they were texting or talking on a cell phone than while undistracted. The results indicate that distracted driving, particularly texting, may lead to reduced safety and traffic flow, thus having a negative impact on traffic operations. No significant differences were detected between age groups, suggesting that all drivers, regardless of age, may drive in a manner that impacts safety and traffic flow negatively when distracted. Copyright © 2013 Elsevier Ltd. All rights reserved.

Selfish X chromosomes and speciation.

PubMed

Patten, Manus M

2017-12-27

In two papers published at about the same time almost thirty years ago, Frank (Evolution, 45, 1991a, 262) and Hurst and Pomiankowski (Genetics, 128, 1991, 841) independently suggested that divergence of meiotic drive systems-comprising genes that cheat meiosis and genes that suppress this cheating-might provide a general explanation for Haldane's rule and the large X-effect in interspecific hybrids. Although at the time, the idea was met with skepticism and a conspicuous absence of empirical support, the tide has since turned. Some of the clearest mechanistic explanations we have for hybrid male sterility involve meiotic drive systems, and several other cases of hybrid sterility are suggestive of a role for meiotic drive. In this article, I review these ideas and their descendants and catalog the current evidence for the meiotic drive model of speciation. In addition, I suggest that meiotic drive is not the only intragenomic conflict to involve the X chromosome and contribute to hybrid incompatibility. Sexually and parentally antagonistic selection pressures can also pit the X chromosome and autosomes against each other. The resulting intragenomic conflicts should lead to co-evolution within populations and divergence between them, thus increasing the likelihood of incompatibilities in hybrids. I provide a sketch of these ideas and interpret some empirical patterns in the light of these additional X-autosome conflicts. © 2017 John Wiley & Sons Ltd.

Texting while driving using Google Glass™: Promising but not distraction-free.

PubMed

He, Jibo; Choi, William; McCarley, Jason S; Chaparro, Barbara S; Wang, Chun

2015-08-01

Texting while driving is risky but common. This study evaluated how texting using a Head-Mounted Display, Google Glass, impacts driving performance. Experienced drivers performed a classic car-following task while using three different interfaces to text: fully manual interaction with a head-down smartphone, vocal interaction with a smartphone, and vocal interaction with Google Glass. Fully manual interaction produced worse driving performance than either of the other interaction methods, leading to more lane excursions and variable vehicle control, and higher workload. Compared to texting vocally with a smartphone, texting using Google Glass produced fewer lane excursions, more braking responses, and lower workload. All forms of texting impaired driving performance compared to undistracted driving. These results imply that the use of Google Glass for texting impairs driving, but its Head-Mounted Display configuration and speech recognition technology may be safer than texting using a smartphone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Traction drive automatic transmission for gas turbine engine driveline

DOEpatents

Carriere, Donald L.

1984-01-01

A transaxle driveline for a wheeled vehicle has a high speed turbine engine and a torque splitting gearset that includes a traction drive unit and a torque converter on a common axis transversely arranged with respect to the longitudinal centerline of the vehicle. The drive wheels of the vehicle are mounted on a shaft parallel to the turbine shaft and carry a final drive gearset for driving the axle shafts. A second embodiment of the final drive gearing produces an overdrive ratio between the output of the first gearset and the axle shafts. A continuously variable range of speed ratios is produced by varying the position of the drive rollers of the traction unit. After starting the vehicle from rest, the transmission is set for operation in the high speed range by engaging a first lockup clutch that joins the torque converter impeller to the turbine for operation as a hydraulic coupling.

Application of traction drives as servo mechanisms

NASA Technical Reports Server (NTRS)

Loewenthal, S. H.; Rohn, D. A.; Steinetz, B. M.

1985-01-01

The suitability of traction drives for a wide class of aerospace control mechanisms is examined. Potential applications include antenna or solar array drive positioners, robotic joints, control moment gyro (CMG) actuators and propeller pitch change mechanisms. In these and similar applications the zero backlash, high torsional stiffness, low hysteresis and torque ripple characteristics of traction drives are of particular interest, as is the ability to run without liquid lubrication in certain cases. Wear and fatigue considerations for wet and dry operation are examined along with the tribological performance of several promising self lubricating polymers for traction contracts. The speed regulation capabilities of variable ratio traction drives are reviewed. A torsional stiffness analysis described suggests that traction contacts are relatively stiff compared to gears and are significantly stiffer than the other structural elements in the prototype CMG traction drive analyzed. Discussion is also given of an advanced turboprop propeller pitch change mechanism that incorporates a traction drive.

cAMP-responsive Element-binding Protein (CREB) and cAMP Co-regulate Activator Protein 1 (AP1)-dependent Regeneration-associated Gene Expression and Neurite Growth*

PubMed Central

Ma, Thong C.; Barco, Angel; Ratan, Rajiv R.; Willis, Dianna E.

2014-01-01

To regenerate damaged axons, neurons must express a cassette of regeneration-associated genes (RAGs) that increases intrinsic growth capacity and confers resistance to extrinsic inhibitory cues. Here we show that dibutyrl-cAMP or forskolin combined with constitutive-active CREB are superior to either agent alone in driving neurite growth on permissive and inhibitory substrates. Of the RAGs examined, only arginase 1 (Arg1) expression correlated with the increased neurite growth induced by the cAMP/CREB combination, both of which were AP1-dependent. This suggests that cAMP-induced AP1 activity is necessary and interacts with CREB to drive expression of RAGs relevant for regeneration and demonstrates that combining a small molecule (cAMP) with an activated transcription factor (CREB) stimulates the gene expression necessary to enhance axonal regeneration. PMID:25296755

A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

NASA Astrophysics Data System (ADS)

Noël, Emily S.; Verhoeven, Manon; Lagendijk, Anne Karine; Tessadori, Federico; Smith, Kelly; Choorapoikayil, Suma; den Hertog, Jeroen; Bakkers, Jeroen

2013-11-01

Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

The toxin and antidote puzzle

PubMed Central

2011-01-01

Insects carry out essential ecological functions, such as pollination, but also cause extensive damage to agricultural crops and transmit human diseases such as malaria and dengue fever. Advances in insect transgenesis are making it increasingly feasible to engineer genes conferring desirable phenotypes, and gene drive systems are required to spread these genes into wild populations. Medea provides one solution, being able to spread into a population from very low initial frequencies through the action of a maternally-expressed toxin linked to a zygotically-expressed antidote. Several other toxin-antidote combinations are imaginable that distort the offspring ratio in favor of a desired transgene, or drive the population towards an all-male crash. We explore two such systems—Semele, which is capable of spreading a desired transgene into an isolated population in a confined manner; and Merea, which is capable of inducing a local population crash when located on the Z chromosome of a Lepidopteron pest. PMID:21876382

Driving violations and health promotion behaviors among undergraduate students: Self-report of on-road behavior.

PubMed

Korn, Liat; Weiss, Yossi; Rosenbloom, Tova

2017-11-17

The purposes of this study are to characterize Israeli undergraduate students' driving violations in the terms of problem behavior theory and to identify whether there is any relationship between driving violations and health risk behaviors, daring behaviors, excitement seeking, and health promotion behaviors. This study is based on a structured self-reported anonymous questionnaire distributed to undergraduate students in an academic institution. The sample included 533 undergraduate students (374 females and 159 males). The mean age was 23.4 (SD = 1.4, range = 5). A higher prevalence of self-reported driving violations was found among males in comparison to females. All substance use measures were positively related to driving violations; for example, use of cigarettes (OR = 4.287, P <.001) and water pipes (odds ratio [OR] = 3.000, P <.001) as well as binge drinking (OR = 5.707, P <.001) and regular cannabis smoking (OR = 5.667, P <.001) raise the probability of committing rare driving violations. The strongest predictive factors for the frequent driving violations group were alcohol consumption-related variables: binge drinking (OR = 2.560, P <.01) and drunkenness (OR = 2.284, P <.05). Strong odd ratios were also found between the frequent driving violations group and selling or dealing drugs (12.143, P <.001), and stealing something valuable (13.680, P <.001). The strongest predicted variable for the rare driving violations group was physical confrontation due to verbal disagreement (3.439, P <.05) and the concept that selling or dealing drugs is socially acceptable (2.521, P <.05). The probability of executing rare driving violations was higher for subjects who reported intense physical workout regimens (OR = 1.638, P <.05). Problem behavior theory succeeded in explaining health risk behavior and driving violations. This study shows that bachelors tend to be more involved in risk behaviors, such as substance use, excitement-seeking behaviors, and daring behaviors and are active physically and thus constitute a risk group for driving violations. As such, intervention resources should be directed toward this group.

Understanding multidecadal variability in ENSO amplitude

NASA Astrophysics Data System (ADS)

Russell, A.; Gnanadesikan, A.

2013-12-01

Sea surface temperatures (SSTs) in the tropical Pacific vary as a result of the coupling between the ocean and atmosphere driven largely by the El Niño - Southern Oscillation (ENSO). ENSO has a large impact on the local climate and hydrology of the tropical Pacific, as well as broad-reaching effects on global climate. ENSO amplitude is known to vary on long timescales, which makes it very difficult to quantify its response to climate change and constrain the physical processes that drive it. In order to assess the extent of unforced multidecadal changes in ENSO variability, a linear regression of local SST changes is applied to the GFDL CM2.1 model 4000-yr pre-industrial control run. The resulting regression coefficient strengths, which represent the sensitivity of SST changes to thermocline depth and zonal wind stress, vary by up to a factor of 2 on multi-decadal time scales. This long-term modulation in ocean-atmosphere coupling is highly correlated with ENSO variability, but do not explain the reasons for such variability. Variation in the relationship between SST changes and wind stress points to a role for changing stratification in the central equatorial Pacific in modulating ENSO amplitudes with stronger stratification reducing the response to winds. The main driving mechanism we have identified for higher ENSO variance are changes in the response of zonal winds to SST anomalies. The shifting convection and precipitation patterns associated with the changing state of the atmosphere also contribute to the variability of the regression coefficients. These mechanisms drive much of the variability in ENSO amplitude and hence ocean-atmosphere coupling in the tropical Pacific.

[CRISPR-Cas9, a new chance for somatic gene therapy].

PubMed

Jordan, Bertrand

2015-11-01

Targeted modification of genes ("gene editing") is made much easier by the recently developed CRISPR-Cas9 system. This has raised alarm about possible uses of this technology for germline modification of the human genome; however this technology has less controversial applications, notably for somatic gene therapy with already some striking demonstrations in animal systems. Because of its precision and relative ease of use, CRISPR can be expected to drive a revolution in gene therapy and to turn it into a more mainstream approach. © 2015 médecine/sciences – Inserm.

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.

PubMed

Trigos, Anna S; Pearson, Richard B; Papenfuss, Anthony T; Goode, David L

2017-06-13

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

PubMed Central

Trigos, Anna S.; Pearson, Richard B.; Papenfuss, Anthony T.; Goode, David L.

2017-01-01

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer. PMID:28484005

Strong Magnetic Field Induced Changes of Gene Expression in Arabidopsis

NASA Astrophysics Data System (ADS)

Paul, A.-L.; Ferl, R. J.; Klingenberg, B.; Brooks, J. S.; Morgan, A. N.; Yowtak, J.; Meisel, M. W.

2005-07-01

We review our studies of the biological impact of magnetic field strengths of up to 30 T on transgenic arabidopsis plants engineered with a stress response gene consisting of the alcohol dehydrogenase (Adh) gene promoter driving the β-glucuronidase (GUS) gene reporter. Field strengths in excess of 15 T induce expression of the Adh/GUS transgene in the roots and leaves. Microarray analyses indicate that such field strengths have a far reaching effect on the genome. Wide spread induction of stress-related genes and transcription factors, and a depression of genes associated with cell wall metabolism are prominent examples.

Variable-Displacement Hydraulic Drive Unit

NASA Technical Reports Server (NTRS)

Lang, D. J.; Linton, D. J.; Markunas, A.

1986-01-01

Hydraulic power controlled through multiple feedback loops. In hydraulic drive unit, power closely matched to demand, thereby saving energy. Hydraulic flow to and from motor adjusted by motor-control valve connected to wobbler. Wobbler angle determines motor-control-valve position, which in turn determines motor displacement. Concept applicable to machine tools, aircraft controls, and marine controls.

Driving and Low Vision: Validity of Assessments for Predicting Performance of Drivers

ERIC Educational Resources Information Center

Strong, J. Graham; Jutai, Jeffrey W.; Russell-Minda, Elizabeth; Evans, Mal

2008-01-01

The authors conducted a systematic review to examine whether vision-related assessments can predict the driving performance of individuals who have low vision. The results indicate that measures of visual field, contrast sensitivity, cognitive and attention-based tests, and driver screening tools have variable utility for predicting real-world…

Modeling take-over performance in level 3 conditionally automated vehicles.

PubMed

Gold, Christian; Happee, Riender; Bengler, Klaus

2018-07-01

Taking over vehicle control from a Level 3 conditionally automated vehicle can be a demanding task for a driver. The take-over determines the controllability of automated vehicle functions and thereby also traffic safety. This paper presents models predicting the main take-over performance variables take-over time, minimum time-to-collision, brake application and crash probability. These variables are considered in relation to the situational and driver-related factors time-budget, traffic density, non-driving-related task, repetition, the current lane and driver's age. Regression models were developed using 753 take-over situations recorded in a series of driving simulator experiments. The models were validated with data from five other driving simulator experiments of mostly unrelated authors with another 729 take-over situations. The models accurately captured take-over time, time-to-collision and crash probability, and moderately predicted the brake application. Especially the time-budget, traffic density and the repetition strongly influenced the take-over performance, while the non-driving-related tasks, the lane and drivers' age explained a minor portion of the variance in the take-over performances. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Baculovirus Immediate-Early Gene, ie1, Promoter Drives Efficient Expression of a Transgene in Both Drosophila melanogaster and Bombyx mori

PubMed Central

Masumoto, Mika; Ohde, Takahiro; Shiomi, Kunihiro; Yaginuma, Toshinobu; Niimi, Teruyuki

2012-01-01

Many promoters have been used to drive expression of heterologous transgenes in insects. One major obstacle in the study of non-model insects is the dearth of useful promoters for analysis of gene function. Here, we investigated whether the promoter of the immediate-early gene, ie1, from the Bombyx mori nucleopolyhedrovirus (BmNPV) could be used to drive efficient transgene expression in a wide variety of insects. We used a piggyBac-based vector with a 3xP3-DsRed transformation marker to generate a reporter construct; this construct was used to determine the expression patterns driven by the BmNPV ie1 promoter; we performed a detailed investigation of the promoter in transgene expression pattern in Drosophila melanogaster and in B. mori. Drosophila and Bombyx belong to different insect orders (Diptera and Lepidoptera, respectively); however, and to our surprise, ie1 promoter-driven expression was evident in several tissues (e.g., prothoracic gland, midgut, and tracheole) in both insects. Furthermore, in both species, the ie1 promoter drove expression of the reporter gene from a relatively early embryonic stage, and strong ubiquitous ie1 promoter-driven expression continued throughout the larval, pupal, and adult stages by surface observation. Therefore, we suggest that the ie1 promoter can be used as an efficient expression driver in a diverse range of insect species. PMID:23152896

Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development

PubMed Central

Takeda, Haruna; Rust, Alistair G.; Ward, Jerrold M.; Yew, Christopher Chin Kuan; Jenkins, Nancy A.; Copeland, Neal G.

2016-01-01

Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4+/− mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC. PMID:27006499

Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development.

PubMed

Takeda, Haruna; Rust, Alistair G; Ward, Jerrold M; Yew, Christopher Chin Kuan; Jenkins, Nancy A; Copeland, Neal G

2016-04-05

Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC.

Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms.

PubMed

Liu, Tsung-Li; Upadhyayula, Srigokul; Milkie, Daniel E; Singh, Ved; Wang, Kai; Swinburne, Ian A; Mosaliganti, Kishore R; Collins, Zach M; Hiscock, Tom W; Shea, Jamien; Kohrman, Abraham Q; Medwig, Taylor N; Dambournet, Daphne; Forster, Ryan; Cunniff, Brian; Ruan, Yuan; Yashiro, Hanako; Scholpp, Steffen; Meyerowitz, Elliot M; Hockemeyer, Dirk; Drubin, David G; Martin, Benjamin L; Matus, David Q; Koyama, Minoru; Megason, Sean G; Kirchhausen, Tom; Betzig, Eric

2018-04-20

True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes that we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution, without inducing undue stress on either. We combined lattice light-sheet microscopy with adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Luciferase assay to study the activity of a cloned promoter DNA fragment.

PubMed

Solberg, Nina; Krauss, Stefan

2013-01-01

Luciferase based assays have become an invaluable tool for the analysis of cloned promoter DNA fragments, both for verifying the ability of a potential promoter fragment to drive the expression of a luciferase reporter gene in various cellular contexts, and for dissecting binding elements in the promoter. Here, we describe the use of the Dual-Luciferase(®) Reporter Assay System created by Promega (Promega Corporation, Wisconsin, USA) to study the cloned 6.7 kilobases (kb) mouse (m) Tcf3 promoter DNA fragment in mouse embryonic derived neural stem cells (NSC). In this system, the expression of the firefly luciferase driven by the cloned mTcf3 promoter DNA fragment (including transcription initiation sites) is correlated with a co-transfected control reporter expressing Renilla luciferase from the herpes simplex virus (HSV) thymidine kinase promoter. Using an internal control reporter allows to normalize the activity of the experimental reporter to the internal control, which minimizes experimental variability.

Nonstationary time series prediction combined with slow feature analysis

NASA Astrophysics Data System (ADS)

Wang, G.; Chen, X.

2015-01-01

Almost all climate time series have some degree of nonstationarity due to external driving forces perturbations of the observed system. Therefore, these external driving forces should be taken into account when reconstructing the climate dynamics. This paper presents a new technique of combining the driving force of a time series obtained using the Slow Feature Analysis (SFA) approach, then introducing the driving force into a predictive model to predict non-stationary time series. In essence, the main idea of the technique is to consider the driving forces as state variables and incorporate them into the prediction model. To test the method, experiments using a modified logistic time series and winter ozone data in Arosa, Switzerland, were conducted. The results showed improved and effective prediction skill.

Impact of mobile phone use on car-following behaviour of young drivers.

PubMed

Saifuzzaman, Mohammad; Haque, Md Mazharul; Zheng, Zuduo; Washington, Simon

2015-09-01

Multitasking, such as the concurrent use of a mobile phone and operating a motor vehicle, is a significant distraction that impairs driving performance and is becoming a leading cause of motor vehicle crashes. This study investigates the impact of mobile phone conversations on car-following behaviour. The CARRS-Q Advanced Driving Simulator was used to test a group of young Australian drivers aged 18-26 years on a car-following task in three randomised phone conditions: baseline (no phone conversation), hands-free and handheld. Repeated measure ANOVA was applied to examine the effect of mobile phone distraction on selected car-following variables such as driving speed, spacing, and time headway. Overall, drivers tended to select slower driving speeds, larger vehicle spacings, and longer time headways when they were engaged in either hands-free or handheld phone conversations, suggesting possible risk compensatory behaviour. In addition, phone conversations while driving influenced car-following behaviour such that variability was increased in driving speeds, vehicle spacings, and acceleration and decelerations. To further investigate car-following behaviour of distracted drivers, driver time headways were modelled using Generalized Estimation Equation (GEE). After controlling for various exogenous factors, the model predicts an increase of 0.33s in time headway when a driver is engaged in hands-free phone conversation and a 0.75s increase for handheld phone conversation. The findings will improve the collective understanding of distraction on driving performance, in particular car following behaviour which is most critical in the determination of rear-end crashes. Copyright © 2015 Elsevier Ltd. All rights reserved.

New target genes of MITF-induced microRNA-211 contribute to melanoma cell invasion.

PubMed

Margue, Christiane; Philippidou, Demetra; Reinsbach, Susanne E; Schmitt, Martina; Behrmann, Iris; Kreis, Stephanie

2013-01-01

The non-coding microRNAs (miRNA) have tissue- and disease-specific expression patterns. They down-regulate target mRNAs, which likely impacts on most fundamental cellular processes. Differential expression patterns of miRNAs are currently being exploited for identification of biomarkers for early disease diagnosis, prediction of progression for melanoma and other cancers and as promising drug targets, since they can easily be inhibited or replaced in a given cellular context. Before successfully manipulating miRNAs in clinical settings, their precise expression levels, endogenous functions and thus their target genes have to be determined. MiR-211, a melanocyte lineage-specific small non-coding miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia-associated transcription factor (MITF). By transcriptionally up-regulating TRPM1, MITF, which is critical for both melanocyte differentiation and survival and for melanoma progression, indirectly drives the expression of miR-211. Expression of this miRNA is often reduced in melanoma samples. Here, we investigated functional roles of miR-211 by identifying and studying new target genes. We show that MITF-correlated miR-211 expression levels are mostly but not always reduced in a panel of 11 melanoma cell lines and in primary and metastatic melanoma compared to normal melanocytes and nevi, respectively. MiR-211 itself only marginally impacted on cell invasion and migration, while perturbation of some new miR-211 target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased invasion. These results and the variable expression levels of miR-211 raise serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA and/or as a biomarker for melanoma.

Difficulties of Drivers With Dyslexia When Reading Traffic Signs: Analysis of Reading, Eye Gazes, and Driving Performance.

PubMed

Tejero, Pilar; Insa, Beatriz; Roca, Javier

2018-03-01

A group of adult individuals with dyslexia and a matched group of normally reading individuals participated in a driving simulation experiment. Participants were asked to read the word presented on every direction traffic sign encountered along a route, as far as possible from the sign, maintaining driving performance. Word frequency and word length were manipulated as within-subject factors. We analyzed (a) reading accuracy, (b) how far the sign was when the participant started to give the response, (c) where the participant looked during the time leading up to the response, and (d) the variability of the vehicle's speed during that time and during driving on similar segments of the route that did not present the traffic signs. Individuals with dyslexia showed lower levels of performance in the reading task, the roles of word frequency and word length were more influential for them, and there was larger variability of the vehicle's speed during the time they were attempting to read the traffic sign, which did not occur during their driving on similar segments that did not present the targeted traffic signs. Therefore, the specific needs of individuals with dyslexia on the road should be considered in plans aimed at increasing traffic safety and fluidity.

Genome-wide diversity and selective pressure in the human rhinovirus

PubMed Central

Kistler, Amy L; Webster, Dale R; Rouskin, Silvi; Magrini, Vince; Credle, Joel J; Schnurr, David P; Boushey, Homer A; Mardis, Elaine R; Li, Hao; DeRisi, Joseph L

2007-01-01

Background The human rhinoviruses (HRV) are one of the most common and diverse respiratory pathogens of humans. Over 100 distinct HRV serotypes are known, yet only 6 genomes are available. Due to the paucity of HRV genome sequence, little is known about the genetic diversity within HRV or the forces driving this diversity. Previous comparative genome sequence analyses indicate that recombination drives diversification in multiple genera of the picornavirus family, yet it remains unclear if this holds for HRV. Results To resolve this and gain insight into the forces driving diversification in HRV, we generated a representative set of 34 fully sequenced HRVs. Analysis of these genomes shows consistent phylogenies across the genome, conserved non-coding elements, and only limited recombination. However, spikes of genetic diversity at both the nucleotide and amino acid level are detectable within every locus of the genome. Despite this, the HRV genome as a whole is under purifying selective pressure, with islands of diversifying pressure in the VP1, VP2, and VP3 structural genes and two non-structural genes, the 3C protease and 3D polymerase. Mapping diversifying residues in these factors onto available 3-dimensional structures revealed the diversifying capsid residues partition to the external surface of the viral particle in statistically significant proximity to antigenic sites. Diversifying pressure in the pleconaril binding site is confined to a single residue known to confer drug resistance (VP1 191). In contrast, diversifying pressure in the non-structural genes is less clear, mapping both nearby and beyond characterized functional domains of these factors. Conclusion This work provides a foundation for understanding HRV genetic diversity and insight into the underlying biology driving evolution in HRV. It expands our knowledge of the genome sequence space that HRV reference serotypes occupy and how the pattern of genetic diversity across HRV genomes differs from other picornaviruses. It also reveals evidence of diversifying selective pressure in both structural genes known to interact with the host immune system and in domains of unassigned function in the non-structural 3C and 3D genes, raising the possibility that diversification of undiscovered functions in these essential factors may influence HRV fitness and evolution. PMID:17477878

The UT-A Urea Transporter Promoter, UT-Aα, Targets Principal Cells of the Renal Inner Medullary Collecting Duct

PubMed Central

Fenton, Robert A.; Shodeinde, Adetola; Knepper, Mark A.

2006-01-01

The urea transporters, UT-A1 and UT-A3, two members of the UT-A gene family, are localized to the terminal portion of the inner medullary collecting duct (IMCD). In this manuscript, we demonstrate that 4.2-kb of the 5′-flanking region of the UT-A gene (UT-Aα promoter) is sufficient to drive the IMCD-specific expression of a heterologous reporter gene, β-galactosidase (β-Gal), in transgenic mice. RT-PCR, immunoblotting and immunohistochemistry demonstrate that within the kidney, transgene expression is confined to the terminal portion of the IMCD. Co-localization studies with aquaporin 2 show that expression is localized to the principal cells of the IMCD2 and IMCD3 regions. Utilizing β-Gal activity assays, we further show that within the kidney, the β-Gal transgene can be regulated by both water restriction and glucocorticoids, similar to the regulation of the endogenous UT-A gene. These results demonstrate that 4.2-kb of the UT-Aα promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific and cell-specific fashion in transgenic mice PMID:16091580

Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

PubMed

Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

2016-03-03

Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

Evaluating the effectiveness of a post-license education program for young novice drivers in Belgium.

PubMed

Brijs, Kris; Cuenen, Ariane; Brijs, Tom; Ruiter, Robert A C; Wets, Geert

2014-05-01

The disproportionately large number of traffic accidents of young novice drivers highlights the need for an effective driver education program. The Goals for Driving Education (GDE) matrix shows that driver education must target both lower and higher levels of driver competences. Research has indicated that current education programs do not emphasize enough the higher levels, for example awareness and insight. This has raised the importance of insight programs. On the Road (OtR), a Flemish post-license driver education program, is such an insight program that aims to target these higher levels. The program focus is on risky driving behavior like speeding and drink driving. In addition, the program addresses risk detection and risk-related knowledge. The goal of the study was to do an effect evaluation of this insight program at immediate post-test and 2 months follow-up. In addition, the study aimed to generalize the results of this program to comparable programs in order to make usable policy recommendations. A questionnaire based on the Theory of Planned Behavior (TPB) was used in order to measure participants' safety consciousness of speeding and drink driving. Moreover, we focused on risk detection and risk-related knowledge. Participants (N=366) were randomly assigned to a baseline-follow-up group or a post-test-follow-up group. Regarding speeding and driving, we found OtR to have little effect on the TPB variables. Regarding risk detection, we found no significant effect, even though participants clearly needed substantial improvement when stepping into the program. Regarding risk-related knowledge, the program did result in a significant improvement at post-test and follow-up. It is concluded that the current program format is a good starting point, but that it requires further attention to enhance high level driving skills. Program developers are encouraged to work in a more evidence-based manner when they select target variables and methods to influence these variables. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tumor suppressor roles of CENP-E and Nsl1 in Drosophila epithelial tissues.

PubMed

Clemente-Ruiz, Marta; Muzzopappa, Mariana; Milán, Marco

2014-01-01

Depletion of spindle assembly checkpoint (SAC) genes in Drosophila epithelial tissues leads to JNK-dependent programmed cell death and additional blockade of the apoptotic program drives tumorigenesis. A recent report proposes that chromosomal instability (CIN) is not the driving force in the tumorigenic response of the SAC-deficient tissue, and that checkpoint proteins exert a SAC-independent tumor suppressor role. This notion is based on observations that the depletion of CENP-E levels or prevention of Bub3 from binding to the kinetochore in Drosophila tissues unable to activate the apoptotic program induces CIN but does not cause hyperproliferation. Here we re-examined this proposal. In contrast to the previous report, we observed that depletion of CENP-E or Nsl1-the latter mediating kinetochore targeting of Bub3-in epithelial tissues unable to activate the apoptotic program induces significant levels of aneuploidy and drives tumor-like growth. The induction of the JNK transcriptional targets Wingless, a mitogenic molecule, and MMP1, a matrix metaloproteinase 1 involved in basement membrane degradation was also observed in these tumors. An identical response of the tissue was previously detected upon depletion of several SAC genes or genes involved in spindle assembly, chromatin condensation, and cytokinesis, all of which have been described to cause CIN. All together, these results reinforce the role of CIN in driving tumorigenesis in Drosophila epithelial tissues and question the proposed SAC-independent roles of checkpoint proteins in suppressing tumorigenesis. Differences in aneuploidy rates might explain the discrepancy between the previous report and our results.

Transcriptional response to West Nile virus infection in the zebra finch (Taeniopygia guttata)

USGS Publications Warehouse

Newhouse, Daniel J.; Hofmeister, Erik K.; Balakrishnan, Christopher N.

2017-01-01

West Nile virus (WNV) is a widespread arbovirus that imposes a significant cost to both human and wildlife health. WNV exists in a bird-mosquito transmission cycle in which passerine birds act as the primary reservoir host. As a public health concern, the mammalian immune response to WNV has been studied in detail. Little, however, is known about the avian immune response to WNV. Avian taxa show variable susceptibility to WNV and what drives this variation is unknown. Thus, to study the immune response to WNV in birds, we experimentally infected captive zebra finches (Taeniopygia guttata). Zebra finches provide a useful model, as like many natural avian hosts they are moderately susceptible to WNV and thus provide sufficient viremia to infect mosquitoes. We performed RNAseq in spleen tissue during peak viremia to provide an overview of the transcriptional response. In general, we find strong parallels with the mammalian immune response to WNV, including upregulation of five genes in the Rig-I-like receptor signalling pathway, and offer insights into avian-specific responses. Together with complementary immunological assays, we provide a model of the avian immune response to WNV and set the stage for future comparative studies among variably susceptible populations and species.

High taxonomic variability despite stable functional structure across microbial communities.

PubMed

Louca, Stilianos; Jacques, Saulo M S; Pires, Aliny P F; Leal, Juliana S; Srivastava, Diane S; Parfrey, Laura Wegener; Farjalla, Vinicius F; Doebeli, Michael

2016-12-05

Understanding the processes that are driving variation of natural microbial communities across space or time is a major challenge for ecologists. Environmental conditions strongly shape the metabolic function of microbial communities; however, other processes such as biotic interactions, random demographic drift or dispersal limitation may also influence community dynamics. The relative importance of these processes and their effects on community function remain largely unknown. To address this uncertainty, here we examined bacterial and archaeal communities in replicate 'miniature' aquatic ecosystems contained within the foliage of wild bromeliads. We used marker gene sequencing to infer the taxonomic composition within nine metabolic functional groups, and shotgun environmental DNA sequencing to estimate the relative abundances of these groups. We found that all of the bromeliads exhibited remarkably similar functional community structures, but that the taxonomic composition within individual functional groups was highly variable. Furthermore, using statistical analyses, we found that non-neutral processes, including environmental filtering and potentially biotic interactions, at least partly shaped the composition within functional groups and were more important than spatial dispersal limitation and demographic drift. Hence both the functional structure and taxonomic composition within functional groups of natural microbial communities may be shaped by non-neutral and roughly separate processes.

Recent advances in understanding vitiligo.

PubMed

Manga, Prashiela; Elbuluk, Nada; Orlow, Seth J

2016-01-01

Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.

Regulatory elements driving the expression of skeletal lineage reporters differ during bone development and adulthood.

PubMed

Stiers, Pieter-Jan; van Gastel, Nick; Moermans, Karen; Stockmans, Ingrid; Carmeliet, Geert

2017-12-01

To improve bone healing or regeneration more insight in the fate and role of the different skeletal cell types is required. Mouse models for fate mapping and lineage tracing of skeletal cells, using stage-specific promoters, have advanced our understanding of bone development, a process that is largely recapitulated during bone repair. However, validation of these models is often only performed during development, whereas proof of the activity and specificity of the used promoters during the bone regenerative process is limited. Here, we show that the regulatory elements of the 6kb collagen type II promoter are not adequate to drive gene expression during bone repair. Similarly, the 2.3kb promoter of collagen type I lacks activity in adult mice, but the 3.2kb promoter is suitable. Furthermore, Cre-mediated fate mapping allows the visualization of progeny, but this label retention may hinder to distinguish these cells from ones with active expression of the marker at later time points. Together, our results show that the lineage-specific regulatory elements driving gene expression during bone development differ from those required later in life and during bone repair, and justify validation of lineage-specific cell tracing and gene silencing strategies during fracture healing and bone regenerative applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Electromagnetic interference modeling and suppression techniques in variable-frequency drive systems

NASA Astrophysics Data System (ADS)

Yang, Le; Wang, Shuo; Feng, Jianghua

2017-11-01

Electromagnetic interference (EMI) causes electromechanical damage to the motors and degrades the reliability of variable-frequency drive (VFD) systems. Unlike fundamental frequency components in motor drive systems, high-frequency EMI noise, coupled with the parasitic parameters of the trough system, are difficult to analyze and reduce. In this article, EMI modeling techniques for different function units in a VFD system, including induction motors, motor bearings, and rectifierinverters, are reviewed and evaluated in terms of applied frequency range, model parameterization, and model accuracy. The EMI models for the motors are categorized based on modeling techniques and model topologies. Motor bearing and shaft models are also reviewed, and techniques that are used to eliminate bearing current are evaluated. Modeling techniques for conventional rectifierinverter systems are also summarized. EMI noise suppression techniques, including passive filter, Wheatstone bridge balance, active filter, and optimized modulation, are reviewed and compared based on the VFD system models.

Analysis of field-oriented controlled induction motor drives under sensor faults and an overview of sensorless schemes.

PubMed

Arun Dominic, D; Chelliah, Thanga Raj

2014-09-01

To obtain high dynamic performance on induction motor drives (IMD), variable voltage and variable frequency operation has to be performed by measuring speed of rotation and stator currents through sensors and fed back them to the controllers. When the sensors are undergone a fault, the stability of control system, may be designed for an industrial process, is disturbed. This paper studies the negative effects on a 12.5 hp induction motor drives when the field oriented control system is subjected to sensor faults. To illustrate the importance of this study mine hoist load diagram is considered as shaft load of the tested machine. The methods to recover the system from sensor faults are discussed. In addition, the various speed sensorless schemes are reviewed comprehensively. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Simulation of drive of mechanisms, working in specific conditions

NASA Astrophysics Data System (ADS)

Ivanovskaya, A. V.; Rybak, A. T.

2018-05-01

This paper presents a method for determining the dynamic loads on the lifting actuator device other than the conventional methods, for example, ship windlass. For such devices, the operation of their drives is typical under special conditions: different environments, the influence of hydrometeorological factors, a high level of vibration, variability of loading, etc. Hoisting devices working in such conditions are not considered in the standard; however, relevant studies concern permissible parameters of the drive devices of this kind. As an example, the article studied the work deck lifting devices - windlass. To construct a model, the windlass is represented by a rod of the variable cross-section. As a result, a mathematical model of the longitudinal oscillations of such rod is obtained. Analytic dependencies have also been obtained to determine the natural frequencies of the lowest forms of oscillations, which are necessary and are the basis for evaluating the parameters of operation of this type of the device.

A network-based, integrative study to identify core biological pathways that drive breast cancer clinical subtypes

PubMed Central

Dutta, B; Pusztai, L; Qi, Y; André, F; Lazar, V; Bianchini, G; Ueno, N; Agarwal, R; Wang, B; Shiang, C Y; Hortobagyi, G N; Mills, G B; Symmans, W F; Balázsi, G

2012-01-01

Background: The rapid collection of diverse genome-scale data raises the urgent need to integrate and utilise these resources for biological discovery or biomedical applications. For example, diverse transcriptomic and gene copy number variation data are currently collected for various cancers, but relatively few current methods are capable to utilise the emerging information. Methods: We developed and tested a data-integration method to identify gene networks that drive the biology of breast cancer clinical subtypes. The method simultaneously overlays gene expression and gene copy number data on protein–protein interaction, transcriptional-regulatory and signalling networks by identifying coincident genomic and transcriptional disturbances in local network neighborhoods. Results: We identified distinct driver-networks for each of the three common clinical breast cancer subtypes: oestrogen receptor (ER)+, human epidermal growth factor receptor 2 (HER2)+, and triple receptor-negative breast cancers (TNBC) from patient and cell line data sets. Driver-networks inferred from independent datasets were significantly reproducible. We also confirmed the functional relevance of a subset of randomly selected driver-network members for TNBC in gene knockdown experiments in vitro. We found that TNBC driver-network members genes have increased functional specificity to TNBC cell lines and higher functional sensitivity compared with genes selected by differential expression alone. Conclusion: Clinical subtype-specific driver-networks identified through data integration are reproducible and functionally important. PMID:22343619

Microbial Gene Abundance and Expression Patterns across a River to Ocean Salinity Gradient

PubMed Central

Fortunato, Caroline S.; Crump, Byron C.

2015-01-01

Microbial communities mediate the biogeochemical cycles that drive ecosystems, and it is important to understand how these communities are affected by changing environmental conditions, especially in complex coastal zones. As fresh and marine waters mix in estuaries and river plumes, the salinity, temperature, and nutrient gradients that are generated strongly influence bacterioplankton community structure, yet, a parallel change in functional diversity has not been described. Metagenomic and metatranscriptomic analyses were conducted on five water samples spanning the salinity gradient of the Columbia River coastal margin, including river, estuary, plume, and ocean, in August 2010. Samples were pre-filtered through 3 μm filters and collected on 0.2 μm filters, thus results were focused on changes among free-living microbial communities. Results from metagenomic 16S rRNA sequences showed taxonomically distinct bacterial communities in river, estuary, and coastal ocean. Despite the strong salinity gradient observed over sampling locations (0 to 33), the functional gene profiles in the metagenomes were very similar from river to ocean with an average similarity of 82%. The metatranscriptomes, however, had an average similarity of 31%. Although differences were few among the metagenomes, we observed a change from river to ocean in the abundance of genes encoding for catabolic pathways, osmoregulators, and metal transporters. Additionally, genes specifying both bacterial oxygenic and anoxygenic photosynthesis were abundant and expressed in the estuary and plume. Denitrification genes were found throughout the Columbia River coastal margin, and most highly expressed in the estuary. Across a river to ocean gradient, the free-living microbial community followed three different patterns of diversity: 1) the taxonomy of the community changed strongly with salinity, 2) metabolic potential was highly similar across samples, with few differences in functional gene abundance from river to ocean, and 3) gene expression was highly variable and generally was independent of changes in salinity. PMID:26536246

Microbial Gene Abundance and Expression Patterns across a River to Ocean Salinity Gradient.

PubMed

Fortunato, Caroline S; Crump, Byron C

2015-01-01

Microbial communities mediate the biogeochemical cycles that drive ecosystems, and it is important to understand how these communities are affected by changing environmental conditions, especially in complex coastal zones. As fresh and marine waters mix in estuaries and river plumes, the salinity, temperature, and nutrient gradients that are generated strongly influence bacterioplankton community structure, yet, a parallel change in functional diversity has not been described. Metagenomic and metatranscriptomic analyses were conducted on five water samples spanning the salinity gradient of the Columbia River coastal margin, including river, estuary, plume, and ocean, in August 2010. Samples were pre-filtered through 3 μm filters and collected on 0.2 μm filters, thus results were focused on changes among free-living microbial communities. Results from metagenomic 16S rRNA sequences showed taxonomically distinct bacterial communities in river, estuary, and coastal ocean. Despite the strong salinity gradient observed over sampling locations (0 to 33), the functional gene profiles in the metagenomes were very similar from river to ocean with an average similarity of 82%. The metatranscriptomes, however, had an average similarity of 31%. Although differences were few among the metagenomes, we observed a change from river to ocean in the abundance of genes encoding for catabolic pathways, osmoregulators, and metal transporters. Additionally, genes specifying both bacterial oxygenic and anoxygenic photosynthesis were abundant and expressed in the estuary and plume. Denitrification genes were found throughout the Columbia River coastal margin, and most highly expressed in the estuary. Across a river to ocean gradient, the free-living microbial community followed three different patterns of diversity: 1) the taxonomy of the community changed strongly with salinity, 2) metabolic potential was highly similar across samples, with few differences in functional gene abundance from river to ocean, and 3) gene expression was highly variable and generally was independent of changes in salinity.

The Landscape of A-to-I RNA Editome Is Shaped by Both Positive and Purifying Selection

PubMed Central

Kong, Yimeng; Pan, Bohu; Chen, Longxian; Wang, Hongbing; Hao, Pei; Li, Xuan

2016-01-01

The hydrolytic deamination of adenosine to inosine (A-to-I editing) in precursor mRNA induces variable gene products at the post-transcription level. How and to what extent A-to-I RNA editing diversifies transcriptome is not fully characterized in the evolution, and very little is known about the selective constraints that drive the evolution of RNA editing events. Here we present a study on A-to-I RNA editing, by generating a global profile of A-to-I editing for a phylogeny of seven Drosophila species, a model system spanning an evolutionary timeframe of approximately 45 million years. Of totally 9281 editing events identified, 5150 (55.5%) are located in the coding sequences (CDS) of 2734 genes. Phylogenetic analysis places these genes into 1,526 homologous families, about 5% of total gene families in the fly lineages. Based on conservation of the editing sites, the editing events in CDS are categorized into three distinct types, representing events on singleton genes (type I), and events not conserved (type II) or conserved (type III) within multi-gene families. While both type I and II events are subject to purifying selection, notably type III events are positively selected, and highly enriched in the components and functions of the nervous system. The tissue profiles are documented for three editing types, and their critical roles are further implicated by their shifting patterns during holometabolous development and in post-mating response. In conclusion, three A-to-I RNA editing types are found to have distinct evolutionary dynamics. It appears that nervous system functions are mainly tested to determine if an A-to-I editing is beneficial for an organism. The coding plasticity enabled by A-to-I editing creates a new class of binary variations, which is a superior alternative to maintain heterozygosity of expressed genes in a diploid mating system. PMID:27467689

Gene sequence variability of the three surface proteins of human respiratory syncytial virus (HRSV) in Texas.

PubMed

Tapia, Lorena I; Shaw, Chad A; Aideyan, Letisha O; Jewell, Alan M; Dawson, Brian C; Haq, Taha R; Piedra, Pedro A

2014-01-01

Human respiratory syncytial virus (HRSV) has three surface glycoproteins: small hydrophobic (SH), attachment (G) and fusion (F), encoded by three consecutive genes (SH-G-F). A 270-nt fragment of the G gene is used to genotype HRSV isolates. This study genotyped and investigated the variability of the gene and amino acid sequences of the three surface proteins of HRSV strains collected from 1987 to 2005 from one center. Sixty original clinical isolates and 5 prototype strains were analyzed. Sequences containing SH, F and G genes were generated, and multiple alignments and phylogenetic trees were analyzed. Genetic variability by protein domains comparing virus genotypes was assessed. Complete sequences of the SH-G-F genes were obtained for all 65 samples: HRSV-A = 35; HRSV-B = 30. In group A strains, genotypes GA5 and GA2 were predominant. For HRSV-B strains, the genotype GB4 was predominant from 1992 to 1994 and only genotype BA viruses were detected in 2004-2005. Different genetic variability at nucleotide level was detected between the genes, with G gene being the most variable and the highest variability detected in the 270-nt G fragment that is frequently used to genotype the virus. High variability (>10%) was also detected in the signal peptide and transmembrane domains of the F gene of HRSV A strains. Variability among the HRSV strains resulting in non-synonymous changes was detected in hypervariable domains of G protein, the signal peptide of the F protein, a not previously defined domain in the F protein, and the antigenic site Ø in the pre-fusion F. Divergent trends were observed between HRSV -A and -B groups for some functional domains. A diverse population of HRSV -A and -B genotypes circulated in Houston during an 18 year period. We hypothesize that diverse sequence variation of the surface protein genes provide HRSV strains a survival advantage in a partially immune-protected community.

Gene Sequence Variability of the Three Surface Proteins of Human Respiratory Syncytial Virus (HRSV) in Texas

PubMed Central

Tapia, Lorena I.; Shaw, Chad A.; Aideyan, Letisha O.; Jewell, Alan M.; Dawson, Brian C.; Haq, Taha R.; Piedra, Pedro A.

2014-01-01

Human respiratory syncytial virus (HRSV) has three surface glycoproteins: small hydrophobic (SH), attachment (G) and fusion (F), encoded by three consecutive genes (SH-G-F). A 270-nt fragment of the G gene is used to genotype HRSV isolates. This study genotyped and investigated the variability of the gene and amino acid sequences of the three surface proteins of HRSV strains collected from 1987 to 2005 from one center. Sixty original clinical isolates and 5 prototype strains were analyzed. Sequences containing SH, F and G genes were generated, and multiple alignments and phylogenetic trees were analyzed. Genetic variability by protein domains comparing virus genotypes was assessed. Complete sequences of the SH-G-F genes were obtained for all 65 samples: HRSV-A = 35; HRSV-B = 30. In group A strains, genotypes GA5 and GA2 were predominant. For HRSV-B strains, the genotype GB4 was predominant from 1992 to 1994 and only genotype BA viruses were detected in 2004–2005. Different genetic variability at nucleotide level was detected between the genes, with G gene being the most variable and the highest variability detected in the 270-nt G fragment that is frequently used to genotype the virus. High variability (>10%) was also detected in the signal peptide and transmembrane domains of the F gene of HRSV A strains. Variability among the HRSV strains resulting in non-synonymous changes was detected in hypervariable domains of G protein, the signal peptide of the F protein, a not previously defined domain in the F protein, and the antigenic site Ø in the pre-fusion F. Divergent trends were observed between HRSV -A and -B groups for some functional domains. A diverse population of HRSV -A and -B genotypes circulated in Houston during an 18 year period. We hypothesize that diverse sequence variation of the surface protein genes provide HRSV strains a survival advantage in a partially immune-protected community. PMID:24625544

Genetic Competence Drives Genome Diversity in Bacillus subtilis

PubMed Central

Chevreux, Bastien; Serra, Cláudia R; Schyns, Ghislain; Henriques, Adriano O

2018-01-01

Abstract Prokaryote genomes are the result of a dynamic flux of genes, with increases achieved via horizontal gene transfer and reductions occurring through gene loss. The ecological and selective forces that drive this genomic flexibility vary across species. Bacillus subtilis is a naturally competent bacterium that occupies various environments, including plant-associated, soil, and marine niches, and the gut of both invertebrates and vertebrates. Here, we quantify the genomic diversity of B. subtilis and infer the genome dynamics that explain the high genetic and phenotypic diversity observed. Phylogenomic and comparative genomic analyses of 42 B. subtilis genomes uncover a remarkable genome diversity that translates into a core genome of 1,659 genes and an asymptotic pangenome growth rate of 57 new genes per new genome added. This diversity is due to a large proportion of low-frequency genes that are acquired from closely related species. We find no gene-loss bias among wild isolates, which explains why the cloud genome, 43% of the species pangenome, represents only a small proportion of each genome. We show that B. subtilis can acquire xenologous copies of core genes that propagate laterally among strains within a niche. While not excluding the contributions of other mechanisms, our results strongly suggest a process of gene acquisition that is largely driven by competence, where the long-term maintenance of acquired genes depends on local and global fitness effects. This competence-driven genomic diversity provides B. subtilis with its generalist character, enabling it to occupy a wide range of ecological niches and cycle through them. PMID:29272410

Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase.

PubMed

Yancopoulos, G D; Blackwell, T K; Suh, H; Hood, L; Alt, F W

1986-01-31

We have recently proposed that a common recombinase performs all of the many variable region gene assembly events in B and T cells, and that the specificity of these joining events is mediated by regulating the "accessibility" of the involved gene segments. To test this possibility, we have introduced "accessible" T cell receptor (TCR) variable region gene segments into a pre-B cell line capable of recombining endogenous and transfected immunoglobulin (Ig) variable region gene segments. Although the corresponding "inaccessible" endogenous TCR gene segments do not rearrange in this line or in B cells in general, the introduced TCR gene segments join very frequently and, in fact, closely resemble introduced Ig gene segments in their recombination characteristics. These observations suggest a new role for conventional Ig transcriptional enhancers--recombinational enhancement. Our studies provide insight into additional aspects of the joining mechanism such as N region insertion, aberrant joining, and recombination-recognition sequence requirements for joining.

Rates of evolution in stress-related genes are associated with habitat preference in two Cardamine lineages

PubMed Central

2012-01-01

Background Elucidating the selective and neutral forces underlying molecular evolution is fundamental to understanding the genetic basis of adaptation. Plants have evolved a suite of adaptive responses to cope with variable environmental conditions, but relatively little is known about which genes are involved in such responses. Here we studied molecular evolution on a genome-wide scale in two species of Cardamine with distinct habitat preferences: C. resedifolia, found at high altitudes, and C. impatiens, found at low altitudes. Our analyses focussed on genes that are involved in stress responses to two factors that differentiate the high- and low-altitude habitats, namely temperature and irradiation. Results High-throughput sequencing was used to obtain gene sequences from C. resedifolia and C. impatiens. Using the available A. thaliana gene sequences and annotation, we identified nearly 3,000 triplets of putative orthologues, including genes involved in cold response, photosynthesis or in general stress responses. By comparing estimated rates of molecular substitution, codon usage, and gene expression in these species with those of Arabidopsis, we were able to evaluate the role of positive and relaxed selection in driving the evolution of Cardamine genes. Our analyses revealed a statistically significant higher rate of molecular substitution in C. resedifolia than in C. impatiens, compatible with more efficient positive selection in the former. Conversely, the genome-wide level of selective pressure is compatible with more relaxed selection in C. impatiens. Moreover, levels of selective pressure were heterogeneous between functional classes and between species, with cold responsive genes evolving particularly fast in C. resedifolia, but not in C. impatiens. Conclusions Overall, our comparative genomic analyses revealed that differences in effective population size might contribute to the differences in the rate of protein evolution and in the levels of selective pressure between the C. impatiens and C. resedifolia lineages. The within-species analyses also revealed evolutionary patterns associated with habitat preference of two Cardamine species. We conclude that the selective pressures associated with the habitats typical of C. resedifolia may have caused the rapid evolution of genes involved in cold response. PMID:22257588

Spermatogenesis Drives Rapid Gene Creation and Masculinization of the X Chromosome in Stalk-Eyed Flies (Diopsidae).

PubMed

Baker, Richard H; Narechania, Apurva; DeSalle, Rob; Johns, Philip M; Reinhardt, Josephine A; Wilkinson, Gerald S

2016-03-26

Throughout their evolutionary history, genomes acquire new genetic material that facilitates phenotypic innovation and diversification. Developmental processes associated with reproduction are particularly likely to involve novel genes. Abundant gene creation impacts the evolution of chromosomal gene content and general regulatory mechanisms such as dosage compensation. Numerous studies in model organisms have found complex and, at times contradictory, relationships among these genomic attributes highlighting the need to examine these patterns in other systems characterized by abundant sexual selection. Therefore, we examined the association among novel gene creation, tissue-specific gene expression, and chromosomal gene content within stalk-eyed flies. Flies in this family are characterized by strong sexual selection and the presence of a newly evolved X chromosome. We generated RNA-seq transcriptome data from the testes for three species within the family and from seven additional tissues in the highly dimorphic species,Teleopsis dalmanni Analysis of dipteran gene orthology reveals dramatic testes-specific gene creation in stalk-eyed flies, involving numerous gene families that are highly conserved in other insect groups. Identification of X-linked genes for the three species indicates that the X chromosome arose prior to the diversification of the family. The most striking feature of this X chromosome is that it is highly masculinized, containing nearly twice as many testes-specific genes as expected based on its size. All the major processes that may drive differential sex chromosome gene content-creation of genes with male-specific expression, development of male-specific expression from pre-existing genes, and movement of genes with male-specific expression-are elevated on the X chromosome ofT. dalmanni This masculinization occurs despite evidence that testes expressed genes do not achieve the same levels of gene expression on the X chromosome as they do on the autosomes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Identification of landscape features influencing gene flow: How useful are habitat selection models?

Treesearch

Gretchen H. Roffler; Michael K. Schwartz; Kristine Pilgrim; Sandra L. Talbot; George K. Sage; Layne G. Adams; Gordon Luikart

2016-01-01

Understanding how dispersal patterns are influenced by landscape heterogeneity is critical for modeling species connectivity. Resource selection function (RSF) models are increasingly used in landscape genetics approaches. However, because the ecological factors that drive habitat selection may be different from those influencing dispersal and gene flow, it is...

WUS and STM-based reporter genes for studying meristem development in poplar

USDA-ARS?s Scientific Manuscript database

We describe the development of a reporter system for monitoring meristem initiation in poplar using promoters of poplar homologs to the meristem-active regulatory genes WUSCHEL (WUS) and SHOOTMERISTEMLESS (STM). When ~3 kb of the 5’ flanking regions of close homologs were used to drive expression o...

Does the parasite-mediated selection drive the MHC class IIB diversity in wild populations of European chub (Squalius cephalus)?

PubMed

Seifertová, Mária; Jarkovský, Jiří; Šimková, Andrea

2016-04-01

The genes of major histocompatibility complex (MHC) provide an excellent opportunity to study host-parasite relationships because they are expected to evolve in response to parasites and variation in parasite communities. In this study, we investigated the potential role of parasite-mediated selection acting on MHC class IIB (DAB) genes in European chub (Squalius cephalus) natural populations. We found significant differences between populations in metazoan parasites, neutral and adaptive genetic diversities. The analyses based on pairwise data revealed that populations with dissimilar MHC allelic profiles were geographically distant populations with significantly different diversity in microsatellites and a dissimilar composition of parasite communities. The results from the generalized estimating equations method (GEE) on the level of individuals revealed that metazoan parasite load in European chub was influenced by the diversity of DAB alleles as well as by the diversity of neutral genetic markers and host traits reflecting condition and immunocompetence. The multivariate co-inertia analysis showed specific associations between DAB alleles and parasite species. DAB1-like alleles were more involved in associations with ectoparasites, while DAB3-like alleles were positively associated with endoparasites which could suggest potential differences between DAB genes caused by different selection pressure. Our study revealed that parasite-mediated selection is not the only variable affecting MHC diversity in European chub; however, we strongly support the role of neutral processes as the main driver of DAB diversity across populations. In addition, our study contributes to the understanding of the evolution of MHC genes in wild living fish.

Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism

PubMed Central

Maguire, S. M.; Phelps, S. M.

2017-01-01

DNA methylation can cause stable changes in neuronal gene expression, but we know little about its role in individual differences in the wild. In this study, we focus on the vasopressin 1a receptor (avpr1a), a gene extensively implicated in vertebrate social behaviour, and explore natural variation in DNA methylation, genetic polymorphism and neuronal gene expression among 30 wild prairie voles (Microtus ochrogaster). Examination of CpG density across 8 kb of the locus revealed two distinct CpG islands overlapping promoter and first exon, characterized by few CpG polymorphisms. We used a targeted bisulfite sequencing approach to measure DNA methylation across approximately 3 kb of avpr1a in the retrosplenial cortex, a brain region implicated in male space use and sexual fidelity. We find dramatic variation in methylation across the avrp1a locus, with pronounced diversity near the exon–intron boundary and in a genetically variable putative enhancer within the intron. Among our wild voles, differences in cortical avpr1a expression correlate with DNA methylation in this putative enhancer, but not with the methylation status of the promoter. We also find an unusually high number of polymorphic CpG sites (polyCpGs) in this focal enhancer. One polyCpG within this enhancer (polyCpG 2170) may drive variation in expression either by disrupting transcription factor binding motifs or by changing local DNA methylation and chromatin silencing. Our results contradict some assumptions made within behavioural epigenetics, but are remarkably concordant with genome-wide studies of gene regulation. PMID:28280564

DEFINING MOLECULAR AND CELLULAR RESPONSES AFTER LOW AND HIGH LINEAR ENERGY TRANSFER RADIATIONS TO DEVELOP BIOMARKERS OF CARCINOGENIC RISK OR THERAPEUTIC OUTCOME

PubMed Central

Story, Michael; Ding, Liang-hao; Brock, William A.; Ang, K. Kian; Alsbeih, Ghazi; Minna, John; Park, Seongmi; Das, Amit

2015-01-01

The variability in radiosensitivity across the human population is in part governed by genetic factors. The ability to predict therapeutic response, identify individuals at greatest risk for adverse clinical responses after therapeutic radiation doses, or identify individuals at high risk for carcinogenesis from environmental or medical radiation exposures has a medical and economic impact on both the individual and society at-large. As radiotherapy incorporates particles, particularly particles larger than protons, into therapy the need for such discriminators, that is, biomarkers will become ever more important. Cellular assays for survival, DNA repair or chromatid/chromosomal analysis have been used to identify at risk individuals but they are not clinically applicable. Newer approaches such as genome wide analysis of gene expression or single nucleotide polymorphisms, and small copy number variations within chromosomes are examples of technologies being applied to the discovery process. Gene expression analysis of primary or immortalized human cells suggests that there are distinct gene expression patterns associated with radiation exposure to both low and high linear energy transfer radiations and that those most radiosensitive are discernible by their basal gene expression patterns. However, because the genetic alterations that drive radioresponse may be subtle and cumulative, the need for large sample sizes of specific cell or tissue types is required. A systems biology approach will ultimately be necessary. Potential biomarkers from cell lines or animal models will require validation in a human setting where possible, and before being considered as a credible biomarker some understanding of the molecular mechanism is necessary. PMID:23032890

Domestication drive the changes of immune and digestive system of Eurasian perch (Perca fluviatilis).

PubMed

Chen, Xiaowen; Wang, Jun; Qian, Long; Gaughan, Sarah; Xiang, Wei; Ai, Tao; Fan, Zhenming; Wang, Chenghui

2017-01-01

Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process.

Epigenomic regulation of oncogenesis by chromatin remodeling.

PubMed

Kumar, R; Li, D-Q; Müller, S; Knapp, S

2016-08-25

Disruption of the intricate gene expression program represents one of major driving factors for the development, progression and maintenance of human cancer, and is often associated with acquired therapeutic resistance. At the molecular level, cancerous phenotypes are the outcome of cellular functions of critical genes, regulatory interactions of histones and chromatin remodeling complexes in response to dynamic and persistent upstream signals. A large body of genetic and biochemical evidence suggests that the chromatin remodelers integrate the extracellular and cytoplasmic signals to control gene activity. Consequently, widespread dysregulation of chromatin remodelers and the resulting inappropriate expression of regulatory genes, together, lead to oncogenesis. We summarize the recent developments and current state of the dysregulation of the chromatin remodeling components as the driving mechanism underlying the growth and progression of human tumors. Because chromatin remodelers, modifying enzymes and protein-protein interactions participate in interpreting the epigenetic code, selective chromatin remodelers and bromodomains have emerged as new frontiers for pharmacological intervention to develop future anti-cancer strategies to be used either as single-agent or in combination therapies with chemotherapeutics or radiotherapy.

Domestication drive the changes of immune and digestive system of Eurasian perch (Perca fluviatilis)

PubMed Central

Chen, Xiaowen; Wang, Jun; Qian, Long; Gaughan, Sarah; Xiang, Wei; Ai, Tao; Fan, Zhenming; Wang, Chenghui

2017-01-01

Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process. PMID:28257494

Biomechanical cell regulatory networks as complex adaptive systems in relation to cancer.

PubMed

Feller, Liviu; Khammissa, Razia Abdool Gafaar; Lemmer, Johan

2017-01-01

Physiological structure and function of cells are maintained by ongoing complex dynamic adaptive processes in the intracellular molecular pathways controlling the overall profile of gene expression, and by genes in cellular gene regulatory circuits. Cytogenetic mutations and non-genetic factors such as chronic inflammation or repetitive trauma, intrinsic mechanical stresses within extracellular matrix may induce redirection of gene regulatory circuits with abnormal reactivation of embryonic developmental programmes which can now drive cell transformation and cancer initiation, and later cancer progression and metastasis. Some of the non-genetic factors that may also favour cancerization are dysregulation in epithelial-mesenchymal interactions, in cell-to-cell communication, in extracellular matrix turnover, in extracellular matrix-to-cell interactions and in mechanotransduction pathways. Persistent increase in extracellular matrix stiffness, for whatever reason, has been shown to play an important role in cell transformation, and later in cancer cell invasion. In this article we review certain cell regulatory networks driving carcinogenesis, focussing on the role of mechanical stresses modulating structure and function of cells and their extracellular matrices.

Virtual Genomes in Flux: An Interplay of Neutrality and Adaptability Explains Genome Expansion and Streamlining

PubMed Central

Cuypers, Thomas D.; Hogeweg, Paulien

2012-01-01

The picture that emerges from phylogenetic gene content reconstructions is that genomes evolve in a dynamic pattern of rapid expansion and gradual streamlining. Ancestral organisms have been estimated to possess remarkably rich gene complements, although gene loss is a driving force in subsequent lineage adaptation and diversification. Here, we study genome dynamics in a model of virtual cells evolving to maintain homeostasis. We observe a pattern of an initial rapid expansion of the genome and a prolonged phase of mutational load reduction. Generally, load reduction is achieved by the deletion of redundant genes, generating a streamlining pattern. Load reduction can also occur as a result of the generation of highly neutral genomic regions. These regions can expand and contract in a neutral fashion. Our study suggests that genome expansion and streamlining are generic patterns of evolving systems. We propose that the complex genotype to phenotype mapping in virtual cells as well as in their biological counterparts drives genome size dynamics, due to an emerging interplay between adaptation, neutrality, and evolvability. PMID:22234601

Unveiling the pan-genome of the SXT/R391 family of ICEs: molecular characterisation of new variable regions of SXT/R391-like ICEs detected in Pseudoalteromonas sp. and Vibrio scophthalmi.

PubMed

Rodríguez-Blanco, Arturo; Lemos, Manuel L; Osorio, Carlos R

2016-08-01

Integrating conjugative elements (ICEs) of the SXT/R391 family have been identified in fish-isolated bacterial strains collected from marine aquaculture environments of the northwestern Iberian Peninsula. Here we analysed the variable regions of two ICEs, one preliminarily characterised in a previous study (ICEVscSpa3) and one newly identified (ICEPspSpa1). Bacterial strains harboring these ICEs were phylogenetically assigned to Vibrio scophthalmi and Pseudoalteromonas sp., thus constituting the first evidence of SXT/R391-like ICEs in the genus Pseudoalteromonas to date. Variable DNA regions, which confer element-specific properties to ICEs of this family, were characterised. Interestingly, the two ICEs contained 29 genes not found in variable DNA insertions of previously described ICEs. Most notably, variable gene content for ICEVscSpa3 showed similarity to genes potentially involved in housekeeping functions of replication, nucleotide metabolism and transcription. For these genes, closest homologues were found clustered in the genome of Pseudomonas psychrotolerans L19, suggesting a transfer as a block to ICEVscSpa3. Genes encoding antibiotic resistance, restriction modification systems and toxin/antitoxin systems were absent from hotspots of ICEVscSpa3. In contrast, the variable gene content of ICEPspSpa1 included genes involved in restriction/modification functions in two different hotspots and genes related to ICE maintenance. The present study unveils a relatively large number of novel genes in SXT/R391-ICEs, and demonstrates the major role of ICE elements as contributors to horizontal gene transfer.

A Comparison of Actual and Perceived Problem Drinking among Driving while Intoxicated (DWI) Offenders

ERIC Educational Resources Information Center

Barry, Adam E.; Dennis, Maurice

2011-01-01

Problem drinkers account for a large proportion of those convicted of driving while intoxicated (DWI). Nevertheless, specific rates of problem drinking among DWI offenders have been shown to exhibit wide variability. Therefore, we seek to (a) present the rate and severity of problem drinking among a sample of DWI offenders, (b) contrast…

Diversification in continental island archipelagos: new evidence on the roles of fragmentation, colonization and gene flow on the genetic divergence of Aegean Nigella (Ranunculaceae).

PubMed

Jaros, Ursula; Tribsch, Andreas; Comes, Hans Peter

2018-02-12

Disentangling the relative roles of past fragmentation (vicariance), colonization (dispersal) and post-divergence gene flow in the genetic divergence of continental island organisms remains a formidable challenge. Amplified fragment length polymorphisms (AFLPs) were used to (1) gain further insights into the biogeographical processes underlying the Pleistocene diversification of the Aegean Nigella arvensis complex; (2) evaluate the role of potential key factors driving patterns of population genetic variability (mating system, geographical isolation and historical contingencies); and (3) test the robustness of conclusions previously drawn from chloroplast (cp) DNA. Genetic diversity was analysed for 235 AFLP markers from 48 populations (497 individuals) representing 11 taxa of the complex using population genetic methods and Bayesian assignment tests. Most designated taxa are identifiable as genetically distinct units. Both fragmentation and dispersal-driven diversification processes occurred at different geological time scales, from Early to Late Pleistocene, specifically (1) sea barrier-induced vicariant speciation in the Cyclades, the Western Cretan Strait and Ikaria; and (2) bi-regional colonizations of the 'Southern Aegean Island Arc' from the Western vs. Eastern Aegean mainland, followed by allopatric divergences in Crete vs. Rhodos and Karpathos/Kasos. Outcrossing island taxa experienced drift-related demographic processes that are magnified in the two insular selfing species. Population genetic differentiation on the mainland seems largely driven by dispersal limitation, while in the Central Aegean it may still be influenced by historical events (island fragmentation and sporadic long-distance colonization). The biogeographical history of Aegean Nigella is more complex than expected for a strictly allopatric vicariant model of divergence. Nonetheless, the major phylogeographical boundaries of this radiation are largely congruent with the geography and history of islands, with little evidence for ongoing gene exchange between divergent taxa. The present results emphasize the need to investigate further biological and landscape features and contemporary vs. historical processes in driving population divergence and taxon diversification in Aegean plant radiations. © The Author(s) 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Promoter architecture dictates cell-to-cell variability in gene expression.

PubMed

Jones, Daniel L; Brewster, Robert C; Phillips, Rob

2014-12-19

Variability in gene expression among genetically identical cells has emerged as a central preoccupation in the study of gene regulation; however, a divide exists between the predictions of molecular models of prokaryotic transcriptional regulation and genome-wide experimental studies suggesting that this variability is indifferent to the underlying regulatory architecture. We constructed a set of promoters in Escherichia coli in which promoter strength, transcription factor binding strength, and transcription factor copy numbers are systematically varied, and used messenger RNA (mRNA) fluorescence in situ hybridization to observe how these changes affected variability in gene expression. Our parameter-free models predicted the observed variability; hence, the molecular details of transcription dictate variability in mRNA expression, and transcriptional noise is specifically tunable and thus represents an evolutionarily accessible phenotypic parameter. Copyright © 2014, American Association for the Advancement of Science.

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

Lee Kerkhof

The focus of our research was to provide a comprehensive study of the bacterioplankton populations off the coast of New Jersey near the Rutgers University marine field station using terminal restriction fragment polymorphism analysis (TRFLP) coupled to 16S rRNA genes for large data set studies. Our three revised objectives to this study became: (1) to describe bacterioplankton population dynamics in the Mid Atlantic Bight using TRFLP analysis of 16S rRNA genes. (2) to determine whether spatial and temporal factors are driving bacterioplankton community dynamics in the MAB using monthly samping along our transect line over a 2-year period. (3) tomore » identify dominant members of a coastal bacterioplankton population by clonal library analysis of 16S rDNA genes and sequencing of PCR product corresponding to specific TRFLP peaks in the data set. Although open ocean time-series sites have been areas of microbial research for years, relatively little was known about the population dynamics of bacterioplankton communities in the coastal ocean on kilometer spatial and seasonal temporal scales. To gain a better understanding of microbial community variability, monthly samples of bacterial biomass were collected in 1995-1996 along a 34-km transect near the Long-Term Ecosystem Observatory (LEO-15) off the New Jersey coast. Surface and bottom sampling was performed at seven stations along a transect line with depths ranging from 1 to 35m (n=178). The data revealed distinct temporal patterns among the bacterioplankton communities in the Mid-Atlantic Bight rather than grouping by sample location or depth (figure 2-next page). Principal components analysis models supported the temporal patterns. In addition, partial least squares regression modeling could not discern a significant correlation from traditional oceanographic physical and phytoplankton nutrient parameters on overall bacterial community variability patterns at LEO-15. These results suggest factors not traditionally measured during oceanographic studies are structuring coastal microbial communities.« less

A new scheme of general hybrid projective complete dislocated synchronization

NASA Astrophysics Data System (ADS)

Chu, Yan-dong; Chang, Ying-Xiang; An, Xin-lei; Yu, Jian-Ning; Zhang, Jian-Gang

2011-03-01

Based on the Lyapunov stability theorem, a new type of chaos synchronization, general hybrid projective complete dislocated synchronization (GHPCDS), is proposed under the framework of drive-response systems. The difference between the GHPCDS and complete synchronization is that every state variable of drive system does not equal the corresponding state variable, but equal other ones of response system while evolving in time. The GHPCDS includes complete dislocated synchronization, dislocated anti-synchronization and projective dislocated synchronization as its special item. As examples, the Lorenz chaotic system, Rössler chaotic system, hyperchaotic Chen system and hyperchaotic Lü system are discussed. Numerical simulations are given to show the effectiveness of these methods.

Research on the supercapacitor support schemes for LVRT of variable-frequency drive in the thermal power plant

NASA Astrophysics Data System (ADS)

Han, Qiguo; Zhu, Kai; Shi, Wenming; Wu, Kuayu; Chen, Kai

2018-02-01

In order to solve the problem of low voltage ride through(LVRT) of the major auxiliary equipment’s variable-frequency drive (VFD) in thermal power plant, the scheme of supercapacitor paralleled in the DC link of VFD is put forward, furthermore, two solutions of direct parallel support and voltage boost parallel support of supercapacitor are proposed. The capacitor values for the relevant motor loads are calculated according to the law of energy conservation, and they are verified by Matlab simulation. At last, a set of test prototype is set up, and the test results prove the feasibility of the proposed schemes.

Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives.

PubMed

Maranhão, Geraldo Neves De A; Brito, Alaan Ubaiara; Leal, Anderson Marques; Fonseca, Jéssica Kelly Silva; Macêdo, Wilson Negrão

2015-09-22

In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD) for use in Photovoltaic Pumping Systems (PVPS) is proposed. The fuzzy logic system (FLS) used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR) is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC) voltage level in the VSD with a good performance.

Variable/Multispeed Rotorcraft Drive System Concepts

NASA Technical Reports Server (NTRS)

Stevens, Mark A.; Handschuh, Robert F.; Lewicki, David G.

2009-01-01

Several recent studies for advanced rotorcraft have identified the need for variable, or multispeed-capable rotors. A speed change of up to 50 percent has been proposed for future rotorcraft to improve vehicle performance. Varying rotor speed during flight not only requires a rotor capable of performing effectively over the extended operation speed and load range, but also requires an advanced propulsion system to provide the required speed changes. A study has been completed, which investigated possible drive system arrangements to accommodate up to the 50 percent speed change. These concepts are presented. The most promising configurations are identified and will be developed for future validation testing.

Modelling landscape change in paddy fields using logistic regression and GIS

NASA Astrophysics Data System (ADS)

Franjaya, E. E.; Syartinilia; Setiawan, Y.

2018-05-01

Paddy field in karawang district, as an important agricultural land in west java, has been decreased since 1994. From previous study, paddy fields dominantly turned into built area. The changes were almost occured in the middle area of the district where roadways, industries, settlements, and commercial buildings were existed. These were estimated as driving forces. But, we still need to prove it. This study aimed to construct the paddy field probability change model, subsequently the driving forces will be obtained. GIS combined with logistic regression using environmental variables were used as main method in this study. Ten environmental variables were elevation 0–500 m, elevation>500 m, slope<8%, slope>8%, CBD, build up area, river, irrigation, toll and national roadway, and collector and local roadway. The result indicated that four variables were significantly played as driving forces (slope>8%, CBD area, build up area, and collector and local roadway). Paddy field has high, medium, and low probability to change which covered about 27.8%, 7.8%, and 64.4% area in Karawang respectively. Based on landscape ecology, the recommendation that suitable with landscape change is adaptive management.

Extended Visual Glances Away from the Roadway are Associated with ADHD- and Texting-Related Driving Performance Deficits in Adolescents.

PubMed

Kingery, Kathleen M; Narad, Megan; Garner, Annie A; Antonini, Tanya N; Tamm, Leanne; Epstein, Jeffery N

2015-08-01

The purpose of the research study was to determine whether ADHD- and texting-related driving impairments are mediated by extended visual glances away from the roadway. Sixty-one adolescents (ADHD =28, non-ADHD =33; 62% male; 11% minority) aged 16-17 with a valid driver's license were videotaped while engaging in a driving simulation that included a No Distraction, Hands-Free Phone Conversation, and Texting condition. Two indicators of visual inattention were coded: 1) percentage of time with eyes diverted from the roadway; and 2) number of extended (greater than 2 s) visual glances away from the roadway. Adolescents with ADHD displayed significantly more visual inattention to the roadway on both visual inattention measures. Increased lane position variability among adolescents with ADHD compared to those without ADHD during the Hands-Free Phone Conversation and Texting conditions was mediated by an increased number of extended glances away from the roadway. Similarly, texting resulted in decreased visual attention to the roadway. Finally, increased lane position variability during texting was also mediated by the number of extended glances away from the roadway. Both ADHD and texting impair visual attention to the roadway and the consequence of this visual inattention is increased lane position variability. Visual inattention is implicated as a possible mechanism for ADHD- and texting-related deficits and suggests that driving interventions designed to address ADHD- or texting-related deficits in adolescents need to focus on decreasing extended glances away from the roadway.

Driving Control for Electric Power Assisted Wheelchair Based on Regenerative Brake

NASA Astrophysics Data System (ADS)

Seki, Hirokazu; Takahashi, Kazuki; Tadakuma, Susumu

This paper describes a novel safety driving control scheme for electric power assisted wheelchairs based on the regenerative braking system. “Electric power assisted wheelchair” which assists the driving force by electric motors is expected to be widely used as a mobility support system for elderly people and disabled people, however, the safe and secure driving performance especially on downhill roads must be further improved because electric power assisted wheelchairs have no braking devices. The proposed control system automatically switches the driving mode, from “assisting mode” to “braking mode”, based on the wheelchair's velocity and the declined angle and smoothly suppresses the wheelchair's acceleration based on variable duty ratio control in order to realize the safety driving and to improve the ride quality. Some experiments on the practical roads and subjective evaluation show the effectiveness of the proposed control system.

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma | Office of Cancer Genomics

Cancer.gov

In a recent Nature article, Morin et al. uncovered a novel role for chromatin modification in driving the progression of two non-Hodgkin lymphomas (NHLs), follicular lymphoma and diffuse large B-cell lymphoma. Through DNA and RNA sequencing of 117 tumor samples and 10 assorted cell lines, the authors identified and validated 109 genes with multiple mutations in these B-cell NHLs. Of the 109 genes, several genes not previously linked to lymphoma demonstrated positive selection for mutation including two genes involved in histone modification, MLL2 and MEF2B.

Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.

PubMed

Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich

2004-03-01

By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.

Traction Drives for Zero Stick-Slip Robots, and Reaction Free, Momentum Balanced Systems

NASA Technical Reports Server (NTRS)

Anderson, William J.; Shipitalo, William; Newman, Wyatt

1995-01-01

Two differential (dual input, single output) drives (a roller-gear and a pure roller), and a momentum balanced (single input, dual output) drive (pure roller ) were designed, fabricated, and tested. The differential drives are each rated at 295 rad/sec (2800 rpm) input speed, 450 N-m (4,000 in-lbf) output torque. The momentum balanced drive is rated at 302 rad/sec (2880 rpm) input speed, and dual output torques of 434N-m (3840 in-lbf). The Dual Input Differential Roller-Gear Drive (DC-700) has a planetary roller-gear system with a reduction ratio (one input driving the output with the second input fixed) of 29.23: 1. The Dual Input Differential Roller Drive (DC-500) has a planetary roller system with a reduction ratio of approximately 24:1. Each of the differential drives features dual roller-gear or roller arrangements consisting of a sun, four first row planets, four second row planets, and a ring. The Momentum Balanced (Grounded Ring) Drive (DC-400) has a planetary roller system with a reduction ratio of 24:1 with both outputs counterrotating at equal speed. Its single roller cluster consists of a sun, five first and five second row planets, a roller cage or spider and a ring. Outputs are taken from both the roller cage and the ring which counterrotate. Test results reported for all three drives include angular and torque ripple (linearity and cogging), viscous and Coulomb friction, and forward and reverse power efficiency. Of the two differential drives, the Differential Roller Drive had better linearity and less cogging than did the Differential Roller-Gear Drive, but it had higher friction and lower efficiency (particularly at low power throughput levels). Use of full preloading rather than a variable preload system in the Differential Roller Drive assessed a heavy penalty in part load efficiency. Maximum measured efficiency (ratio of power out to power in) was 95% for the Differential Roller-Gear Drive and 86% for the Differential Roller Drive. The Momentum Balanced (Grounded Ring) Drive performed as expected kinematically. Reduction r-atios to the two counterrotating outputs (design nominal=24:1) were measured to be 23.98:1 and 24.12:1 at zero load.. At 25ONm (2200 in-lbf) output torque the ratio changed 2% due to roller creep. This drive was the smoothest of all three as determined from linearity and cogging tests, and maximum measured efficiency (ratio of power out to power in) was 95%. The disadvantages of full preloading as comvared to variable preload were apparent in this drive as in the Differential Roller Drive. Efficiencies at part load were low, but improved dramatically with increases in torque. These were consistent with friction measurements which indicated losses primarily from Coulomb friction. The initial preload level setting was low so roller slip was encountered at higher torques during testing.

Variability of particle number emissions from diesel and hybrid diesel-electric buses in real driving conditions.

PubMed

Sonntag, Darrell B; Gao, H Oliver; Holmén, Britt A

2008-08-01

A linear mixed model was developed to quantify the variability of particle number emissions from transit buses tested in real-world driving conditions. Two conventional diesel buses and two hybrid diesel-electric buses were tested throughout 2004 under different aftertreatments, fuels, drivers, and bus routes. The mixed model controlled the confounding influence of factors inherent to on-board testing. Statistical tests showed that particle number emissions varied significantly according to the after treatment, bus route, driver, bus type, and daily temperature, with only minor variability attributable to differences between fuel types. The daily setup and operation of the sampling equipment (electrical low pressure impactor) and mini-dilution system contributed to 30-84% of the total random variability of particle measurements among tests with diesel oxidation catalysts. By controlling for the sampling day variability, the model better defined the differences in particle emissions among bus routes. In contrast, the low particle number emissions measured with diesel particle filters (decreased by over 99%) did not vary according to operating conditions or bus type but did vary substantially with ambient temperature.

Heterologous gene expression driven by carbonic anhydrase gene promoter in Dunaliella salina

NASA Astrophysics Data System (ADS)

Chai, Yurong; Lu, Yumin; Wang, Tianyun; Hou, Weihong; Xue, Lexun

2006-12-01

Dunaliella salina, a halotolerant unicellular green alga without a rigid cell wall, can live in salinities ranging from 0.05 to 5 mol/L NaCl. These features of D. salina make it an ideal host for the production of antibodies, oral vaccine, and commercially valuable polypeptides. To produce high level of heterologous proteins from D. salina, highly efficient promoters are required to drive expression of target genes under controlled condition. In the present study, we cloned a 5' franking region of 1.4 kb from the carbonic anhydrase ( CAH) gene of D. salina by genomic walking and PCR. The fragment was ligated to the pMD18-T vector and characterized. Sequence analysis indicated that this region contained conserved motifs, including a TATA- like box and CAAT-box. Tandem (GT)n repeats that had a potential role of transcriptional control, were also found in this region. The transcription start site (TSS) of the CAH gene was determined by 5' RACE and nested PCR method. Transformation assays showed that the 1.4 kb fragment was able to drive expression of the selectable bar (bialaphos resistance) gene when the fusion was transformed into D. salina by biolistics. Northern blotting hybridizations showed that the bar transcript was most abundant in cells grown in 2 mol/L NaCl, and less abundant in 0.5 mol/L NaCl, indicating that expression of the bar gene was induced at high salinity. These results suggest the potential use of the CAH gene promoter to induce the expression of heterologous genes in D. salina under varied salt condition.

Gene conversion and positive selection driving the evolution of the Caenorhabditis ssp. ZIM/HIM-8 protein family.

PubMed

Liu, Qingpo

2009-03-01

In C. elegans, four C2H2 zinc-finger proteins (ZIM-1, ZIM-2, ZIM-3, and HIM-8), which are arranged in tandem, mediate chromosome-specific pairing and synapsis during meiosis. The zim/him-8 genes from three Caenorhabditis species were contrasted in an effort to investigate the mechanisms driving their evolution. Here it is shown that the preservation of higher degree of sequence similarity in the N-terminal portion, particularly in several regions within the second exon between paralogous zim genes (especially between zim-1 and zim-3), is due to independent interparalogue gene conversions. However, the evolutionary force is not uniformly strong across species. The present data reveal that more frequent gene conversion events have occurred in C. elegans, whereas only gene conversions between zim-1 and zim-3 are detected in C. remanei. Although gene conversions are predicted to be present among zim-1, zim-2, and zim-3 in C. briggsae, the conversion tracts between zim-1/zim-2 and zim-2/zim-3 are very short. Moreover, positive selection analysis was performed on the basis of the significantly discordant phylogenies reconstructed using the N- and C-terminal sequences, respectively. Several codon sites located in the regions that are supposed not to have experienced gene conversions are predicted to be under the influence of positive selection. In comparison, stronger positive selection has acted on the C-terminal region relative to the N-terminal region. Thus, the zim/him-8 genes that evolve concertedly have also been shown to undergo adaptive diversifying selection.

The other white-nose syndrome transcriptome: Tolerant and susceptible hosts respond differently to the pathogen Pseudogymnoascus destructans.

PubMed

Davy, Christina M; Donaldson, Michael E; Willis, Craig K R; Saville, Barry J; McGuire, Liam P; Mayberry, Heather; Wilcox, Alana; Wibbelt, Gudrun; Misra, Vikram; Bollinger, Trent; Kyle, Christopher J

2017-09-01

Mitigation of emerging infectious diseases that threaten global biodiversity requires an understanding of critical host and pathogen responses to infection. For multihost pathogens where pathogen virulence or host susceptibility is variable, host-pathogen interactions in tolerant species may identify potential avenues for adaptive evolution in recently exposed, susceptible hosts. For example, the fungus Pseudogymnoascus destructans causes white-nose syndrome (WNS) in hibernating bats and is responsible for catastrophic declines in some species in North America, where it was recently introduced. Bats in Europe and Asia, where the pathogen is endemic, are only mildly affected. Different environmental conditions among Nearctic and Palearctic hibernacula have been proposed as an explanation for variable disease outcomes, but this hypothesis has not been experimentally tested. We report the first controlled, experimental investigation of response to P. destructans in a tolerant, European species of bat (the greater mouse-eared bat, Myotis myotis ). We compared body condition, disease outcomes and gene expression in control (sham-exposed) and exposed M. myotis that hibernated under controlled environmental conditions following treatment. Tolerant M. myotis experienced extremely limited fungal growth and did not exhibit symptoms of WNS. However, we detected no differential expression of genes associated with immune response in exposed bats, indicating that immune response does not drive tolerance of P. destructans in late hibernation. Variable responses to P. destructans among bat species cannot be attributed solely to environmental or ecological factors. Instead, our results implicate coevolution with the pathogen, and highlight the dynamic nature of the "white-nose syndrome transcriptome." Interspecific variation in response to exposure by the host (and possibly pathogen) emphasizes the importance of context in studies of the bat-WNS system, and robust characterization of genetic responses to exposure in various hosts and the pathogen should precede any attempts to use particular bat species as generalizable "model hosts."

Heritability of DUI convictions: a twin study of driving under the influence of alcohol.

PubMed

Anum, Emmanuel A; Silberg, Judy; Retchin, Sheldon M

2014-02-01

The study was undertaken to assess the relative contributions of genetic and environmental influences on drunk-driving. Driving records of a cohort of male and female twins (N = 17,360) from the Mid-Atlantic Twin Registry were examined. Structural equation models were used to estimate the magnitude of genetic and environmental effects on male and female phenotypes, and test for gender differences. There were significant gender and age effects. Compared with females, males were five times more likely to engage in driving under the influence. Among persons aged 21-49 years, the risk for drunk-driving was eight times that for those aged 50+ years and five times greater than those ≤20 years. In both males and females, aged 21-49 years, a large proportion (57%) of the variance in drunk-driving was due to genetic factors and the remaining 43% due to individual specific environmental influences. Drunk-driving is under significant genetic influence in both males and females. Our findings suggest that a different set of genes influence DUIs in men and women.

Unifying measures of gene function and evolution.

PubMed

Wolf, Yuri I; Carmel, Liran; Koonin, Eugene V

2006-06-22

Recent genome analyses revealed intriguing correlations between variables characterizing the functioning of a gene, such as expression level (EL), connectivity of genetic and protein-protein interaction networks, and knockout effect, and variables describing gene evolution, such as sequence evolution rate (ER) and propensity for gene loss. Typically, variables within each of these classes are positively correlated, e.g. products of highly expressed genes also have a propensity to be involved in many protein-protein interactions, whereas variables between classes are negatively correlated, e.g. highly expressed genes, on average, evolve slower than weakly expressed genes. Here, we describe principal component (PC) analysis of seven genome-related variables and propose biological interpretations for the first three PCs. The first PC reflects a gene's 'importance', or the 'status' of a gene in the genomic community, with positive contributions from knockout lethality, EL, number of protein-protein interaction partners and the number of paralogues, and negative contributions from sequence ER and gene loss propensity. The next two PCs define a plane that seems to reflect the functional and evolutionary plasticity of a gene. Specifically, PC2 can be interpreted as a gene's 'adaptability' whereby genes with high adaptability readily duplicate, have many genetic interaction partners and tend to be non-essential. PC3 also might reflect the role of a gene in organismal adaptation albeit with a negative rather than a positive contribution of genetic interactions; we provisionally designate this PC 'reactivity'. The interpretation of PC2 and PC3 as measures of a gene's plasticity is compatible with the observation that genes with high values of these PCs tend to be expressed in a condition- or tissue-specific manner. Functional classes of genes substantially vary in status, adaptability and reactivity, with the highest status characteristic of the translation system and cytoskeletal proteins, highest adaptability seen in cellular processes and signalling genes, and top reactivity characteristic of metabolic enzymes.

Examining relationships between anxiety and dangerous driving.

PubMed

Dula, Chris S; Adams, Cristi L; Miesner, Michael T; Leonard, Robin L

2010-11-01

Driving anxiety that has developed following crashes has been studied relatively frequently, but anxiety per se and its effects on driving has not as yet garnered much attention in the literature. The current study included 1121 participants and found higher levels of general anxiety were related to a wide variety of dangerous driving behaviors. While there were clear and expected sex differences on many dangerous driving variables, there were still more such differences with regard to anxiety levels and independent of sex, higher levels of anxiety were associated with greater levels of dangerous driving. Of particular import, it was found that the high anxiety group had caused significantly more crashes and engaged in more DUI episodes than the low and/or medium anxiety groups. Taken as a whole, the results suggest there is a tremendous need for more research in the area of anxiety and dangerous driving and that interventions for highly anxious drivers may well be warranted. 2010 Elsevier Ltd. All rights reserved.

Neighborhood environment and physical activity among older adults: do the relationships differ by driving status?

PubMed

Ding, Ding; Sallis, James F; Norman, Gregory J; Frank, Lawrence D; Saelens, Brian E; Kerr, Jacqueline; Conway, Terry L; Cain, Kelli; Hovell, Melbourne F; Hofstetter, C Richard; King, Abby C

2014-07-01

Some attributes of neighborhood environments are associated with physical activity among older adults. This study examined whether the associations were moderated by driving status. Older adults from neighborhoods differing in walkability and income completed written surveys and wore accelerometers (N = 880, mean age = 75 years, 56% women). Neighborhood environments were measured by geographic information systems and validated questionnaires. Driving status was defined on the basis of a driver's license, car ownership, and feeling comfortable to drive. Outcome variables included accelerometer-based physical activity and self-reported transport and leisure walking. Multilevel generalized linear regression was used. There was no significant Neighborhood Attribute × Driving Status interaction with objective physical activity or reported transport walking. For leisure walking, almost all environmental attributes were positive and significant among driving older adults but not among nondriving older adults (five significant interactions at p < .05). The findings suggest that driving status is likely to moderate the association between neighborhood environments and older adults' leisure walking.

Correlates of drug use and driving among undergraduate college students.

PubMed

Kohn, Christine; Saleheen, Hassan; Borrup, Kevin; Rogers, Steve; Lapidus, Garry

2014-01-01

Drug use by drivers is a significant and growing highway safety problem. College students are an important population to understand drugged driving. The objective of this study was to examine correlates of drugged driving among undergraduate college students. We conducted an anonymous, confidential, 24-question survey at a large New England public university during the 2010-2011 academic year among undergraduates in courses that met a graduation requirement. Data include demographics; academics; housing status; lifestyle; personal values; high school/college drug use; and driving following alcohol use, drug use, or both; and as a passenger with a driver who used alcohol, drugs, or both. Descriptive statistics were calculated. Chi-square tests compared driver alcohol use, drug use, or both with demographic, academic, and lifestyle variables. Logistic regression analyses were performed with drugged driving as the dependent variable. Odds ratios and corresponding 95 percent confidence intervals were calculated for each of the potential explanatory variables in relation to the outcome. Four hundred forty-four of 675 students completed surveys (66% participation rate). Participants were representative of the student body with a mean age of 19.4 (±1.3 years), 51 percent male, 75 percent white, and 10 percent Hispanic. Seventy-eight percent lived on campus, 93 percent had a driver's license, and 37 percent had access to a car. Students disagreed that cannabinoids impair driving (18%) compared to other drugs (17%), stimulants (13%), depressants (11%), hallucinogens (8%), and alcohol (7%). Twenty-three percent drove after alcohol use and 22 percent drove after drug use. Forty-one percent reported having been a passenger with a driver who had been drinking and 37 percent with a driver using drugs. Drugged driving was more likely among males vs. females (30% vs. 14%, P < .01), those living off campus (34% vs. 19%, P < .01), those reporting that parties are important (33% vs. 14%, P < .01), those reporting that community service is not important (28% vs. 18%, P < .05), those reporting that religion is not important (28% vs. 14%, P < .01), and those reporting personal drug use in high school (75% vs. 14%, P < .01) and well as that their best friends used drugs in high school (42% vs. 12%, P < .01) and college (50% vs. 8%, P < .01). Those factors most associated with drugged driving included using drugs in high school (odds ratio [OR] = 9.5, 95% confidence interval [CI]: 4.6-19.6) and best friends in college used drugs regularly (OR = 6.2, 95% CI: 3.4-11.6). Self-reported drugged driving and riding as a passenger with a drugged driver is common among subgroups of college students. The identification of undergraduate subgroups at risk for drugged driving will guide the design and implementation of traffic safety activities.

Self-Regulation of Driving Behavior in People with Parkinson Disease.

PubMed

Stolwyk, Renerus J; Scally, Karen A; Charlton, Judith L; Bradshaw, John L; Iansek, Robert; Georgiou-Karistianis, Nellie

2015-06-01

To determine the extent and nature of driving self-regulation in drivers with Parkinson disease (PD) and factors associated with self-regulatory practices. Although people with PD have consistently been shown to have driving impairments, few studies have examined self-regulatory driving practices and their relationship to driving performance. We used a self-report driving questionnaire to examine driving self-regulation in 37 drivers with PD and 37 healthy age-matched controls. We also analyzed factors associated with self-regulatory practices, primarily demographic, disease-related, psychological, and simulated driving performance variables. The drivers with PD reported significantly higher rates of self-perceived decline in their driving ability (P=0.008) and driving significantly shorter distances per week (P=0.004) than controls. Unfamiliar situations (P=0.009), in-car distractions (P<0.001), low visibility conditions (P=0.004), and long journeys (P=0.003) were particularly challenging for the drivers with PD, and their pattern of driving avoidance mirrored these difficulties. The use of self-regulatory strategies among drivers with PD was associated with female sex (rho=0.42, P=0.009) and perceived decline in driving ability (rho=-0.55, P<0.001), but not with age or objective measures of disease severity, cognition, or simulated driving performance. Drivers with PD reported driving less overall and restricting their driving to avoid particularly difficult circumstances. Further research is warranted on effective use of self-regulation strategies to improve driving performance in people with PD.

Computer Simulations and Literature Survey of Continuously Variable Transmissions for Use in Buses

DOT National Transportation Integrated Search

1981-12-01

Numerous studies have been conducted on the concept of flywheel energy storage for buses. Flywheel systems require a continuously variable transmission (CVT) of some type to transmit power between the flywheel and the drive wheels. However, a CVT can...

Variable message fog hazard warning signs to control vehicle operating characteristics : interim report, Interstate 5, North Albany.

DOT National Transportation Integrated Search

1972-04-01

This project is aimed at determining the effectiveness of variable message signs in controlling traffic on an Interstate highway during periods of hazardous driving conditions such as fog, vehicle accidents, or congestion. : The effectiveness of the ...

STOCHASTIC DESCRIPTION OF SUBGRID POLLUTANT VARIABILITY IN CMAQ

EPA Science Inventory

This paper describes a tool for investigating and describing fine scale spatial variability in model concentration fields with the goal of improving the use of air quality models for driving exposure modeling to assess human risk to hazardous air pollutants or air toxics. Region...

Variable-speed, portable routing skate

NASA Technical Reports Server (NTRS)

Pesch, W. A.

1967-01-01

Lightweight, portable, variable-speed routing skate is used on heavy metal subassemblies which are impractical to move to a stationary machine. The assembly, consisting of the housing with rollers, router, and driving mechanism with transmission, weighs about forty pounds. Both speed and depth of cut are adjustable.

Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine.

PubMed

Lambers Heerspink, Hiddo J; Oberbauer, Rainer; Perco, Paul; Heinzel, Andreas; Heinze, Georg; Mayer, Gert; Mayer, Bernd

2015-08-01

Diabetic kidney disease (DKD) is a complex, multifactorial disease and is associated with a high risk of renal and cardiovascular morbidity and mortality. Clinical practice guidelines for diabetes recommend essentially identical treatments for all patients without taking into account how the individual responds to the instituted therapy. Yet, individuals vary widely in how they respond to medications and therefore optimal therapy differs between individuals. Understanding the underlying molecular mechanisms of variability in drug response will help tailor optimal therapy. Polymorphisms in genes related to drug pharmacokinetics have been used to explore mechanisms of response variability in DKD, but with limited success. The complex interaction between genetic make-up and environmental factors on the abundance of proteins and metabolites renders pharmacogenomics alone insufficient to fully capture response variability. A complementary approach is to attribute drug response variability to individual variability in underlying molecular mechanisms involved in the progression of disease. The interplay of different processes (e.g. inflammation, fibrosis, angiogenesis, oxidative stress) appears to drive disease progression, but the individual contribution of each process varies. Drugs at the other hand address specific targets and thereby interfere in certain disease-associated processes. At this level, biomarkers may help to gain insight into which specific pathophysiological processes are involved in an individual followed by a rational assessment whether a specific drug's mode of action indeed targets the relevant process at hand. This article describes the conceptual background and data-driven workflow developed by the SysKid consortium aimed at improving characterization of the molecular mechanisms underlying DKD at the interference of the molecular impact of individual drugs in order to tailor optimal therapy to individual patients. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

DNA transposon-based gene vehicles - scenes from an evolutionary drive

PubMed Central

2013-01-01

DNA transposons are primitive genetic elements which have colonized living organisms from plants to bacteria and mammals. Through evolution such parasitic elements have shaped their host genomes by replicating and relocating between chromosomal loci in processes catalyzed by the transposase proteins encoded by the elements themselves. DNA transposable elements are constantly adapting to life in the genome, and self-suppressive regulation as well as defensive host mechanisms may assist in buffering ‘cut-and-paste’ DNA mobilization until accumulating mutations will eventually restrict events of transposition. With the reconstructed Sleeping Beauty DNA transposon as a powerful engine, a growing list of transposable elements with activity in human cells have moved into biomedical experimentation and preclinical therapy as versatile vehicles for delivery and genomic insertion of transgenes. In this review, we aim to link the mechanisms that drive transposon evolution with the realities and potential challenges we are facing when adapting DNA transposons for gene transfer. We argue that DNA transposon-derived vectors may carry inherent, and potentially limiting, traits of their mother elements. By understanding in detail the evolutionary journey of transposons, from host colonization to element multiplication and inactivation, we may better exploit the potential of distinct transposable elements. Hence, parallel efforts to investigate and develop distinct, but potent, transposon-based vector systems will benefit the broad applications of gene transfer. Insight and clever optimization have shaped new DNA transposon vectors, which recently debuted in the first DNA transposon-based clinical trial. Learning from an evolutionary drive may help us create gene vehicles that are safer, more efficient, and less prone for suppression and inactivation. PMID:24320156

Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

PubMed

Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

1990-11-01

Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia.

Lymphotoxin activation by human T-cell leukemia virus type I-infected cell lines: role for NF-kappa B.

PubMed Central

Paul, N L; Lenardo, M J; Novak, K D; Sarr, T; Tang, W L; Ruddle, N H

1990-01-01

Human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of biologically active lymphotoxin (LT; tumor necrosis factor-beta) protein and LT mRNA. To understand the regulation of LT transcription by HTLV-I, we analyzed the ability of a series of deletions of the LT promoter to drive the chloramphenicol acetyltransferase (CAT) reporter gene in HTLV-I-positive MT-2 cells. The smallest LT promoter fragment (-140 to +77) that was able to drive CAT activity contained a site that was similar to the immunoglobulin kappa-chain NF-kappa B-binding site. Since the HTLV-I tax gene activates the nuclear form of NF-kappa B, this finding suggested a possible means of HTLV-I activation of LT production. We found that the LT kappa B-like site specifically formed a complex with NF-kappa B-containing nuclear extract from MT-2, C81-66-45, and other activated T cells. Mutation of the LT kappa B site in the context of the LT promoter (-293 to +77) (mutant M1) reduced the ability of the promoter to drive the CAT gene in HTLV-I-infected and noninfected human T-cell lines. These data suggest a general role for NF-kappa B activation in the induction of LT gene transcription. Activation of LT in HTLV-I-infected cells may explain the pathology associated with HTLV-I infection, including the hypercalcemia that is prevalent in adult T-cell leukemia. Images PMID:1976820

Genomic Heat Shock Element Sequences Drive Cooperative Human Heat Shock Factor 1 DNA Binding and Selectivity*

PubMed Central

Jaeger, Alex M.; Makley, Leah N.; Gestwicki, Jason E.; Thiele, Dennis J.

2014-01-01

The heat shock transcription factor 1 (HSF1) activates expression of a variety of genes involved in cell survival, including protein chaperones, the protein degradation machinery, anti-apoptotic proteins, and transcription factors. Although HSF1 activation has been linked to amelioration of neurodegenerative disease, cancer cells exhibit a dependence on HSF1 for survival. Indeed, HSF1 drives a program of gene expression in cancer cells that is distinct from that activated in response to proteotoxic stress, and HSF1 DNA binding activity is elevated in cycling cells as compared with arrested cells. Active HSF1 homotrimerizes and binds to a DNA sequence consisting of inverted repeats of the pentameric sequence nGAAn, known as heat shock elements (HSEs). Recent comprehensive ChIP-seq experiments demonstrated that the architecture of HSEs is very diverse in the human genome, with deviations from the consensus sequence in the spacing, orientation, and extent of HSE repeats that could influence HSF1 DNA binding efficacy and the kinetics and magnitude of target gene expression. To understand the mechanisms that dictate binding specificity, HSF1 was purified as either a monomer or trimer and used to evaluate DNA-binding site preferences in vitro using fluorescence polarization and thermal denaturation profiling. These results were compared with quantitative chromatin immunoprecipitation assays in vivo. We demonstrate a role for specific orientations of extended HSE sequences in driving preferential HSF1 DNA binding to target loci in vivo. These studies provide a biochemical basis for understanding differential HSF1 target gene recognition and transcription in neurodegenerative disease and in cancer. PMID:25204655

Nonstationary time series prediction combined with slow feature analysis

NASA Astrophysics Data System (ADS)

Wang, G.; Chen, X.

2015-07-01

Almost all climate time series have some degree of nonstationarity due to external driving forces perturbing the observed system. Therefore, these external driving forces should be taken into account when constructing the climate dynamics. This paper presents a new technique of obtaining the driving forces of a time series from the slow feature analysis (SFA) approach, and then introduces them into a predictive model to predict nonstationary time series. The basic theory of the technique is to consider the driving forces as state variables and to incorporate them into the predictive model. Experiments using a modified logistic time series and winter ozone data in Arosa, Switzerland, were conducted to test the model. The results showed improved prediction skills.

Mediterranean scrubland and elevation drive gene flow of a Mediterranean carnivore, the Egyptian mongoose Herpestes ichneumon (Herpestidae)

Treesearch

Tania Barros; Samuel A. Cushman; Joao Carvalho; Carlos Fonseca

2016-01-01

Identifying the environmental features affecting gene flow across a species range is of extreme importance for conservation planning. We investigated the genetic structure of the Egyptian mongoose (Herpestes ichneumon) in Western Iberian Peninsula by analyzing the correlations between genetic distances and landscape resistance models. We evaluated several...

Worthy of their name: how floods drive outbreaks of two major floodwater mosquitoes (Diptera: Culicidae).

PubMed

Berec, Ludĕk; Gelbic, Ivan; Sebesta, Oldrich

2014-01-01

An understanding of how climate variables drive seasonal dynamics of mosquito populations is critical to mitigating negative impacts of potential outbreaks, including both nuisance effects and risk of mosquito-borne infectious disease. Here, we identify climate variables most affecting seasonal dynamics of two major floodwater mosquitoes, Aedes vexans (Meigen, 1830) and Aedes sticticus (Meigen, 1838) (Diptera: Culicidae), along the lower courses of the Dyje River, at the border between the Czech Republic and Austria. Monthly trap counts of both floodwater mosquitoes varied both across sites and years. Despite this variability, both models used to fit the observed data at all sites (and especially that for Ae. sticticus) and site-specific models fitted the observed data quite well. The most important climate variables we identified-temperature and especially flooding-were driving seasonal dynamics of both Aedes species. We suggest that flooding determines seasonal peaks in the monthly mosquito trap counts while temperature modulates seasonality in these counts. Hence, floodwater mosquitoes indeed appear worthy of their name. Moreover, the climate variables we considered for modeling were able reasonably to predict mosquito trap counts in the month ahead. Our study can help in planning flood management; timely notification of people, given that these mosquitoes are a real nuisance in this region; public health policy management to mitigate risk from such mosquito-borne diseases as that caused in humans by the Tahyna virus; and anticipating negative consequences of climate change, which are expected only to worsen unless floods, or the mosquitoes themselves, are satisfactorily managed.

Ergonomic evaluation of interior design of Shoka vehicle and proposing recommendations for improvement.

PubMed

Mazloumi, Adel; Mohammadreze, Fallah

2012-01-01

One of the applications of ergonomics disciplinary is designing driver workstation compatible to users' characteristics. The aim of this study was evaluation of interior design of Shoka vehicle with respect to the accommodation for Iranian population and proposing suggestions for customizing design of this vehicle. This study was a descriptive-analytical study conducted among thirty men from Iranian drivers population in 5, 50, 95 percentiles of the stature variable. Objective variables related to the occupant packaging and vehicle visual aspects including anthropometric variables, frontal, lateral, and side view and so on were investigated first. Then, subjective variables related to the driver mental workload and body comfort discomfort were studied using BMDMW and comfort questionnaires during 2-hour driving trial sessions. Occupant packaging variables and hand-arm angle showed the least accommodation percent (%53). Seating angles showed low accommodation as well (%73). Among three percentile groups there were no significant differences between the mean values of mental workload during two hours driving task. And, the mean value related to the comfort discomfort was 3.9 during driving sessions. Considering the findings in this study, it can be conclude that seating angles need correction and optimization. Taking mental workload results into account, it can be concluded that the interior design of the studied car had no influence on drivers' mental workload. From the aspect of comfort discomfort, Shoka vehicle showed neutral state among drivers. Optimizing seating angles, decreasing vibration, correcting stiffness of seating pan are suggested for customization of the ergonomics aspect of this vehicle.

Mileage, car ownership, experience of punishment avoidance, and the risky driving of young drivers.

PubMed

Scott-Parker, B; Watson, B; King, M J; Hyde, M K

2011-12-01

Young drivers are at greatest risk of injury or death from a car crash in the first 6 months of independent driving. In Queensland, the graduated driver licensing (GDL) program was extensively modified in July 2007 in order to reduce this risk. Increased mileage and car ownership have been found to play a role in risky driving, offenses, and crashes; however, GDL programs typically do not consider these variables. In addition, young novice drivers' experiences of punishment avoidance have not previously been examined. This article explores the mileage (duration and distance), car ownership, and punishment avoidance behaviors of young newly licensed intermediate (provisional) drivers and their relationship to risky driving, crashes, and offenses. Drivers (n = 1032) aged 17 to 19 years recruited from across Queensland for longitudinal research completed survey 1 exploring prelicense and learner experiences and sociodemographic characteristics. survey 2 explored the same variables with a subset of these drivers (n = 341) after they had completed their first 6 months of independent driving. Most young drivers in survey 2 reported owning a vehicle and paying attention to police presence. Drivers who had their own cars reported significantly greater mileage and more risky driving. Novices who drove more kilometers, spent more hours each week driving, or avoided actual and anticipated police presence were more likely to report risky driving. These drivers were also more likely to report being detected by police for a driving-related offense. The media, parents, friends, and other drivers play a pivotal role in informing novices of on-road police enforcement operations. GDL programs should incorporate education for the parent and novice driver regarding the increased risks associated with greater driving, particularly when the novice driver owns a vehicle. Parents should be encouraged to delay exclusive access to a vehicle. Parents should also consider whether their young novices will deliberately avoid police if they are aware of their location. This may reinforce not only the risky behavior but also young novices' beliefs that their parents condone this behavior.

Changes of Excitability in M1 Induced by Neuromuscular Electrical Stimulation Differ Between Presence and Absence of Voluntary Drive

ERIC Educational Resources Information Center

Sugawara, Kenichi; Tanabe, Shigeo; Higashi, Toshio; Tsurumi, Takamasa; Kasai, Tatsuya

2011-01-01

The aim of this study is to investigate excitability changes in the human motor cortex induced by variable therapeutic electrical stimulations (TESs) with or without voluntary drive. We recorded motor-evoked potentials (MEPs) from extensor and flexor carpi radialis (FCR) muscles at rest and during FCR muscle contraction after the application of…

Effects of vibration on occupant driving performance under simulated driving conditions.

PubMed

Azizan, Amzar; Fard, M; Azari, Michael F; Jazar, Reza

2017-04-01

Although much research has been devoted to the characterization of the effects of whole-body vibration on seated occupants' comfort, drowsiness induced by vibration has received less attention to date. There are also little validated measurement methods available to quantify whole body vibration-induced drowsiness. Here, the effects of vibration on drowsiness were investigated. Twenty male volunteers were recruited for this experiment. Drowsiness was measured in a driving simulator, before and after 30-min exposure to vibration. Gaussian random vibration, with 1-15 Hz frequency bandwidth was used for excitation. During the driving session, volunteers were required to obey the speed limit of 100 kph and maintain a steady position on the left-hand lane. A deviation in lane position, steering angle variability, and speed deviation were recorded and analysed. Alternatively, volunteers rated their subjective drowsiness by Karolinska Sleepiness Scale (KSS) scores every 5-min. Following 30-min of exposure to vibration, a significant increase of lane deviation, steering angle variability, and KSS scores were observed in all volunteers suggesting the adverse effects of vibration on human alertness level. Copyright © 2016 Elsevier Ltd. All rights reserved.

R2d2 Drives Selfish Sweeps in the House Mouse.

PubMed

Didion, John P; Morgan, Andrew P; Yadgary, Liran; Bell, Timothy A; McMullan, Rachel C; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J; Campbell, Karl J; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J; Crowley, James J; Chesler, Elissa J; Förster, Daniel W; French, John E; Gabriel, Sofia I; Gatti, Daniel M; Garland, Theodore; Giagia-Athanasopoulou, Eva B; Giménez, Mabel D; Grize, Sofia A; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C; Herman, Jeremy S; Holt, James M; Hua, Kunjie; Jolley, Wesley J; Lindholm, Anna K; López-Fuster, María J; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P; Searle, Jeremy B; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L; Thomas-Laemont, Patricia; Threadgill, David W; Ventura, Jacint; Weinstock, George M; Pomp, Daniel; Churchill, Gary A; Pardo-Manuel de Villena, Fernando

2016-06-01

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

R2d2 Drives Selfish Sweeps in the House Mouse

PubMed Central

Didion, John P.; Morgan, Andrew P.; Yadgary, Liran; Bell, Timothy A.; McMullan, Rachel C.; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J.; Campbell, Karl J.; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J.; Crowley, James J.; Chesler, Elissa J.; Förster, Daniel W.; French, John E.; Gabriel, Sofia I.; Gatti, Daniel M.; Garland, Theodore; Giagia-Athanasopoulou, Eva B.; Giménez, Mabel D.; Grize, Sofia A.; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C.; Herman, Jeremy S.; Holt, James M.; Hua, Kunjie; Jolley, Wesley J.; Lindholm, Anna K.; López-Fuster, María J.; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P.; Searle, Jeremy B.; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L.; Thomas-Laemont, Patricia; Threadgill, David W.; Ventura, Jacint; Weinstock, George M.; Pomp, Daniel; Churchill, Gary A.; Pardo-Manuel de Villena, Fernando

2016-01-01

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. PMID:26882987

The big five personality factors as predictors of driving status in older adults.

PubMed

Gadbois, Emily A; Dugan, Elizabeth

2015-02-01

Although factors including cognitive and health status have been associated with driving cessation in older adults, the role of psychosocial variables is not well studied. Previous research on young adult drivers has suggested that personality may be related to driving behavior, but this study is among the first to explore the relationship between driving status and the Big Five Model of personality for older adults. Data are from the Health and Retirement Study (2008 wave, n = 4,028). Descriptive, bivariate, and multiple logistic regression analyses were conducted. Neuroticism (β = -0.4511, p < .001) and agreeableness (β = -0.5058, p < .001) were associated with decreased likelihood of driving; extraversion (β = 0.4588, p < .001), openness (β = 0.5903, p < .001), and conscientiousness (β = 0.4077, p < .001) were associated with increased likelihood of driving, although results were partially mediated by including known risk factors. People who limited their driving to nearby locations were the most different from those who no longer drove. Personality adds a unique contribution to the prediction of late-life driving status. © The Author(s) 2014.

Distal regulatory regions restrict the expression of cis-linked genes to the tapetal cells.

PubMed

Franco, Luciana O; de O Manes, Carmem Lara; Hamdi, Said; Sachetto-Martins, Gilberto; de Oliveira, Dulce E

2002-04-24

The oleosin glycine-rich protein genes Atgrp-6, Atgrp-7, and Atgrp-8 occur in clusters in the Arabidopsis genome and are expressed specifically in the tapetum cells. The cis-regulatory regions involved in the tissue-specific gene expression were investigated by fusing different segments of the gene cluster to the uidA reporter gene. Common distal regulatory regions were identified that coordinate expression of the sequential genes. At least two of these genes were regulated spatially by proximal and distal sequences. The cis-acting elements (122 bp upstream of the transcriptional start point) drive the uidA expression to floral tissues, whereas distal 5' upstream regions restrict the gene activity to tapetal cells.

Self-rated driving habits among older adults with clinically-defined mild cognitive impairment, clinically-defined dementia, and normal cognition.

PubMed

O'Connor, Melissa L; Edwards, Jerri D; Bannon, Yvonne

2013-12-01

Older adults with clinically-defined dementia may report reducing their driving more than cognitively normal controls. However, it is unclear how these groups compare to individuals with clinically-defined mild cognitive impairment (MCI) in terms of driving behaviors. The current study investigated self-reported driving habits among adults age 60 and older with clinical MCI (n=41), clinical mild dementia (n=40), and normal cognition (n=43). Participants reported their driving status, driving frequency (days per week), and how often they avoided accessing the community, making left turns, driving at night, driving in unfamiliar areas, driving on high-traffic roads, and driving in bad weather. After adjusting for education, a MANCOVA revealed that participants with MCI and dementia avoided unfamiliar areas and high-traffic roads significantly more than normal participants. Participants with dementia also avoided left turns and accessing the community more than those with normal cognition and MCI (p<0.05 for all). The other driving variables did not significantly differ between groups. Thus, older adults with clinically-defined MCI, as well as those with dementia, avoided some complex driving situations more than cognitively intact adults. However, all diagnostic groups had similar rates of driving cessation and frequency. Future research should examine the safety implications of such findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sources of Variance in Baseline Gene Expression in the Rodent Liver

PubMed Central

Corton, J. Christopher; Bushel, Pierre R.; Fostel, Jennifer; O'Lone, Raegan B.

2012-01-01

The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variation due to individual, environmental, and technical factors. Analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in liver gene expression in the rodent. Here, studies which highlight contributions of different factors to gene expression variability in the rodent liver are discussed including a large meta-analysis of rat liver, which identified genes that vary in control animals in the absence of chemical treatment. Genes and their pathways that are the most and least variable were identified in a number of these studies. Life stage, fasting, sex, diet, circadian rhythm and liver lobe source can profoundly influence gene expression in the liver. Recognition of biological and technical factors that contribute to variability of background gene expression can help the investigator in the design of an experiment that maximizes sensitivity and reduces the influence of confounders that may lead to misinterpretation of genomic changes. The factors that contribute to variability in liver gene expression in rodents are likely analogous to those contributing to human interindividual variability in drug response and chemical toxicity. Identification of batteries of genes that are altered in a variety of background conditions could be used to predict responses to drugs and chemicals in appropriate models of the human liver. PMID:22230429

A description of neck motor performance, neck pain, fatigue, and mental effort while driving in a sample with chronic whiplash-associated disorders.

PubMed

Takasaki, Hiroshi; Treleaven, Julia; Johnston, Venerina; Van den Hoorn, Wolbert; Rakotonirainy, Andry; Jull, Gwendolen

2014-08-01

Individuals with chronic whiplash-associated disorders (WADs) often note driving as a difficult task. This study's aims were to (1) compare, while driving, neck motor performance, mental effort, and fatigue in individuals with chronic WAD against healthy controls and (2) investigate the relationships of these variables and neck pain to self-reported driving difficulty in the WAD group. This study involved 14 participants in each group (WAD and control). Measures included self-reported driving difficulty and measures of neck pain intensity, overall fatigue, mental effort, and neck motor performance (head rotation and upper trapezius activity) while driving a simulator. The WAD group had greater absolute path of head rotation in a simulated city area and used greater mental effort (P = 0.04), but there were no differences in other measures while driving compared with the controls (all P ≥ 0.05). Self-reported driving difficulty correlated moderately with neck pain intensity, fatigue level, and maximum velocity of head rotation while driving in the WAD group (all P < 0.05). Individuals with chronic WAD do not seem to have impaired neck motor performance while driving yet use greater mental effort. Neck pain, fatigue, and maximum head rotation velocity could be potential contributors to self-reported driving difficulty in this group.

Forward and reverse mutagenesis in C. elegans

PubMed Central

Kutscher, Lena M.; Shaham, Shai

2014-01-01

Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

Impacts of Interannual Variability in Biogenic VOC Emissions near Transitional Ozone Production Regimes

NASA Astrophysics Data System (ADS)

Geddes, J.

2017-12-01

Due to successful NOx emission controls, summertime ozone production chemistry in urban areas across North America is transitioning from VOC-limited to increasingly NOx-limited. In some regions where ozone production sensitivity is in transition, interannual variability in surrounding biogenic VOC emissions could drive fluctuations in the prevailing chemical regime and modify the impact of anthropogenic emission changes. I use satellite observations of HCHO and NO2 column density, along with a long-term simulation of atmospheric chemistry, to investigate the impact of interannual variability in biogenic isoprene sources near large metro areas. Peak emissions of isoprene in the model can vary by up to 20-60% in any given year compared to the long term mean, and this variability drives the majority of the variability in simulated local HCHO:NO2 ratios (a common proxy for ozone production sensitivity). The satellite observations confirm increasingly NOx-limited chemical regimes with large interannual variability. In several instances, the model and satellite observations suggest that variability in biogenic isoprene emissions could shift summertime ozone production from generally VOC- to generally NOx- sensitive (or vice versa). This would have implications for predicting the air quality impacts of anthropogenic emission changes in any given year, and suggests that drivers of biogenic emissions need to be well understood.

State Space Model with hidden variables for reconstruction of gene regulatory networks.

PubMed

Wu, Xi; Li, Peng; Wang, Nan; Gong, Ping; Perkins, Edward J; Deng, Youping; Zhang, Chaoyang

2011-01-01

State Space Model (SSM) is a relatively new approach to inferring gene regulatory networks. It requires less computational time than Dynamic Bayesian Networks (DBN). There are two types of variables in the linear SSM, observed variables and hidden variables. SSM uses an iterative method, namely Expectation-Maximization, to infer regulatory relationships from microarray datasets. The hidden variables cannot be directly observed from experiments. How to determine the number of hidden variables has a significant impact on the accuracy of network inference. In this study, we used SSM to infer Gene regulatory networks (GRNs) from synthetic time series datasets, investigated Bayesian Information Criterion (BIC) and Principle Component Analysis (PCA) approaches to determining the number of hidden variables in SSM, and evaluated the performance of SSM in comparison with DBN. True GRNs and synthetic gene expression datasets were generated using GeneNetWeaver. Both DBN and linear SSM were used to infer GRNs from the synthetic datasets. The inferred networks were compared with the true networks. Our results show that inference precision varied with the number of hidden variables. For some regulatory networks, the inference precision of DBN was higher but SSM performed better in other cases. Although the overall performance of the two approaches is compatible, SSM is much faster and capable of inferring much larger networks than DBN. This study provides useful information in handling the hidden variables and improving the inference precision.

A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

PubMed

Portales-Casamar, Elodie; Swanson, Douglas J; Liu, Li; de Leeuw, Charles N; Banks, Kathleen G; Ho Sui, Shannan J; Fulton, Debra L; Ali, Johar; Amirabbasi, Mahsa; Arenillas, David J; Babyak, Nazar; Black, Sonia F; Bonaguro, Russell J; Brauer, Erich; Candido, Tara R; Castellarin, Mauro; Chen, Jing; Chen, Ying; Cheng, Jason C Y; Chopra, Vik; Docking, T Roderick; Dreolini, Lisa; D'Souza, Cletus A; Flynn, Erin K; Glenn, Randy; Hatakka, Kristi; Hearty, Taryn G; Imanian, Behzad; Jiang, Steven; Khorasan-zadeh, Shadi; Komljenovic, Ivana; Laprise, Stéphanie; Liao, Nancy Y; Lim, Jonathan S; Lithwick, Stuart; Liu, Flora; Liu, Jun; Lu, Meifen; McConechy, Melissa; McLeod, Andrea J; Milisavljevic, Marko; Mis, Jacek; O'Connor, Katie; Palma, Betty; Palmquist, Diana L; Schmouth, Jean-François; Swanson, Magdalena I; Tam, Bonny; Ticoll, Amy; Turner, Jenna L; Varhol, Richard; Vermeulen, Jenny; Watkins, Russell F; Wilson, Gary; Wong, Bibiana K Y; Wong, Siaw H; Wong, Tony Y T; Yang, George S; Ypsilanti, Athena R; Jones, Steven J M; Holt, Robert A; Goldowitz, Daniel; Wasserman, Wyeth W; Simpson, Elizabeth M

2010-09-21

The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination "knockins" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type-specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.

High GC Content Cas9-Mediated Genome-Editing and Biosynthetic Gene Cluster Activation in Saccharopolyspora erythraea.

PubMed

Liu, Yong; Wei, Wen-Ping; Ye, Bang-Ce

2018-05-18

The overexpression of bacterial secondary metabolite biosynthetic enzymes is the basis for industrial overproducing strains. Genome editing tools can be used to further improve gene expression and yield. Saccharopolyspora erythraea produces erythromycin, which has extensive clinical applications. In this study, the CRISPR-Cas9 system was used to edit genes in the S. erythraea genome. A temperature-sensitive plasmid containing the PermE promoter, to drive Cas9 expression, and the Pj23119 and PkasO promoters, to drive sgRNAs, was designed. Erythromycin esterase, encoded by S. erythraea SACE_1765, inactivates erythromycin by hydrolyzing the macrolactone ring. Sequencing and qRT-PCR confirmed that reporter genes were successfully inserted into the SACE_1765 gene. Deletion of SACE_1765 in a high-producing strain resulted in a 12.7% increase in erythromycin levels. Subsequent PermE- egfp knock-in at the SACE_0712 locus resulted in an 80.3% increase in erythromycin production compared with that of wild type. Further investigation showed that PermE promoter knock-in activated the erythromycin biosynthetic gene clusters at the SACE_0712 locus. Additionally, deletion of indA (SACE_1229) using dual sgRNA targeting without markers increased the editing efficiency to 65%. In summary, we have successfully applied Cas9-based genome editing to a bacterial strain, S. erythraea, with a high GC content. This system has potential application for both genome-editing and biosynthetic gene cluster activation in Actinobacteria.

Long-Term and Short-Term Evolutionary Impacts of Transposable Elements on Drosophila

PubMed Central

Lee, Yuh Chwen G.; Langley, Charles H.

2012-01-01

Transposable elements (TEs) are considered to be genomic parasites and their interactions with their hosts have been likened to the coevolution between host and other nongenomic, horizontally transferred pathogens. TE families, however, are vertically inherited as integral segments of the nuclear genome. This transmission strategy has been suggested to weaken the selective benefits of host alleles repressing the transposition of specific TE variants. On the other hand, the elevated rates of TE transposition and high incidences of deleterious mutations observed during the rare cases of horizontal transfers of TE families between species could create at least a transient process analogous to the influence of horizontally transmitted pathogens. Here, we formally address this analogy, using empirical and theoretical analysis to specify the mechanism of how host–TE interactions may drive the evolution of host genes. We found that host TE-interacting genes actually have more pervasive evidence of adaptive evolution than immunity genes that interact with nongenomic pathogens in Drosophila. Yet, both our theoretical modeling and empirical observations comparing Drosophila melanogaster populations before and after the horizontal transfer of P elements, which invaded D. melanogaster early last century, demonstrated that horizontally transferred TEs have only a limited influence on host TE-interacting genes. We propose that the more prevalent and constant interaction with multiple vertically transmitted TE families may instead be the main force driving the fast evolution of TE-interacting genes, which is fundamentally different from the gene-for-gene interaction of host–pathogen coevolution. PMID:22997235

A transgenic model of transactivation by the Tax protein of HTLV-I.

PubMed

Bieberich, C J; King, C M; Tinkle, B T; Jay, G

1993-09-01

The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax.

[Construction and expression analysis of the zebrafish heart-specific transgenetic vector based on Tol2 transposable element].

PubMed

Chen, Tingfang; Luo, Na; Xie, Huaping; Wu, Xiushan; Deng, Yun

2010-02-01

In an effort to generate a desired expression construct for making heart-specific expression transgenic zebrafish, a Tol2 plasmid, which can drive EGFP reporter gene specifically expressed in the heart, was modified using subcloning technology. An IRES fragment bearing multiple cloning site (MCS) was amplified directly from pIRES2-EGFP plasmid and was inserted between the CMLC2 promoter and EGFP fragment of the pDestTol2CG vector. This recombinant expression plasmid pTol2-CMLC2-IRES-EGFP can drive any interested gene specifically expressed in the zebrafish heart along with EGFP reporter gene. To test the effectiveness of this new expression plasmid, we constructed pTol2-CMLC2-RED-IRES-EGFP plasmid by inserting another reporter gene DsRed-Monome into MCS downstream of the CMLC2 promoter and injected this transgenic recombinant plasmid into one-cell stage embryos of zebrafish. Under fluorescence microscope, both the red fluorescence and the green fluorescence produced by pTol2-CMLC2-RED-IRES-EGFP were detected specifically in the heart tissue in the same expression pattern. This novel expression construct pTol2-CMLC2-IRES-EGFP will become an important tool for our research on identifying heart development candidate genes' function using zebrafish as a model.

The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host–parasite interaction

PubMed Central

Jackson, Andrew P.; Otto, Thomas D.; Darby, Alistair; Ramaprasad, Abhinay; Xia, Dong; Echaide, Ignacio Eduardo; Farber, Marisa; Gahlot, Sunayna; Gamble, John; Gupta, Dinesh; Gupta, Yask; Jackson, Louise; Malandrin, Laurence; Malas, Tareq B.; Moussa, Ehab; Nair, Mridul; Reid, Adam J.; Sanders, Mandy; Sharma, Jyotsna; Tracey, Alan; Quail, Mike A.; Weir, William; Wastling, Jonathan M.; Hall, Neil; Willadsen, Peter; Lingelbach, Klaus; Shiels, Brian; Tait, Andy; Berriman, Matt; Allred, David R.; Pain, Arnab

2014-01-01

Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5′ ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. PMID:24799432

Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons

PubMed Central

Zhang, Guangfan; Titlow, William B.; Biecker, Stephanie M.; Stromberg, Arnold J.

2016-01-01

Abstract A developmental program of epigenetic repression prepares each mammalian olfactory sensory neuron (OSN) to strongly express one allele from just one of hundreds of odorant receptor (OR) genes, but what completes this process of OR gene choice by driving the expression of this allele is incompletely understood. Conditional deletion experiments in mice demonstrate that Lhx2 is necessary for normal expression frequencies of nearly all ORs and all trace amine-associated receptors, irrespective of whether the deletion of Lhx2 is initiated in immature or mature OSNs. Given previous evidence that Lhx2 binds OR gene control elements, these findings indicate that Lhx2 is directly involved in driving OR expression. The data also support the conclusion that OR expression is necessary to allow immature OSNs to complete differentiation and become mature. In contrast to the robust effects of conditional deletion of Lhx2, the loss of Emx2 has much smaller effects and more often causes increased expression frequencies. Lhx2:Emx2 double mutants show opposing effects on Olfr15 expression that reveal independent effects of these two transcription factors. While Lhx2 is necessary for OR expression that supports OR gene choice, Emx2 can act differently; perhaps by helping to control the availability of OR genes for expression. PMID:27822500

Fungal-specific subunits of the Candida albicans mitochondrial complex I drive diverse cell functions including cell wall synthesis.

PubMed

She, Xiaodong; Khamooshi, Kasra; Gao, Yin; Shen, Yongnian; Lv, Yuxia; Calderone, Richard; Fonzi, William; Liu, Weida; Li, Dongmei

2015-09-01

Our published research has focused on the role of Goa1p, an apparent regulator of the Candida albicans mitochondrial complex I (CI). Lack of Goa1p affects optimum cell growth, CI activity and virulence. Eukaryotic CI is composed of a core of 14 alpha-proteobacterial subunit proteins and a variable number of supernumerary subunit proteins. Of the latter group of proteins, one (NUZM) is fungal specific and the other (NUXM) is found in fungi, algae and plants, but is not a mammalian CI subunit protein. We have established that NUXM is orf19.6607 and NUZM is orf19.287 in C. albicans. Herein, we validate both subunit proteins as NADH:ubiquinone oxidoreductases (NUO) and annotate their gene functions. To accomplish these objectives, we compared null mutants of each with wild type (WT) and gene-reconstituted strains. Genetic mutants of genes NUO1 (orf19.6607) and NUO2 (orf19.287), not surprisingly, each had reduced oxygen consumption, decreased mitochondrial redox potential, decreased CI activity, increased reactive oxidant species (ROS) and decreased chronological ageing in vitro. Loss of either gene results in disassembly of CI. Transcriptional profiling of both mutants indicated significant down-regulation of genes of carbon metabolism, as well as up-regulation of mitochondrial-associated gene families that may occur to compensate for the loss of CI activity. Profiling of both mutants also demonstrated a loss of cell wall β-mannosylation but not in a conserved CI subunit (ndh51Δ). The profiling data may indicate specific functions driven by the enzymatic activity of Nuo1p and Nuo2p. Of importance, each mutant is also avirulent in a murine blood-borne, invasive model of candidiasis associated with their reduced colonization of tissues. Based on their fungal specificity and roles in virulence, we suggest both as drug targets for antifungal drug discovery. © 2015 John Wiley & Sons Ltd.

Vehicle ownership and other predictors of teenagers risky driving behavior: Evidence from a naturalistic driving study.

PubMed

Gershon, Pnina; Ehsani, Johnathon; Zhu, Chunming; O'Brien, Fearghal; Klauer, Sheila; Dingus, Tom; Simons-Morton, Bruce

2018-06-08

Risky driving behavior may contribute to the high crash risk among teenage drivers. The current naturalistic driving study assessed predictors for teenagers' kinematic risky driving (KRD) behavior and the interdependencies between them. The private vehicles of 81 novice teenage drivers were equipped with data acquisition system that recorded driving kinematics, miles driven, and video recordings of the driver, passengers and the driving environment. Psychosocial measures were collected using questionnaires administered at licensure. Poisson regression analyses and model selection were used to assess factors associated with teens' risky driving behavior and the interactions between them. Driving own vs shared vehicle, driving during the day vs at night, and driving alone vs with passengers were significantly associated with higher KRD rates (Incidence rate ratios (IRRs) of 1.60, 1.41, and 1.28, respectively). Teenagers reporting higher vs lower levels of parental trust had significantly lower KRD rates (IRR = 0.58). KRD rates were 88% higher among teenagers driving with a passenger in their own vehicle compared to teenagers driving with a passenger in a shared vehicle. Similarly, KRD rates during the day were 74% higher among teenagers driving their own vehicle compared to those driving a shared vehicle. Novice teenagers' risky driving behavior varied according to driver attributes and contextual aspects of the driving environment. As such, examining teenagers' risky driving behavior should take into account multiple contributing factors and their interactions. The variability in risky driving according to the driving context can inform the development of targeted interventions to reduce the crash risk of novice teenage drivers. Copyright © 2018 Elsevier Ltd. All rights reserved.

CRISPR-based screening of genomic island excision events in bacteria.

PubMed

Selle, Kurt; Klaenhammer, Todd R; Barrangou, Rodolphe

2015-06-30

Genomic analysis of Streptococcus thermophilus revealed that mobile genetic elements (MGEs) likely contributed to gene acquisition and loss during evolutionary adaptation to milk. Clustered regularly interspaced short palindromic repeats-CRISPR-associated genes (CRISPR-Cas), the adaptive immune system in bacteria, limits genetic diversity by targeting MGEs including bacteriophages, transposons, and plasmids. CRISPR-Cas systems are widespread in streptococci, suggesting that the interplay between CRISPR-Cas systems and MGEs is one of the driving forces governing genome homeostasis in this genus. To investigate the genetic outcomes resulting from CRISPR-Cas targeting of integrated MGEs, in silico prediction revealed four genomic islands without essential genes in lengths from 8 to 102 kbp, totaling 7% of the genome. In this study, the endogenous CRISPR3 type II system was programmed to target the four islands independently through plasmid-based expression of engineered CRISPR arrays. Targeting lacZ within the largest 102-kbp genomic island was lethal to wild-type cells and resulted in a reduction of up to 2.5-log in the surviving population. Genotyping of Lac(-) survivors revealed variable deletion events between the flanking insertion-sequence elements, all resulting in elimination of the Lac-encoding island. Chimeric insertion sequence footprints were observed at the deletion junctions after targeting all of the four genomic islands, suggesting a common mechanism of deletion via recombination between flanking insertion sequences. These results established that self-targeting CRISPR-Cas systems may direct significant evolution of bacterial genomes on a population level, influencing genome homeostasis and remodeling.

Guidelines for research on drugged driving

PubMed Central

Walsh, J. Michael; Verstraete, Alain G.; Huestis, Marilyn A.; Mørland, Jørg

2009-01-01

Aim A major problem in assessing the true public health impact of drug-use on driving and overall traffic safety is that the variables being measured across studies vary significantly. In studies reported in a growing global literature, basic parameters assessed, analytical techniques and drugs tested are simply not comparable due to lack of standardization in the field. These shortcomings severely limit the value of this research to add knowledge to the field. A set of standards to harmonize research findings is sorely needed. This project was initiated by several international organizations to develop guidelines for research on drugged driving. Methods A September 2006 meeting of international experts discussed the harmonization of protocols for future research on drugged driving. The principal objective of the meeting was to develop a consensus report setting guidelines, standards, core data variables and other controls that would form the basis for future international research. A modified Delphi method was utilized to develop draft guidelines. Subsequently, these draft guidelines were posted on the internet for global review, and comments received were integrated into the final document. Results The Guidelines Document is divided into three major sections, each focusing upon different aspects of drugged driving research (e.g. roadside surveys, prevalence studies, hospital studies, fatality and crash investigations, etc.) within the critical issue areas of ‘behavior’, ‘epidemiology’ and ‘toxicology’. The behavioral section contains 32 specific recommendations; (2) epidemiology 40 recommendations; and (3) toxicology 64 recommendations. Conclusions It is anticipated that these guidelines will improve significantly the overall quality of drugged driving research and facilitate future cross-study comparisons nationally and globally. PMID:18855814

Sleep Homeostasis and Synaptic Plasticity

DTIC Science & Technology

2017-06-01

accrued through learning. But how is wake experience translated into sleep drive? Where in the brain does this occur? Is there a discrete sleep drive...neuronal activity in discrete parts of the brain. At the same time, neuronal biochemistry is very similar – flies and man respond in a similar manner to...null phenotypes by expressing rescue construct in discrete regions Task 1C: Verify rescue brain areas by RNAi knockdown (in wildtype) of gene in areas

Remote SST Forcing and Local Land-Atmosphere Moisture Coupling as Drivers of Amazon Temperature and Carbon Cycle Variability

NASA Astrophysics Data System (ADS)

Levine, P. A.; Xu, M.; Chen, Y.; Randerson, J. T.; Hoffman, F. M.

2017-12-01

Interannual variability of climatic conditions in the Amazon rainforest is associated with El Niño-Southern Oscillation (ENSO) and ocean-atmosphere interactions in the North Atlantic. Sea surface temperature (SST) anomalies in these remote ocean regions drive teleconnections with Amazonian surface air temperature (T), precipitation (P), and net ecosystem production (NEP). While SST-driven NEP anomalies have been primarily linked to T anomalies, it is unclear how much the T anomalies result directly from SST forcing of atmospheric circulation, and how much result indirectly from decreases in precipitation that, in turn, influence surface energy fluxes. Interannual variability of P associated with SST anomalies lead to variability in soil moisture (SM), which would indirectly affect T via partitioning of turbulent heat fluxes between the land surface and the atmosphere. To separate the direct and indirect influence of the SST signal on T and NEP, we performed a mechanism-denial experiment to decouple SST and SM anomalies. We used the Accelerated Climate Modeling for Energy (ACMEv0.3), with version 5 of the Community Atmosphere Model and version 4.5 of the Community Land Model. We forced the model with observed SSTs from 1982-2016. We found that SST and SM variability both contribute to T and NEP anomalies in the Amazon, with relative contributions depending on lag time and location within the Amazon basin. SST anomalies associated with ENSO drive most of the T variability at shorter lag times, while the ENSO-driven SM anomalies contribute more to T variability at longer lag times. SM variability and the resulting influence on T anomalies are much stronger in the eastern Amazon than in the west. Comparing modeled T with observations demonstrate that SST alone is sufficient for simulating the correct timing of T variability, but SM anomalies are necessary for simulating the correct magnitude of the T variability. Modeled NEP indicated that variability in carbon fluxes results from both SST and SM anomalies. As with T, SM anomalies affect NEP at a much longer lag time than SST anomalies. These results highlight the role of land-atmosphere coupling in driving climate variability within the Amazon, and suggest that land atmospheric coupling may amplify and delay carbon cycle responses to ocean-atmosphere teleconnections.

Cannabis effects on driving lateral control with and without alcohol.

PubMed

Hartman, Rebecca L; Brown, Timothy L; Milavetz, Gary; Spurgin, Andrew; Pierce, Russell S; Gorelick, David A; Gaffney, Gary; Huestis, Marilyn A

2015-09-01

Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood Δ(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. Current occasional (≥1×/last 3 months, ≤3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17h, 0.42h) and after (1.4h, 2.3h) driving that occurred 0.5-1.3h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. In N=18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1μg/L during driving increased SDLP similar to 0.05 and 0.08g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5μg/L THC+0.05g/210L alcohol showing similar SDLP to 0.08g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. SDLP was a sensitive cannabis-related lateral control impairment measure. During drive blood THC ≥8.2μg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation. Published by Elsevier Ireland Ltd.

Drive-amplitude-modulation atomic force microscopy: From vacuum to liquids

PubMed Central

Jaafar, Miriam; Cuenca, Mariano; Melcher, John; Raman, Arvind

2012-01-01

Summary We introduce drive-amplitude-modulation atomic force microscopy as a dynamic mode with outstanding performance in all environments from vacuum to liquids. As with frequency modulation, the new mode follows a feedback scheme with two nested loops: The first keeps the cantilever oscillation amplitude constant by regulating the driving force, and the second uses the driving force as the feedback variable for topography. Additionally, a phase-locked loop can be used as a parallel feedback allowing separation of the conservative and nonconservative interactions. We describe the basis of this mode and present some examples of its performance in three different environments. Drive-amplutide modulation is a very stable, intuitive and easy to use mode that is free of the feedback instability associated with the noncontact-to-contact transition that occurs in the frequency-modulation mode. PMID:22563531

Drive Control Scheme of Electric Power Assisted Wheelchair Based on Neural Network Learning of Human Wheelchair Operation Characteristics

NASA Astrophysics Data System (ADS)

Tanohata, Naoki; Seki, Hirokazu

This paper describes a novel drive control scheme of electric power assisted wheelchairs based on neural network learning of human wheelchair operation characteristics. “Electric power assisted wheelchair” which enhances the drive force of the operator by employing electric motors is expected to be widely used as a mobility support system for elderly and disabled people. However, some handicapped people with paralysis of the muscles of one side of the body cannot maneuver the wheelchair as desired because of the difference in the right and left input force. Therefore, this study proposes a neural network learning system of such human wheelchair operation characteristics and a drive control scheme with variable distribution and assistance ratios. Some driving experiments will be performed to confirm the effectiveness of the proposed control system.

Perceptual load in central and peripheral regions and its effects on driving performance: advertizing billboards.

PubMed

Marciano, Hadas; Yeshurun, Yaffa

2012-01-01

A broadened version of the perceptual load model was utilized to explore systematically the influence of four variables on driver's behavior: a. levels of load on the road; b. levels of load at the sides of the road; c. event's initial location (on the road vs. at the sides of the road); and d. the presence and size of advertizing billboards. 18 participants participated in two experimental sessions in a driving simulator. One of the sessions contained advertizing billboards and the other session did not. The results indicated that billboards can have a considerable effect on various aspects of driving like the time required responding to a potentially dangerous event or simply the number of accidents occurring during driving, but importantly the effect of billboards on driving was modulated by the levels of perceptual load.

Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.

PubMed

Fox, Rebecca M; Vaishnavi, Aria; Maruyama, Rika; Andrew, Deborah J

2013-05-01

FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously.

Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA

PubMed Central

Fox, Rebecca M.; Vaishnavi, Aria; Maruyama, Rika; Andrew, Deborah J.

2013-01-01

FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously. PMID:23578928

Comprehensive Modeling and Analysis of Rotorcraft Variable Speed Propulsion System With Coupled Engine/Transmission/Rotor Dynamics

NASA Technical Reports Server (NTRS)

DeSmidt, Hans A.; Smith, Edward C.; Bill, Robert C.; Wang, Kon-Well

2013-01-01

This project develops comprehensive modeling and simulation tools for analysis of variable rotor speed helicopter propulsion system dynamics. The Comprehensive Variable-Speed Rotorcraft Propulsion Modeling (CVSRPM) tool developed in this research is used to investigate coupled rotor/engine/fuel control/gearbox/shaft/clutch/flight control system dynamic interactions for several variable rotor speed mission scenarios. In this investigation, a prototypical two-speed Dual-Clutch Transmission (DCT) is proposed and designed to achieve 50 percent rotor speed variation. The comprehensive modeling tool developed in this study is utilized to analyze the two-speed shift response of both a conventional single rotor helicopter and a tiltrotor drive system. In the tiltrotor system, both a Parallel Shift Control (PSC) strategy and a Sequential Shift Control (SSC) strategy for constant and variable forward speed mission profiles are analyzed. Under the PSC strategy, selecting clutch shift-rate results in a design tradeoff between transient engine surge margins and clutch frictional power dissipation. In the case of SSC, clutch power dissipation is drastically reduced in exchange for the necessity to disengage one engine at a time which requires a multi-DCT drive system topology. In addition to comprehensive simulations, several sections are dedicated to detailed analysis of driveline subsystem components under variable speed operation. In particular an aeroelastic simulation of a stiff in-plane rotor using nonlinear quasi-steady blade element theory was conducted to investigate variable speed rotor dynamics. It was found that 2/rev and 4/rev flap and lag vibrations were significant during resonance crossings with 4/rev lagwise loads being directly transferred into drive-system torque disturbances. To capture the clutch engagement dynamics, a nonlinear stick-slip clutch torque model is developed. Also, a transient gas-turbine engine model based on first principles mean-line compressor and turbine approximations is developed. Finally an analysis of high frequency gear dynamics including the effect of tooth mesh stiffness variation under variable speed operation is conducted including experimental validation. Through exploring the interactions between the various subsystems, this investigation provides important insights into the continuing development of variable-speed rotorcraft propulsion systems.

Increased parent limits on teen driving: positive effects from a brief intervention administered at the Motor Vehicle Administration.

PubMed

Simons-Morton, Bruce G; Hartos, Jessica L; Beck, Kenneth H

2004-06-01

The purpose of this study was to determine whether exposure to a brief intervention administered at the Motor Vehicle Administration (MVA) increases parental limits on teen driving. A total of 658 parents and their 16-year-old adolescents were recruited from a local MVA site as adolescents successfully tested for provisional licenses. At the MVA, participating parents completed written surveys about expected teen driving during the 1st month of provisional licensure. One month later, 579 parent-teen dyads completed follow-up telephone interviews about teen driving within the past month. On weeks assigned as intervention, parents were exposed to a video and given the video and a driving agreement to take home. In multivariate linear regression analyses, the results indicated that when controlling for selected demographic and baseline psychosocial variables, intervention parents reported more driving rules, restricted driving, limits for high-speed roads, weekend night restrictions, and overall driving limits than did parents in the control group. When compared to control teens, intervention teens reported more limits on passengers, high-speed roads, and night driving, and on overall driving limits, but there were no differences for overall driving or driving under high-risk conditions. In addition, intervention parents were about 3 times, and intervention teens were about 5 times, more likely than controls to report using a parent-teen driving agreement. These results indicate that brief exposure to intervention at an MVA office may help increase parental limits on teen driving.

Hand on the wheel, mind on the mobile: an analysis of social factors contributing to texting while driving.

PubMed

Seiler, Steven J

2015-02-01

In an era defined by social technology, mobile phones provide constant connection to others. However, they also present a very dangerous situation when people choose to use their mobile phones while driving. In particular, exchanging text messages while driving has resulted in numerous accidents and fatalities. The purpose of this study is to examine social factors that lead people to text while driving. Specifically, using a multivariate logistic regression analysis of data from a 2010 survey by the Pew Research Center, variables for general mobile talk, driving while talking on a mobile, using the Internet on a mobile, sexting, and various motivations for texting were examined to determine factors that increase the likelihood of texting while driving. The findings suggest that people engage in mobile multiplexing (i.e., communication using two or more media on the mobile) while driving. Additionally, exchanging text messages in public, and consequently texting while driving, has become normalized. Furthermore, people are socialized into such behaviors through observing others texting while driving and using a mobile recklessly while driving. Finally, a number of motivations for texting were found to increase the likelihood of texting while driving significantly. Ultimately, the author contends that texting while driving has become a cultural artifact in the United States, which conflicts with driver safety as well as laws prohibiting texting while driving. The findings of this study could inform future awareness campaigns and technology developers to help establish a safer driving environment within the multitasking culture.

Magnetically Controlled Variable Transformer

NASA Technical Reports Server (NTRS)

Kleiner, Charles T.

1994-01-01

Improved variable-transformer circuit, output voltage and current of which controlled by use of relatively small current supplied at relatively low power to control windings on its magnetic cores. Transformer circuits of this type called "magnetic amplifiers" because ratio between controlled output power and power driving control current of such circuit large. This ratio - power gain - can be as large as 100 in present circuit. Variable-transformer circuit offers advantages of efficiency, safety, and controllability over some prior variable-transformer circuits.

Gene variants associated with antisocial behaviour: A latent variable approach

PubMed Central

Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V.; Lee, Maria; Yrigollen, Carolyn M.; Pakstis, Andrew J.; Katsovich, Liliya; Olds, David L.; Grigorenko, Elena L.; Leckman, James F.

2013-01-01

Objective The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation program in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours, and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. Results Eight single-nucleotide polymorphisms (SNPs) from 8 genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all 8 genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid, and cholinergic signaling as well as stress response pathways in mediating susceptibility to antisocial behaviour. Conclusions This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential “co-action” of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the etiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a ‘shared’ variance across genetic risk alleles associated with complex neuropsychiatric dimensional phenotypes using relatively small numbers of well-characterized research participants. PMID:23822756

Protein folding: complex potential for the driving force in a two-dimensional space of collective variables.

PubMed

Chekmarev, Sergei F

2013-10-14

Using the Helmholtz decomposition of the vector field of folding fluxes in a two-dimensional space of collective variables, a potential of the driving force for protein folding is introduced. The potential has two components. One component is responsible for the source and sink of the folding flows, which represent respectively, the unfolded states and the native state of the protein, and the other, which accounts for the flow vorticity inherently generated at the periphery of the flow field, is responsible for the canalization of the flow between the source and sink. The theoretical consideration is illustrated by calculations for a model β-hairpin protein.

Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives

PubMed Central

Maranhão, Geraldo Neves De A.; Brito, Alaan Ubaiara; Leal, Anderson Marques; Fonseca, Jéssica Kelly Silva; Macêdo, Wilson Negrão

2015-01-01

In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD) for use in Photovoltaic Pumping Systems (PVPS) is proposed. The fuzzy logic system (FLS) used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR) is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC) voltage level in the VSD with a good performance. PMID:26402688

Enhancing Entropy and Enthalpy Fluctuations to Drive Crystallization in Atomistic Simulations.

PubMed

Piaggi, Pablo M; Valsson, Omar; Parrinello, Michele

2017-07-07

Crystallization is a process of great practical relevance in which rare but crucial fluctuations lead to the formation of a solid phase starting from the liquid. As in all first order first transitions, there is an interplay between enthalpy and entropy. Based on this idea, in order to drive crystallization in molecular simulations, we introduce two collective variables, one enthalpic and the other entropic. Defined in this way, these collective variables do not prejudge the structure into which the system is going to crystallize. We show the usefulness of this approach by studying the cases of sodium and aluminum that crystallize in the bcc and fcc crystalline structures, respectively. Using these two generic collective variables, we perform variationally enhanced sampling and well tempered metadynamics simulations and find that the systems transform spontaneously and reversibly between the liquid and the solid phases.

Field oriented control of induction motors

NASA Technical Reports Server (NTRS)

Burrows, Linda M.; Zinger, Don S.; Roth, Mary Ellen

1990-01-01

Induction motors have always been known for their simple rugged construction, but until lately were not suitable for variable speed or servo drives due to the inherent complexity of the controls. With the advent of field oriented control (FOC), however, the induction motor has become an attractive option for these types of drive systems. An FOC system which utilizes the pulse population modulation method to synthesize the motor drive frequencies is examined. This system allows for a variable voltage to frequency ratio and enables the user to have independent control of both the speed and torque of an induction motor. A second generation of the control boards were developed and tested with the next point of focus being the minimization of the size and complexity of these controls. Many options were considered with the best approach being the use of a digital signal processor (DSP) due to its inherent ability to quickly evaluate control algorithms. The present test results of the system and the status of the optimization process using a DSP are discussed.

Influence of the optimization methods on neural state estimation quality of the drive system with elasticity.

PubMed

Orlowska-Kowalska, Teresa; Kaminski, Marcin

2014-01-01

The paper deals with the implementation of optimized neural networks (NNs) for state variable estimation of the drive system with an elastic joint. The signals estimated by NNs are used in the control structure with a state-space controller and additional feedbacks from the shaft torque and the load speed. High estimation quality is very important for the correct operation of a closed-loop system. The precision of state variables estimation depends on the generalization properties of NNs. A short review of optimization methods of the NN is presented. Two techniques typical for regularization and pruning methods are described and tested in detail: the Bayesian regularization and the Optimal Brain Damage methods. Simulation results show good precision of both optimized neural estimators for a wide range of changes of the load speed and the load torque, not only for nominal but also changed parameters of the drive system. The simulation results are verified in a laboratory setup.

Automatic Welding Control Using a State Variable Model.

DTIC Science & Technology

1979-06-01

A-A10 610 NAVEAL POSTGRADUATE SCH4O.M CEAY CA0/ 13/ SAUTOMATIC WELDING CONTROL USING A STATE VARIABLE MODEL.W()JUN 79 W V "my UNCLASSIFIED...taverse Drive Unit // Jbint Path /Fixed Track 34 (servomotor positioning). Additional controls of heave (vertical), roll (angular rotation about the

Behavioral science and the study of gene-nutrition and gene-physical activity interactions in obesity research.

PubMed

Faith, Myles S

2008-12-01

This report summarizes emerging opportunities for behavioral science to help advance the field of gene-environment and gene-behavior interactions, based on presentations at The National Cancer Institute (NCI) Workshop, "Gene-Nutrition and Gene-Physical Activity Interactions in the Etiology of Obesity." Three opportunities are highlighted: (i) designing potent behavioral "challenges" in experiments, (ii) determining viable behavioral phenotypes for genetics studies, and (iii) identifying specific measures of the environment or environmental exposures. Additional points are underscored, including the need to incorporate novel findings from neuroimaging studies regarding motivation and drive for eating and physical activity. Advances in behavioral science theory and methods can play an important role in advancing understanding of gene-brain-behavior relationships in obesity onset.

Lateral gene transfer in a heavy metal-contaminated-groundwater microbial community

DOE PAGES

Hemme, Christopher L.; Green, Stefan J.; Rishishwar, Lavanya; ...

2016-04-05

Here, unraveling the drivers controlling the response and adaptation of biological communities to environmental change, especially anthropogenic activities, is a central but poorly understood issue in ecology and evolution. Comparative genomics studies suggest that lateral gene transfer (LGT) is a major force driving microbial genome evolution, but its role in the evolution of microbial communities remains elusive.

Gene expression analysis of human adipose tissue-derived stem cells during the initial steps of in vitro osteogenesis.

PubMed

Robert, Anny Waloski; Angulski, Addeli Bez Batti; Spangenberg, Lucia; Shigunov, Patrícia; Pereira, Isabela Tiemy; Bettes, Paulo Sergio Loiacono; Naya, Hugo; Correa, Alejandro; Dallagiovanna, Bruno; Stimamiglio, Marco Augusto

2018-03-16

Mesenchymal stem cells (MSCs) have been widely studied with regard to their potential use in cell therapy protocols and regenerative medicine. However, a better comprehension about the factors and molecular mechanisms driving cell differentiation is now mandatory to improve our chance to manipulate MSC behavior and to benefit future applications. In this work, we aimed to study gene regulatory networks at an early step of osteogenic differentiation. Therefore, we analyzed both the total mRNA and the mRNA fraction associated with polysomes on human adipose tissue-derived stem cells (hASCs) at 24 h of osteogenesis induction. The RNA-seq results evidenced that hASC fate is not compromised with osteogenesis at this time and that 21 days of continuous cell culture stimuli are necessary for full osteogenic differentiation of hASCs. Furthermore, early stages of osteogenesis induction involved gene regulation that was linked to the management of cell behavior in culture, such as the control of cell adhesion and proliferation. In conclusion, although discrete initial gene regulation related to osteogenesis occur, the first 24 h of induction is not sufficient to trigger and drive in vitro osteogenic differentiation of hASCs.

Divergent functional isoforms drive niche specialisation for nutrient acquisition and use in rumen microbiome.

PubMed

Rubino, Francesco; Carberry, Ciara; M Waters, Sinéad; Kenny, David; McCabe, Matthew S; Creevey, Christopher J

2017-04-01

Many microbes in complex competitive environments share genes for acquiring and utilising nutrients, questioning whether niche specialisation exists and if so, how it is maintained. We investigated the genomic signatures of niche specialisation in the rumen microbiome, a highly competitive, anaerobic environment, with limited nutrient availability determined by the biomass consumed by the host. We generated individual metagenomic libraries from 14 cows fed an ad libitum diet of grass silage and calculated functional isoform diversity for each microbial gene identified. The animal replicates were used to calculate confidence intervals to test for differences in diversity of functional isoforms between microbes that may drive niche specialisation. We identified 153 genes with significant differences in functional isoform diversity between the two most abundant bacterial genera in the rumen (Prevotella and Clostridium). We found Prevotella possesses a more diverse range of isoforms capable of degrading hemicellulose, whereas Clostridium for cellulose. Furthermore, significant differences were observed in key metabolic processes indicating that isoform diversity plays an important role in maintaining their niche specialisation. The methods presented represent a novel approach for untangling complex interactions between microorganisms in natural environments and have resulted in an expanded catalogue of gene targets central to rumen cellulosic biomass degradation.

Voltage directive drive with claw pole motor and control without rotor position indicator

NASA Astrophysics Data System (ADS)

Stroenisch, Volker Ewald

Design and testing of a voltage directive drive for synchronous variable speed claw pole motor and control without rotor position indicator is described. Economic analysis of the designed regulation is performed. Computations of stationary and dynamic behavior are given and experimental operational behavior is determined. The motors can be used for electric transportation vehicles, diesel motors, and electric railway engines.

Prediction of Driving Safety in Individuals with Homonymous Hemianopia and Quadrantanopia from Clinical Neuroimaging

PubMed Central

Vaphiades, Michael S.; Kline, Lanning B.; McGwin, Gerald; Owsley, Cynthia; Shah, Ritu; Wood, Joanne M.

2014-01-01

Background. This study aimed to determine whether it is possible to predict driving safety of individuals with homonymous hemianopia or quadrantanopia based upon a clinical review of neuroimages that are routinely available in clinical practice. Methods. Two experienced neuroophthalmologists viewed a summary report of the CT/MRI scans of 16 participants with homonymous hemianopic or quadrantanopic field defects which indicated the site and extent of the lesion and they made predictions regarding whether participants would be safe/unsafe to drive. Driving safety was independently defined at the time of the study using state-recorded motor vehicle crashes (all crashes and at-fault) for the previous 5 years and ratings of driving safety determined through a standardized on-road driving assessment by a certified driving rehabilitation specialist. Results. The ability to predict driving safety was highly variable regardless of the driving safety measure, ranging from 31% to 63% (kappa levels ranged from −0.29 to 0.04). The level of agreement between the neuroophthalmologists was only fair (kappa = 0.28). Conclusions. Clinical evaluation of summary reports of currently available neuroimages by neuroophthalmologists is not predictive of driving safety. Future research should be directed at identifying and/or developing alternative tests or strategies to better enable clinicians to make these predictions. PMID:24683493

Prediction of driving safety in individuals with homonymous hemianopia and quadrantanopia from clinical neuroimaging.

PubMed

Vaphiades, Michael S; Kline, Lanning B; McGwin, Gerald; Owsley, Cynthia; Shah, Ritu; Wood, Joanne M

2014-01-01

Background. This study aimed to determine whether it is possible to predict driving safety of individuals with homonymous hemianopia or quadrantanopia based upon a clinical review of neuroimages that are routinely available in clinical practice. Methods. Two experienced neuroophthalmologists viewed a summary report of the CT/MRI scans of 16 participants with homonymous hemianopic or quadrantanopic field defects which indicated the site and extent of the lesion and they made predictions regarding whether participants would be safe/unsafe to drive. Driving safety was independently defined at the time of the study using state-recorded motor vehicle crashes (all crashes and at-fault) for the previous 5 years and ratings of driving safety determined through a standardized on-road driving assessment by a certified driving rehabilitation specialist. Results. The ability to predict driving safety was highly variable regardless of the driving safety measure, ranging from 31% to 63% (kappa levels ranged from -0.29 to 0.04). The level of agreement between the neuroophthalmologists was only fair (kappa = 0.28). Conclusions. Clinical evaluation of summary reports of currently available neuroimages by neuroophthalmologists is not predictive of driving safety. Future research should be directed at identifying and/or developing alternative tests or strategies to better enable clinicians to make these predictions.

Ancient DNA reveals selection acting on genes associated with hypoxia response in pre-Columbian Peruvian Highlanders in the last 8500 years.

PubMed

Fehren-Schmitz, Lars; Georges, Lea

2016-03-21

Archaeological evidence shows that humans began living in the high altitude Andes approximately 12,000 years ago. Andean highlanders are known to have developed the most complex societies of pre-Columbian South America despite challenges to their health and reproductive success resulting from chronic exposure to hypoxia. While the physiological adaptations to this environmental stressor are well studied in contemporary Andean highlanders, the molecular evolutionary processes associated with such adaptations remain unclear. We aim to better understand how humans managed to demographically establish in this harsh environment by addressing a central question: did exposure to hypoxia drive adaptation via natural selection within Andean populations or did an existing phenotype--characterized by reduced susceptibility to hypoxic stress--enable human settlement of the Andes? We genotyped three variable loci within the NOS3 and EGLN1 genes previously associated with adaptation to high altitude in 150 ancient human DNA samples from Peruvian high altitude and coastal low altitude sites in a time frame between ~8500-560 BP. We compare the data of 109 successful samples to forward simulations of genetic drift with natural selection and find that selection, rather than drift, explains the gradual frequency changes observed in the highland populations for two of the three SNPs.

Ancient DNA reveals selection acting on genes associated with hypoxia response in pre-Columbian Peruvian Highlanders in the last 8500 years

PubMed Central

Fehren-Schmitz, Lars; Georges, Lea

2016-01-01

Archaeological evidence shows that humans began living in the high altitude Andes approximately 12,000 years ago. Andean highlanders are known to have developed the most complex societies of pre-Columbian South America despite challenges to their health and reproductive success resulting from chronic exposure to hypoxia. While the physiological adaptations to this environmental stressor are well studied in contemporary Andean highlanders, the molecular evolutionary processes associated with such adaptations remain unclear. We aim to better understand how humans managed to demographically establish in this harsh environment by addressing a central question: did exposure to hypoxia drive adaptation via natural selection within Andean populations or did an existing phenotype –characterized by reduced susceptibility to hypoxic stress–enable human settlement of the Andes? We genotyped three variable loci within the NOS3 and EGLN1 genes previously associated with adaptation to high altitude in 150 ancient human DNA samples from Peruvian high altitude and coastal low altitude sites in a time frame between ~8500–560 BP. We compare the data of 109 successful samples to forward simulations of genetic drift with natural selection and find that selection, rather than drift, explains the gradual frequency changes observed in the highland populations for two of the three SNPs. PMID:26996763

Re-evaluation of the immunological Big Bang.

PubMed

Flajnik, Martin F

2014-11-03

Classically the immunological 'Big Bang' of adaptive immunity was believed to have resulted from the insertion of a transposon into an immunoglobulin superfamily gene member, initiating antigen receptor gene rearrangement via the RAG recombinase in an ancestor of jawed vertebrates. However, the discovery of a second, convergent adaptive immune system in jawless fish, focused on the so-called variable lymphocyte receptors (VLRs), was arguably the most exciting finding of the past decade in immunology and has drastically changed the view of immune origins. The recent report of a new lymphocyte lineage in lampreys, defined by the antigen receptor VLRC, suggests that there were three lymphocyte lineages in the common ancestor of jawless and jawed vertebrates that co-opted different antigen receptor supertypes. The transcriptional control of these lineages during development is predicted to be remarkably similar in both the jawless (agnathan) and jawed (gnathostome) vertebrates, suggesting that an early 'division of labor' among lymphocytes was a driving force in the emergence of adaptive immunity. The recent cartilaginous fish genome project suggests that most effector cytokines and chemokines were also present in these fish, and further studies of the lamprey and hagfish genomes will determine just how explosive the Big Bang actually was. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sensible use of antisense: how to use oligonucleotides as research tools.

PubMed

Myers, K J; Dean, N M

2000-01-01

In the past decade, there has been a vast increase in the amount of gene sequence information that has the potential to revolutionize the way diseases are both categorized and treated. Old diagnoses, largely anatomical or descriptive in nature, are likely to be superceded by the molecular characterization of the disease. The recognition that certain genes drive key disease processes will also enable the rational design of gene-specific therapeutics. Antisense oligonucleotides represent a technology that should play multiple roles in this process.

Extended visual glances away from the roadway are associated with ADHD- and texting-related driving performance deficits in adolescents

PubMed Central

Kingery, Kathleen M.; Narad, Megan; Garner, Annie A.; Antonini, Tanya N.; Tamm, Leanne; Epstein, Jeffery N.

2014-01-01

The purpose of the research study was to determine whether ADHD- and texting-related driving impairments are mediated by extended visual glances away from the roadway. Sixty-one adolescents (ADHD = 28, non-ADHD = 33; 62% male; 11% minority) aged 16–17 with a valid driver’s license were videotaped while engaging in a driving simulation that included a No Distraction, Hands-Free Phone Conversation, and Texting condition. Two indicators of visual inattention were coded: 1) percentage of time with eyes diverted from the roadway; and 2) number of extended (greater than 2 seconds) visual glances away from the roadway. Adolescents with ADHD displayed significantly more visual inattention to the roadway on both visual inattention measures. Increased lane position variability among adolescents with ADHD compared to those without ADHD during the Hands-Free Phone Conversation and Texting conditions was mediated by an increased number of extended glances away from the roadway. Similarly, texting resulted in decreased visual attention to the roadway. Finally, increased lane position variability during texting was also mediated by the number of extended glances away from the roadway. Both ADHD and texting impair visual attention to the roadway and the consequence of this visual inattention is increased lane position variability. Visual inattention is implicated as a possible mechanism for ADHD- and texting-related deficits and suggests that driving interventions designed to address ADHD- or texting-related deficits in adolescents need to focus on decreasing extended glances away from the roadway. PMID:25416444

Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

PubMed

Reynolds, Chandra A; Gatz, Margaret; Christensen, Kaare; Christiansen, Lene; Dahl Aslan, Anna K; Kaprio, Jaakko; Korhonen, Tellervo; Kremen, William S; Krueger, Robert; McGue, Matt; Neiderhiser, Jenae M; Pedersen, Nancy L

2016-01-01

Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.

A-Mating-Type Gene Expression Can Drive Clamp Formation in the Bipolar Mushroom Pholiota microspora (Pholiota nameko) ▿

PubMed Central

Yi, Ruirong; Mukaiyama, Hiroyuki; Tachikawa, Takashi; Shimomura, Norihiro; Aimi, Tadanori

2010-01-01

In the bipolar basidiomycete Pholiota microspora, a pair of homeodomain protein genes located at the A-mating-type locus regulates mating compatibility. In the present study, we used a DNA-mediated transformation system in P. microspora to investigate the homeodomain proteins that control the clamp formation. When a single homeodomain protein gene (A3-hox1 or A3-hox2) from the A3 monokaryon strain was transformed into the A4 monokaryon strain, the transformants produced many pseudoclamps but very few clamps. When two homeodomain protein genes (A3-hox1 and A3-hox2) were transformed either separately or together into the A4 monokaryon, the ratio of clamps to the clamplike cells in the transformants was significantly increased to ca. 50%. We therefore concluded that the gene dosage of homeodomain protein genes is important for clamp formation. When the sip promoter was connected to the coding region of A3-hox1 and A3-hox2 and the fused fragments were introduced into NGW19-6 (A4), the transformants achieved more than 85% clamp formation and exhibited two nuclei per cell, similar to the dikaryon (NGW12-163 × NGW19-6). The results of real-time reverse transcription-PCR confirmed that sip promoter activity is greater than that of the native promoter of homeodomain protein genes in P. microspora. Thus, we concluded that nearly 100% clamp formation requires high expression levels of homeodomain protein genes and that altered expression of the A-mating-type genes alone is sufficient to drive true clamp formation. PMID:20453073

Restriction to gene flow is associated with changes in the molecular basis of pyrethroid resistance in the malaria vector Anopheles funestus

PubMed Central

Barnes, Kayla G.; Irving, Helen; Chiumia, Martin; Mzilahowa, Themba; Coleman, Michael; Hemingway, Janet; Wondji, Charles S.

2017-01-01

Resistance to pyrethroids, the sole insecticide class recommended for treating bed nets, threatens the control of major malaria vectors, including Anopheles funestus. Effective management of resistance requires an understanding of the dynamics and mechanisms driving resistance. Here, using genome-wide transcription and genetic diversity analyses, we show that a shift in the molecular basis of pyrethroid resistance in southern African populations of this species is associated with a restricted gene flow. Across the most highly endemic and densely populated regions in Malawi, An. funestus is resistant to pyrethroids, carbamates, and organochlorides. Genome-wide microarray-based transcription analysis identified overexpression of cytochrome P450 genes as the main mechanism driving this resistance. The most up-regulated genes include cytochrome P450s (CYP) CYP6P9a, CYP6P9b and CYP6M7. However, a significant shift in the overexpression profile of these genes was detected across a south/north transect, with CYP6P9a and CYP6P9b more highly overexpressed in the southern resistance front and CYP6M7 predominant in the northern front. A genome-wide genetic structure analysis of southern African populations of An. funestus from Zambia, Malawi, and Mozambique revealed a restriction of gene flow between populations, in line with the geographical variation observed in the transcriptomic analysis. Genetic polymorphism analysis of the three key resistance genes, CYP6P9a, CYP6P9b, and CYP6M7, support barriers to gene flow that are shaping the underlying molecular basis of pyrethroid resistance across southern Africa. This barrier to gene flow is likely to impact the design and implementation of resistance management strategies in the region. PMID:28003461

[Construction of screening system for mutation of negative regulatory genes in Streptomyces].

PubMed

Zhu, Yu; Feng, Chi; Tan, Huarong; Tian, Yuqing

2013-10-04

We aimed to create a novel report system for screening the mutation of the negative regulatory genes, especially for those repressing the expression of cryptic antibiotics clusters. We used marker-free gene disruption strategy, which combines with the "REDIRECT (Rapid Efficient Directed Recombination Time Saving)" technology and in vivo site-specific recombination by Streptomyces phage phiBT1 integrase, to construct a scbR2/inoA double mutant strain of S. coelicolor M145. This strain was used as the host of the report system. For the construction of the reporter plasmid, the ScbR2 repressed promoter of cpkO from CPK (cryptic polyketide) cluster was used to drive the expression of a promoterless conserved gene inoA of S. coelicolor. Then the reporter plasmid was introduced into the host strain described above to test the availability of inoA as a reporter gene in this system. The scbR2/inoA double mutant strain gave rise to a bald pheno type on MM medium in the absence of inositol, and produced yellow pigmented secondary metabolite by the disruption of scbR2 to release the repression of cpkO, a pathway specific activator gene situated in CPK cluster. After introducing the reporter plasmid into this test stain, the resulting strain recovered the phenotype as wild-type strain, indicating that the promoter of cpkO can drive the expression of inoA in scbR2 mutant and consequently restore the biosynthesis of inositol. Our results indicated that inoA can be used as a novel reporter gene for Streptomyces, especially for detecting the activation of the "silent" promoter. This report system might be available for screening the mutation of the negative regulatory genes for the cryptic secondary metabolic gene clusters.

Selection Pressure in CD8+ T-cell Epitopes in the pol Gene of HIV-1 Infected Individuals in Colombia. A Bioinformatic Approach

PubMed Central

Acevedo-Sáenz, Liliana; Ochoa, Rodrigo; Rugeles, Maria Teresa; Olaya-García, Patricia; Velilla-Hernández, Paula Andrea; Diaz, Francisco J.

2015-01-01

One of the main characteristics of the human immunodeficiency virus is its genetic variability and rapid adaptation to changing environmental conditions. This variability, resulting from the lack of proofreading activity of the viral reverse transcriptase, generates mutations that could be fixed either by random genetic drift or by positive selection. Among the forces driving positive selection are antiretroviral therapy and CD8+ T-cells, the most important immune mechanism involved in viral control. Here, we describe mutations induced by these selective forces acting on the pol gene of HIV in a group of infected individuals. We used Maximum Likelihood analyses of the ratio of non-synonymous to synonymous mutations per site (dN/dS) to study the extent of positive selection in the protease and the reverse transcriptase, using 614 viral sequences from Colombian patients. We also performed computational approaches, docking and algorithmic analyses, to assess whether the positively selected mutations affected binding to the HLA molecules. We found 19 positively-selected codons in drug resistance-associated sites and 22 located within CD8+ T-cell epitopes. A high percentage of mutations in these epitopes has not been previously reported. According to the docking analyses only one of those mutations affected HLA binding. However, algorithmic methods predicted a decrease in the affinity for the HLA molecule in seven mutated peptides. The bioinformatics strategies described here are useful to identify putative positively selected mutations associated with immune escape but should be complemented with an experimental approach to define the impact of these mutations on the functional profile of the CD8+ T-cells. PMID:25803098

Which Genes Drive Cancers? - TCGA

Cancer.gov

Associate Professor of Medicine at the Dana-Farber Cancer Institute, William Hahn, describes the method his lab has developed to tease apart the crucial driver mutations from passenger mutations in ovarian cancer.

Development of Permanent Magnet Reluctance Motor Suitable for Variable-Speed Drive for Electric Vehicle

NASA Astrophysics Data System (ADS)

Sakai, Kazuto; Takahashi, Norio; Shimomura, Eiji; Arata, Masanobu; Nakazawa, Yousuke; Tajima, Toshinobu

Regarding environmental and energy issues, increasing importance has been placed on energy saving in various systems. To save energy, it would be desirable if the total efficiency of various types of equipment were increased.Recently, a hybrid electric vehicle (HEV) and an electric vehicle (EV) have been developed. The use of new technologies will eventually lead to the realization of the new- generation vehicle with high efficiency. One new technology is the variable-speed drive over a wide range of speeds. The motor driving systems of the EV or the HEV must operate in the variable-speed range of up to 1:5. This has created the need for a high-efficiency motor that is capable of operation over a wide speed range. In this paper, we describe the concept of a novel permanent magnet reluctance motor (PRM) and discuss its characteristics. We developed the PRM, which has the capability of operating over a wide speed range with high efficiency. The PRM has a rotor with a salient pole, which generates magnetic anisotropy. In addition, the permanent magnets embedded in the rotor core counter the q-axis flux by the armature reaction. Then, the power density and the power factor increase. The PRM produces reluctance torque and torque by permanent magnet (PM) flux. The reluctance torque is 1 to 2 times larger than the PM torque. When the PRM operates over a constant-power speed range, the field component of the current will be regulated to maintain a constant voltage. The output power of the developed PRM is 8 to 250kW. It is clarified that the PRM operates at a wide variable-speed range (1:5) with high efficiency (92-97%). It is concluded that the PRM has high performance over a wide constant-power speed range. In addition, the PRM is constructed using a small PM, so that we can solve the problem of cost. Thus, the PRM is a superior machine that is suited for variable-speed drive applications.

Effect of promoter architecture on the cell-to-cell variability in gene expression.

PubMed

Sanchez, Alvaro; Garcia, Hernan G; Jones, Daniel; Phillips, Rob; Kondev, Jané

2011-03-01

According to recent experimental evidence, promoter architecture, defined by the number, strength and regulatory role of the operators that control transcription, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect variability in gene expression in a systematic rather than case-by-case fashion. In this article we make such a systematic investigation, based on a microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcriptional output from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can be used to test kinetic models of gene regulation. The emphasis of the discussion is on prokaryotic gene regulation, but our analysis can be extended to eukaryotic cells as well.

Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression

PubMed Central

Sanchez, Alvaro; Garcia, Hernan G.; Jones, Daniel; Phillips, Rob; Kondev, Jané

2011-01-01

According to recent experimental evidence, promoter architecture, defined by the number, strength and regulatory role of the operators that control transcription, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect variability in gene expression in a systematic rather than case-by-case fashion. In this article we make such a systematic investigation, based on a microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcriptional output from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can be used to test kinetic models of gene regulation. The emphasis of the discussion is on prokaryotic gene regulation, but our analysis can be extended to eukaryotic cells as well. PMID:21390269

Autosomal Dominant Cataract: Intrafamilial Phenotypic Variability, Interocular Asymmetry, and Variable Progression in Four Chilean Families

PubMed Central

Shafie, Suraiya M.; Barria von-Bischhoffshausen, Fernando R.; Bateman, J. Bronwyn

2006-01-01

PURPOSE To document intrafamilial and interocular phenotypic variability of autosomal dominant cataract (ADC). DESIGN Prospective observational case series. METHODS We performed ophthalmologic examination in four Chilean ADC families. RESULTS The families exhibited variability with respect to morphology, location with the lens, color and density of cataracts among affected members. We documented asymmetry between eyes in the morphology, location within the lens, color and density of cataracts, and a variable rate of progression. CONCLUSIONS The cataracts in these families exhibit wide intrafamilial and interocular phenotypic variability, supporting the premise that the mutated genes are expressed differentially in individuals and between eyes; other genes or environmental factors may be the bases for this variability. Marked progression among some family members underscores the variable clinical course of a common mutation within a family. Like retinitis pigmentosa, classification of ADC will be most useful if based on the gene and specific mutation. PMID:16564818

Size-fraction partitioning of community gene transcription and nitrogen metabolism in a marine oxygen minimum zone.

PubMed

Ganesh, Sangita; Bristow, Laura A; Larsen, Morten; Sarode, Neha; Thamdrup, Bo; Stewart, Frank J

2015-12-01

The genetic composition of marine microbial communities varies at the microscale between particle-associated (PA; >1.6 μm) and free-living (FL; 0.2-1.6 μm) niches. It remains unclear, however, how metabolic activities differ between PA and FL fractions. We combined rate measurements with metatranscriptomics to quantify PA and FL microbial activity in the oxygen minimum zone (OMZ) of the Eastern Tropical North Pacific, focusing on dissimilatory processes of the nitrogen (N) cycle. Bacterial gene counts were 8- to 15-fold higher in the FL compared with the PA fraction. However, rates of all measured N cycle processes, excluding ammonia oxidation, declined significantly following particle (>1.6 μm) removal. Without particles, rates of nitrate reduction to nitrite (1.5-9.4nMNd(-1)) fell to zero and N2 production by denitrification (0.5-1.7nMNd(-1)) and anammox (0.3-1.9nMNd(-1)) declined by 53-85%. The proportional representation of major microbial taxa and N cycle gene transcripts in metatranscriptomes followed fraction-specific trends. Transcripts encoding nitrate reductase were uniform among PA and FL fractions, whereas anammox-associated transcripts were proportionately enriched up to 15-fold in the FL fraction. In contrast, transcripts encoding enzymes for N2O and N2 production by denitrification were enriched up to 28-fold in PA samples. These patterns suggest that the majority of N cycle activity, excluding N2O and N2 production by denitrification, is confined to a FL majority that is critically dependent on access to particles, likely as a source of organic carbon and inorganic N. Variable particle distributions may drive heterogeneity in N cycle activity and gene expression in OMZs.

Size-fraction partitioning of community gene transcription and nitrogen metabolism in a marine oxygen minimum zone

PubMed Central

Ganesh, Sangita; Bristow, Laura A; Larsen, Morten; Sarode, Neha; Thamdrup, Bo; Stewart, Frank J

2015-01-01

The genetic composition of marine microbial communities varies at the microscale between particle-associated (PA; >1.6 μm) and free-living (FL; 0.2–1.6 μm) niches. It remains unclear, however, how metabolic activities differ between PA and FL fractions. We combined rate measurements with metatranscriptomics to quantify PA and FL microbial activity in the oxygen minimum zone (OMZ) of the Eastern Tropical North Pacific, focusing on dissimilatory processes of the nitrogen (N) cycle. Bacterial gene counts were 8- to 15-fold higher in the FL compared with the PA fraction. However, rates of all measured N cycle processes, excluding ammonia oxidation, declined significantly following particle (>1.6 μm) removal. Without particles, rates of nitrate reduction to nitrite (1.5–9.4nMNd−1) fell to zero and N2 production by denitrification (0.5–1.7nMNd−1) and anammox (0.3–1.9nMNd−1) declined by 53–85%. The proportional representation of major microbial taxa and N cycle gene transcripts in metatranscriptomes followed fraction-specific trends. Transcripts encoding nitrate reductase were uniform among PA and FL fractions, whereas anammox-associated transcripts were proportionately enriched up to 15-fold in the FL fraction. In contrast, transcripts encoding enzymes for N2O and N2 production by denitrification were enriched up to 28-fold in PA samples. These patterns suggest that the majority of N cycle activity, excluding N2O and N2 production by denitrification, is confined to a FL majority that is critically dependent on access to particles, likely as a source of organic carbon and inorganic N. Variable particle distributions may drive heterogeneity in N cycle activity and gene expression in OMZs. PMID:25848875

Population Dynamics of Genetic Regulatory Networks

NASA Astrophysics Data System (ADS)

Braun, Erez

2005-03-01

Unlike common objects in physics, a biological cell processes information. The cell interprets its genome and transforms the genomic information content, through the action of genetic regulatory networks, into proteins which in turn dictate its metabolism, functionality and morphology. Understanding the dynamics of a population of biological cells presents a unique challenge. It requires to link the intracellular dynamics of gene regulation, through the mechanism of cell division, to the level of the population. We present experiments studying adaptive dynamics of populations of genetically homogeneous microorganisms (yeast), grown for long durations under steady conditions. We focus on population dynamics that do not involve random genetic mutations. Our experiments follow the long-term dynamics of the population distributions and allow to quantify the correlations among generations. We focus on three interconnected issues: adaptation of genetically homogeneous populations following environmental changes, selection processes on the population and population variability and expression distributions. We show that while the population exhibits specific short-term responses to environmental inputs, it eventually adapts to a robust steady-state, largely independent of external conditions. Cycles of medium-switch show that the adapted state is imprinted in the population and that this memory is maintained for many generations. To further study population adaptation, we utilize the process of gene recruitment whereby a gene naturally regulated by a specific promoter is placed under a different regulatory system. This naturally occurring process has been recognized as a major driving force in evolution. We have recruited an essential gene to a foreign regulatory network and followed the population long-term dynamics. Rewiring of the regulatory network allows us to expose their complex dynamics and phase space structure.

Draft genome assembly of the Bengalese finch, Lonchura striata domestica, a model for motor skill variability and learning

PubMed Central

Mets, David G; Brainard, Michael S

2018-01-01

Abstract Background Vocal learning in songbirds has emerged as a powerful model for sensorimotor learning. Neurobehavioral studies of Bengalese finch (Lonchura striata domestica) song, naturally more variable and plastic than songs of other finch species, have demonstrated the importance of behavioral variability for initial learning, maintenance, and plasticity of vocalizations. However, the molecular and genetic underpinnings of this variability and the learning it supports are poorly understood. Findings To establish a platform for the molecular analysis of behavioral variability and plasticity, we generated an initial draft assembly of the Bengalese finch genome from a single male animal to 151× coverage and an N50 of 3.0 MB. Furthermore, we developed an initial set of gene models using RNA-seq data from 8 samples that comprise liver, muscle, cerebellum, brainstem/midbrain, and forebrain tissue from juvenile and adult Bengalese finches of both sexes. Conclusions We provide a draft Bengalese finch genome and gene annotation to facilitate the study of the molecular-genetic influences on behavioral variability and the process of vocal learning. These data will directly support many avenues for the identification of genes involved in learning, including differential expression analysis, comparative genomic analysis (through comparison to existing avian genome assemblies), and derivation of genetic maps for linkage analysis. Bengalese finch gene models and sequences will be essential for subsequent manipulation (molecular or genetic) of genes and gene products, enabling novel mechanistic investigations into the role of variability in learned behavior. PMID:29618046

Draft genome assembly of the Bengalese finch, Lonchura striata domestica, a model for motor skill variability and learning.

PubMed

Colquitt, Bradley M; Mets, David G; Brainard, Michael S

2018-03-01

Vocal learning in songbirds has emerged as a powerful model for sensorimotor learning. Neurobehavioral studies of Bengalese finch (Lonchura striata domestica) song, naturally more variable and plastic than songs of other finch species, have demonstrated the importance of behavioral variability for initial learning, maintenance, and plasticity of vocalizations. However, the molecular and genetic underpinnings of this variability and the learning it supports are poorly understood. To establish a platform for the molecular analysis of behavioral variability and plasticity, we generated an initial draft assembly of the Bengalese finch genome from a single male animal to 151× coverage and an N50 of 3.0 MB. Furthermore, we developed an initial set of gene models using RNA-seq data from 8 samples that comprise liver, muscle, cerebellum, brainstem/midbrain, and forebrain tissue from juvenile and adult Bengalese finches of both sexes. We provide a draft Bengalese finch genome and gene annotation to facilitate the study of the molecular-genetic influences on behavioral variability and the process of vocal learning. These data will directly support many avenues for the identification of genes involved in learning, including differential expression analysis, comparative genomic analysis (through comparison to existing avian genome assemblies), and derivation of genetic maps for linkage analysis. Bengalese finch gene models and sequences will be essential for subsequent manipulation (molecular or genetic) of genes and gene products, enabling novel mechanistic investigations into the role of variability in learned behavior.

The influence of music on mental effort and driving performance.

PubMed

Ünal, Ayça Berfu; Steg, Linda; Epstude, Kai

2012-09-01

The current research examined the influence of loud music on driving performance, and whether mental effort mediated this effect. Participants (N=69) drove in a driving simulator either with or without listening to music. In order to test whether music would have similar effects on driving performance in different situations, we manipulated the simulated traffic environment such that the driving context consisted of both complex and monotonous driving situations. In addition, we systematically kept track of drivers' mental load by making the participants verbally report their mental effort at certain moments while driving. We found that listening to music increased mental effort while driving, irrespective of the driving situation being complex or monotonous, providing support to the general assumption that music can be a distracting auditory stimulus while driving. However, drivers who listened to music performed as well as the drivers who did not listen to music, indicating that music did not impair their driving performance. Importantly, the increases in mental effort while listening to music pointed out that drivers try to regulate their mental effort as a cognitive compensatory strategy to deal with task demands. Interestingly, we observed significant improvements in driving performance in two of the driving situations. It seems like mental effort might mediate the effect of music on driving performance in situations requiring sustained attention. Other process variables, such as arousal and boredom, should also be incorporated to study designs in order to reveal more on the nature of how music affects driving. Copyright © 2012 Elsevier Ltd. All rights reserved.

Extended driving impairs nocturnal driving performances.

PubMed

Sagaspe, Patricia; Taillard, Jacques; Akerstedt, Torbjorn; Bayon, Virginie; Espié, Stéphane; Chaumet, Guillaume; Bioulac, Bernard; Philip, Pierre

2008-01-01

Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3-5 am, 1-5 am and 9 pm-5 am) on open highway. Fourteen young healthy men (mean age [+/-SD] = 23.4 [+/-1.7] years) participated Inappropriate line crossings (ILC) in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3-5 am) driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05) for the intermediate (1-5 am) driving session and by 4.0 (CI, 1.7 to 9.4; P<.001) for the long (9 pm-5 am) driving session. Compared to the reference session (9-10 pm), the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001), 15.4 (CI, 4.6 to 51.5; P<.001) and 24.3 (CI, 7.4 to 79.5; P<.001), respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05) and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01). At night, extended driving impairs driving performances and therefore should be limited.

Translocations in epithelial cancers

PubMed Central

Chad Brenner, J.; Chinnaiyan, Arul M.

2009-01-01

Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial cancers and the recent technological advances that increase the speed and reliability of recurrent gene fusion discovery are explored. PMID:19406209

What controls the variability of oxygen in the subpolar North Pacific?

NASA Astrophysics Data System (ADS)

Takano, Yohei

Dissolved oxygen is a widely observed chemical quantity in the oceans along with temperature and salinity. Changes in the dissolved oxygen have been observed over the world oceans. Observed oxygen in the Ocean Station Papa (OSP, 50°N, 145°W) in the Gulf of Alaska exhibits strong variability over interannual and decadal timescales, however, the mechanisms driving the observed variability are not yet fully understood. Furthermore, irregular sampling frequency and relatively short record length make it difficult to detect a low-frequency variability. Motivated by these observations, we investigate the mechanisms driving the low-frequency variability of oxygen in the subpolar North Pacific. The specific purposes of this study are (1) to evaluate the robustness of the observed low-frequency variability of dissolved oxygen and (2) to determine the mechanisms driving the observed variability using statistical data analysis and numerical simulations. To evaluate the robustness of the low-frequency variability, we conducted spectral analyses on the observed oxygen at OSP. To address the irregular sampling frequency we randomly sub-sampled the raw data to form 500 ensemble members with a regular time interval, and then performed spectral analyses. The resulting power spectrum of oxygen exhibits a robust low-frequency variability and a statistically significant spectral peak is identified at a timescale of 15--20 years. The wintertime oceanic barotropic streamfunction is significantly correlated with the observed oxygen anomaly at OSP with a north-south dipole structure over the North Pacific. We hypothesize that the observed low-frequency variability is primarily driven by the variability of large-scale ocean circulation in the North Pacific. To test this hypothesis, we simulate the three-dimensional distribution of oxygen anomaly between 1952 to 2001 using data-constrained circulation fields. The simulated oxygen anomaly shows an outstanding variability in the Gulf of Alaska, showing that this region is a hotspot of oxygen fluctuation. Anomalous advection acting on the climatological mean oxygen gradient is the source of oxygen variability in this simulation. Empirical Orthogonal Function (EOF) analyses of the simulated oxygen show that the two dominant modes of the oxygen anomaly explains more than 50% of oxygen variance over the North Pacific, that are closely related to the dominant modes of climate variability in the North Pacific (Pacific Decadal Oscillation and North Pacific Oscillation). Our results imply the important link between large-scale climate fluctuations, ocean circulation and biogeochemical tracers in the North Pacific.

A technology to measure multiple driving behaviors without self-report or participant reactivity.

PubMed Central

Boyce, T E; Geller, E S

2001-01-01

An in-vehicle information system (IVIS) was used to videotape drivers (N = 61) without their knowledge while driving 22 miles in normal traffic. The drivers were told that they were participating in a study of direction following and map reading. Two data-coding procedures were used to analyze videotapes. Safety-related behaviors were counted during consecutive 15-s intervals of a driving trial, and the occurrence of certain safety-related behaviors was assessed under critical conditions. These two methods of data coding were assessed for practicality, reliability, and sensitivity. Interobserver agreement for the five different driving behaviors ranged from 85% to 95%. Within-subject variability in safe driving was more pronounced among younger drivers and decreased as a function of age. Contrary to previous research that has relied on self-reports, driver risk taking did not vary significantly as a function of gender. These results are used to illustrate the capabilities of the technology introduced here to design and evaluate behavior-analytic interventions to increase safe driving. PMID:11317986

Female Behaviour Drives Expression and Evolution of Gustatory Receptors in Butterflies

PubMed Central

Briscoe, Adriana D.; Macias-Muñoz, Aide; Kozak, Krzysztof M.; Walters, James R.; Yuan, Furong; Jamie, Gabriel A.; Martin, Simon H.; Dasmahapatra, Kanchon K.; Ferguson, Laura C.; Mallet, James; Jacquin-Joly, Emmanuelle; Jiggins, Chris D.

2013-01-01

Secondary plant compounds are strong deterrents of insect oviposition and feeding, but may also be attractants for specialist herbivores. These insect-plant interactions are mediated by insect gustatory receptors (Grs) and olfactory receptors (Ors). An analysis of the reference genome of the butterfly Heliconius melpomene, which feeds on passion-flower vines (Passiflora spp.), together with whole-genome sequencing within the species and across the Heliconius phylogeny has permitted an unprecedented opportunity to study the patterns of gene duplication and copy-number variation (CNV) among these key sensory genes. We report in silico gene predictions of 73 Gr genes in the H. melpomene reference genome, including putative CO2, sugar, sugar alcohol, fructose, and bitter receptors. The majority of these Grs are the result of gene duplications since Heliconius shared a common ancestor with the monarch butterfly or the silkmoth. Among Grs but not Ors, CNVs are more common within species in those gene lineages that have also duplicated over this evolutionary time-scale, suggesting ongoing rapid gene family evolution. Deep sequencing (∼1 billion reads) of transcriptomes from proboscis and labial palps, antennae, and legs of adult H. melpomene males and females indicates that 67 of the predicted 73 Gr genes and 67 of the 70 predicted Or genes are expressed in these three tissues. Intriguingly, we find that one-third of all Grs show female-biased gene expression (n = 26) and nearly all of these (n = 21) are Heliconius-specific Grs. In fact, a significant excess of Grs that are expressed in female legs but not male legs are the result of recent gene duplication. This difference in Gr gene expression diversity between the sexes is accompanied by a striking sexual dimorphism in the abundance of gustatory sensilla on the forelegs of H. melpomene, suggesting that female oviposition behaviour drives the evolution of new gustatory receptors in butterfly genomes. PMID:23950722

Quantitative assessment of drivers of recent global temperature variability: an information theoretic approach

NASA Astrophysics Data System (ADS)

Bhaskar, Ankush; Ramesh, Durbha Sai; Vichare, Geeta; Koganti, Triven; Gurubaran, S.

2017-12-01

Identification and quantification of possible drivers of recent global temperature variability remains a challenging task. This important issue is addressed adopting a non-parametric information theory technique, the Transfer Entropy and its normalized variant. It distinctly quantifies actual information exchanged along with the directional flow of information between any two variables with no bearing on their common history or inputs, unlike correlation, mutual information etc. Measurements of greenhouse gases: CO2, CH4 and N2O; volcanic aerosols; solar activity: UV radiation, total solar irradiance ( TSI) and cosmic ray flux ( CR); El Niño Southern Oscillation ( ENSO) and Global Mean Temperature Anomaly ( GMTA) made during 1984-2005 are utilized to distinguish driving and responding signals of global temperature variability. Estimates of their relative contributions reveal that CO2 ({˜ } 24 %), CH4 ({˜ } 19 %) and volcanic aerosols ({˜ }23 %) are the primary contributors to the observed variations in GMTA. While, UV ({˜ } 9 %) and ENSO ({˜ } 12 %) act as secondary drivers of variations in the GMTA, the remaining play a marginal role in the observed recent global temperature variability. Interestingly, ENSO and GMTA mutually drive each other at varied time lags. This study assists future modelling efforts in climate science.

Microstructure and mesh sensitivities of mesoscale surrogate driving force measures for transgranular fatigue cracks in polycrystals

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

Castelluccio, Gustavo M.; McDowell, David L.

The number of cycles required to form and grow microstructurally small fatigue cracks in metals exhibits substantial variability, particularly for low applied strain amplitudes. This variability is commonly attributed to the heterogeneity of cyclic plastic deformation within the microstructure, and presents a challenge to minimum life design of fatigue resistant components. Our paper analyzes sources of variability that contribute to the driving force of transgranular fatigue cracks within nucleant grains. We also employ crystal plasticity finite element simulations that explicitly render the polycrystalline microstructure and Fatigue Indicator Parameters (FIPs) averaged over different volume sizes and shapes relative to the anticipatedmore » fatigue damage process zone. Volume averaging is necessary to both achieve description of a finite fatigue damage process zone and to regularize mesh dependence in simulations. Furthermore, results from constant amplitude remote applied straining are characterized in terms of the extreme value distributions of volume averaged FIPs. Grain averaged FIP values effectively mitigate mesh sensitivity, but they smear out variability within grains. Furthermore, volume averaging over bands that encompass critical transgranular slip planes appear to present the most attractive approach to mitigate mesh sensitivity while preserving variability within grains.« less

Microstructure and mesh sensitivities of mesoscale surrogate driving force measures for transgranular fatigue cracks in polycrystals

DOE PAGES

Castelluccio, Gustavo M.; McDowell, David L.

2015-05-22

The number of cycles required to form and grow microstructurally small fatigue cracks in metals exhibits substantial variability, particularly for low applied strain amplitudes. This variability is commonly attributed to the heterogeneity of cyclic plastic deformation within the microstructure, and presents a challenge to minimum life design of fatigue resistant components. Our paper analyzes sources of variability that contribute to the driving force of transgranular fatigue cracks within nucleant grains. We also employ crystal plasticity finite element simulations that explicitly render the polycrystalline microstructure and Fatigue Indicator Parameters (FIPs) averaged over different volume sizes and shapes relative to the anticipatedmore » fatigue damage process zone. Volume averaging is necessary to both achieve description of a finite fatigue damage process zone and to regularize mesh dependence in simulations. Furthermore, results from constant amplitude remote applied straining are characterized in terms of the extreme value distributions of volume averaged FIPs. Grain averaged FIP values effectively mitigate mesh sensitivity, but they smear out variability within grains. Furthermore, volume averaging over bands that encompass critical transgranular slip planes appear to present the most attractive approach to mitigate mesh sensitivity while preserving variability within grains.« less

Mouse alpha1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast.

PubMed

Dacquin, Romain; Starbuck, Michael; Schinke, Thorsten; Karsenty, Gérard

2002-06-01

Cell- and time-specific gene inactivation should enhance our knowledge of bone biology. Implementation of this technique requires construction of transgenic mouse lines expressing Cre recombinase in osteoblasts, the bone forming cell. We tested several promoter fragments for their ability to drive efficient Cre expression in osteoblasts. In the first mouse transgenic line, the Cre gene was placed under the control of the 2.3-kb proximal fragment of the alpha1(I)-collagen promoter, which is expressed at high levels in osteoblasts throughout their differentiation. Transgenic mice expressing this transgene in bone were bred with the ROSA26 reporter (R26R) strain in which the ROSA26 locus is targeted with a conditional LacZ reporter cassette. In R26R mice, Cre expression and subsequent Cre-mediated recombination lead to expression of the LacZ reporter gene, an event that can be monitored by LacZ staining. LacZ staining was detected in virtually all osteoblasts of alpha1(I)-Cre;R26R mice indicating that homologous recombination occurred in these cells. No other cell type stained blue. In the second line studied, the 1.3-kb fragment of osteocalcin gene 2 (OG2) promoter, which is active in differentiated osteoblasts, was used to drive Cre expression. OG2-Cre mice expressed Cre specifically in bone. However, cross of OG2-Cre mice with R26R mice did not lead to any detectable LacZ staining in osteoblasts. Lastly, we tested a more active artificial promoter derived from the OG2 promoter. The artificial OG2-Cre transgene was expressed by reverse transcriptase-polymerase chain reaction in cartilage and bone samples. After cross of the artificial OG2-Cre mice with R26R mice, we detected a LacZ staining in articular chondrocytes but not in osteoblasts. Our data suggest that the only promoter able to drive Cre expression at a level sufficient to induce recombination in osteoblasts is the alpha1(I)-collagen promoter. Copyright 2002 Wiley-Liss, Inc.

A downscaling scheme for atmospheric variables to drive soil-vegetation-atmosphere transfer models

NASA Astrophysics Data System (ADS)

Schomburg, A.; Venema, V.; Lindau, R.; Ament, F.; Simmer, C.

2010-09-01

For driving soil-vegetation-transfer models or hydrological models, high-resolution atmospheric forcing data is needed. For most applications the resolution of atmospheric model output is too coarse. To avoid biases due to the non-linear processes, a downscaling system should predict the unresolved variability of the atmospheric forcing. For this purpose we derived a disaggregation system consisting of three steps: (1) a bi-quadratic spline-interpolation of the low-resolution data, (2) a so-called `deterministic' part, based on statistical rules between high-resolution surface variables and the desired atmospheric near-surface variables and (3) an autoregressive noise-generation step. The disaggregation system has been developed and tested based on high-resolution model output (400m horizontal grid spacing). A novel automatic search-algorithm has been developed for deriving the deterministic downscaling rules of step 2. When applied to the atmospheric variables of the lowest layer of the atmospheric COSMO-model, the disaggregation is able to adequately reconstruct the reference fields. Applying downscaling step 1 and 2, root mean square errors are decreased. Step 3 finally leads to a close match of the subgrid variability and temporal autocorrelation with the reference fields. The scheme can be applied to the output of atmospheric models, both for stand-alone offline simulations, and a fully coupled model system.

Two-step optimization of pressure and recovery of reverse osmosis desalination process.

PubMed

Liang, Shuang; Liu, Cui; Song, Lianfa

2009-05-01

Driving pressure and recovery are two primary design variables of a reverse osmosis process that largely determine the total cost of seawater and brackish water desalination. A two-step optimization procedure was developed in this paper to determine the values of driving pressure and recovery that minimize the total cost of RO desalination. It was demonstrated that the optimal net driving pressure is solely determined by the electricity price and the membrane price index, which is a lumped parameter to collectively reflect membrane price, resistance, and service time. On the other hand, the optimal recovery is determined by the electricity price, initial osmotic pressure, and costs for pretreatment of raw water and handling of retentate. Concise equations were derived for the optimal net driving pressure and recovery. The dependences of the optimal net driving pressure and recovery on the electricity price, membrane price, and costs for raw water pretreatment and retentate handling were discussed.

Using driving simulators to assess driving safety.

PubMed

Boyle, Linda Ng; Lee, John D

2010-05-01

Changes in drivers, vehicles, and roadways pose substantial challenges to the transportation safety community. Crash records and naturalistic driving data are useful for examining the influence of past or existing technology on drivers, and the associations between risk factors and crashes. However, they are limited because causation cannot be established and technology not yet installed in production vehicles cannot be assessed. Driving simulators have become an increasingly widespread tool to understand evolving and novel technologies. The ability to manipulate independent variables in a randomized, controlled setting also provides the added benefit of identifying causal links. This paper introduces a special issue on simulator-based safety studies. The special issue comprises 25 papers that demonstrate the use of driving simulators to address pressing transportation safety problems and includes topics as diverse as neurological dysfunction, work zone design, and driver distraction. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

The impact of personality on driving safety among Chinese high-speed railway drivers.

PubMed

Guo, Ming; Wei, Wei; Liao, Ganli; Chu, Fulei

2016-07-01

This study explored the impact of personality traits on driving safety in high-speed railway drivers. A sample of high-speed railway drivers in Beijing (N=214) completed a questionnaire, including information on personality traits and background variables. The NEO Five Factor Inventory (NEO-FFI) was administered to characterize participants based on five personality traits: Neuroticism, Extraversion, Agreeableness, Openness to Experience, and Conscientiousness. The survey data were combined with naturalistic data of accident involvement and risky driving behavior in China. Poisson regression results show that drivers with high Conscientiousness and Extraversion caused fewer accidents. Higher Conscientiousness and lower Agreeableness were related to less frequent risky driving behavior. Education level and age negatively moderated the relation between certain personality traits and driving safety. The findings suggest that personality traits should be considered when selecting and training high-speed railway drivers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genomic Signature of Kin Selection in an Ant with Obligately Sterile Workers

PubMed Central

Warner, Michael R.; Mikheyev, Alexander S.

2017-01-01

Abstract Kin selection is thought to drive the evolution of cooperation and conflict, but the specific genes and genome-wide patterns shaped by kin selection are unknown. We identified thousands of genes associated with the sterile ant worker caste, the archetype of an altruistic phenotype shaped by kin selection, and then used population and comparative genomic approaches to study patterns of molecular evolution at these genes. Consistent with population genetic theoretical predictions, worker-upregulated genes experienced reduced selection compared with genes upregulated in reproductive castes. Worker-upregulated genes included more taxonomically restricted genes, indicating that the worker caste has recruited more novel genes, yet these genes also experienced reduced selection. Our study identifies a putative genomic signature of kin selection and helps to integrate emerging sociogenomic data with longstanding social evolution theory. PMID:28419349

The Mhc class II of the Black grouse (Tetrao tetrix) consists of low numbers of B and Y genes with variable diversity and expression.

PubMed

Strand, Tanja; Westerdahl, Helena; Höglund, Jacob; V Alatalo, Rauno; Siitari, Heli

2007-09-01

We found that the Black grouse (Tetrao tetrix) possess low numbers of Mhc class II B (BLB) and Y (YLB) genes with variable diversity and expression. We have therefore shown, for the first time, that another bird species (in this case, a wild lek-breeding galliform) shares several features of the simple Mhc of the domestic chicken (Gallus gallus). The Black grouse BLB genes showed the same level of polymorphism that has been reported in chicken, and we also found indications of balancing selection in the peptide-binding regions. The YLB genes were less variable than the BLB genes, also in accordance with earlier studies in chicken, although their functional significance still remains obscure. We hypothesize that the YLB genes could have been under purifying selection, just as the mammal Mhc-E gene cluster.

A large-scale study of the random variability of a coding sequence: a study on the CFTR gene.

PubMed

Modiano, Guido; Bombieri, Cristina; Ciminelli, Bianca Maria; Belpinati, Francesca; Giorgi, Silvia; Georges, Marie des; Scotet, Virginie; Pompei, Fiorenza; Ciccacci, Cinzia; Guittard, Caroline; Audrézet, Marie Pierre; Begnini, Angela; Toepfer, Michael; Macek, Milan; Ferec, Claude; Claustres, Mireille; Pignatti, Pier Franco

2005-02-01

Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (n(g) approximately 100-150 genes). In the present investigation, a large random European population sample (average n(g) approximately 1500) was studied for a single gene, the CFTR (Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q > 0.005), much lower than that of the synonymous (S) substitutions, but they showed a similar rate of subpolymorphic (q < 0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic.

Response variables for evaluation of the effectiveness of conservation corridors.

PubMed

Gregory, Andrew J; Beier, Paul

2014-06-01

Many studies have evaluated effectiveness of corridors by measuring species presence in and movement through small structural corridors. However, few studies have assessed whether these response variables are adequate for assessing whether the conservation goals of the corridors have been achieved or considered the costs or lag times involved in measuring the response variables. We examined 4 response variables-presence of the focal species in the corridor, interpatch movement via the corridor, gene flow, and patch occupancy--with respect to 3 criteria--relevance to conservation goals, lag time (fewest generations at which a positive response to the corridor might be evident with a particular variable), and the cost of a study when applying a particular variable. The presence variable had the least relevance to conservation goals, no lag time advantage compared with interpatch movement, and only a moderate cost advantage over interpatch movement or gene flow. Movement of individual animals between patches was the most appropriate response variable for a corridor intended to provide seasonal migration, but it was not an appropriate response variable for corridor dwellers, and for passage species it was only moderately relevant to the goals of gene flow, demographic rescue, and recolonization. Response variables related to gene flow provided a good trade-off among cost, relevance to conservation goals, and lag time. Nonetheless, the lag time of 10-20 generations means that evaluation of conservation corridors cannot occur until a few decades after a corridor has been established. Response variables related to occupancy were most relevant to conservation goals, but the lag time and costs to detect corridor effects on occupancy were much greater than the lag time and costs to detect corridor effects on gene flow. © 2014 Society for Conservation Biology.

Assessing dangerous driving behavior during driving inattention: Psychometric adaptation and validation of the Attention-Related Driving Errors Scale in China.

PubMed

Qu, Weina; Ge, Yan; Zhang, Qian; Zhao, Wenguo; Zhang, Kan

2015-07-01

Driver inattention is a significant cause of motor vehicle collisions and incidents. The purpose of this study was to translate the Attention-Related Driving Error Scale (ARDES) into Chinese and to verify its reliability and validity. A total of 317 drivers completed the Chinese version of the ARDES, the Dula Dangerous Driving Index (DDDI), the Attention-Related Cognitive Errors Scale (ARCES) and the Mindful Attention Awareness Scale (MAAS) questionnaires. Specific sociodemographic variables and traffic violations were also measured. Psychometric results confirm that the ARDES-China has adequate psychometric properties (Cronbach's alpha=0.88) to be a useful tool for evaluating proneness to attentional errors in the Chinese driving population. First, ARDES-China scores were positively correlated with both DDDI scores and number of accidents in the prior year; in addition, ARDES-China scores were a significant predictor of dangerous driving behavior as measured by DDDI. Second, we found that ARDES-China scores were strongly correlated with ARCES scores and negatively correlated with MAAS scores. Finally, different demographic groups exhibited significant differences in ARDES scores; in particular, ARDES scores varied with years of driving experience. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessing Cognitive Ability and Simulator-Based Driving Performance in Poststroke Adults

PubMed Central

Falkmer, Torbjörn; Willstrand, Tania Dukic

2017-01-01

Driving is an important activity of daily living, which is increasingly relied upon as the population ages. It has been well-established that cognitive processes decline following a stroke and these processes may influence driving performance. There is much debate on the use of off-road neurological assessments and driving simulators as tools to predict driving performance; however, the majority of research uses unlicensed poststroke drivers, making the comparability of poststroke adults to that of a control group difficult. It stands to reason that in order to determine whether simulators and cognitive assessments can accurately assess driving performance, the baseline should be set by licenced drivers. Therefore, the aim of this study was to assess differences in cognitive ability and driving simulator performance in licensed community-dwelling poststroke drivers and controls. Two groups of licensed drivers (37 poststroke and 43 controls) were assessed using several cognitive tasks and using a driving simulator. The poststroke adults exhibited poorer cognitive ability; however, there were no differences in simulator performance between groups except that the poststroke drivers demonstrated less variability in driver headway. The application of these results as a prescreening toolbox for poststroke drivers is discussed. PMID:28559646

Intentions and willingness to drive while drowsy among university students: An application of an extended theory of planned behavior model.

PubMed

Lee, Clark J; Geiger-Brown, Jeanne; Beck, Kenneth H

2016-08-01

A web-based questionnaire was used to assess the utility of constructs from the Theory of Planned Behavior (TPB) and the Prototype Willingness Model (PWM) to predict intentions and willingness to engage in drowsy driving in a sample of 450 university students. Those students who reported more favorable attitudes and subjective norm and greater perceived control and willingness in relation to drowsy driving behavior were more likely to report stronger intentions to engage in drowsy driving behavior. Augmenting the TPB constructs with the PWM construct of willingness significantly explained up to an additional 8 percent of the variance in drowsy driving intention. Perceived behavioral control and willingness were consistently the strongest predictors of drowsy driving intention in the augmented model, which together with the control (personal) variables explained up to 70 percent of the variance in intention. Thus, the Theory of Planned Behavior and the Prototype Willingness Model may be useful for understanding motivational influences on drowsy driving behavior in young people and present promising theoretical frameworks for designing more effective interventions against drowsy driving in this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gender differences and demographic influences in perceived concern for driver safety and support for impaired driving countermeasures.

PubMed

Butters, Jennifer; Mann, Robert E; Wickens, Christine M; Boase, Paul

2012-12-01

Driving safety, impaired driving, and legislation to address these concerns remain important issues. It is imperative countermeasures be targeted toward the most appropriate groups. This paper explores the potential relationship between gender and driving attitudes toward safety issues and impaired-driving countermeasures. The data are from the 2007 Impaired Driving Survey commissioned by Transport Canada and Mothers Against Drunk Driving (MADD) Canada. The survey is a, stratified by region, telephone survey of 1,514 Canadian drivers 18years of age and older with a valid driver's license who had driven within the past 30days. The findings illustrate a consistent impact of gender on these issues. Other variables were also identified as relevant factors although less consistently. Current findings suggest that strategies for building support for interventions, or for changing risk perception/concern for risky driving behaviors should be tailored by gender to maximize the potential for behavior change. This information may assist program and policy developers through the identification of more or less receptive target groups. Future research directions are also presented. Copyright © 2012 National Safety Council and Elsevier Ltd. All rights reserved.

Effectiveness and acceptance of the intelligent speeding prediction system (ISPS).

PubMed

Zhao, Guozhen; Wu, Changxu

2013-03-01

The intelligent speeding prediction system (ISPS) is an in-vehicle speed assistance system developed to provide quantitative predictions of speeding. Although the ISPS's prediction of speeding has been validated, whether the ISPS can regulate a driver's speed behavior or whether a driver accepts the ISPS needs further investigation. Additionally, compared to the existing intelligent speed adaptation (ISA) system, whether the ISPS performs better in terms of reducing excessive speeds and improving driving safety needs more direct evidence. An experiment was conducted to assess and compare the effectiveness and acceptance of the ISPS and the ISA. We conducted a driving simulator study with 40 participants. System type served as a between-subjects variable with four levels: no speed assistance system, pre-warning system developed based on the ISPS, post-warning system ISA, and combined pre-warning and ISA system. Speeding criterion served as a within-subjects variable with two levels: lower (posted speed limit plus 1 mph) and higher (posted speed limit plus 5 mph) speed threshold. Several aspects of the participants' driving speed, speeding measures, lead vehicle response, and subjective measures were collected. Both pre-warning and combined systems led to greater minimum time-to-collision. The combined system resulted in slower driving speed, fewer speeding exceedances, shorter speeding duration, and smaller speeding magnitude. The results indicate that both pre-warning and combined systems have the potential to improve driving safety and performance. Copyright © 2012 Elsevier Ltd. All rights reserved.

TCGA study of genetic drivers of melanoma

Cancer.gov

A comprehensive analysis of the genome of cutaneous melanoma has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive the development of this disease.

Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri.

PubMed

Wang, Guo-Dong; Zhang, Bao-Lin; Zhou, Wei-Wei; Li, Yong-Xin; Jin, Jie-Qiong; Shao, Yong; Yang, He-Chuan; Liu, Yan-Hu; Yan, Fang; Chen, Hong-Man; Jin, Li; Gao, Feng; Zhang, Yaoguang; Li, Haipeng; Mao, Bingyu; Murphy, Robert W; Wake, David B; Zhang, Ya-Ping; Che, Jing

2018-05-29

Tibetan frogs, Nanorana parkeri , are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation. Copyright © 2018 the Author(s). Published by PNAS.

Dynamometer Research Facilities | Wind | NREL

Science.gov Websites

drivetrains by replacing the rotor and blades of a turbine with a powerful motor. The National Renewable -horsepower variable-speed induction motor, with AC grid connections of 120, 240, and 480 volts (V) and a dynamometer features a 3,351-horsepower (hp), 415-amp AC induction motor with variable-frequency drive that

Noncognitive Variables as Predictors of Achievement in Freshmen English. AIR 1996 Annual Forum Paper.

ERIC Educational Resources Information Center

House, J. Daniel; Prion, Susan K.

This study investigated the correlation between noncognitive variables and academic success in a freshman composition course. A sample of 257 freshmen taking an introductory English course completed a survey assessing their attitudes and achievement expectancies. The questionnaire measured self-ratings of overall academic ability, drive to…

Attention following traumatic brain injury: Neuropsychological and driving simulator data, and association with sleep, sleepiness, and fatigue.

PubMed

Beaulieu-Bonneau, Simon; Fortier-Brochu, Émilie; Ivers, Hans; Morin, Charles M

2017-03-01

The objectives of this study were to compare individuals with traumatic brain injury (TBI) and healthy controls on neuropsychological tests of attention and driving simulation performance, and explore their relationships with participants' characteristics, sleep, sleepiness, and fatigue. Participants were 22 adults with moderate or severe TBI (time since injury ≥ one year) and 22 matched controls. They completed three neuropsychological tests of attention, a driving simulator task, night-time polysomnographic recordings, and subjective ratings of sleepiness and fatigue. Results showed that participants with TBI exhibited poorer performance compared to controls on measures tapping speed of information processing and sustained attention, but not on selective attention measures. On the driving simulator task, a greater variability of the vehicle lateral position was observed in the TBI group. Poorer performance on specific subsets of neuropsychological variables was associated with poorer sleep continuity in the TBI group, and with a greater increase in subjective sleepiness in both groups. No significant relationship was found between cognitive performance and fatigue. These findings add to the existing evidence that speed of information processing is still impaired several years after moderate to severe TBI. Sustained attention could also be compromised. Attention seems to be associated with sleep continuity and daytime sleepiness; this interaction needs to be explored further.

Effects of work zone configurations and traffic density on performance variables and subjective workload.

PubMed

Shakouri, Mahmoud; Ikuma, Laura H; Aghazadeh, Fereydoun; Punniaraj, Karthy; Ishak, Sherif

2014-10-01

This paper investigates the effect of changing work zone configurations and traffic density on performance variables and subjective workload. Data regarding travel time, average speed, maximum percent braking force and location of lane changes were collected by using a full size driving simulator. The NASA-TLX was used to measure self-reported workload ratings during the driving task. Conventional lane merge (CLM) and joint lane merge (JLM) were modeled in a driving simulator, and thirty participants (seven female and 23 male), navigated through the two configurations with two levels of traffic density. The mean maximum braking forces was 34% lower in the JLM configuration, and drivers going through the JLM configuration remained in the closed lane longer. However, no significant differences in speed were found between the two merge configurations. The analysis of self-reported workload ratings show that participants reported 15.3% lower total workload when driving through the JLM. In conclusion, the implemented changes in the JLM make it a more favorable merge configuration in both high and low traffic densities in terms of optimizing traffic flow by increasing the time and distance cars use both lanes, and in terms of improving safety due to lower braking forces and lower reported workload. Copyright © 2014 Elsevier Ltd. All rights reserved.

Experimental verification and comparison of the rubber V- belt continuously variable transmission models

NASA Astrophysics Data System (ADS)

Grzegożek, W.; Dobaj, K.; Kot, A.

2016-09-01

The paper includes the analysis of the rubber V-belt cooperation with the CVT transmission pulleys. The analysis of the forces and torques acting in the CVT transmission was conducted basing on calculated characteristics of the centrifugal regulator and the torque regulator. The accurate estimation of the regulator surface curvature allowed for calculation of the relation between the driving wheel axial force, the engine rotational speed and the gear ratio of the CVT transmission. Simplified analytical models of the rubber V-belt- pulley cooperation are based on three basic approaches. The Dittrich model assumes two contact regions on the driven and driving wheel. The Kim-Kim model considers, in addition to the previous model, also the radial friction. The radial friction results in the lack of the developed friction area on the driving pulley. The third approach, formulated in the Cammalleri model, assumes variable sliding angle along the wrap arch and describes it as a result the belt longitudinal and cross flexibility. Theoretical torque on the driven and driving wheel was calculated on the basis of the known regulators characteristics. The calculated torque was compared to the measured loading torque. The best accordance, referring to the centrifugal regulator range of work, was obtained for the Kim-Kim model.

Examination of associations between risky driving behaviors and hazardous drinking among a sample of college students.

PubMed

Martin, Ryan J; Cox, Melissa J; Chaney, Beth H; Knowlden, Adam P

2018-06-21

Hazardous drinking is associated with other risky behaviors and negative health-related outcomes. This study examined co-variation between hazardous drinking scores and the following risky driving behaviors: falling asleep while driving, texting (receiving and sending) while driving, and driving after consuming alcohol. The participants in this study were a sample of undergraduate students (N = 1,298) who were enrolled in an introductory health course at a large, Southeastern university in Spring 2016 and completed an online health survey that assessed hazardous drinking, falling asleep while driving, texting while driving, and driving after consuming alcohol. We conducted a series of two-step regression analyses to examine co-variation between hazardous drinking scores (using the AUDIT-C) and the risky driving behaviors of interest. We found that the majority of participants did not drink and drive (91.8%) nor did they fall asleep while driving (80.4%); however, the majority did read a text while driving (81.7%) and sent a text while driving (75.3%). In the full multivariable model, hazardous drinking score was positively associated with drinking and driving (Step 2 OR = 1.28, 95% CI: 1.18, 1.38) and sending a text message while driving (Step 2 b = 0.19, p = .01). Hazardous drinking score was also positively associated with reading a text while driving (Step 1 b = 0.14, p<.001) and falling asleep while driving (Step 1 b = 0.02, p=.02) in the model only controlling for demographic characteristics. The analyses also indicated co-variability between the following risky driving behaviors: (1) drinking and driving/reading a text message while driving, (2) drinking and driving/falling asleep and driving, (3) reading a text while driving/sending a text while driving, and (4) sending a text while driving/sleeping and driving. The findings of this study indicate a need for interventions discouraging both hazardous drinking and risky driving behaviors in college student populations; recommendations to reduce risky driving and hazardous drinking are discussed.

The nuclear 18S ribosomal RNA gene as a source of phylogenetic information in the genus Taenia.

PubMed

Yan, Hongbin; Lou, Zhongzi; Li, Li; Ni, Xingwei; Guo, Aijiang; Li, Hongmin; Zheng, Yadong; Dyachenko, Viktor; Jia, Wanzhong

2013-03-01

Most species of the genus Taenia are of considerable medical and veterinary significance. In this study, complete nuclear 18S rRNA gene sequences were obtained from seven members of genus Taenia [Taenia multiceps, Taenia saginata, Taenia asiatica, Taenia solium, Taenia pisiformis, Taenia hydatigena, and Taenia taeniaeformis] and a phylogeny inferred using these sequences. Most of the variable sites fall within the variable regions, V1-V5. We show that sequences from the nuclear 18S ribosomal RNA gene have considerable promise as sources of phylogenetic information within the genus Taenia. Furthermore, given that almost all the variable sites lie within defined variable portions of that gene, it will be appropriate and economical to sequence only those regions for additional species of Taenia.

Fatigue in Younger and Older Drivers: Effectiveness of an Alertness-Maintaining Task.

PubMed

Song, Woojin; Woon, Fu L; Doong, Alice; Persad, Carol; Tijerina, Louis; Pandit, Pooja; Cline, Carol; Giordani, Bruno

2017-09-01

The aim of this study was to examine the effects of an alertness-maintaining task (AMT) in older, fatigued drivers. Fatigue during driving increases crash risk, and previous research suggests that alertness and driving in younger adults may be improved using a secondary AMT during boring, fatigue-eliciting drives. However, the potential impact of an AMT on driving has not been investigated in older drivers whose ability to complete dual tasks has been shown to decline and therefore may be negatively affected with an AMT in driving. Younger ( n = 29) and older drivers ( n = 39) participated in a 50-minute simulated drive designed to induce fatigue, followed by four 10-minute sessions alternating between driving with and without an AMT. Younger drivers were significantly more affected by fatigue on driving performance than were older drivers but benefitted significantly from the AMT. Older drivers did not demonstrate increased driver errors with fatigue, and driving did not deteriorate significantly during participation in the AMT condition, although their speed was significantly more variable with the AMT. Consistent with earlier research, an AMT applied during fatiguing driving is effective in improving alertness and reducing driving errors in younger drivers. Importantly, older drivers were relatively unaffected by fatigue, and use of an AMT did not detrimentally affect their driving performance. These results support the potential use of an AMT as a new automotive technology to improve fatigue and promote driver safety, though the benefits of such technology may differ between different age groups.

The combination of two training approaches to improve older adults' driving safety.

PubMed

Bédard, Michel; Porter, Michelle M; Marshall, Shawn; Isherwood, Ivy; Riendeau, Julie; Weaver, Bruce; Tuokko, Holly; Molnar, Frank; Miller-Polgar, Jan

2008-03-01

An increasing number of older adults rely on the automobile for transportation. Educational approaches based on the specific needs of older drivers may help to optimize safe driving. We examined if the combination of an in-class education program with on-road education would lead to improvements in older drivers' knowledge of safe driving practices and on-road driving evaluations. We used a multisite, randomized controlled trial approach. Participants in the intervention group received the in-class and on-road education; those in the control group waited and were offered the education afterwards. We measured knowledge of safe driving practices before and after the in-class component of the program and on-road driving skills before and after the whole program. Participants' knowledge improved from 61% of correct answers before the in-class education component to 81% after (p < .001). The on-road evaluation results suggested improvements on some aspects of safe driving (e.g., moving in roadway, p < .05) but not on others. The results of this study demonstrate that education programs focused on the needs of older drivers may help improve their knowledge of safe driving practices and actual driving performance. Further research is required to determine if these changes will affect other variables such as driver confidence and crash rates.

Challenges in Characterizing and Controlling Complex Cellular Systems

NASA Astrophysics Data System (ADS)

Wikswo, John

2011-03-01

Multicellular dynamic biological processes such as developmental differentiation, wound repair, disease, aging, and even homeostasis can be represented by trajectories through a phase space whose extent reflects the genetic, post-translational, and metabolic complexity of the process - easily extending to tens of thousands of dimensions. Intra- and inter-cellular sensing and regulatory systems and their nested, redundant, and non-linear feed-forward and feed-back controls create high-dimensioned attractors in this phase space. Metabolism provides free energy to drive non-equilibrium processes and dynamically reconfigure attractors. Studies of single molecules and cells provide only minimalist projections onto a small number of axes. It may be difficult to infer larger-scale emergent behavior from linearized experiments that perform only small amplitude perturbations on a limited number of the dimensions. Complete characterization may succeed for bounded component problems, such as an individual cell cycle or signaling cascade, but larger systems problems will require a coarse-grained approach. Hence a new experimental and analytical framework is needed. Possibly one could utilize high-amplitude, multi-variable driving of the system to infer coarse-grained, effective models, which in turn can be tested by their ability to control systems behavior. Navigation at will between attractors in a high-dimensioned dynamical system will provide not only detailed knowledge of the shape of attractor basins, but also measures of underlying stochastic events such as noise in gene expression or receptor binding and how both affect system stability and robustness. Needed for this are wide-bandwidth methods to sense and actuate large numbers of intracellular and extracellular variables and automatically and rapidly infer dynamic control models. The success of this approach may be determined by how broadly the sensors and actuators can span the full dimensionality of the phase space. Supported by the Defense Threat Reduction Agency HDTRA-09-1-0013, NIH National Institute on Drug Abuse RC2DA028981, the National Academies Keck Futures Initiative, and the Vanderbilt Institute for Integrative Biosystems Research and Education.

Adaptive Evolution of Extreme Acidophile Sulfobacillus thermosulfidooxidans Potentially Driven by Horizontal Gene Transfer and Gene Loss

PubMed Central

Zhang, Xian; Liu, Xueduan; Liang, Yili; Guo, Xue; Xiao, Yunhua; Ma, Liyuan; Miao, Bo; Liu, Hongwei; Peng, Deliang; Huang, Wenkun; Zhang, Yuguang

2017-01-01

ABSTRACT Recent phylogenomic analysis has suggested that three strains isolated from different copper mine tailings around the world were taxonomically affiliated with Sulfobacillus thermosulfidooxidans. Here, we present a detailed investigation of their genomic features, particularly with respect to metabolic potentials and stress tolerance mechanisms. Comprehensive analysis of the Sulfobacillus genomes identified a core set of essential genes with specialized biological functions in the survival of acidophiles in their habitats, despite differences in their metabolic pathways. The Sulfobacillus strains also showed evidence for stress management, thereby enabling them to efficiently respond to harsh environments. Further analysis of metabolic profiles provided novel insights into the presence of genomic streamlining, highlighting the importance of gene loss as a main mechanism that potentially contributes to cellular economization. Another important evolutionary force, especially in larger genomes, is gene acquisition via horizontal gene transfer (HGT), which might play a crucial role in the recruitment of novel functionalities. Also, a successful integration of genes acquired from archaeal donors appears to be an effective way of enhancing the adaptive capacity to cope with environmental changes. Taken together, the findings of this study significantly expand the spectrum of HGT and genome reduction in shaping the evolutionary history of Sulfobacillus strains. IMPORTANCE Horizontal gene transfer (HGT) and gene loss are recognized as major driving forces that contribute to the adaptive evolution of microbial genomes, although their relative importance remains elusive. The findings of this study suggest that highly frequent gene turnovers within microorganisms via HGT were necessary to incur additional novel functionalities to increase the capacity of acidophiles to adapt to changing environments. Evidence also reveals a fascinating phenomenon of potential cross-kingdom HGT. Furthermore, genome streamlining may be a critical force in driving the evolution of microbial genomes. Taken together, this study provides insights into the importance of both HGT and gene loss in the evolution and diversification of bacterial genomes. PMID:28115381

Adaptive Evolution of Extreme Acidophile Sulfobacillus thermosulfidooxidans Potentially Driven by Horizontal Gene Transfer and Gene Loss.

PubMed

Zhang, Xian; Liu, Xueduan; Liang, Yili; Guo, Xue; Xiao, Yunhua; Ma, Liyuan; Miao, Bo; Liu, Hongwei; Peng, Deliang; Huang, Wenkun; Zhang, Yuguang; Yin, Huaqun

2017-04-01

Recent phylogenomic analysis has suggested that three strains isolated from different copper mine tailings around the world were taxonomically affiliated with Sulfobacillus thermosulfidooxidans Here, we present a detailed investigation of their genomic features, particularly with respect to metabolic potentials and stress tolerance mechanisms. Comprehensive analysis of the Sulfobacillus genomes identified a core set of essential genes with specialized biological functions in the survival of acidophiles in their habitats, despite differences in their metabolic pathways. The Sulfobacillus strains also showed evidence for stress management, thereby enabling them to efficiently respond to harsh environments. Further analysis of metabolic profiles provided novel insights into the presence of genomic streamlining, highlighting the importance of gene loss as a main mechanism that potentially contributes to cellular economization. Another important evolutionary force, especially in larger genomes, is gene acquisition via horizontal gene transfer (HGT), which might play a crucial role in the recruitment of novel functionalities. Also, a successful integration of genes acquired from archaeal donors appears to be an effective way of enhancing the adaptive capacity to cope with environmental changes. Taken together, the findings of this study significantly expand the spectrum of HGT and genome reduction in shaping the evolutionary history of Sulfobacillus strains. IMPORTANCE Horizontal gene transfer (HGT) and gene loss are recognized as major driving forces that contribute to the adaptive evolution of microbial genomes, although their relative importance remains elusive. The findings of this study suggest that highly frequent gene turnovers within microorganisms via HGT were necessary to incur additional novel functionalities to increase the capacity of acidophiles to adapt to changing environments. Evidence also reveals a fascinating phenomenon of potential cross-kingdom HGT. Furthermore, genome streamlining may be a critical force in driving the evolution of microbial genomes. Taken together, this study provides insights into the importance of both HGT and gene loss in the evolution and diversification of bacterial genomes. Copyright © 2017 American Society for Microbiology.

Assessment of the utility of the tomato fruit-specific E8 promoter for driving vaccine antigen expression.

PubMed

He, Zhu-Mei; Jiang, Xiao-Ling; Qi, Yu; Luo, Di-Qing

2008-06-01

To assess the utility of the tomato fruit-specific E8 gene's promoter for driving vaccine antigen expression in plant, the 2.2 kb and 1.1 kb E8 promoters were isolated and sequenced from Lycopersicon esculentum cv. Jinfeng #1. The 1.1 kb promoter was fused to vaccine antigen HBsAg M gene for the transfer to Nicotiana tabacum, and the CaMV 35S promoter was used for comparison. Cholera toxin B (ctb) gene under the control of the 1.1 kb promoter was transformed into both N. tabacum and L. esculentum. Southern blot hybridization confirmed the stable integration of the target genes into the tomato and tobacco genomes. ELISA assay showed that the expression product of HBsAg M gene under the control of the 1.1 kb E8 promoter could not be detected in transgenic tobacco tissues such as leaves, flowers, and seeds. In contrast, the expression of HBsAg M gene driven by CaMV 35S promoter could be detected in transgenic tobacco. ELISA assay for CTB proved that the 1.1 kb E8 promoter was able to direct the expression of exotic gene in ripe fruits of transgenic tomato, but expression was absent in leaf, flower, and unripe fruit of tomato, and CTB protein was not detected in transgenic tobacco tissues such as leaves, flowers, and seeds when the gene was under the control of the 1.1 kb E8 promoter. The results indicated that the E8 promoter acted not only in an organ-specific, but also in a species-specific fashion in plant transformation.

Social Networking Site Use While Driving: ADHD and the Mediating Roles of Stress, Self-Esteem and Craving

PubMed Central

Turel, Ofir; Bechara, Antoine

2016-01-01

Background: Adults who present ADHD symptoms have an increased risk for vehicle accidents. One conceivable overlooked account for this association is the possibility that people with ADHD symptoms use rewarding technologies such as social networking sites (SNS) while driving, more than others. The objective of this study was to understand if and how ADHD symptoms can promote SNS use while driving and specifically to conceptualize and examine mechanisms which may underlie this association. To do so, ADHD is viewed in this study as an underlying syndrome that promotes SNS use while driving in a manner similar to how addictive syndromes promote compulsive seeking of drug rewards. Methods: Time-lagged survey data regarding ADHD, stress, self-esteem, SNS craving experience, SNS use while driving, and control variables were collected from a sample of 457 participants who use a popular SNS (Facebook) and drive, after face-validity examination with a panel of five users and pretest with a sample of 47. These data were subjected to structural equation modeling (SEM) analyses using the frequency of ADHD symptoms measured with ASRS v1.1 Part A as a continuous variable, as well as multivariate analysis of variance using ADHD classification based on ASRS v1.1 scoring guidelines. Results: ADHD symptoms promoted increased stress and reduced self-esteem, which in turn, together with ADHD symptoms, increased one's cravings to use the SNS. These cravings ultimately translated into increased SNS use while driving. Using the ASRS v1.1 classification, people having symptoms highly consistent with ADHD presented elevated levels of stress, cravings to use the SNS, and SNS use while driving, as well as decreased levels of self-esteem. Cravings to use the SNS among men were more potent than among women. Conclusion: SNS use while driving may be more prevalent than previously assumed and may be indirectly associated with ADHD symptoms. It is a new form of impulsive and risky behavior which is more common among people with symptoms compatible with ADHD than among others. Consistent with addiction and decision making models, SNS use while driving can be viewed as a form of a compensatory reward seeking behavior. As such, prevention and reduction interventions that target the mediating perceptions and states should be devised. PMID:27065923

Social Networking Site Use While Driving: ADHD and the Mediating Roles of Stress, Self-Esteem and Craving.

PubMed

Turel, Ofir; Bechara, Antoine

2016-01-01

Adults who present ADHD symptoms have an increased risk for vehicle accidents. One conceivable overlooked account for this association is the possibility that people with ADHD symptoms use rewarding technologies such as social networking sites (SNS) while driving, more than others. The objective of this study was to understand if and how ADHD symptoms can promote SNS use while driving and specifically to conceptualize and examine mechanisms which may underlie this association. To do so, ADHD is viewed in this study as an underlying syndrome that promotes SNS use while driving in a manner similar to how addictive syndromes promote compulsive seeking of drug rewards. Time-lagged survey data regarding ADHD, stress, self-esteem, SNS craving experience, SNS use while driving, and control variables were collected from a sample of 457 participants who use a popular SNS (Facebook) and drive, after face-validity examination with a panel of five users and pretest with a sample of 47. These data were subjected to structural equation modeling (SEM) analyses using the frequency of ADHD symptoms measured with ASRS v1.1 Part A as a continuous variable, as well as multivariate analysis of variance using ADHD classification based on ASRS v1.1 scoring guidelines. ADHD symptoms promoted increased stress and reduced self-esteem, which in turn, together with ADHD symptoms, increased one's cravings to use the SNS. These cravings ultimately translated into increased SNS use while driving. Using the ASRS v1.1 classification, people having symptoms highly consistent with ADHD presented elevated levels of stress, cravings to use the SNS, and SNS use while driving, as well as decreased levels of self-esteem. Cravings to use the SNS among men were more potent than among women. SNS use while driving may be more prevalent than previously assumed and may be indirectly associated with ADHD symptoms. It is a new form of impulsive and risky behavior which is more common among people with symptoms compatible with ADHD than among others. Consistent with addiction and decision making models, SNS use while driving can be viewed as a form of a compensatory reward seeking behavior. As such, prevention and reduction interventions that target the mediating perceptions and states should be devised.

Genomic and Epigenomic Alterations in Cancer.

PubMed

Chakravarthi, Balabhadrapatruni V S K; Nepal, Saroj; Varambally, Sooryanarayana

2016-07-01

Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.

PubMed

Jackson, Andrew P; Otto, Thomas D; Darby, Alistair; Ramaprasad, Abhinay; Xia, Dong; Echaide, Ignacio Eduardo; Farber, Marisa; Gahlot, Sunayna; Gamble, John; Gupta, Dinesh; Gupta, Yask; Jackson, Louise; Malandrin, Laurence; Malas, Tareq B; Moussa, Ehab; Nair, Mridul; Reid, Adam J; Sanders, Mandy; Sharma, Jyotsna; Tracey, Alan; Quail, Mike A; Weir, William; Wastling, Jonathan M; Hall, Neil; Willadsen, Peter; Lingelbach, Klaus; Shiels, Brian; Tait, Andy; Berriman, Matt; Allred, David R; Pain, Arnab

2014-06-01

Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5' ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

The relationship between biomechanical variables and driving performance during the golf swing.

PubMed

Chu, Yungchien; Sell, Timothy C; Lephart, Scott M

2010-09-01

Swing kinematic and ground reaction force data from 308 golfers were analysed to identify the variables important to driving ball velocity. Regression models were applied at four selected events in the swing. The models accounted for 44-74% of variance in ball velocity. Based on the regression analyses, upper torso-pelvis separation (the X-Factor), delayed release (i.e. the initiation of movement) of the arms and wrists, trunk forward and lateral tilting, and weight-shifting during the swing were significantly related to ball velocity. Our results also verify several general coaching ideas that were considered important to increased ball velocity. The results of this study may serve as both skill and strength training guidelines for golfers.

Capacitor regenerative braking system of electric wheelchair for senior citizen based on variable frequency chopper control.

PubMed

Takahashi, Yoshiaki; Seki, Hirokazu

2009-01-01

This paper proposes a novel regenerative braking control system of electric wheelchairs for senior citizen. "Electric powered wheelchair", which generates the driving force by electric motors according to the human operation, is expected to be widely used as a mobility support system for elderly people. This study focuses on the braking control to realize the safety and smooth stopping motion using the regenerative braking control technique based on fuzzy algorithm. The ride quality improvement and energy recycling can be expected by the proposed control system with stopping distance estimation and variable frequency control on the step-up/down chopper type of capacitor regenerative circuit. Some driving experiments confirm the effectiveness of the proposed control system.

Multiswitching combination synchronisation of non-identical fractional-order chaotic systems

NASA Astrophysics Data System (ADS)

Bhat, Muzaffar Ahmad; Khan, Ayub

2018-06-01

In this paper, multiswitching combination synchronisation (MSCS) scheme has been investigated in a class of three non-identical fractional-order chaotic systems. The fractional-order Lorenz and Chen systems are taken as the drive systems. The combination of multidrive systems is then synchronised with the fractional-order Lü chaotic system. In MSCS, the state variables of the two drive systems synchronise with different state variables of the response system, simultaneously. Based on the stability of fractional-order chaotic systems, the MSCS of three fractional-order non-identical systems has been investigated. For the synchronisation of three non-identical fractional-order chaotic systems, suitable controllers have been designed. Theoretical analysis and numerical results are presented to demonstrate the validity and feasibility of the applied method.

Concepts for Variable/Multi-Speed Rotorcraft Drive System

NASA Technical Reports Server (NTRS)

Stevens, Mark A.; Handschuh, Robert F.; Lewicki, David G.

2008-01-01

In several recent studies and on-going developments for advanced rotorcraft, the need for variable or multi-speed capable rotors has been raised. A speed change of up to 50 percent has been proposed for future rotorcraft to improve overall vehicle performance. Accomplishing rotor speed changes during operation requires both a rotor that can perform effectively over the operation speed/load range, and a propulsion system that can enable these speed changes. A study has been completed to investigate possible drive system arrangements that can accommodate up to the 50 percent speed change. Several concepts will be presented and evaluated. The most promising configurations will be identified and developed for future testing in a sub-scaled test facility to validate operational capability.

TCGA study of genetic drivers of melanoma - TCGA

Cancer.gov

A comprehensive analysis of the genome of cutaneous melanoma has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive the development of this disease.

TCGA study improves understanding of thyroid cancer genetics - TCGA

Cancer.gov

A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive disease development.

Chromatin reorganisation in Epstein-Barr virus-infected cells and its role in cancer development.

PubMed

West, Michelle J

2017-10-01

The oncogenic Epstein-Barr virus (EBV) growth transforms B cells and drives lymphoma and carcinoma development. The virus encodes four key transcription factors (EBNA2, EBNA3A, EBNA3B and EBNA3C) that hijack host cell factors to bind gene control elements and reprogramme infected B cells. These viral factors predominantly target long-range enhancers to alter the expression of host cell genes that control B cell growth and survival and facilitate virus persistence. Enhancer and super-enhancer binding by these EBNAs results in large-scale reorganisation of three-dimensional enhancer-promoter architecture to drive the overexpression of oncogenes, the silencing of tumour suppressors and the modulation of transcription, cell-cycle progression, migration and adhesion. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Gene Therapy for Cardiovascular Disease

PubMed Central

2003-01-01

The last decade has seen substantial advances in the development of gene therapy strategies and vector technology for the treatment of a diverse number of diseases, with a view to translating the successes observed in animal models into the clinic. Perhaps the overwhelming drive for the increase in vascular gene transfer studies is the current lack of successful long-term pharmacological treatments for complex cardiovascular diseases. The increase in cardiovascular disease to epidemic proportions has also led many to conclude that drug therapy may have reached a plateau in its efficacy and that gene therapy may represent a realistic solution to a long-term problem. Here, we discuss gene delivery approaches and target diseases. PMID:12721517

A DNA methylation map of human cancer at single base-pair resolution.

PubMed

Vidal, E; Sayols, S; Moran, S; Guillaumet-Adkins, A; Schroeder, M P; Royo, R; Orozco, M; Gut, M; Gut, I; Lopez-Bigas, N; Heyn, H; Esteller, M

2017-10-05

Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination.

Effects of Recent Regional Soil Moisture Variability on Global Net Ecosystem CO2 Exchange

NASA Astrophysics Data System (ADS)

Jones, L. A.; Madani, N.; Kimball, J. S.; Reichle, R. H.; Colliander, A.

2017-12-01

Soil moisture exerts a major regional control on the inter-annual variability of the global land sink for atmospheric CO2. In semi-arid regions, annual biomass production is closely coupled to variability in soil moisture availability, while in cold-season-affected regions, summer drought offsets the effects of advancing spring phenology. Availability of satellite solar-induced fluorescence (SIF) observations and improvements in atmospheric inversions has led to unprecedented ability to monitor atmospheric sink strength. However, discrepancies still exist between such top-down estimates as atmospheric inversion and bottom-up process and satellite driven models, indicating that relative strength, mechanisms, and interaction of driving factors remain poorly understood. We use soil moisture fields informed by Soil Moisture Active Passive Mission (SMAP) observations to compare recent (2015-2017) and historic (2000-2014) variability in net ecosystem land-atmosphere CO2 exchange (NEE). The operational SMAP Level 4 Carbon (L4C) product relates ground-based flux tower measurements to other bottom-up and global top-down estimates to underlying soil moisture and other driving conditions using data-assimilation-based SMAP Level 4 Soil Moisture (L4SM). Droughts in coastal Brazil, South Africa, Eastern Africa, and an anomalous wet period in Eastern Australia were observed by L4C. A seasonal seesaw pattern of below-normal sink strength at high latitudes relative to slightly above-normal sink strength for mid-latitudes was also observed. Whereas SMAP-based soil moisture is relatively informative for short-term temporal variability, soil moisture biases that vary in space and with season constrain the ability of the L4C estimates to accurately resolve NEE. Such biases might be caused by irrigation and plant-accessible ground-water. Nevertheless, SMAP L4C daily NEE estimates connect top-down estimates to variability of effective driving factors for accurate estimates of regional-to-global land-atmosphere CO2 exchange.

BASiCS: Bayesian Analysis of Single-Cell Sequencing Data

PubMed Central

Vallejos, Catalina A.; Marioni, John C.; Richardson, Sylvia

2015-01-01

Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels in seemingly homogeneous populations of cells. However, these experiments are prone to high levels of unexplained technical noise, creating new challenges for identifying genes that show genuine heterogeneous expression within the population of cells under study. BASiCS (Bayesian Analysis of Single-Cell Sequencing data) is an integrated Bayesian hierarchical model where: (i) cell-specific normalisation constants are estimated as part of the model parameters, (ii) technical variability is quantified based on spike-in genes that are artificially introduced to each analysed cell’s lysate and (iii) the total variability of the expression counts is decomposed into technical and biological components. BASiCS also provides an intuitive detection criterion for highly (or lowly) variable genes within the population of cells under study. This is formalised by means of tail posterior probabilities associated to high (or low) biological cell-to-cell variance contributions, quantities that can be easily interpreted by users. We demonstrate our method using gene expression measurements from mouse Embryonic Stem Cells. Cross-validation and meaningful enrichment of gene ontology categories within genes classified as highly (or lowly) variable supports the efficacy of our approach. PMID:26107944

BASiCS: Bayesian Analysis of Single-Cell Sequencing Data.

PubMed

Vallejos, Catalina A; Marioni, John C; Richardson, Sylvia

2015-06-01

Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels in seemingly homogeneous populations of cells. However, these experiments are prone to high levels of unexplained technical noise, creating new challenges for identifying genes that show genuine heterogeneous expression within the population of cells under study. BASiCS (Bayesian Analysis of Single-Cell Sequencing data) is an integrated Bayesian hierarchical model where: (i) cell-specific normalisation constants are estimated as part of the model parameters, (ii) technical variability is quantified based on spike-in genes that are artificially introduced to each analysed cell's lysate and (iii) the total variability of the expression counts is decomposed into technical and biological components. BASiCS also provides an intuitive detection criterion for highly (or lowly) variable genes within the population of cells under study. This is formalised by means of tail posterior probabilities associated to high (or low) biological cell-to-cell variance contributions, quantities that can be easily interpreted by users. We demonstrate our method using gene expression measurements from mouse Embryonic Stem Cells. Cross-validation and meaningful enrichment of gene ontology categories within genes classified as highly (or lowly) variable supports the efficacy of our approach.

MULTIPLE DIFFERENTIAL ROTARY MECHANICAL DRIVE

DOEpatents

Smits, R.G.

1964-01-28

This patent relates to a mechanism suitable for such applications as driving two spaced-apart spools which carry a roll film strip under conditions where the film movement must be rapidly started, stopped, and reversed while maintaining a constant tension on the film. The basic drive is provided by a variable speed, reversible rnotor coupled to both spools through a first differential mechanism and driving both spools in the same direction. A second motor, providing a constant torque, is connected to the two spools through a second differential mechanism and is coupled to impart torque to one spool in a first direction anid to the other spool in the reverse direction thus applying a constant tension to the film passing over the two spools irrespective of the speed or direction of rotation thereof. (AEC)

Study on the association between drug‑resistance and gene mutations of the active efflux pump acrAB‑tolC gene and its regulatory genes.

PubMed

Ma, Quan-Ping; Su, Liang; Liu, Jing-Wen; Yao, Ming-Xiao; Yuan, Guang-Ying

2018-06-01

The aim of the present study was to investigate the correlation between the multi‑drug resistance of Shigella flexneri and the drug‑resistant gene cassette carried by integrons; in the meanwhile, to detect the associations between drug‑resistance and gene mutations of the active efflux pump acrAB‑tolC gene and its regulatory genes, including marOR, acrR and soxS. A total of 158 isolates were isolated from the stool samples of 1,026 children with diarrhoea aged 14 years old between May 2012 and October 2015 in Henan. The K‑B method was applied for the determination of drug resistance of Shigella flexneri, and polymerase chain reaction amplification was used for class 1, 2 and 3 integrase genes. Enzyme digestion and sequence analysis were performed for the variable regions of positive strains. Based on the drug sensitivity assessment, multi‑drug resistant strains that were resistant to five or more antibiotics, and sensitive strains were selected for amplification. Their active efflux pump genes, acrA and acrB, and regulatory genes, marOR, acrR and soxS, were selected for sequencing. The results revealed that 91.1% of the 158 strains were multi‑resistant to ampicillin, chloramphenicol, tetracycline and streptomycin, and 69.6% of the strains were multi‑resistant to sulfamethoxazole/trimethoprim. The resistance to ceftazidime, ciprofloxacin and levofloxacin was <32.9%. All strains (100%) were sensitive to cefoxitin, cefoperazone/sulbactam and imipenem. The rate of the class 1 integron positivity was 91.9% (144/158). Among these class 1 integron‑positive strains, 18 strains exhibited the resistance gene cassette dfrV in the variable region of the strain, four strains exhibited dfrA17‑aadA5 in the variable region and 140 strains exhibited blaOXA‑30‑aadA1 in the variable region. Four strains showed no resistance gene in the variable regions. The rate of class 2 integron positivity was 86.1% (136/158), and all positive strains harboured the dfrA1‑sat1‑aadA resistance gene cassette in the variable region. The class 3 integrase gene was not detected in these strains. The gene sequencing showed the deletion of base CATT in the 36, 37, 38, 39 site in the marOR gene, which is a regulatory gene of the active efflux pump, AcrAB‑TolC. Taken together, the multi‑drug resistance of Shigella flexneri was closely associated with gene mutations of class 1 and 2 integrons and the marOR gene.

[Gene method for inconsistent hydrological frequency calculation. I: Inheritance, variability and evolution principles of hydrological genes].

PubMed

Xie, Ping; Wu, Zi Yi; Zhao, Jiang Yan; Sang, Yan Fang; Chen, Jie

2018-04-01

A stochastic hydrological process is influenced by both stochastic and deterministic factors. A hydrological time series contains not only pure random components reflecting its inheri-tance characteristics, but also deterministic components reflecting variability characteristics, such as jump, trend, period, and stochastic dependence. As a result, the stochastic hydrological process presents complicated evolution phenomena and rules. To better understand these complicated phenomena and rules, this study described the inheritance and variability characteristics of an inconsistent hydrological series from two aspects: stochastic process simulation and time series analysis. In addition, several frequency analysis approaches for inconsistent time series were compared to reveal the main problems in inconsistency study. Then, we proposed a new concept of hydrological genes origined from biological genes to describe the inconsistent hydrolocal processes. The hydrologi-cal genes were constructed using moments methods, such as general moments, weight function moments, probability weight moments and L-moments. Meanwhile, the five components, including jump, trend, periodic, dependence and pure random components, of a stochastic hydrological process were defined as five hydrological bases. With this method, the inheritance and variability of inconsistent hydrological time series were synthetically considered and the inheritance, variability and evolution principles were fully described. Our study would contribute to reveal the inheritance, variability and evolution principles in probability distribution of hydrological elements.

A regulatory toolbox of MiniPromoters to drive selective expression in the brain

PubMed Central

Portales-Casamar, Elodie; Swanson, Douglas J.; Liu, Li; de Leeuw, Charles N.; Banks, Kathleen G.; Ho Sui, Shannan J.; Fulton, Debra L.; Ali, Johar; Amirabbasi, Mahsa; Arenillas, David J.; Babyak, Nazar; Black, Sonia F.; Bonaguro, Russell J.; Brauer, Erich; Candido, Tara R.; Castellarin, Mauro; Chen, Jing; Chen, Ying; Cheng, Jason C. Y.; Chopra, Vik; Docking, T. Roderick; Dreolini, Lisa; D'Souza, Cletus A.; Flynn, Erin K.; Glenn, Randy; Hatakka, Kristi; Hearty, Taryn G.; Imanian, Behzad; Jiang, Steven; Khorasan-zadeh, Shadi; Komljenovic, Ivana; Laprise, Stéphanie; Liao, Nancy Y.; Lim, Jonathan S.; Lithwick, Stuart; Liu, Flora; Liu, Jun; Lu, Meifen; McConechy, Melissa; McLeod, Andrea J.; Milisavljevic, Marko; Mis, Jacek; O'Connor, Katie; Palma, Betty; Palmquist, Diana L.; Schmouth, Jean-François; Swanson, Magdalena I.; Tam, Bonny; Ticoll, Amy; Turner, Jenna L.; Varhol, Richard; Vermeulen, Jenny; Watkins, Russell F.; Wilson, Gary; Wong, Bibiana K. Y.; Wong, Siaw H.; Wong, Tony Y. T.; Yang, George S.; Ypsilanti, Athena R.; Jones, Steven J. M.; Holt, Robert A.; Goldowitz, Daniel; Wasserman, Wyeth W.; Simpson, Elizabeth M.

2010-01-01

The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination “knockins” in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5′ of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type–specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies. PMID:20807748

Sylvatic plague reduces genetic variability in black-tailed prairie dogs.

PubMed

Trudeau, Kristie M; Britten, Hugh B; Restani, Marco

2004-04-01

Small, isolated populations are vulnerable to loss of genetic diversity through in-breeding and genetic drift. Sylvatic plague due to infection by the bacterium Yersinia pestis caused an epizootic in the early 1990s resullting in declines and extirpations of many black-tailed prairie dog (Cynomys ludovicianus) colonies in north-central Montana, USA. Plague-induced population bottlenecks may contribute to significant reductions in genetic variability. In contrast, gene flow maintains genetic variability within colonies. We investigated the impacts of the plague epizootic and distance to nearest colony on levels of genetic variability in six prairie dog colonies sampled between June 1999 and July 2001 using 24 variable randomly amplified polymorphic DNA (RAPD) markers. Number of effective alleles per locus (n(e)) and gene diversity (h) were significantly decreased in the three colonies affected by plague that were recovering from the resulting bottlenecks compared with the three colonies that did not experience plague. Genetic variability was not significantly affected by geographic distance between colonies. The majority of variance in gene fieqnencies was found within prairie clog colonies. Conservation of genetic variability in black-tailed prairie dogs will require the preservation of both large and small colony complexes and the gene flow amonog them.

Addiction, Drinking Behavior, and Driving Under the Influence

PubMed Central

Sloan, Frank A.; Chepke, Lindsey M.; Davis, Dontrell V.

2012-01-01

Using a survey of drinkers (N=1,634), we evaluated alternative explanations of heavy and binge drinking, driving under the influence (DUI), DUI arrests, speeding citations, and chargeable accidents. Explanations included socializing, short-term decision-making, unrealistic optimism, risk preferring behavior, and addiction. Most consistent relationships were between substance use and alcohol addiction and dependent variables for (1) binge drinking and (2) DUI episodes. Respondent characteristics (age, marital and employment status, race) had important roles for DUI arrests. Drinker-drivers and those arrested for DUI are partially overlapping groups with implications for treatment and policies detecting and incapacitating persons from drinking and driving. PMID:24304171

Addiction, drinking behavior, and driving under the influence.

PubMed

Sloan, Frank A; Eldred, Lindsey M; Davis, Dontrell V

2014-05-01

Using a survey of drinkers (N = 1,634), we evaluated alternative explanations of heavy and binge drinking, driving under the influence (DUI), DUI arrests, speeding citations, and chargeable accidents. Explanations included socializing, short-term decision-making, unrealistic optimism, risk preferring behavior, and addiction. Most consistent relationships were between substance use and alcohol addiction and dependent variables for (1) binge drinking and (2) DUI episodes. Respondent characteristics (age, marital and employment status, race, etc.) had important roles for DUI arrests. Drinker-drivers and those arrested for DUI are partially overlapping groups with implications for treatment and policies detecting and incapacitating persons from drinking and driving.

Temporal Variability of North Atlantic Carbon Fluxes and their Sensitivity to the Meridional Overturning Circulation

NASA Astrophysics Data System (ADS)

Brown, P.; McDonagh, E.; Sanders, R.; King, B.; Watson, A. J.; Schuster, U.; Henson, S.

2016-02-01

The North Atlantic plays a critical role in the global carbon cycle both as a region of substantial air-sea carbon dioxide uptake and as a location for the transfer of CO2 to depth on climatically-important timescales. While the magnitude of surface fluxes is relatively well constrained, our understanding of the processes that drive variability in ocean-atmosphere exchange and subsequent subsurface carbon accumulation is not as well defined. Here we present observation-derived high-resolution estimates of short-term 10-day meridional ocean carbon transport variability across the subtropical North Atlantic for 2004-2012. Substantial seasonal, sub-annual and interannual transport variability is observed that is highly sensitive to the strength of the Atlantic Meridional Overturning Circulation. While the recently identified multi-year decrease in AMOC strength similarly impacts carbon transports, its full effect is masked by the northwards transport of increasing surface CO2 levels. A 30% slowdown in the meridional circulation in 2009-2010 and the anomalous effects it had on the transport, storage and divergence of heat and freshwater in the subtropical and subpolar gyres and local wind regimes are investigated for their impact on local air-sea CO2 fluxes. Temperature and salt content anomalies identified in each gyre are found to drive (subtropics) or hinder (subpolar) additional carbon uptake from the atmosphere by affecting the physical solubility pump for CO2. Additionally their simultaneous effect on mixed layer depth and the vertical supply of nutrients to the surface is shown to magnify the CO2 flux observed by driving anomalous primary production rates.

Street racing video games and risk-taking driving: An Internet survey of automobile enthusiasts.

PubMed

Vingilis, Evelyn; Seeley, Jane; Wiesenthal, David L; Wickens, Christine M; Fischer, Peter; Mann, Robert E

2013-01-01

The purpose of this study was to examine the relationships among risky driving attitudes, self-perceptions as a risky driver, playing of "drive'em up" (which rewarded players for frequent traffic and other violations) and "circuit" racing video games as well as self-reported risky driving through a web-based survey of car and racing club members in relation to a socio-cognitive model of the effects of racing video game playing. An Internet questionnaire was developed and included: (1) self-perceptions as a risky driver scales (Driver Thrill Seeking and Competitive Attitude Toward Driving); (2) attitudes regarding street racing; (3) street racing video game playing, and (4) self-reported risky driving (Risk-Taking Driving Scale). A sequential logistic regression was performed entering age and driving exposure as control variables in the first block, self-perceptions as a risky driver in the second block, attitudes in the third block and playing "drive'em up" and "circuit" racing games in the last block to examine their effects on self-reported risk-taking driving. A total of 503 survey respondents were included in the analyses and only 20% reported any risk-taking driving. Higher score on the Competitive Attitude Toward Driving Scale, more positive attitudes toward street racing, and more frequent reported playing of "drive'em up" video games were associated with higher odds on the self-reported Risk-Taking Driving Scale. However, the Driver Thrill Seeking Scale and "circuit" video game playing failed to predict self-reported risk-taking driving. Self-perceptions as a risky driver, positive attitudes toward risky driving and "drive'em up" street-racing games, but not "circuit" racing games, are associated with increased risk-taking driving. These findings are congruent with experimental studies in which games that reward driving violations increased risk taking, suggesting that risk taking may be a function of type of street racing game played by affecting self-perceptions as a risky driver. Copyright © 2012 Elsevier Ltd. All rights reserved.

Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease

PubMed Central

Nuytemans, Karen; Bademci, Guney; Inchausti, Vanessa; Dressen, Amy; Kinnamon, Daniel D.; Mehta, Arpit; Wang, Liyong; Züchner, Stephan; Beecham, Gary W.; Martin, Eden R.; Scott, William K.

2013-01-01

Objective: Recently, vacuolar protein sorting 35 (VPS35) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) have been identified as 2 causal Parkinson disease (PD) genes. We used whole exome sequencing for rapid, parallel analysis of variations in these 2 genes. Methods: We performed whole exome sequencing in 213 patients with PD and 272 control individuals. Those rare variants (RVs) with <5% frequency in the exome variant server database and our own control data were considered for analysis. We performed joint gene-based tests for association using RVASSOC and SKAT (Sequence Kernel Association Test) as well as single-variant test statistics. Results: We identified 3 novel VPS35 variations that changed the coded amino acid (nonsynonymous) in 3 cases. Two variations were in multiplex families and neither segregated with PD. In EIF4G1, we identified 11 (9 nonsynonymous and 2 small indels) RVs including the reported pathogenic mutation p.R1205H, which segregated in all affected members of a large family, but also in 1 unaffected 86-year-old family member. Two additional RVs were found in isolated patients only. Whereas initial association studies suggested an association (p = 0.04) with all RVs in EIF4G1, subsequent testing in a second dataset for the driving variant (p.F1461) suggested no association between RVs in the gene and PD. Conclusions: We confirm that the specific EIF4G1 variation p.R1205H seems to be a strong PD risk factor, but is nonpenetrant in at least one 86-year-old. A few other select RVs in both genes could not be ruled out as causal. However, there was no evidence for an overall contribution of genetic variability in VPS35 or EIF4G1 to PD development in our dataset. PMID:23408866