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Sample records for agonist carbachol car

  1. The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse.

    PubMed

    Yang, C; Brown, R E

    2014-01-31

    Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 μM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods

  2. Allosteric agonists of the calcium receptor (CaR): fluorine and SF5 analogues of cinacalcet.

    PubMed

    Chia, Poh Wai; Brennan, Sarah C; Slawin, Alexandra M Z; Riccardi, Daniela; O'Hagan, David

    2012-10-21

    Three selectively fluorinated cinacalcet analogues are prepared and their activity as calcium-sensing receptor (CaR) agonists is assessed. Individual (2R,1'R)-2 and (2S,1'R)-3 fluorocinacalcet diastereoisomers were prepared using the MacMillan asymmetric fluorination reaction. Assays with the recombinant human CaR revealed that both diastereoisomers have a similar potency to each other although slightly lower (75-80%) than that of cinacalcet 1. The SF(5)-cinacalcet analogue 4 was prepared from meta-pentafluorosulfanyl benzyl alcohol and has ~75% agonist activity relative to cinacalcet 1 indicating that the SF(5) group can replace the CF(3) group and retain significant bioactivity.

  3. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    SciTech Connect

    Zhang, Ying; Li, Jianguo

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  4. Carbachol-induced colonic mucus formation requires transport via NKCC1, K+ channels and CFTR

    PubMed Central

    Lindén, Sara K.; Alwan, Ala H.; Scholte, Bob J.; Hansson, Gunnar C.; Sjövall, Henrik

    2016-01-01

    The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co-transport, basolateral K+ channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K+ channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol-induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules. PMID:25139191

  5. Asymmetrical, agonist-induced fluctuations in local extracellular [Ca2+] in intact polarized epithelia

    PubMed Central

    Caroppo, Rosa; Gerbino, Andrea; Debellis, Lucantonio; Kifor, Olga; Soybel, David I.; Brown, Edward M.; Hofer, Aldebaran M.; Curci, Silvana

    2001-01-01

    We recently proposed that extracellular Ca2+ ions participate in a novel form of intercellular communication involving the extracellular Ca2+-sensing receptor (CaR). Here, using Ca2+-selective microelectrodes, we directly measured the profile of agonist-induced [Ca2+]ext changes in restricted domains near the basolateral or luminal membranes of polarized gastric acid-secreting cells. The Ca2+-mobilizing agonist carbachol elicited a transient, La3+-sensitive decrease in basolateral [Ca2+] (average ≈250 µM, but as large as 530 µM). Conversely, carbachol evoked an HgCl2-sensitive increase in [Ca2+] (average ≈400 µM, but as large as 520 µM) in the lumen of single gastric glands. Both responses were significantly reduced by pre-treatment with sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pump inhibitors or with the intracellular Ca2+ chelator BAPTA-AM. Immunofluores cence experiments demonstrated an asymmetric localization of plasma membrane Ca2+ ATPase (PMCA), which appeared to be partially co-localized with CaR and the gastric H+/K+-ATPase in the apical membrane of the acid-secreting cells. Our data indicate that agonist stimulation results in local fluctuations in [Ca2+]ext that would be sufficient to modulate the activity of the CaR on neighboring cells. PMID:11707403

  6. Cars, Cars, Cars

    ERIC Educational Resources Information Center

    McIntosh, Phyllis

    2013-01-01

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

  7. Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons

    PubMed Central

    Meng, Wei; Wang, Song-Hua; Li, Dong-Feng

    2016-01-01

    Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production. PMID:26904300

  8. Neocortical 40 Hz oscillations during carbachol-induced rapid eye movement sleep and cataplexy.

    PubMed

    Torterolo, Pablo; Castro-Zaballa, Santiago; Cavelli, Matías; Chase, Michael H; Falconi, Atilio

    2016-02-01

    Higher cognitive functions require the integration and coordination of large populations of neurons in cortical and subcortical regions. Oscillations in the gamma band (30-45 Hz) of the electroencephalogram (EEG) have been involved in these cognitive functions. In previous studies, we analysed the extent of functional connectivity between cortical areas employing the 'mean squared coherence' analysis of the EEG gamma band. We demonstrated that gamma coherence is maximal during alert wakefulness and is almost absent during rapid eye movement (REM) sleep. The nucleus pontis oralis (NPO) is critical for REM sleep generation. The NPO is considered to exert executive control over the initiation and maintenance of REM sleep. In the cat, depending on the previous state of the animal, a single microinjection of carbachol (a cholinergic agonist) into the NPO can produce either REM sleep [REM sleep induced by carbachol (REMc)] or a waking state with muscle atonia, i.e. cataplexy [cataplexy induced by carbachol (CA)]. In the present study, in cats that were implanted with electrodes in different cortical areas to record polysomnographic activity, we compared the degree of gamma (30-45 Hz) coherence during REMc, CA and naturally-occurring behavioural states. Gamma coherence was maximal during CA and alert wakefulness. In contrast, gamma coherence was almost absent during REMc as in naturally-occurring REM sleep. We conclude that, in spite of the presence of somatic muscle paralysis, there are remarkable differences in cortical activity between REMc and CA, which confirm that EEG gamma (≈40 Hz) coherence is a trait that differentiates wakefulness from REM sleep.

  9. Reversion of muscarinic autoreceptor agonist-induced acetylcholine decrease and learning impairment by dynorphin A (1–13), an endogenous κ-opioid receptor agonist

    PubMed Central

    Hiramatsu, Masayuki; Murasawa, Hiroyasu; Mori, Hiromasa; Kameyama, Tsutomu

    1998-01-01

    We investigated whether carbachol, a muscarinic receptor agonist, induces learning and memory impairment, and if so, dynorphin A (1–13), an endogenous κ-opioid receptor agonist, ameliorates the impairment of learning and memory induced by carbachol, by use of a step-through type passive avoidance task.Carbachol induced a dose-related dual response. Carbachol (1.66 pmol per rat) administered directly into the hippocampus significantly shortened the step-through latency, while lower (0.166 pmol per rat) and higher (16.6 pmol per rat) doses of carbachol did not induce learning or memory impairment.Dynorphin A (1–13) (0.5 nmol per rat, i.c.v.) administered 5 min after carbachol injection significantly reversed carbachol-induced impairment of learning and memory.Perfusion with carbachol (3×10−4 M) significantly decreased acetylcholine release in the hippocampus during perfusion as determined by in vivo brain microdialysis. This decrease in acetylcholine release was suppressed by co-perfusion with a low dose of atropine (10−7 M).Dynorphin A (1–13) (0.5 nmol per rat, i.c.v.) immediately before carbachol perfusion completely blocked this decrease in extracellular acetylcholine concentration induced by carbachol.These antagonistic effects of dynorphin A (1–13) were abolished by treatment with nor-binaltorphimine (5.44 nmol per rat, i.c.v.), a selective κ-opioid receptor antagonist, 5 min before dynorphin A (1–13) treatment.These results suggest that the neuropeptide dynorphin A (1–13) ameliorates the carbachol-induced impairment of learning and memory, accompanied by attenuation of the reductions in acetylcholine release which may be associated with dysfunction of presynaptic cholinergic neurones via κ-opioid receptors. PMID:9535021

  10. Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells

    SciTech Connect

    Hepler, J.R.; Harden, T.K.

    1986-03-05

    Formation of the inositol phosphates (InsP), InsP/sub 3/, InsP/sub 2/, and InsP/sub 1/ was increased in a concentration dependent manner (K/sub 0.5/ approx. 5 ..mu..M) by GTP..sigma..S in washed membranes prepared from /sup 3/H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTP..gamma..S and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 ..mu..M GTP..gamma..S, carbachol stimulated (K/sub 0.5/ approx. 10 ..mu.. M) the formation of InsP above the level achieved with GTP..gamma..S alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 ..mu..M carbachol was GTP..gamma..S > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTP..gamma..S or GTP..gamma..S plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTP..gamma..S in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells.

  11. Effects of aerosolized histamine and carbachol in the conscious horse.

    PubMed Central

    Mirbahar, K B; McDonell, W N; Bignell, W; Eyre, P

    1985-01-01

    Pulmonary function tests were performed in seven conscious, standing horses. Changes in pulmonary mechanics and ventilation volumes were measured after inhalation challenge with saline (baseline), histamine (1% w/v solution for 5 min) and carbachol (0.5% w/v solution for 3 min). Comparisons between baseline and posthistamine values revealed a significant (P less than 0.05) increase in nonelastic work of breathing (Wb), maximum change in transpulmonary pressure (max delta Ppl), and pulmonary resistance (RL), while dynamic compliance (Cdyn) decreased (P less than 0.05). Tripelennamine completely abolished these histamine induced changes suggesting the involvement of H1 receptors. A nonsignificant increase occurred in functional residual capacity. However, the amount of nitrogen retained in the lung at the end of a nitrogen washout test was significantly (P less than 0.05) greater after histamine when compared to baseline values. The effect of carbachol was qualitatively similar to that of histamine, Wb and max delta Ppl increased while Cdyn decreased (P less than 0.05). The increase in lower RL reached statistical significance (P less than 0.05) only at the beginning of expiration (/ 25% VT). The present investigation demonstrates that the physiological measurements of lung function could be carried out in conscious, unsedated horses and that the pulmonary function test methods could be used as a tool for study of drug induced changes in pulmonary mechanics. PMID:4016587

  12. Heart rate variability during carbachol-induced REM sleep and cataplexy.

    PubMed

    Torterolo, Pablo; Castro-Zaballa, Santiago; Cavelli, Matías; Velasquez, Noelia; Brando, Victoria; Falconi, Atilio; Chase, Michael H; Migliaro, Eduardo R

    2015-09-15

    The nucleus pontis oralis (NPO) exerts an executive control over REM sleep. Cholinergic input to the NPO is critical for REM sleep generation. In the cat, a single microinjection of carbachol (a cholinergic agonist) into the NPO produces either REM sleep (REMc) or wakefulness with muscle atonia (cataplexy, CA). In order to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings from chronically prepared cats during REMc, CA as well as during sleep and wakefulness. Subsequently, we performed statistical and spectral analyses of the HRV. The heart rate was greater during CA compared to REMc, NREM or REM sleep. Spectral analysis revealed that the low frequency band (LF) power was significantly higher during REM sleep in comparison to REMc and CA. Furthermore, we found that during CA there was a decrease in coupling between the RR intervals plot (tachogram) and respiratory activity. In contrast, compared to natural behavioral states, during REMc and CA there were no significant differences in the HRV based upon the standard deviation of normal RR intervals (SDNN) and the mean squared difference of successive intervals (rMSSD). In conclusion, there were differences in the HRV during naturally-occurring REM sleep compared to REMc. In addition, in spite of the same muscle atonia, the HRV was different during REMc and CA. Therefore, the neuronal network that controls the HRV during REM sleep can be dissociated from the one that generates the muscle atonia during this state.

  13. Cholinergic and glutamatergic agonists induce gamma frequency activity in dorsal subcoeruleus nucleus neurons

    PubMed Central

    Simon, Christen; Kezunovic, Nebojsa; Williams, D. Keith; Urbano, Francisco J.

    2011-01-01

    The dorsal subcoeruleus nucleus (SubCD) is involved in generating two signs of rapid eye movement (REM) sleep: muscle atonia and ponto-geniculo-occipital (PGO) waves. We tested the hypothesis that single cell and/or population responses of SubCD neurons are capable of generating gamma frequency activity in response to intracellular stimulation or receptor agonist activation. Whole cell patch clamp recordings (immersion chamber) and population responses (interface chamber) were conducted on 9- to 20-day-old rat brain stem slices. All SubCD neurons (n = 103) fired at gamma frequency when subjected to depolarizing steps. Two statistically distinct populations of neurons were observed, which were distinguished by their high (>80 Hz, n = 24) versus low (35–80 Hz, n = 16) initial firing frequencies. Both cell types exhibited subthreshold oscillations in the gamma range (n = 43), which may underlie the gamma band firing properties of these neurons. The subthreshold oscillations were blocked by the sodium channel blockers tetrodotoxin (TTX, n = 21) extracellularly and N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314) intracellularly (n = 5), indicating they were sodium channel dependent. Gamma frequency subthreshold oscillations were observed in response to the nonspecific cholinergic receptor agonist carbachol (CAR, n = 11, d = 1.08) and the glutamate receptor agonists N-methyl-d-aspartic acid (NMDA, n = 12, d = 1.09) and kainic acid (KA, n = 13, d = 0.96), indicating that cholinergic and glutamatergic inputs may be involved in the activation of these subthreshold currents. Gamma band activity also was observed in population responses following application of CAR (n = 4, P < 0.05), NMDA (n = 4, P < 0.05) and KA (n = 4, P < 0.05). Voltage-sensitive, sodium channel-dependent gamma band activity appears to be a part of the intrinsic membrane properties of SubCD neurons. PMID:21543743

  14. Car Art.

    ERIC Educational Resources Information Center

    Meilach, Dona Z.

    2002-01-01

    Discusses car art and its appeal to boys and girls. Describes the popularity of customizing cars, focusing on this as a future career for students. Includes a list of project ideas that focuses on car art. (CMK)

  15. Phosphoinositides metabolism in primary culture of dog thyroid cells: Effects of thyrotropin and carbachol

    SciTech Connect

    Taguchi, M.; Field, J.B. )

    1990-04-01

    Thyrotropin (TSH) and carbachol stimulated in a dose-dependent manner the accumulation of 3H-glycerophosphoinositol (GPI), 3H-inositol monophosphate (IP1), 3H-inositol bisphosphate (IP2) and 3H-inositol trisphosphate (IP3) in primary cultures of dog thyroid cells prelabeled with myo-(2-3H)inositol. TSH, 250 mU/mL, stimulated 3H-IP3 level after a 10-minute incubation while 10 mU/mL TSH increased it during a 60-minute incubation. The effect of carbachol was more rapid and greater than that of TSH. Carbachol, 100 mumol/L, elevated 3H-IP3 after a 2-minute incubation and 3H-IP3 formation was increased by as little as 1 mumol/L carbachol. TSH stimulation was observed only if the cells were deprived of TSH for 5 days before being labeled with 3H-inositol. Prolongation of the labeling period or addition of TSH, (Bu)2cAMP or carbachol during the labeling increased 3H-inositol incorporation into polyphoinositides (PIPs). When the cells were labeled without any other addition, control and TSH-stimulated 3H-IP3 levels increased in parallel with 3H-PIP levels. However, TSH or carbachol-stimulated 3H-IP3 levels did not increase in proportion to 3H-PIPs level when the cells were labeled with TSH or (Bu)2cAMP. Thus, the ratio of 3H-IP3/3H-PIPs (both control and TSH or carbachol-stimulated) decreased in the cells labeled with TSH or (Bu)2cAMP, which might reflect TSH stimulation of 3H-inositol incorporation into PIPs pool(s) that do not participate in hormone-induced hydrolysis of PIPs.

  16. Agonist activation of arachidonate-regulated Ca2+-selective (ARC) channels in murine parotid and pancreatic acinar cells.

    PubMed

    Mignen, Olivier; Thompson, Jill L; Yule, David I; Shuttleworth, Trevor J

    2005-05-01

    ARC channels (arachidonate-regulated Ca(2+)-selective channels) are a novel type of highly Ca(2+)-selective channel that are specifically activated by low concentrations of agonist-induced arachidonic acid. This activation occurs in the absence of any depletion of internal Ca(2+) stores (i.e. they are 'non-capacitative'). Previous studies in HEK293 cells have shown that these channels provide the predominant pathway for the entry of Ca(2+) seen at low agonist concentrations where oscillatory [Ca(2+)](i) signals are typically produced. In contrast, activation of the more widely studied store-operated Ca(2+) channels (e.g. CRAC channels) is only seen at higher agonist concentrations where sustained 'plateau-type'[Ca(2+)](i) responses are observed. We have now demonstrated the presence of ARC channels in both parotid and pancreatic acinar cells and shown that, again, they are specifically activated by the low concentrations of appropriate agonists (carbachol in the parotid, and both carbachol and cholecystokinin in the pancreas) that are associated with oscillatory [Ca(2+)](i) signals in these cells. Uncoupling the receptor-mediated activation of cytosolic phospholipase A(2) (cPLA(2)) with isotetrandrine reduces the activation of the ARC channels by carbachol and, correspondingly, markedly inhibits the [Ca(2+)](i) signals induced by low carbachol concentrations, whilst those signals seen at high agonist concentrations are essentially unaffected. Interestingly, in the pancreatic acinar cells, activation by cholecystokinin induces a current through the ARC channels that is only approximately 60% of that seen with carbachol. This is consistent with previous reports indicating that carbachol-induced [Ca(2+)](i) signals in these cells are much more dependent on Ca(2+) entry than are the cholecystokinin-induced responses.

  17. The C. elegans VIG-1 and FRM-1 modulate carbachol-stimulated ERK1/2 activation in chinese hamster ovary cells expressing the muscarinic acetylcholine receptor GAR-3.

    PubMed

    Shin, Youngmi; Cho, Nam Jeong

    2014-04-01

    Many neurotransmitter receptors are known to interact with a variety of intracellular proteins that modulate signaling processes. In an effort to understand the molecular mechanism by which acetylcholine (ACh) signaling is modulated, we searched for proteins that interact with GAR-3, the Caenorhabditis elegans homolog of muscarinic ACh receptors. We isolated two proteins, VIG-1 and FRM-1, in a yeast two-hybrid screen of a C. elegans cDNA library using the third intracellular (i3) loop of GAR-3 as bait. To test whether these proteins regulate ACh signaling, we utilized Chinese hamster ovary (CHO) cells stably expressing GAR-3 (GAR-3/CHO cells). Previously we have shown that the cholinergic agonist carbachol stimulates extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation in an atropine-sensitive manner in this cell line. When VIG-1 was transiently expressed in GAR-3/CHO cells, carbachol-stimulated ERK1/2 activation was substantially reduced. In contrast, transient expression of FRM-1 significantly enhanced carbachol-stimulated ERK1/2 activation. Neither VIG-1 nor FRM-1 expression appeared to alter the affinity between GAR-3 and carbachol. In support of this notion, expression of these proteins did not affect GAR-3-mediated phospholipase C activation. To verify the modulation of ERK1/2 activity by VIG-1 and FRM-1, we used an i3 loop deletion mutant of GAR-3 (termed GAR-3Δi3). Carbachol treatment evoked robust ERK1/2 activation in CHO cells stably expressing the deletion mutant (GAR-3Δi3/CHO cells). However, transient expression of either VIG-1 or FRM-1 had little effect on carbachol-stimulated ERK1/2 activation in GAR-3Δi3/CHO cells. Taken together, these results indicate that VIG-1 and FRM-1 regulate GAR-3-mediated ERK1/2 activation by interacting with the i3 loop of GAR-3.

  18. Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons.

    PubMed Central

    Kelly, J F; Furukawa, K; Barger, S W; Rengen, M R; Mark, R J; Blanc, E M; Roth, G S; Mattson, M P

    1996-01-01

    Cholinergic pathways serve important functions in learning and memory processes, and deficits in cholinergic transmission occur in Alzheimer disease (AD). A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C, resulting in the liberation of inositol trisphosphate and Ca2+ release from intracellular stores. We now report that amyloid beta-peptide (Abeta), which forms plaques in the brain in AD, impairs muscarinic receptor activation of G proteins in cultured rat cortical neurons. Exposure of rodent fetal cortical neurons to Abeta25-35 and Abeta1-40 resulted in a concentration and time-dependent attenuation of carbachol-induced GTPase activity without affecting muscarinic receptor ligand binding parameters. Downstream events in the signal transduction cascade were similarly attenuated by Abeta. Carbachol-induced accumulation of inositol phosphates (IP, IP2, IP3, and IP4) was decreased and calcium imaging studies revealed that carbachol-induced release of calcium was severely impaired in neurons pretreated with Abeta. Muscarinic cholinergic signal transduction was disrupted with subtoxic levels of exposure to AP. The effects of Abeta on carbachol-induced GTPase activity and calcium release were attenuated by antioxidants, implicating free radicals in the mechanism whereby Abeta induced uncoupling of muscarinic receptors. These data demonstrate that Abeta disrupts muscarinic receptor coupling to G proteins that mediate induction of phosphoinositide accumulation and calcium release, findings that implicate Abeta in the impairment of cholinergic transmission that occurs in AD. PMID:8692890

  19. Spontaneous ventilation and respiratory motor output during carbachol-induced atonia of REM sleep in the decerebrate cat.

    PubMed

    Tojima, H; Kubin, L; Kimura, H; Davies, R O

    1992-10-01

    Microinjections of carbachol into the pons induce a state that resembles rapid eye movement (REM) sleep in intact cats and, in decerebrate, artificially ventilated cats, produce postural atonia accompanied by a powerful depression of the respiratory motor output. In this study, pontine carbachol was used in decerebrate, spontaneously breathing cats to assess the effects of mechanical and chemical respiratory reflexes on the magnitude and pattern of the carbachol-induced depression of breathing, and to determine whether the depression is altered in those animals in which rapid eye movements are present. Phrenic nerve activity and tidal volume were only transiently depressed at the onset of the carbachol-induced postural atonia, whereas the decrease in respiratory rate and the depressions of hypoglossal and intercostal activities persisted until the response was reversed by a pontine microinjection of atropine 15-101 minutes after the onset of carbachol response. Ventilation was reduced to 70% of control during the steady-state conditions. The irregularity of breathing, characterized by the inter-quartile ranges of the distributions of the peak phrenic nerve activity and respiratory timing, did not increase following pontine carbachol. Neither vagotomy nor vigorous eye movements were associated with increased breathing irregularity. This contrasts with the irregular breathing (with minor average changes in ventilation) typical of natural REM sleep. We propose that the carbachol-injected decerebrate cat provides a useful model of the depressant effects that neural events associated with REM sleep may have on breathing.

  20. Effects of nitric acid on carbachol reactivity of the airways in normal and allergic sheep

    SciTech Connect

    Abraham, W.M.; Kim, C.S.; King, M.M.; Oliver, W. Jr.; Yerger, L.

    1982-01-01

    The airway effects of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance after carbachol inhalation were 68% (SD+/- 13%) and 82% (SD+/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post-exposure increases in specific pulmonary flow resistance for the normal and allergic sheep were 108% (SD+/- 51%(P<.06)) and 175% (SD+/- 87% (p<.02)), respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.

  1. Participation of non-neuronal muscarinic receptors in the effect of carbachol with paclitaxel on human breast adenocarcinoma cells. Roles of nitric oxide synthase and arginase.

    PubMed

    Español, Alejandro Javier; Salem, Agustina; Rojo, Daniela; Sales, María Elena

    2015-11-01

    Breast cancer is the most common type of cancer in women and represents a major issue in public health. The most frequent methods to treat these tumors are surgery and/or chemotherapy. The latter can exert not only beneficial effects by reducing tumor growth and metastasis, but also toxic actions on normal tissues. Metronomic therapy involves the use of low doses of cytotoxic drugs alone or in combination to improve efficacy and to reduce adverse effects. We have previously reported that breast tumors highly express functional muscarinic acetylcholine receptors (mAChRs) that regulate tumor progression. For this reason, mAChRs could be considered as therapeutic targets in breast cancer. In this paper, we investigated the ability of a combination of the cytotoxic drug paclitaxel plus carbachol, a cholinergic agonist, at low doses, to induce death in breast tumor MCF-7 cells, via mAChR activation, and the role of nitric oxide synthase (NOS) and arginase in this effect. We observed that the combination of carbachol plus paclitaxel at subthreshold doses significantly increased cytotoxicity in tumor cells without affecting MCF-10A cells, derived from human normal mammary gland. This effect was reduced in the presence of the muscarinic antagonist atropine. The combination also increased nitric oxide production by NOS1 and NOS3 via mAChR activation, concomitantly with an up-regulation of NOS3 expression. The latter effects were accompanied by a reduction in arginase II activity. In conclusion, our work demonstrates that mAChRs expressed in breast tumor cells could be considered as candidates to become targets for metronomic therapy in cancer treatment.

  2. In vitro effect of nicorandil on the carbachol-induced contraction of the lower esophageal sphincter of the rat.

    PubMed

    Shimbo, Tomonori; Adachi, Takeshi; Fujisawa, Susumu; Hongoh, Mai; Ohba, Takayoshi; Ono, Kyoichi

    2016-08-01

    The lower esophageal sphincter (LES) is a specialized region of the esophageal smooth muscle that allows the passage of a swallowed bolus into the stomach. Nitric oxide (NO) plays a major role in LES relaxation. Nicorandil possesses dual properties of a NO donor and an ATP-sensitive potassium channel (KATP channel) agonist, and is expected to reduce LES tone. This study investigated the mechanisms underlying the effects of nicorandil on the LES. Rat LES tissues were placed in an organ bath, and activities were recorded using an isometric force transducer. Carbachol-induced LES contraction was significantly inhibited by KATP channel agonists in a concentration-dependent manner; pinacidil > nicorandil ≈ diazoxide. Nicorandil-induced relaxation of the LES was prevented by pretreatment with glibenclamide, whereas N(G)-nitro-l-arginine methyl ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin were ineffective at preventing nicorandil-induced LES relaxation. Furthermore, nicorandil did not affect high K(+)-induced LES contraction. Reverse-transcription polymerase chain reaction analysis and immunohistochemistry revealed expression of KCNJ8 (Kir6.1), KCNJ11 (Kir6.2), ABCC8 (SUR1) and ABCC9 (SUR2) subunits of the KATP channel in the rat lower esophagus. These findings indicate that nicorandil causes LES relaxation chiefly by activating the KATP channel, and that it may provide an additional pharmacological tool for the treatment of spastic esophageal motility disorders.

  3. Car Sickness

    MedlinePlus

    ... or Animals Genitals and Urinary Tract Glands & Growth Head Neck & Nervous System Heart Infections Learning Disabilities Obesity Orthopedic ... Vaccine Preventable Diseases Healthy Children > Health Issues > Conditions > Head Neck & Nervous System > Car Sickness Health Issues Listen Español ...

  4. Flying Cars

    NASA Technical Reports Server (NTRS)

    Crow, Steven

    1996-01-01

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

  5. Marked increases in mucociliary clearance produced by synergistic secretory agonists or inhibition of the epithelial sodium channel

    PubMed Central

    Joo, Nam Soo; Jeong, Jin Hyeok; Cho, Hyung-Ju; Wine, Jeffrey J.

    2016-01-01

    Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca2+-activated chloride channels mediate anion/fluid secretion. MCCV was increased by the cAMP-elevating agonists, forskolin or isoproterenol (10 μM) and by the Ca2+-elevating agonist, carbachol (0.3 μM). The CFTR-selective inhibitor, CFTRinh-172, modestly reduced MCCV-increases induced by forskolin or isoproterenol but not increases induced by carbachol. The ENaC inhibitor benzamil increased basal MCCV as well as MCCV increases produced by forskolin or carbachol. MCC velocity was most dramatically accelerated by the synergistic combination of forskolin and carbachol, which produced near-maximal clearance rates regardless of prior treatment with CFTR or ENaC inhibitors. In CF airways, where CFTR-mediated secretion (and possibly synergistic MCC) is lost, ENaC inhibition via exogenous agents may provide therapeutic benefit, as has long been proposed. PMID:27830759

  6. Effect of carbachol on intestinal mucosal blood flow, activity of Na+-K+-ATPase, expression of aquaporin-1, and intestinal absorption rate during enteral resuscitation of burn shock in rats.

    PubMed

    Bao, Chengmei; Hu, Sen; Zhou, Guoyong; Tian, Yijun; Wu, Yan; Sheng, Zhiyong

    2010-01-01

    We investigated the effect of carbachol (CAR, a cholinergic agent) on intestinal mucosal blood flow (IMBF), activity of Na-K-ATPase, expression of aquaporin (AQP)-1, and intestinal absorption rate during enteral resuscitation of a 35%TBSA scald in rats with a glucose electrolyte solution (GES). One hundred male Wistar rats were randomly divided into five groups: sham scald (N group); scald without fluid resuscitation (S group); scald resuscitated with enteral GES alone (GES group); scald resuscitated with enteral CAR alone (CAR group); and scald resuscitated with enteral CAR plus GES (GES/CAR group). The rats were inflicted 35%TBSA third degree of scald injury on the back with boiling water (100 degrees C, 15 seconds) in all groups, except the sham scald group. A catheter was inserted into the proximal duodenum (5 cm distal to pylorus) and distal ileum (5 cm proximal to cecum), of each rats through laparotomy, thus a segment of intestine was virtually isolated to form a loop for inlet and outlet of introduced fluid. In N, GES, and GES/CAR groups, fluids were introduced 30 minutes after scald injury. The speed of fluid infusion was 4 ml/kg/1%TBSA for 4 hours. CAR (60 microg/kg) was injected into the intestinal lumen at 30-minute after injury in CAR and GES/CAR groups. At 2 and 4 hours after scald, intestinal absorption rate of water and Na, and IMBF were determined, respectively. Then, animals were killed, and specimens of intestinal tissue were obtained for the determination of the activity of Na-K-ATPase, hematoxylin-eosin coloring, and expression of AQP-1. The intestinal absorption rate was reduced markedly in GES group compared with sham scald group at 2 and 4 hours after scald, and absorption rate of small intestine in GES/CAR was significantly higher than that in GES group (P < .05). It was also found that there was significant decrease in IMBF, activity of Na-K-ATPase, and expression of AQP-1 in scald group compared with the sham group. However, in GES/CAR

  7. Car sick.

    PubMed

    Renner, M G

    1988-01-01

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

  8. Population synaptic potentials evoked in lumbar motoneurons following stimulation of the nucleus reticularis gigantocellularis during carbachol-induced atonia.

    PubMed

    Yamuy, J; Jiménez, I; Morales, F; Rudomin, P; Chase, M

    1994-03-14

    The effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on lumbar spinal cord motoneurons was studied in the decerebrate cat using sucrose-gap recordings from ventral roots. The NRGc was stimulated ipsi- and contralaterally before and during atonia elicited by the microinjection of carbachol into the pontine reticular formation. Prior to carbachol administration, the NRGc-induced response recorded from the sucrose-gap consisted of two consecutive excitatory population synaptic potentials followed by a long-lasting, small amplitude inhibitory population synaptic potential. Following carbachol injection, the same NRGc stimulus evoked a distinct, large amplitude inhibitory population synaptic potential, whereas the excitatory population synaptic potentials decreased in amplitude. In addition, after carbachol administration, the amplitude of the monosynaptic excitatory population synaptic potential, which was evoked by stimulation of group Ia afferents in hindlimb nerves, was reduced by 18 to 43%. When evoked at the peak of the NRGc-induced inhibitory response, this potential was further decreased in amplitude. Systemic strychnine administration (0.07-0.1 mg/kg, i.v.) blocked the NRGc-induced inhibitory population synaptic potential and promoted an increase in the amplitude of the excitatory population synaptic potentials induced by stimulation of the NRGc and group Ia afferents. These data indicate that during the state of carbachol-induced atonia, the NRGc effects on ipsi- and contralateral spinal cord motoneurons are predominantly inhibitory and that glycine is likely to be involved in this inhibitory process. These results support the hypothesis that the nucleus reticularis gigantocellularis is part of the system responsible for state-dependent somatomotor inhibition that occurs during active sleep.

  9. Analysis of agonist dissociation constants as assessed by functional antagonism in guinea pig left atria

    SciTech Connect

    Molenaar, P.; Malta, E.

    1986-04-01

    In electrically driven guinea pig left atria, positive inotropic responses to (-)-isoprenaline and the selective beta 1-adrenoceptor agonist RO363 were obtained in the absence and in the presence of the functional antagonists adenosine, carbachol, gallopamil, nifedipine, and Ro 03-7894. Each of the functional antagonists reduced the maximum response to both agonists and produced nonparallel rightward shifts in the cumulative concentration effect curves. For both agonists, dissociation constants (KA) were calculated using the equation described by Furchgott (1966) for irreversible antagonism. For RO363, which is a partial agonist with high agonist activity, the equations outlined for functional interaction by Mackay (1981) were also employed to calculate KA values. The KA values obtained by each method were compared with the dissociation constants (KD) for the two agonists determined from their ability to displace the radioligand (-)-(/sup 125/I)iodocyanopindolol from beta 1-adrenoceptors in guinea pig left atrial membrane preparations. The estimates of KA varied substantially from KD values. The KD values were taken as more accurate estimates of the true values for the dissociation constants because a high degree of correlation exists between pKD and pD2 values for a number of other beta-adrenoceptor agonists that behave as partial agonists and between pKD and pKB values for a number of beta-adrenoceptor antagonists. Thus, it appears that there are serious limitations in the current theory for using functional antagonism as a means of obtaining agonist dissociation constants.

  10. Cellular mechanisms underlying carbachol-induced oscillations of calcium-dependent membrane current in smooth muscle cells from mouse anococcygeus

    PubMed Central

    Wayman, Christopher P; McFadzean, Ian; Gibson, Alan; Tucker, John F

    1997-01-01

    At a holding potential of −40 mV, carbachol (50 μM) produced a complex pattern of inward currents in single smooth muscle cells freshly isolated from the mouse anococcygeus. Membrane currents were monitored by the whole-cell configuration of the patch-clamp technique. Previous work has identified the first, transient component as a calcium-activated chloride current (ICl(Ca)) and the second sustained component as a store depletion-operated non-selective cation current (IDOC). The object of the present study was to examine the cellular mechanisms underlying the third component, a series of inward current oscillations (Ioscil) superimposed on IDOC.Carbachol-induced Ioscil (amplitude 97±11 pA; frequency 0.26±0.02 Hz) was inhibited by the chloride channel blocker anthracene-9-carboxylic acid (A-9-C; 1 mM), and by inclusion of 1 mM EGTA in the patch-pipette filling solution.In calcium-free extracellular medium (plus 1 mM EGTA), carbachol produced an initial burst of oscillatory current which lasted 94 s before decaying to zero; Ioscil could be restored by re-admission of calcium. The frequency, but not the amplitude, of Ioscil increased with increasing concentrations of extracellular calcium (0.5–10 mM).Inclusion of the inositol triphosphate (IP3) receptor antagonist heparin (5 mg ml−1) in the patch-pipette filling solution, or pretreatment of cells with the sarcoplasmic reticulum (SR) calcium ATPase inhibitor cyclopiazonic acid (CPA; 10 μM), prevented the activation of Ioscil by carbachol. Caffeine (10 mM) activated both ICl(Ca) and IDOC and prevented the induction of Ioscil by carbachol. Caffeine and CPA also abolished Ioscil in the presence of carbachol, as did both a low (3 μM) and a high (30 μM) concentration of ryanodine.Carbachol-induced Ioscil was abolished by the general calcium entry blocker SKF 96365 (10 μM) and by Cd2+ (100 μM), but was unaffected by La3+ (400 μM). As found previously, IDOC was also blocked by

  11. Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol, and phosphatidic acid.

    PubMed

    Takuwa, Y; Takuwa, N; Rasmussen, H

    1986-11-05

    The effects of carbachol on polyphosphoinositides and 1,2-diacylglycerol metabolism were investigated in bovine tracheal smooth muscle by measuring both lipid mass and the turnover of [3H]inositol-labeled phosphoinositides. Carbachol induces a rapid reduction in the mass of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate and a rapid increase in the mass of 1,2-diacylglycerol and phosphatidic acid. These changes in lipid mass are sustained for at least 60 min. The level of phosphatidylinositol shows a delayed and progressive decrease during a 60-min period of carbachol stimulation. The addition of atropine reverses these responses completely. Carbachol stimulates a rapid loss in [3H]inositol radioactivity from phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate associated with production of [3H]inositol trisphosphate. The carbachol-induced change in the mass of phosphoinositides and phosphatidic acid is not affected by removal of extracellular Ca2+ and does not appear to be secondary to an increase in intracellular Ca2+. These results indicate that carbachol causes phospholipase C-mediated polyphosphoinositide breakdown, resulting in the production of inositol trisphosphate and a sustained increase in the actual content of 1,2-diacylglycerol. These results strongly suggest that carbachol-induced contraction is mediated by the hydrolysis of polyphosphoinositides with the resulting generation of two messengers: inositol 1,4,5-trisphosphate and 1,2-diacylglycerol.

  12. Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol, and phosphatidic acid

    SciTech Connect

    Takuwa, Y.; Takuwa, N.; Rasmussen, H.

    1986-11-05

    The effects of carbachol on polyphosphoinositides and 1,2-diacylglycerol metabolism were investigated in bovine tracheal smooth muscle by measuring both lipid mass and the turnover of (/sup 3/H)inositol-labeled phosphoinositides. Carbachol induces a rapid reduction in the mass of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate and a rapid increase in the mass of 1,2-diacylglycerol and phosphatidic acid. These changes in lipid mass are sustained for at least 60 min. The level of phosphatidylinositol shows a delayed and progressive decrease during a 60-min period of carbachol stimulation. The addition of atropine reverses these responses completely. Carbachol stimulates a rapid loss in (/sup 3/H)inositol radioactivity from phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate associated with production of (/sup 3/H)inositol trisphosphate. The carbachol-induced change in the mass of phosphoinositides and phosphatidic acid is not affected by removal of extracellular Ca/sup 2 +/ and does not appear to be secondary to an increase in intracellular Ca/sup 2 +/. These results indicate that carbachol causes phospholipase C-mediated polyphosphoinositide breakdown, resulting in the production of inositol trisphosphate and a sustained increase in the actual content of 1,2-diacylglycerol. These results strongly suggest that carbachol-induced contraction is mediated by the hydrolysis of polyphosphoinositides with the resulting generation of two messengers: inositol 1,4,5-trisphosphate and 1,2-diacylglycerol.

  13. A5 cells are silenced when REM sleep-like signs are elicited by pontine carbachol.

    PubMed

    Fenik, Victor; Marchenko, Vitaliy; Janssen, Patrick; Davies, Richard O; Kubin, Leszek

    2002-10-01

    The A5 noradrenergic neurons are considered important for cardiorespiratory regulation. We hypothesized that A5 cells are silenced during rapid eye movement (REM) sleep, thereby contributing to cardiorespiratory changes and suppression of hypoglossal (XII) motoneuronal activity. We used an anesthetized, paralyzed, and artificially ventilated rat in which pontine microinjections of carbachol trigger signs of REM sleep, including hippocampal theta rhythm, motor suppression, and silencing of locus coeruleus neurons. All 16 putative noradrenergic A5 cells recorded were strongly suppressed when the REM sleep-like episodes were elicited and also after intravenous clonidine. Antidromic mapping showed that none of six neurons tested projected to the XII nucleus, whereas three of five projected to the nucleus of the solitary tract and two of four to the rostral ventrolateral medulla. Bilateral microinjections of clonidine into the A5 regions did not alter XII nerve activity. These data suggest that A5 neurons are silenced during natural REM sleep. This will lead to decreased norepinephrine release and may alter synaptic transmission in the nucleus of the solitary tract and rostral ventrolateral medulla without, however, a detectable impact on XII motoneurons.

  14. Regional development of carbachol-, glutamate-, norepinephrine-, and serotonin-stimulated phosphoinositide metabolism in rat brain.

    PubMed

    Balduini, W; Candura, S M; Costa, L G

    1991-09-19

    Phosphoinositide metabolism stimulated by activation of cholinergic muscarinic, glutamatergic, alpha-adrenergic and serotoninergic receptors was measured in brain regions of the developing rats. Accumulation of [3H]inositol phosphates ([3H]InsPs) in [3H]inositol-prelabeled slices from cerebral cortex, hippocampus, brainstem and cerebellum was measured as an index of phosphoinositide metabolism. Large age-, neurotransmitter receptor-, and brain region-dependent differences were found. Carbachol-stimulated [3H]InsPs accumulation peaked on postnatal day 7 in cerebral cortex and hippocampus while in cerebellum and brainstem the effect of muscarinic stimulation was maximal at birth and then declined to adulthood. The effect of glutamate also showed a peak on day 7 in hippocampus and brainstem and a developmentally related decrease in cerebral cortex. In the cerebellum, on the other hand, the response to glutamate remained sustained through adulthood. Stimulation of phosphoinositide metabolism by norepinephrine increased with age in hippocampus and cerebral cortex, but decreased in the cerebellum, while the effect of serotonin did not change significantly with age except in cerebellum. These changes in receptor-stimulated phosphoinositide metabolism do not parallel, for the most part, the ontogeny of receptor recognition sites. Activation of the phosphoinositide metabolism pathway leads to an increase in intracellular calcium levels and to stimulation of protein kinase C, which are believed to play significant roles in cellular proliferation and differentiation. Thus, the differential ability of neurotransmitters to stimulate phosphoinositide hydrolysis might play a role in the development of brain regions.

  15. Car Seat Safety

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Car Seat Safety KidsHealth > For Parents > Car Seat Safety ... certified child passenger safety technician.) Guidelines for Choosing Car Seats Choose a seat with a label that ...

  16. s-Carboxymethylcysteine inhibits carbachol-induced constriction of epithelium-denuded rat and human airway preparations.

    PubMed

    Pavlovic, Dragan; Frieling, Helge; Usichenko, Taras; Nedeljkov, Vladimir; Nafissi, Thais; Lehmann, Christian; Aubier, Michel; Wendt, Michael

    2008-05-01

    1. The effects of s-carboxymethyl-L-cysteine (S-CMC), either administered orally to rats or incubated with tissue preparations from rats and humans, on isometric contractions of tracheal smooth muscle were investigated in the present study using an improved in vitro model of tracheal tube or ring preparations. The involvement of the tracheal epithelium in the observed effects was also investigated. 2. The experimental model permitted selective perfusion of the airway tube, luminal-IN or serosal-OUT, and measurement of airway smooth muscle contraction or relaxation in preparations with (+) or without (-) epithelium (Ep), excluding direct effects of airway mucus. 3. We found that oral pretreatment of rats with S-CMC (mixed with water; 200 mg/kg per day for 2 weeks), but not short pre-incubation of preparations in vitro (10(-3) mol/L S-CMC for 1 h), diminished the sensitivity of -Ep preparations to carbachol compared with controls (EC(50) (-log(10) mol/L) values: 5.5 +/- 0.1 vs 5.8 +/- 0.1, respectively, for IN perfusion (P < 0.005); 5.6 +/- 0.1 vs 5.9 +/- 0.1, respectively, for OUT perfusion (P < 0.005)), whereas the sensitivity of preparations to aminophylline was not affected. Normal sensitivity to carbachol stimulation was re-established if preparations were pre-incubated with capsaicin. 4. It was also found that longer pre-incubation (4 h) of ring-preparations of human bronchus with S-CMC (10(-5) mol/L) in vitro resulted in a diminished response to carbachol stimulation. 5. In conclusion, S-CMC had small inhibitory effects on the sensitivity of rat and human airway smooth muscle to carbachol, particularly in endothelium-denuded preparations. Whether the epithelium was responding to S-CMC by producing some contracting factor(s) requires further investigation.

  17. Stimulation of phosphatidylcholine breakdown by thrombin and carbachol but not by tyrosine kinase receptor ligands in cells transfected with M1 muscarinic receptors. Rapid desensitization of phosphocholine-specific (PC) phospholipase D but sustained activity of PC-phospholipase C.

    PubMed

    McKenzie, F R; Seuwen, K; Pouysségur, J

    1992-11-15

    In order to evaluate the possible contribution of phospholipase D (PLD) stimulation to the mitogenic response, a screening of a variety of different compounds, some of which are known to be potent mitogens, was performed using the well characterized Chinese hamster lung fibroblast (CCL39) cell line. In wild type CCL39 cells, or derivatives expressing high levels of either the human M1 muscarinic receptor (Hm1) or the human epidermal growth factor (EGF) receptor (39M1-81 and 39ER22 clones, respectively), thrombin, a potent mitogen for all three cell types, elicited the rapid activation of PLD (t1/2 activation, 30 s). Carbachol-mediated activation of the Hm1 receptor in the 39M1-81 clone, which is not a mitogenic signal, produced a similarly rapid although greater activation of PLD. Addition of EGF to the 39ER22 clone was able to provoke both a mitogenic response and stimulate PLD, albeit a comparatively small effect. In each case, the stimulation of PLD correlated closely with the ability to stimulate inositol phospholipid breakdown and was entirely dependent on the activation of protein kinase C. Moreover, the ability of both thrombin and carbachol to stimulate PLD was found to be rapidly desensitized, with a similar time course of desensitization (t1/2 desensitization, 90 s). It has recently been reported that an increase in phospholipase C (PLC)-mediated phosphocholine (PC) hydrolysis by either addition of agonist or by extracellular addition of PC-specific PLC enzyme constitutes a mitogenic signal. In this regard, in addition to stimulation of PLD, thrombin and carbachol were both able to stimulate the activity of a phosphocholine-specific phospholipase C (PC-PLC), which did not appear to desensitize within the time course employed. By contrast, EGF was unable to elicit the stimulation of PC-PLC. Ligands such as fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF), which bind to and activate receptors with intrinsic tyrosine kinase activity

  18. Nitric oxide donor beta2-agonists: furoxan derivatives containing the fenoterol moiety and related furazans.

    PubMed

    Buonsanti, M Federica; Bertinaria, Massimo; Stilo, Antonella Di; Cena, Clara; Fruttero, Roberta; Gasco, Alberto

    2007-10-04

    The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromolar or submicromolar concentration when tested on guinea pig tracheal rings precontracted with carbachol. Among the furoxan derivatives, the NO contribution to trachea relaxation was evident with product 15b at micromolar concentrations. All the new NO-donor hybrids were able to dilate rat aortic strips precontracted with phenylephrine. Both furoxan and furazan derivatives displayed antioxidant activity greater than that of fenoterol.

  19. Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor.

    PubMed

    Lin, Wenwei; Yang, Lei; Chai, Sergio C; Lu, Yan; Chen, Taosheng

    2016-01-27

    Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) are master regulators of endobiotic and xenobiotic metabolism and disposition. Because CAR is constitutively active in certain cellular contexts, inhibiting CAR might reduce drug-induced hepatotoxicity and resensitize drug-resistant cancer cells to chemotherapeutic drugs. We recently reported a novel CAR inhibitor/inverse agonist CINPA1 (11). Here, we have obtained or designed 54 analogs of CINPA1 and used a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate their CAR inhibition potency. Many of the 54 analogs showed CAR inverse agonistic activities higher than those of CINPA1, which has an IC50 value of 687 nM. Among them, 72 has an IC50 value of 11.7 nM, which is about 59-fold more potent than CINPA1 and over 10-fold more potent than clotrimazole (an IC50 value of 126.9 nM), the most potent CAR inverse agonist in a biochemical assay previously reported by others. Docking studies provide a molecular explanation of the structure-activity relationship (SAR) observed experimentally. To our knowledge, this effort is the first chemistry endeavor in designing and identifying potent CAR inverse agonists based on a novel chemical scaffold, leading to 72 as the most potent CAR inverse agonist so far. The 54 chemicals presented are novel and unique tools for characterizing CAR's function, and the SAR information gained from these 54 analogs could guide future efforts to develop improved CAR inverse agonists.

  20. Nigramide J is a novel potent inverse agonist of the human constitutive androstane receptor

    PubMed Central

    Kanno, Yuichiro; Tanuma, Nobuaki; Yatsu, Tomofumi; Li, Wei; Koike, Kazuo; Inouye, Yoshio

    2014-01-01

    The constitutive androstane receptor (CAR, NR1I3) is very important for drug development and for understanding pharmacokinetic drug–drug interactions. We screened by mammalian one hybrid assay among natural compounds to discover novel ligands of human constitutive androstane receptor (hCAR). hCAR transcriptional activity was measured by luciferase assay and mRNA levels of CYP2B6 and CYP3A4 in HepTR-hCAR cells and human primary hepatocytes were measured by real-time RT-PCR. Nigramide J (NJ) whose efficacy is comparable to those of hitherto known inverse agonists such as clotrimazole, PK11195, and ethinylestradiol. NJ is a naturally occurring cyclohexane-type amide alkaloid that was isolated from the roots of Piper nigrum. The suppressive effect of NJ on the CAR-dependent transcriptional activity was found to be species specific, in the descending order of hCAR, rat CAR, and mouse CAR. The unliganded hCAR-dependent transactivation of reporter and endogenous genes was suppressed by NJ at concentrations higher than 5 μmol/L. The ligand-binding cavity of hCAR was shared by NJ and CITCO, because they were competitive in the binding to hCAR. NJ interfered with the interaction of hCAR with coactivator SRC-1, but not with its interaction with the corepressor NCoR1. Furthermore, NJ is agonist of human pregnane X receptor (hPXR). NJ is a dual ligand of hCAR and hPXR, being an agonist of hPXR and an inverse agonist of hCAR. PMID:25505573

  1. Carbachol- and elevated Ca(2+)-induced translocation of functionally active protein kinase C to the brush border of rabbit ileal Na+ absorbing cells.

    PubMed Central

    Cohen, M E; Wesolek, J; McCullen, J; Rys-Sikora, K; Pandol, S; Rood, R P; Sharp, G W; Donowitz, M

    1991-01-01

    Protein kinase C is involved in mediating the effects of elevated Ca2+ in ileal villus Na+ absorbing cells to inhibit NaCl absorption. The present studies were undertaken to understand the mechanism by which this occurs. The effects of carbachol and the calcium ionophore A23187, agents which elevate intracellular Ca2+ and inhibit NaCl absorption in ileal villus cells, were studied. Carbachol treatment of villus cells caused a rapid decrease in protein kinase C activity in cytosol, with an accompanying increase in microvillus membrane C kinase. Exposure of the villus cells to calcium ionophore also caused a quantitatively similar decrease in cytosol C kinase and increase in C kinase activity in the microvillus membrane. This increase caused by carbachol and Ca2+ ionophore was specific for the microvillus membrane. In fact, 30 s and 10 min after exposure of the cells to carbachol, basolateral membrane protein kinase C decreased, in a time-dependent manner; whereas 10 min of Ca2+ ionophore exposure did not alter basolateral C kinase. Exposure of villus cells to Ca2+ ionophore or carbachol caused similar increases in microvillus membrane diacylglycerol content. As judged by the ability to inhibit Na+/H+ exchange measured in ileal villus cell brush border membrane vesicles, the protein kinase C which translocated to the microvillus membrane was functionally significant. Inhibition of Na+/H+ exchange required ATP and was reversed by the protein kinase C antagonist H-7. In conclusion, the effect of carbachol and Ca2+ ionophore in regulation of ileal NaCl absorption is associated with an increase in microvillus membrane diacylglycerol content and functionally active protein kinase C. The effects of both carbachol and Ca2+ ionophore are different on brush border and basolateral membrane distribution of protein kinase C. Images PMID:1885773

  2. Different rate-limiting activities of intracellular pH regulators for HCO3(-) secretion stimulated by forskolin and carbachol in rat parotid intralobular ducts.

    PubMed

    Ueno, Kaori; Hirono, Chikara; Kitagawa, Michinori; Shiba, Yoshiki; Sugita, Makoto

    2016-11-01

    Intracellular pH (pHi) regulation fundamentally participates in maintaining HCO3(-) release from HCO3(-)-secreting epithelia. We used parotid intralobular ducts loaded with BCECF to investigate the contributions of a carbonic anhydrase (CA), anion channels and a Na(+)-H(+) exchanger (NHE) to pHi regulation for HCO3(-) secretion by cAMP and Ca(2+) signals. Resting pHi was dispersed between 7.4 and 7.9. Forskolin consistently decreased pHi showing the dominance of pHi-lowering activities, but carbachol gathered pHi around 7.6. CA inhibition suppressed the forskolin-induced decrease in pHi, while it allowed carbachol to consistently increase pHi by revealing that carbachol prominently activated NHE via Ca(2+)-calmodulin. Under NHE inhibition, forskolin and carbachol induced the remarkable decreases in pHi, which were slowed predominantly by CA inhibition and by CA or anion channel inhibition, respectively. Our results suggest that forskolin and carbachol primarily activate the pHi-lowering CA and pHi-raising NHE, respectively, to regulate pHi for HCO3(-) secretion.

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

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

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

  4. Cars, Cycles, and Consumers.

    ERIC Educational Resources Information Center

    Idleman, Hillis K. Ed.

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

  5. Electric car arrives - again

    SciTech Connect

    Dunn, S.

    1997-03-01

    The first mass-produced electric cars in modern times are here, although they are expensive, limited in capability and unfamiliar to most prospective consumers. This article presents a brief history of the reintroduction of the modern electric car as well as discussions of the limitations of development, alternative routes to both producing and selling electric cars or some modified version of electric cars, economic incentives and governmental policies, and finally a snapshot description of the future for electric cars. 6 refs., 1 tab.

  6. Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action.

    PubMed

    Stocks, Michael J; Alcaraz, Lilian; Bailey, Andrew; Bonnert, Roger; Cadogan, Elaine; Christie, Jadeen; Dixon, John; Connolly, Stephen; Cook, Anthony; Fisher, Adrian; Flaherty, Alice; Humphries, Alexander; Ingall, Anthony; Jordan, Stephen; Lawson, Mandy; Mullen, Alex; Nicholls, David; Paine, Stuart; Pairaudeau, Garry; Young, Alan

    2014-04-10

    A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination of activities at the human β-adrenoreceptors demonstrated a series of highly potent and selective β2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i.t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultralong acting inhaled β2 receptor agonist with rapid onset of action.

  7. Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action

    PubMed Central

    2014-01-01

    A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination of activities at the human β-adrenoreceptors demonstrated a series of highly potent and selective β2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i.t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultralong acting inhaled β2 receptor agonist with rapid onset of action. PMID:24900851

  8. Carbachol and KCl-induced changes in intracellular free calcium concentration in isolated, fura-2 loaded smooth-muscle cells from the anterior byssus retractor muscle of Mytilus edulis.

    PubMed

    Ishii, N; Simpson, A W; Ashley, C C

    1988-06-16

    Intracellular free calcium concentration [( Ca2+]1) was measured in suspensions of fura-2 loaded smooth-muscle cells isolated from the anterior byssus retractor muscle of Mytilus edulis. Successive application of 5mM carbachol (CCh) and 100mM KCl to the cells transiently elevated [Ca2+]1 from the resting value of 124 +/- 4.5nM (mean +/- S.E., n = 14) to 295 +/- 15.3 and 383 +/- 20.5 nM, respectively. The response to CCh was concentration-dependent with an ED50 of 10(-5) M. Under the microscope, 67 +/- 3.0 and 83 +/- 1.3 % of fura-2 loaded cells contracted on the addition of 5mM CCh and 100mM KCl, respectively. In Ca2+ -free sea water, the CCh induced change in [Ca2+]1 was partially suppressed whereas that induced by KCl was completely abolished, suggesting an agonist-evoked release of stored Ca2+.

  9. Axonal transport of muscarinic cholinergic receptors in rat vagus nerve: high and low affinity agonist receptors move in opposite directions and differ in nucleotide sensitivity

    SciTech Connect

    Zarbin, M.A.; Wamsley, J.K.; Kuhar, M.J.

    1982-07-01

    The presence and transport of muscarinic cholinergic binding sites have been detected in the rat vagus nerve. These binding sites accumulate both proximal and distal to ligatures in a time-dependent manner. The results of double ligature and colchicine experiments are compatible with the notion that the anterogradely transported binding sites move by fast transport. Most of the sites accumulating proximal to ligatures bind the agonist carbachol with high affinity, while most of the sites accumulating distally bind carbachol with a low affinity. Also, the receptors transported in the anterograde direction are affected by a guanine nucleotide analogue (GppNHp), while those transported in the retrograde direction are less, or not, affected. The bulk of the sites along the unligated nerve trunk bind carbachol with a low affinity and are less sensitive to GppNHp modulation than the anterogradely transported sites. These results suggest that some receptors in the vagus may undergo axonal transport in association with regulatory proteins and that receptor molecules undergo changes in their binding and regulatory properties during their life cycle. These data also support the notion that the high and low affinity agonist form of the muscarinic receptor represent different modulated forms of a single receptor molecule.

  10. Antagonism by 8-hydroxy-2(di-n-propylamino)tetraline and other serotonin agonists of muscarinic M1-type receptors coupled to inositol phospholipid breakdown in human IMR-32 and SK-N-MC neuroblastoma cells

    SciTech Connect

    Fowler, C.J. Karolinska Institutet ); Ahlgren, P.C. ); O'Neill, C. )

    1991-01-01

    IMR-32 and SK-N-MC cells were found to contain ({sup 3}H)quinuclidinyl benzilate specific binding sites inhibited by pirenzepine in a manner suggesting the presence of both M1-type and M2-type muscarinic receptor recognition sites. Neither cell had detectable ({sup 3}H)8-OH-DPAT binding sites. Carbachol stimulated the rate of inositol phospholipid breakdown in IMR-32 and SK-N-MC human neuroblastoma cells with an EC{sub 50} value of about 50 {mu}M in both cases. Pirenzepine inhibited the carbachol stimulated inositol phospholipid breakdown in both cells with Hill slopes of unity and IC{sub 50} values of 15 nM (IMR-32) and 12 nM (SK-N-MC). The 5-HT{sub 1A} receptor agonist 8-OH-DPAT competitively inhibited carbachol-stimulated inositol phospholipid breakdown with pA{sub 2} values of 5.78 (IMR-32) and 5.61 (SK-N-MC). The 5-HT agonists 5-MeODMT and buspirone at micromolar concentrations inhibited carbachol-stimulated breakdown in IMR-32 cells. The inhibition by 8-OH-DPAT and 5-MeODMT was not affected by preincubation with (-)alprenolol. 5-HT was without effect on either basal or carbachol-stimulated breakdown. It is concluded that IMR-32 and SK-N-MC neuroblastoma cells express muscarinic M1-type but not serotoninergic receptors coupled to phosphoinositide-specific phospholipase C. 8-OH-DPAT acts as a weak antagonist at these muscarinic receptors.

  11. Phosphorylated nuclear receptor CAR forms a homodimer to repress its constitutive activity for ligand activation.

    PubMed

    Shizu, Ryota; Osabe, Makoto; Perera, Lalith; Moore, Rick; Sueyoshi, Tatsuya; Negishi, Masahiko

    2017-03-06

    Nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and disease development such as diabetes and tumors. CAR inactivates its constitutive activity by phosphorylation at threonine 38. Utilizing receptor for protein kinase 1 (RACK1) as the regulatory subunit, protein phosphatase PP2A dephosphorylates threonine 38 to activate CAR. Here we have demonstrated that CAR undergoes its homodimer-monomer conversion to regulate this dephosphorylation. By co-expressing two differently-tagged CAR proteins in Huh-7 cells, mouse primary hepatocytes and mouse livers, co-immunoprecipitation and two-dimensional gel electrophoresis revealed that CAR can form a homodimer in a configuration in which the PP2A/RACK1 binding site is buried within its dimer interface. Epidermal growth factor (EGF) was found to stimulate CAR homo-dimerization, thus constraining CAR in its inactive form. The agonistic ligand CITCO binds directly to the CAR homodimer and dissociates phosphorylated CAR into its monomer, exposing the PP2A/RACK1 binding site for dephosphorylation. Phenobarbital, which is not a CAR ligand, binds the EGF receptor, reversing the EGF signal to monomerize CAR for its indirect activation. Thus, the homodimer-monomer conversion is the underlying molecular mechanism that regulates CAR activation, by placing phosphorylated threonine 38 as the common target for both direct and in direct activation of CAR.

  12. ELECTRIC MOTOR CARS.

    DTIC Science & Technology

    The electric automobiles studied are designed as the equivalent of their gasoline-engine counterparts in size, comfort, performance, and initial...acceleration. Top speeds comparable to those of small present-day cars are shown to be realizable, though the range between refueling is not. Batteries...noise abatement. The lifetime costs derived can be somewhat lower than those of conventional cars ; therefore it is concluded that electric cars

  13. Genome-wide Analysis of Human Constitutive Androstane Receptor (CAR) Transcriptome in Wild-type and CAR-knockout HepaRG cells

    PubMed Central

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

    2015-01-01

    The constitutive androstane receptor (CAR) modulates the transcription of numerous genes involving drug metabolism, energy homeostasis, and cell proliferation. Most functions of CAR however were defined from animal studies. Given the known species difference of CAR and the significant cross-talk between CAR and the pregnane X receptor (PXR), it is extremely difficult to decipher the exact role of human CAR (hCAR) in gene regulation, relying predominantly on pharmacological manipulations. Here, utilizing a newly generated hCAR-knockout (KO) HepaRG cell line, we carried out RNA-seq analysis of the global transcriptomes in wild-type (WT) and hCAR-KO HepaRG cells treated with CITCO, a selective hCAR agonist, phenobarbital (PB), a dual activator of hCAR and hPXR, or vehicle control. Real-time PCR assays in separate experiments were used to validate RNA-seq findings. Our results indicate that genes encoding drug-metabolizing enzymes are among the main clusters altered by both CITCO and PB. Specifically, CITCO significantly changed the expression of 135 genes in an hCAR-dependent manner, while PB altered the expression of 227 genes in WT cells of which 94 were simultaneously modulated in both cell lines reflecting dual effects of PB on hCAR/PXR. Notably, we found that many genes promoting cell proliferation and tumorigenesis were up-regulated in hCAR-KO cells, suggesting that hCAR may play an important role in cell growth that differs from mouse CAR. Together, our results reveal both novel and known targets of hCAR and support the role of hCAR in maintaining the homeostasis of metabolism and cell proliferation in the liver. PMID:26275810

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

    PubMed

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

    2015-11-01

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

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

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

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

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

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

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

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

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

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

  18. The Electric Cars Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2011-01-01

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

  19. Shuttle car loading system

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

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

  20. Lacrimal gland PKC isoforms are differentially involved in agonist-induced protein secretion.

    PubMed

    Zoukhri, D; Hodges, R R; Sergheraert, C; Toker, A; Dartt, D A

    1997-01-01

    In the present study, we have synthesized and N-myristoylated peptides derived from the pseudosubstrate sequences of protein kinase C (PKC)-alpha, -delta, and -epsilon [Myr-PKC-alpha-(15-28), Myr-PKC-delta-(142-153), and Myr-PKC-epsilon-(149-164)], three isoforms present in rat lacrimal gland, and a peptide derived from the sequence of the endogenous inhibitor of protein kinase A [Myr-PKI-(17-25)]. Lacrimal gland acini were preincubated for 60 min with the myristoylated peptides (10(-10) to 3 x 10(-7) M), then protein secretion was stimulated with a phorbol ester, phorbol 12,13-dibutyrate (10(-6) M); vasoactive intestinal peptide (10(-8) M); a cholinergic agonist, carbachol (10(-5) M); or an alpha 1-adrenergic agonist, phenylephrine (10(-4) M), for 20 min. In intact lacrimal gland acini, Myr-PKC-alpha-(15-28) inhibited phorbol 12,13-dibutyrate-induced protein secretion. This effect was not reproduced by the acetylated peptide or by the myristoylated PKI, which inhibited vasoactive intestinal peptide-induced protein secretion, a response mediated by protein kinase A. Carbachol-induced protein secretion was inhibited by all three peptides. In contrast, phenylephrine-induced protein secretion was inhibited only by Myr-PKC-epsilon-(149-164), whereas Myr-PKC-alpha-(15-28) and Myr-PKC-delta-(142-153) had a stimulatory effect. None of these myristoylated peptides affected the calcium increase evoked by cholinergic or alpha 1-adrenergic agonists. We concluded that phorbol ester- and receptor-induced protein secretion involve different PKC isoforms in lacrimal gland.

  1. Audit of Car Ownership Models

    DTIC Science & Technology

    2002-01-01

    In this report, a review was presented of existing models for car ownership. This review contains a description and comparison of existing Dutch car ...the AVV car ownership models. The car ownership model that AVV uses for most applications is the so-called FACTS model (Forecasting Air pollution...through Car Traffic Simulation). FACTS also provides the future total number of cars that is used as an external total in the Dutch national Model System

  2. Discharge properties of medullary reticulospinal neurons during postural changes induced by intrapontine injections of carbachol, atropine and serotonin, and their functional linkages to hindlimb motoneurons in cats.

    PubMed

    Takakusaki, K; Shimoda, N; Matsuyama, K; Mori, S

    1994-01-01

    The present study was aimed at elucidating the pontomedullary and spinal cord mechanisms of postural atonia induced by microinjection of carbachol and restored by microinjections of serotonin or atropine sulfate into the nucleus reticularis pontis oralis (NRPo). Medullary reticulospinal neurons (n = 132) antidromically activated by stimulating the L1 spinal cord segment were recorded extracellularly. Seventy-eight of them were orthodromically activated with mono- or disynaptic latencies by stimulating the NRPo area at the site where carbachol injections effectively induced postural atonia. Most of these reticulospinal neurons (71 of 78) were located in the nucleus reticularis gigantocellularis (NRGc). Following carbachol injection into the NRPo, discharge rates of the NRGc reticulospinal neurons (29 of 34) increased, while the activity of soleus muscles decreased bilaterally. Serotonin or atropine injections into the same NRPo area resulted in a decrease in the discharge rates of the reticulospinal neurons with a concomitant increase in the levels of hindlimb muscle tone. Membrane potentials of hindlimb extensor and flexor alpha motoneurons (MNs) were hyperpolarized and depolarized by carbachol and serotonin or atropine injections, respectively. In all pairs of reticulospinal neurons and MNs (n = 11), there was a high correlation between the increase in the discharge rates and the degree of membrane hyperpolarization of the MNs. Spike-triggered averaging during carbachol-induced atonia revealed that inhibitory postsynaptic potentials (IPSPs) were evoked in 15 MNs by the discharges of nine reticulospinal neurons. Four of them evoked IPSPs in more than one MN. The mean segmental delay and the mean time to the peak of IPSPs were 1.6 ms and 2.0 ms, respectively. Axonal trajectories of reticulospinal neurons (n = 6), which evoked IPSPs in MNs, were investigated in the lumbosacral segments (L1-S1) by antidromic threshold mapping. The stem axons descended through the

  3. The Electric Car Challenge.

    ERIC Educational Resources Information Center

    Diehl, Brian E.

    1997-01-01

    Describes the Electric Car Challenge during which students applied methods of construction to build lightweight, strong vehicles that were powered by electricity. The activity required problem solving, sheet metal work, electricity, design, and construction skills. (JOW)

  4. [Melatonin receptor agonist].

    PubMed

    Uchiyama, Makoto

    2015-06-01

    Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.

  5. Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytes.

    PubMed

    Chung, Seung-Soo; Ahn, Duck-Sun; Lee, Hong-Ghi; Lee, Young-Ho; Nam, Taick-Sang

    2005-07-01

    The effect of sodium nitroprusside (SNP) on carbachol (CCh)-evoked inward cationic current (Icat) oscillations in guinea-pig ileal longitudinal myocytes was investigated using the whole-cell patch-clamp technique and permeabilized longitudinal muscle strips. SNP (10 microm) completely inhibited I(cat) oscillations evoked by 1 microm CCh. 1H-(1,2,4) Oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 1 microm) almost completely prevented the inhibitory effect of SNP on Icat oscillations. 8-Bromo-guanosine 3',5'-cyclic monophosphate (8-Br-cGMP; 30 microm) in the pipette solution completely abolished Icat oscillations. However, a pipette solution containing Rp-8-Br-cGMP (30 microm) almost completely abolished the inhibitory effect of SNP on Icat oscillations. When the intracellular calcium concentration ([Ca2+]i) was held at a resting level using BAPTA (10 mm) and Ca2+ (4.6 microm) in the pipette solution, CCh (1 microm) evoked only the sustained component of Icat without any oscillations and SNP did not affect the current. A high concentration of inositol 1,4,5-trisphosphate (IP3; 30 microm) in the patch pipette solutions significantly reduced the inhibitory effect of SNP (10 microm) on Icat oscillations. SNP significantly inhibited the Ca2+ release evoked by either CCh or IP3 but not by caffeine in permeabilized preparations of longitudinal muscle strips. These results suggest that the inhibitory effects of SNP on Icat oscillations are mediated, in part, by functional modulation of the IP3 receptor, and not by the inhibition of cationic channels themselves or by muscarinic receptors in the plasma membrane. This inhibition seems to be mediated by an increased cGMP concentration in a protein kinase G-dependent manner.

  6. Comparison of contractions produced by carbachol, thapsigargin and cyclopiazonic acid in the guinea-pig tracheal muscle

    PubMed Central

    Takemoto, M; Takagi, K; Ogino, K; Tomita, T

    1998-01-01

    Thapsigargin (TPG, 3 μM) and cyclopiazonic acid (CPA, 10 μM) slowly increased muscle tone in the guinea-pig isolated tracheal muscle. A large sustained contraction was produced when 2.4 mM Ca2+ was readmitted after 10 min exposure to Ca2+-free solution following 30 min treatment with TPG or CPA.The sustained contraction after Ca2+ readmission was partially inhibited by nifedipine (3 μM) and highly dependent on external Ca2+. The TPG- and CPA-induced sustained contractions were 75% and 67%, respectively, of the sustained contraction produced by carbachol (Cch, 1 μM, EC80) in the presence of nifedipine.The contractions produced by Cch, TPG and CPA were all inhibited by isoprenaline (ISO) and sodium nitroprusside (SNP). In the presence of nifedipine, the IC50 of ISO was 11, 17, and 23 nM and that of SNP was 0.5, 1, 0.8 μM for Cch-, TPG-, and CPA-induced contractions, respectively. The contraction produced by 60 mM K+ was only weakly inhibited by ISO and SNP. As with ISO and SNP, the Cch-, TPG- and CPA-induced contractions were also similarly inhibited by SKF 96365 (100 μM) and cadmium (Cd2+, 100 μM).It was concluded that TPG and CPA increased Ca2+ influx probably via a mechanism activated by Ca2+ depletion of the sarcoplasmic reticulum. The susceptibility of the contraction produced by TPG, CPA and Cch to inhibition by ISO and SNP and also by SKF-96365 and Cd2+ suggests that the contractions use common pathways for increasing intracellular Ca2+, and that the contractions produced by K+ involve a different mechanism. PMID:9723957

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

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

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

  8. Modeling the Mousetrap Car

    ERIC Educational Resources Information Center

    Jumper, William D.

    2012-01-01

    Many high school and introductory college physics courses make use of mousetrap car projects and competitions as a way of providing an engaging hands-on learning experience incorporating Newton's laws, conversion of potential to kinetic energy, dissipative forces, and rotational mechanics. Presented here is a simple analytical and finite element…

  9. Melatonin agonists and insomnia.

    PubMed

    Ferguson, Sally A; Rajaratnam, Shantha M W; Dawson, Drew

    2010-02-01

    The ability of melatonin to shift biological rhythms is well known. As a result, melatonin has been used in the treatment of various circadian rhythm sleep disorders, such as advanced and delayed sleep phase disorders, jet lag and shiftwork disorder. The current evidence for melatonin being efficacious in the treatment of primary insomnia is less compelling. The development of agents that are selective for melatonin receptors provides opportunity to further elucidate the actions of melatonin and its receptors and to develop novel treatments for specific types of sleep disorders. The agonists reviewed here - ramelteon, tasimelteon and agomelatine - all appear to be efficacious in the treatment of circadian rhythm sleep disorders and some types of insomnia. However, further studies are required to understand the mechanisms of action, particularly for insomnia. Clinical application of the agonists requires a good understanding of their phase-dependent properties. Long-term effects of melatonin should be evaluated in large-scale, independent randomized controlled trials.

  10. Beta-Adrenergic Agonists

    PubMed Central

    Barisione, Giovanni; Baroffio, Michele; Crimi, Emanuele; Brusasco, Vito

    2010-01-01

    Inhaled β2-adrenoceptor (β2-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β2-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β2-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction. In particular, phosphorylation mediated by protein kinase A and β-adrenergic receptor kinase are examined in detail. Finally, we discuss the pivotal role of inhaled β2-AR agonists in the treatment of asthma and the concerns about their safety that have been recently raised. PMID:27713285

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

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

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

  12. Design of an intelligent car

    NASA Astrophysics Data System (ADS)

    Na, Yongyi

    2017-03-01

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

  13. Carbachol activates a K+ channel of very small conductance in the basolateral membrane of rat pancreatic acinar cells.

    PubMed

    Köttgen, M; Hoefer, A; Kim, S J; Beschorner, U; Schreiber, R; Hug, M J; Greger, R

    1999-10-01

    Secretion of Cl- requires the presence of a K+ conductance to hyperpolarize the cell, and to provide the driving force for Cl- exit via luminal Cl- channels. In the exocrine pancreas Cl- secretion is mediated by an increase in cytosolic Ca2+ ([Ca2+]i). Two types of Ca2+-activated K+ channels could be shown in pancreatic acinar cells of different species. However, there are no data on Ca2+-activated K+ channels in rat pancreatic acini. Here we examine the basolateral K+ conductance of freshly isolated rat pancreatic acinar cells in cell-attached and cell-excised patch-clamp experiments. Addition of carbachol (CCH, 1 micromol/l) to the bath led to the activation of very small conductance K+ channels in cell-attached patches (n=27), producing a noisy macroscopic outward current. The respective outward conductance increased significantly by a factor of 2.1+/-0.1 (n=27). Noise analysis revealed a Lorentzian noise component with a corner frequency (f(c)) of 30.3+/-3.5 Hz (n=19), consistent with channel activity in these patches. The estimated single-channel conductance was 1.5+/-0.4 pS (n=19). In cell-excised patches (inside out) from cells previously stimulated with CCH, channel activity was only observed in the presence of K+ in the bath solution. Under these conditions f(c) was 47.6+/-11.9 Hz (estimated single-channel conductance 1.1+/-0.2 pS, n=20). The current/voltage relationship of the noise showed weak inward rectification and the reversal potential shifted towards E(K+) when Na+ in the bath was replaced by K+. Channel activity in cell-excised patches was slightly reduced by 10 mmol/l Ba2+ (23.6+/-2.1% of the total outward current) and was completely absent when K+ in the bath was replaced by Na+. Reduction of the [Ca2+]i from 1 mmol/l to 1 micromol/l in cell-excised experiments decreased the current by 52.3+/-12.3% (n=5). Expression of K(v)LQT1, one of the possible candidates for a small-conductance K+ channel in rat pancreatic acinar cells, was shown by reverse

  14. Acute Aerobic Swimming Exercise Induces Distinct Effects in the Contractile Reactivity of Rat Ileum to KCl and Carbachol

    PubMed Central

    Araujo, Layanne C. da Cunha; de Souza, Iara L. L.; Vasconcelos, Luiz H. C.; Brito, Aline de Freitas; Queiroga, Fernando R.; Silva, Alexandre S.; da Silva, Patrícia M.; Cavalcante, Fabiana de Andrade; da Silva, Bagnólia A.

    2016-01-01

    Aerobic exercise promotes short-term physiological changes in the intestinal smooth muscle associated to the ischemia-reperfusion process; however, few studies have demonstrated its effect on the intestinal contractile function. Thus, this work describes our observations regarding the influence of acute aerobic swimming exercise in the contractile reactivity, oxidative stress, and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and acutely exercised (EX-AC) groups. Animals were acclimated by 10, 10, and 30 min of swimming exercise in intercalated days 1 week before exercise. Then they were submitted to forced swimming for 1 h with a metal of 3% of their body weight attached to their body. Animals were euthanized immediately after the exercise section and the ileum was suspended in organ baths for monitoring isotonic contractions. The analysis of lipid peroxidation was performed in order to determinate the malondialdehyde (MDA) levels as a marker of oxidative stress, and intestinal smooth muscle morphology by histological staining. Cumulative concentration-response curves to KCl were altered in the EX-AC with an increase in both its efficacy and potency (Emax = 153.2 ± 2.8%, EC50 = 1.3 ± 0.1 × 10−2 M) compared to the SED group (Emax = 100%, EC50 = 1.8 ± 0.1 × 10−2 M). Interestingly, carbachol had its efficacy and potency reduced in the EX-AC (Emax = 67.1 ± 1.4%, EC50 = 9.8 ± 1.4 × 10−7 M) compared to the SED group (Emax = 100%, EC50 = 2.0 ± 0.2 × 10−7 M). The exercise did not alter the MDA levels in the ileum (5.4 ± 0.6 μ mol/mL) in the EX-AC compared to the SED group (8.4 ± 1.7 μ mol/mL). Moreover, neither the circular nor the longitudinal smooth muscle layers thickness were modified by the exercise (66.2 ± 6.0 and 40.2 ± 2.6 μm, respectively), compared to the SED group (61.6 ± 6.4 and 34.8 ± 3.7 μm, respectively). Therefore, the ileum sensitivity to contractile agents is differentially altered by the acute aerobic

  15. Chem-E-Car Downunder.

    ERIC Educational Resources Information Center

    Rhodes, Martin

    2002-01-01

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

  16. A simple assay for agonist-regulated Cl and K conductances in salt-secreting epithelial cells.

    PubMed

    Venglarik, C J; Bridges, R J; Frizzell, R A

    1990-08-01

    We developed a convenient flux assay that permits simultaneous measurement of Cl and K conductance pathways in Cl-secreting epithelial cells. Monolayers of the colonic tumor cell line T84 were preloaded with 125I and 86Rb, and isotope effluxes were monitored by a sample-replace procedure. The adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agonists forskolin and prostaglandin E2 increased I efflux with little effect on Rb efflux, whereas the Ca-mediated agonists ionomycin, A23187, and carbachol increased both I and Rb effluxes. Simultaneous determinations of I and Cl or Rb and K effluxes indicated that I and Rb provide good measures of the effluxes of Cl and K, respectively. Forskolin- and ionomycin-stimulated I effluxes were inhibited by the Cl-channel blockers diphenylamine-2-dicarboxylate (DPC), 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB), and 2-[cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H- inden-5-yl)oxy]acetic acid (IAA-94) and by high external K. The Rb efflux evoked by ionomycin was inhibited by the K-channel blockers Ba and charybdotoxin. These findings suggest that I and Rb effluxes provide qualitative estimates of agonist-stimulated Cl and K conductance pathways. Thus this method can provide a simple and relatively inexpensive screening assay for Cl and K conductances in cultured cells to assess the effects of agonist, blockers, or genetic manipulations.

  17. A simple assay for agonist-regulated Cl and K conductances in salt-secreting epithelial cells

    SciTech Connect

    Venglarik, C.J.; Bridges, R.J.; Frizzell, R.A. )

    1990-08-01

    We developed a convenient flux assay that permits simultaneous measurement of Cl and K conductance pathways in Cl-secreting epithelial cells. Monolayers of the colonic tumor cell line T84 were preloaded with 125I and 86Rb, and isotope effluxes were monitored by a sample-replace procedure. The adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agonists forskolin and prostaglandin E2 increased I efflux with little effect on Rb efflux, whereas the Ca-mediated agonists ionomycin, A23187, and carbachol increased both I and Rb effluxes. Simultaneous determinations of I and Cl or Rb and K effluxes indicated that I and Rb provide good measures of the effluxes of Cl and K, respectively. Forskolin- and ionomycin-stimulated I effluxes were inhibited by the Cl-channel blockers diphenylamine-2-dicarboxylate (DPC), 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB), and 2-(cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H- inden-5-yl-oxy)acetic acid (IAA-94) and by high external K. The Rb efflux evoked by ionomycin was inhibited by the K-channel blockers Ba and charybdotoxin. These findings suggest that I and Rb effluxes provide qualitative estimates of agonist-stimulated Cl and K conductance pathways. Thus this method can provide a simple and relatively inexpensive screening assay for Cl and K conductances in cultured cells to assess the effects of agonist, blockers, or genetic manipulations.

  18. Girls, Cars, and Science

    NASA Astrophysics Data System (ADS)

    Parks, Beth

    2005-03-01

    For the past two summers, I have run an NSF-funded residential camp for girls ages 14-17. This camp is designed to stimulate girls' interest in science by building on their interest in automobiles. The girls spend half the day in hands-on work with cars at Morrisville State College. The other half of the day is dedicated to laboratory exercises at Colgate University that have been designed to help girls learn the science behind the operation of cars. While it is impossible to assess the long-range impact of this program after only two years, the results seem promising. I will discuss the camp program, with particular emphasis on the laboratory experiments that have been developed, which could easily be incorporated into standard high school or college laboratories.

  19. Usability of car stereo.

    PubMed

    Razza, Bruno Montanari; Paschoarelli, Luis Carlos

    2012-01-01

    Automotive sound systems vary widely in terms of functions and way of use between different brands and models what can bring difficulties and lack of consistency to the user. This study aimed to analyze the usability of car stereo commonly found in the market. Four products were analyzed by task analysis and after use reports and the results indicate serious usability issues with respect to the form of operation, organization, clarity and quality of information, visibility and readability, among others.

  20. New developments in clinical CARS

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  1. Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action potential shortening and GIRK1/4 channel.

    PubMed

    Matsuda, Tomoyuki; Ito, Mie; Ishimaru, Sayoko; Tsuruoka, Noriko; Saito, Tomoaki; Iida-Tanaka, Naoko; Hashimoto, Norio; Yamashita, Toru; Tsuruzoe, Nobutomo; Tanaka, Hikaru; Shigenobu, Koki

    2006-08-01

    Mechanisms for the atria-specific action potential-prolonging action of NIP-142 ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4-methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound that terminates experimental atrial arrhythmia, was examined. In isolated guinea-pig atrial tissue, NIP-142 reversed the shortening of action potential duration induced by either carbachol or adenosine. These effects were mimicked by tertiapin, but not by E-4031. NIP-142 concentration-dependently blocked the human G protein-coupled inwardly rectifying potassium channel current (GIRK1/4 channel current) expressed in HEK-293 cells with an EC50 value of 0.64 microM. At higher concentrations, NIP-142 blocked the human ether a go-go related gene (HERG) channel current with an EC50 value of 44 microM. In isolated guinea-pig papillary muscles, NIP-142 had no effect on the negative inotropic effect of carbachol under beta-adrenergic stimulation, indicating lack of effect on the muscarinic receptor and Gi protein. These results suggest that NIP-142 directly inhibits the acetylcholine-activated potassium current.

  2. Mechanisms underlying activation of transient BK current in rabbit urethral smooth muscle cells and its modulation by IP3-generating agonists.

    PubMed

    Kyle, Barry D; Bradley, Eamonn; Large, Roddy; Sergeant, Gerard P; McHale, Noel G; Thornbury, Keith D; Hollywood, Mark A

    2013-09-15

    We used the perforated patch-clamp technique at 37°C to investigate the mechanisms underlying the activation of a transient large-conductance K(+) (tBK) current in rabbit urethral smooth muscle cells. The tBK current required an elevation of intracellular Ca(2+), resulting from ryanodine receptor (RyR) activation via Ca(2+)-induced Ca(2+) release, triggered by Ca(2+) influx through L-type Ca(2+) (CaV) channels. Carbachol inhibited tBK current by reducing Ca(2+) influx and Ca(2+) release and altered the shape of spike complexes recorded under current-clamp conditions. The tBK currents were blocked by iberiotoxin and penitrem A (300 and 100 nM, respectively) and were also inhibited when external Ca(2+) was removed or the CaV channel inhibitors nifedipine (10 μM) and Cd(2+) (100 μM) were applied. The tBK current was inhibited by caffeine (10 mM), ryanodine (30 μM), and tetracaine (100 μM), suggesting that RyR-mediated Ca(2+) release contributed to the activation of the tBK current. When IP3 receptors (IP3Rs) were blocked with 2-aminoethoxydiphenyl borate (2-APB, 100 μM), the amplitude of the tBK current was not reduced. However, when Ca(2+) release via IP3Rs was evoked with phenylephrine (1 μM) or carbachol (1 μM), the tBK current was inhibited. The effect of carbachol was abolished when IP3Rs were blocked with 2-APB or by inhibition of muscarinic receptors with the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (1 μM). Under current-clamp conditions, bursts of action potentials could be evoked with depolarizing current injection. Carbachol reduced the number and amplitude of spikes in each burst, and these effects were reduced in the presence of 2-APB. In the presence of ryanodine, the number and amplitude of spikes were also reduced, and carbachol was without further effect. These data suggest that IP3-generating agonists can modulate the electrical activity of rabbit urethral smooth muscle cells and may contribute to the effects of

  3. The inhibitory action of cyclic AMP on responses to carbachol dependent on calcium stores in rat gastric smooth muscle.

    PubMed Central

    Ohta, T; Ito, S; Noto, T; Tachibana, R; Nakazato, Y; Ohga, A

    1992-01-01

    1. The effects of cyclic AMP on contraction and Ca(2+)-activated K+ currents induced by carbachol (CCh), caffeine and inositol 1,4,5-trisphosphate (InsP3) were examined in intact and skinned smooth muscle fibres and in whole-cell voltage-clamped smooth muscle cells of the rat stomach. Intracellular Ca2+ level, [Ca2+]i, was monitored in intact muscle fibres loaded with Fura-2. 2. In intact muscle fibres, dibutyryl cyclic AMP, 8-bromo-cyclic AMP and forskolin inhibited a phasic contraction induced by CCh (100 microM) much more extensively than that induced by caffeine (30 mM) in Ca(2+)-free solution containing 2 mM-EGTA. A rise in [Ca2+]i evoked by CCh was also reduced by dibutyryl cyclic AMP. 3. In skinned muscle fibres, InsP3 (40 microM) produced a contraction of amplitude similar to that evoked by caffeine (30 mM) in Ca(2+)-free solution containing 0.05 mM-EGTA. Cyclic AMP suppressed the InsP3-induced contraction to a much greater extent than that induced by caffeine. 4. In cells voltage-clamped at 0 mV, CCh (100 microM) evoked a transient Ca(2+)-activated outward K+ current in 61% of cells tested. After wash-out of CCh, caffeine (10 mM) evoked a similar K+ current in all cells. In cells loaded with cyclic AMP (100 microM), the percentage of cells responding to CCh was reduced to 26% and the magnitude of current response tended to decrease. Cyclic AMP caused a small increase in the caffeine-induced K+ current. 5. An outward current was elicited immediately after the patch membrane was ruptured at a holding potential of 0 mV, using a patch pipette containing InsP3 (40 microM), in 76% of cells tested. In cells treated with dibutyryl cyclic AMP, the percentage of cells responding to InsP3 was reduced to 50% and the magnitude of current response tended to decrease. 6. In intact muscle fibres loaded with Fura-2, the relationship between [Ca2+]i and tension development shifted to the right in the presence of dibutyryl cyclic AMP. In skinned muscle fibres, cyclic AMP

  4. 49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Annual Report of Cars Loaded and Cars Terminated... LOADED AND CARS TERMINATED § 1247.1 Annual Report of Cars Loaded and Cars Terminated. Beginning with the... STB-54, Annual Report of Cars Loaded and Cars Terminated, together with the accompanying...

  5. Denatonium and 6-n-Propyl-2-thiouracil, Agonists of Bitter Taste Receptor, Inhibit Contraction of Various Types of Smooth Muscles in the Rat and Mouse.

    PubMed

    Sakai, Hiroyasu; Sato, Ken; Kai, Yuki; Chiba, Yoshihiko; Narita, Minoru

    2016-01-01

    Recently the global expression of taste 2 receptors (TAS2Rs) on smooth muscle cells in human airways was demonstrated. Here, the effects of agonists of taste receptor, type 2, denatonium and 6-n-propyl-2-thiouracil, on smooth-muscle contraction were examined in the rat and mouse. Contractions induced by carbachol (CCh), high K(+), and sodium fluoride, but not calyculin-A, were inhibited significantly in the presence of a TAS2R agonist in the bronchial smooth muscle of mice. The contraction induced by CCh was inhibited by TAS2R agonists in ileal smooth muscle. Phenylephrine-induced contraction was also inhibited by TAS2R agonists in aortic smooth muscle. Gastrointestinal motility and blood pressure were attenuated by administration of TAS2R agonists in vivo. These findings suggest that TAS2R may be receptor for endogenous biologically active substances as well as for bitter tastes on the tongue. TAS2R signaling could be employed in the development of anti-asthmatic, anti-spasmodic, and anti-hypertensive drugs.

  6. Denatonium and 6-n-Propyl-2-thiouracil, Agonists of Bitter Taste Receptor, Inhibit Contraction of Various Types of Smooth Muscles in the Rat and Mouse.

    PubMed

    Sakai, Hiroyasu; Sato, Ken; Kai, Yuki; Chiba, Yoshihiko; Narita, Minoru

    2016-01-01

    Recently the global expression of taste 2 receptors (TAS2Rs) on smooth muscle cells in human airways was demonstrated. Here, the effects of agonists of taste receptor, type 2, denatonium and 6-n-propyl-2-thiouracil, on smooth-muscle contraction were examined in the rat and mouse. Contractions induced by carbachol (CCh), high K, and sodium fluoride, but not calyculin-A, were inhibited significantly in the presence of a TAS2R agonist in the bronchial smooth muscle of mice. The contraction induced by CCh was inhibited by TAS2R agonists in ileal smooth muscle. Phenylephrine-induced contraction was also inhibited by TAS2R agonists in aortic smooth muscle. Gastrointestinal motility and blood pressure were attenuated by administration of TAS2R agonists in vivo. These findings suggest that TAS2R may be receptor for endogenous biologically active substances as well as for bitter tastes on the tongue. TAS2R signaling could be employed in the development of anti-asthmatic, anti-spasmodic, and anti-hypertensive drugs.

  7. CARS-based silicon photonics

    NASA Astrophysics Data System (ADS)

    Vermeulen, Nathalie; Debaes, Christof; Thienpont, Hugo

    2009-05-01

    In this invited paper, we will first discuss the recent research progress regarding silicon-on-insulator (SOI) Raman wavelength converters, the working principle of which is based on the four-wave mixing process of coherent anti-Stokes Raman scattering (CARS). Next, we will present our research results on other aspects of CARS in SOI waveguides. First, starting from the basic formalism for CARS we will show that, in contrast to what most scientists believe, CARS exchanges energy with the Raman medium in which it takes place and is even able to extract energy (i.e. extract phonons) from it. Furthermore, we will introduce a novel CARS-based approach to reduce the heat dissipation in Raman lasers due to the quantum defect between pump and lasing photons, and we will numerically demonstrate that with this "CARS-based heat mitigation technique" the quantum-defect heating in SOI waveguide Raman lasers could be reduced with as much as 35%.

  8. Lighting innovations in concept cars

    NASA Astrophysics Data System (ADS)

    Berlitz, Stephan; Huhn, Wolfgang

    2005-02-01

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

  9. Cars Spectroscopy of Propellant Flames

    DTIC Science & Technology

    1983-11-01

    Bele,:1t )"(vaiaable Copy AD AD-E4OI 102 TECMNICA._ REPORT ;RLCD-TR-83047 CARS SPECTROSCOPY Of PROPELLANT FLAMES L. E. HARRIS DTIC ii IELECTE0 "" NOV...4. TITLE (mid Subtitle) 5. TYPE OF REPORT & PERIOD COVERED CARS SPECTROSCOPY OF PROPELLANT FLAMES Final Ś. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(a...ea•abo. Broadband CARS CARS spectra Spectroscopy Propellant *0AUINIACT (0w o roemtae 401 N uueedswr Mu $000tit? b7 61"k Auhee) Obtaining useful

  10. Sparks fly over electric cars

    SciTech Connect

    Griffith, V.

    1994-10-01

    While the US automobile industry scrambles to meet 1998 deadlines to put electric vehicles on the market, controversy about the environmental benefits and commercial viability of battery-operated cars is mounting. Circumstances in the US increasingly favor the electric car. Air quality laws in California and Massachusetts now demand that {open_quotes}zero-emission{close_quotes} vehicles comprise 2 percent of total sales in the car market by 1998. Electric cars are the only vehicles to meet such standards so far. Other states are considering similar laws. This article examines the pros and cons of electric vehicle use.

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

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

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

  12. Car versus bicycle: conclusion.

    PubMed

    Ross, David W; Wichman, Carol; Mackinnon, Mike

    2009-01-01

    A 58-year-old man was riding his bicycle and was struck by a car. He was ejected and landed on his back on the pavement of the roadway. He complained of severe pain in his lower back and sacral area. Ground emergency medical services (EMS) arrived to find a pale, diaphoretic man who was alert but in distress. His medical history was negative, and he was taking no medications. The initial heart rate was 130 beats/minute, and the blood pressure was 70 mmHg by palpation. A helicopter air ambulance was requested from the rural scene location to transport the patient to a trauma center. The physical examination by the flight crew demonstrated the patient had not changed from the original EMS assessment, despite the administration of 1 L normal saline intravenously. There were no apparent injuries to his head, neck, chest, or extremities.

  13. 49 CFR 174.615 - Cleaning cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  14. 49 CFR 174.615 - Cleaning cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  15. 49 CFR 174.615 - Cleaning cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  16. 49 CFR 174.615 - Cleaning cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  17. 49 CFR 172.330 - Tank cars and multi-unit tank car tanks.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  18. 49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  19. 49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  1. 49 CFR 1247.1 - Annual Report of Cars Loaded and Cars Terminated.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  2. AAP Updates Recommendations on Car Seats

    MedlinePlus

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

  3. Agonist-activated ion channels

    PubMed Central

    Colquhoun, David

    2006-01-01

    This paper looks at ion channels as an example of the pharmacologist's stock in trade, the action of an agonist on a receptor to produce a response. Looked at in this way, ion channels have been helpful because they are still the only system which is simple enough for quantitative investigation of transduction mechanisms. A short history is given of attempts to elucidate what happens between the time when agonist first binds, and the time when the channel opens. PMID:16402101

  4. Car design and risk of pedestrian deaths.

    PubMed Central

    Robertson, L S

    1990-01-01

    Fatal pedestrian injury rates by cars with relatively sharp front-corner designs were compared to such rates by cars of similar-size with relatively smooth front-corner designs. The relative risk of death by front-corner impact was 26 percent greater among the sharp-cornered cars. Pedestrian death rates from impact with other points on the cars and insurance claim frequencies among the studied cars were similar between the two sets of cars. PMID:2327543

  5. Pervasive Adaptation in Car Crowds

    NASA Astrophysics Data System (ADS)

    Ferscha, Alois; Riener, Andreas

    Advances in the miniaturization and embedding of electronics for microcomputing, communication and sensor/actuator systems, have fertilized the pervasion of technology into literally everything. Pervasive computing technology is particularly flourishing in the automotive domain, exceling the “smart car”, embodying intelligent control mechanics, intelligent driver assistance, safety and comfort systems, navigation, tolling, fleet management and car-to-car interaction systems, as one of the outstanding success stories of pervasive computing. This paper raises the issue of the socio-technical phenomena emerging from the reciprocal interrelationship between drivers and smart cars, particularly in car crowds. A driver-vehicle co-model (DVC-model) is proposed, expressing the complex interactions between the human driver and the in-car and on-car technologies. Both explicit (steering, shifting, overtaking), as well as implicit (body posture, respiration) interactions are considered, and related to the drivers vital state (attentive, fatigue, distracted, aggressive). DVC-models are considered as building blocks in large scale simulation experiments, aiming to analyze and understand adaptation phenomena rooted in the feed-back loops among individual driver behavior and car crowds.

  6. Safety upgrades plug car leaks

    SciTech Connect

    Not Available

    1993-08-01

    To lessen the chance of a chemical leak occurring during rail transport, some companies are improving tank car sturdiness and safety by adding such features as top-loading valves, on-board monitoring devices, and thicker, more impact-resistant hulls. Results include a dramatic drop in the number of rail incidents and leak tank cars. Chemicals Division of Olin Corporation (Stamford, Connecticut) has assigned its name to a new fleet of chlorine, caustic soda and toluene diisocyanate (TDI) tank cars. Each car carries the company's Care[trademark]Car registered trademark. The upgrade is part of a company-wide quality improvement process started in 1986. The company requires acoustic emissions (AE) testing on all hazardous materials tank cars. If an area has a defect, it expands and makes a slight sound when subjected to stress. In an AE test, cars are subject to simulated bumps and jolts as in rail shipment. Electronic sensors transfer any stress noises onto a computer screen, where an operator can pinpoint the trouble source.

  7. Clinical multiphoton and CARS microscopy

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  8. Agonist ligands mediate the transcriptional response of nuclear receptor heterodimers through distinct stoichiometric assemblies with coactivators.

    PubMed

    Pavlin, Mark Remec; Brunzelle, Joseph S; Fernandez, Elias J

    2014-09-05

    The constitutive androstane (CAR) and retinoid X receptors (RXR) are ligand-mediated transcription factors of the nuclear receptor protein superfamily. Functional CAR:RXR heterodimers recruit coactivator proteins, such as the steroid receptor coactivator-1 (SRC1). Here, we show that agonist ligands can potentiate transactivation through both coactivator binding sites on CAR:RXR, which distinctly bind two SRC1 molecules. We also observe that SRC1 transitions from a structurally plastic to a compact form upon binding CAR:RXR. Using small angle x-ray scattering (SAXS) we show that the CAR(tcp):RXR(9c)·SRC1 complex can encompass two SRC1 molecules compared with the CAR(tcp):RXR·SRC1, which binds only a single SRC1. Moreover, sedimentation coefficients and molecular weights determined by analytical ultracentrifugation confirm the SAXS model. Cell-based transcription assays show that disrupting the SRC1 binding site on RXR alters the transactivation by CAR:RXR. These data suggest a broader role for RXR within heterodimers, whereas offering multiple strategies for the assembly of the transcription complex.

  9. Regulation of Drug Disposition Gene Expression in Pregnant Mice with Car Receptor Activation

    PubMed Central

    Bright, Amanda S.; Herrera-Garcia, Guadalupe; Moscovitz, Jamie E.; You, Dahea; Guo, Grace L.; Aleksunes, Lauren M.

    2016-01-01

    More than half of pregnant women use prescription medications in order to maintain both maternal and fetal health. The constitutive androstane receptor (Car) critically affects the disposition of chemicals by regulating the transcription of genes encoding metabolic enzymes and transporters. However, the effects of Car activation on chemical disposition during pregnancy are unclear. This study aims to determine the degree to which pregnancy alters the expression of drug metabolizing enzymes and transporters in response to the pharmacological activation of Car. To test this, pregnant C57BL/6 mice were administered IP doses of vehicle, or a potent Car agonist, TCPOBOP, on gestation days 14, 15 and 16. Hepatic mRNA and protein expression of Car target genes (phase I, II and transporters) were quantified on gestation day 17. Pregnancy-related changes, such as induction of Cyp2b10, Ugt1a1 and Sult1a1 and repression of Ugt1a6, Gsta1, Gsta2 and Mrp6, were observed. Interestingly, the induction of Cyp2b10, Gsta1, Gsta2 and Mrp2-4 mRNAs by TCPOBOP was attenuated in maternal livers suggesting that Car activation is impeded by the biochemical and/or physiological changes that occur during gestation. Taken together, these findings suggest that pregnancy and pharmacological activation of Car can differentially regulate the expression of drug metabolism and transport genes. PMID:27818994

  10. CAR, driving into the future.

    PubMed

    Swales, Karen; Negishi, Masahiko

    2004-07-01

    The nuclear orphan receptor CAR is active in the absence of ligand with the unique capability to be further regulated by activators. A number of these activators, including phenobarbital, do not directly bind to the receptor. Considered a xenobiotic sensing receptor, CAR transcriptionally modifies the expression of genes involved in the metabolism and elimination of xenobiotics and steroids in response to these compounds and other cellular metabolites. Its hepatic expression pattern endows the liver with the ability to protect against not only exogenous but also endogenous insults. The mechanism of CAR activation is complex, involving translocation from the cytoplasm to the nucleus in the presence of activators, followed by further activation steps in the nucleus. Although this mechanism remains under investigation, we have summarized here the cellular signaling pathways elucidated so far and speculate on the mechanism by which CAR activators regulate gene expression through this network.

  11. Car Safety for Special Children.

    ERIC Educational Resources Information Center

    Holland, Suzanne Hauser

    1983-01-01

    Various car seats, harnesses, and vests that can be used with handicapped children are described. Suggestions are also made for improvment when existing equipment is not appropriate. A list of resources on the topic is also provided. (CL)

  12. Getting More Mileage out of Mousetrap Cars

    ERIC Educational Resources Information Center

    Rutherford, Sandra; Wylo, Bonnie

    2004-01-01

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

  13. Art Cars: Transformations of the Mundane

    ERIC Educational Resources Information Center

    Stienecker, Dawn

    2010-01-01

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

  14. 49 CFR 215.203 - Restricted cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  15. 49 CFR 231.6 - Flat cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  16. 49 CFR 231.6 - Flat cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  17. 49 CFR 215.203 - Restricted cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  18. 49 CFR 1037.2 - Cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 8 2014-10-01 2014-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars....

  19. 49 CFR 215.203 - Restricted cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 49 CFR 215.203 - Restricted cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  1. 49 CFR 174.615 - Cleaning cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  2. 49 CFR 231.6 - Flat cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  3. 49 CFR 1037.2 - Cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 8 2013-10-01 2013-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars....

  4. 49 CFR 231.6 - Flat cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  5. 49 CFR 1037.2 - Cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 8 2012-10-01 2012-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars....

  6. 49 CFR 1037.2 - Cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 8 2011-10-01 2011-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars....

  7. 49 CFR 1037.2 - Cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Cars. 1037.2 Section 1037.2 Transportation Other... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is... railroad-leased cars....

  8. 49 CFR 231.6 - Flat cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  9. 49 CFR 215.203 - Restricted cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  10. Cao-sensing receptor (CaR)-mediated activation of K+ channels is blunted in CaR gene-deficient mouse neurons.

    PubMed

    Vassilev, P M; Ho-Pao, C L; Kanazirska, M P; Ye, C; Hong, K; Seidman, C E; Seidman, J G; Brown, E M

    1997-04-14

    The extracellular Ca2+ (Cao)-sensing receptor (CaR) is expressed in hippocampus and other brain regions, suggesting that it could mediate some of the well recognized but poorly understood direct actions of Cao on neuronal function. This study presents evidence that the CaR is functionally coupled to Ca(2+)-activated K+ channels. The effects of CaR agonists on these channels in neurons from wild type (WT) and CaR-deficient (CaR -/-) mice were compared. Neomycin (100 mM) and elevation of Cao from 0.5 to 3 mM significantly increased the probability of channel opening (Po) in neurons from WT but not in those from CaR -/- mice. Thus the CaR activates neuronal K+ channels and could potentially inhibit neuronal excitability and neurotransmission via membrane repolarization.

  11. Phytosphingosine and C2-phytoceramide induce cell death and inhibit carbachol-stimulated phospholipase D activation in Chinese hamster ovary cells expressing the Caenorhabditis elegans muscarinic acetylcholine receptor.

    PubMed

    Lee, J S; Min, D S; Park, C; Park, C S; Cho, N J

    2001-06-15

    Sphingolipid metabolites, such as sphingosine and ceramide, are known to play important roles in cell proliferation, differentiation and apoptosis, but the physiological roles of phytosphingosine (PHS) and phytoceramide (PHC) are poorly understood. In this study we investigated the effects of PHS, C2-PHC (N-acetylPHS) and C6-PHC (N-hexanoylPHS) on cell growth and intracellular signalling enzymes. Treatment of Chinese hamster ovary (CHO) cells with PHS, C2-PHC or C6-PHC resulted in cell death in a time- and dose-dependent manner. C2-PHC induced internucleosomal DNA fragmentation, whereas PHS or C6-PHC had little if any effect on DNA fragmentation under the same experimental conditions. Both PHS and C2-PHC inhibited carbachol-induced activation of phospholipase D (PLD), but not of phospholipase C (PLC), in CHO cells expressing the Caenorhabditis elegans muscarinic acetylcholine receptor (mAChR). On the other hand, no significant effect of C6-PHC on PLD or PLC was observed. Our results show that PHS and C2-PHC exert strong cytotoxic effects on CHO cells and modulate the mAChR-mediated signal transduction pathway.

  12. Production and secretion of chromogranin A and pancreastatin by the human pancreatic carcinoma cell line QGP-1N on stimulation with carbachol.

    PubMed

    Kitayama, N; Tateishi, K; Funakoshi, A; Kono, A; Matsuoka, Y

    1994-08-04

    Chromogranin A (CGA) is thought to be a precursor of pancreastatin (PST). Carbachol (Cch) stimulated the secretion of CGA and PST from QGP-1N cells derived from a human pancreatic islet cell tumor. Atropine inhibited the secretion of both. Sodium fluoride, phorbol ester, and calcium ionophore also stimulated the secretion of both. Cch (10(-5) M) stimulated inositol 1,4,5-trisphosphate production in QGP-1N cells. Stimulation with Cch increased the total amount of PST in the cells and the medium 1.7-fold and decreased the amount of CGA in the cells and medium. QGP-1N cells were labelled with [35S]methionine, and then CGA and PST in the cells and medium were immunoprecipitated with specific antisera, and separated by electrophoresis in polyacrylamide gel. Stimulation with Cch resulted in an increase in the intensity of PST-immunoreactive bands and a decrease in those of CGA-immunoreactive bands. Cch did not increase the cellular level of CGA messenger RNA. These results suggested that (1) the secretion of CGA and PST from QGP-1N cells is regulated mainly through muscarinic receptors coupled with activation of polyphosphoinositide breakdown by a G protein, with intracellular calcium ion and protein kinase C playing a role in the stimulus-secretion coupling and that (2) Cch may induce the secretion of PST and CGA and processing from CGA to PST.

  13. Dopamine agonist therapy in hyperprolactinemia.

    PubMed

    Webster, J

    1999-12-01

    Introduction of the dopamine agonist bromocriptine heralded a major advance in the management of hyperprolactinemic disorders. Although its side effects of nausea, dizziness and headache and its short elimination half-life are limiting factors, its efficacy established it as a reference compound against the activity of which several dopamine agonists, like pergolide, lysuride, metergoline, terguride and dihydroergocristine, fell by the wayside. More recently, two new agents, cabergoline and quinagolide, have been introduced and appear to offer considerable advantages over bromocriptine. Cabergoline, an ergoline D2 agonist, has a long plasma half-life that enables once- or twice-weekly administration. Quinagolide, in contrast, is a nonergot D2 agonist with an elimination half-life intermediate between those of bromocriptine and cabergoline, allowing the drug to be administered once daily. Comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (prolactin suppression, restoration of gonadal function) and in tolerability. In similar studies, quinagolide appeared to have similar efficacy and superior tolerability to that of bromocriptine. Results of a small crossover study indicate that cabergoline is better tolerated, with a trend toward activity superior to that of quinagolide. In hyperprolactinemic men and in women not seeking to become pregnant, cabergoline may be regarded as the treatment of choice.

  14. Nipecotic acid ethyl ester: a cholinergic agonist that may differentiate muscarinic receptor subtypes

    SciTech Connect

    Zorn, S.H.; Duman, R.S.; Enna, S.J.; Krogsgaard-Larsen, P.; Micheletti, R.; Giraldo, E.; Giachetti, A.

    1986-03-05

    Reports indicate that nipecotic acid ethyl ester (NAEE) displays cholinomimetic properties in vivo. In the present study a series of physiological and biochemical tests were conducted to characterize this action. NAEE had a negative inotropic effect on the guinea pig atrium, and stimulated contraction of the guinea pig ileum and isolated mouse stomach strip at concentrations similar to bethanechol (BCH). The atrial and ilial effects were reversed by atropine. Unlike BCH, NAEE had no effect on basal acid secretion in the isolated mouse stomach at concentrations < 100 ..mu..M. NAEE was more potent than carbachol (CCH) in displacing /sup 3/H-ONB binding from rat brain membranes. The potency of NAEE to inhibit antagonist binding in rat heart membranes was enhanced by Mg/sup + +/ (Hill coefficient < 1.0) and reduced by Gpp(NH)p. Like CCH, NAEE inhibited GTP-stimulated adenylate cyclase in rat brain striatal membranes. As compared to CCH, NAEE had little effect (< 5%) as a stimulator of inositol phosphate (IP) production in rat brain slices. The results indicate that NAEE is a direct-acting muscarinic receptor agonist. Moreover, its differential effects on acid secretion, IP accumulation, and adenylate cyclase suggest that it may be useful for defining cholinergic receptor subclasses.

  15. Bile acid homeostasis controls CAR signaling pathways in mouse testis through FXRalpha.

    PubMed

    Martinot, Emmanuelle; Baptissart, Marine; Véga, Aurélie; Sèdes, Lauriane; Rouaisnel, Betty; Vaz, Fred; Saru, Jean-Paul; de Haze, Angélique; Baron, Silvère; Caira, Françoise; Beaudoin, Claude; Volle, David H

    2017-02-09

    Bile acids (BAs) are molecules with endocrine activities controlling several physiological functions such as immunity, glucose homeostasis, testicular physiology and male fertility. The role of the nuclear BA receptor FXRα in the control of BA homeostasis has been well characterized. The present study shows that testis synthetize BAs. We demonstrate that mice invalidated for the gene encoding FXRα have altered BA homeostasis in both liver and testis. In the absence of FXRα, BA exposure differently alters hepatic and testicular expression of genes involved in BA synthesis. Interestingly, Fxrα-/- males fed a diet supplemented with BAs show alterations of testicular physiology and sperm production. This phenotype was correlated with the altered testicular BA homeostasis and the production of intermediate metabolites of BAs which led to the modulation of CAR signaling pathways within the testis. The role of the CAR signaling pathways within testis was validated using specific CAR agonist (TCPOBOP) and inverse agonist (androstanol) that respectively inhibited or reproduced the phenotype observed in Fxrα-/- males fed BA-diet. These data open interesting perspectives to better define how BA homeostasis contributes to physiological or pathophysiological conditions via the modulation of CAR activity.

  16. Bile acid homeostasis controls CAR signaling pathways in mouse testis through FXRalpha

    PubMed Central

    Martinot, Emmanuelle; Baptissart, Marine; Véga, Aurélie; Sèdes, Lauriane; Rouaisnel, Betty; Vaz, Fred; Saru, Jean-Paul; de Haze, Angélique; Baron, Silvère; Caira, Françoise; Beaudoin, Claude; Volle, David H.

    2017-01-01

    Bile acids (BAs) are molecules with endocrine activities controlling several physiological functions such as immunity, glucose homeostasis, testicular physiology and male fertility. The role of the nuclear BA receptor FXRα in the control of BA homeostasis has been well characterized. The present study shows that testis synthetize BAs. We demonstrate that mice invalidated for the gene encoding FXRα have altered BA homeostasis in both liver and testis. In the absence of FXRα, BA exposure differently alters hepatic and testicular expression of genes involved in BA synthesis. Interestingly, Fxrα-/- males fed a diet supplemented with BAs show alterations of testicular physiology and sperm production. This phenotype was correlated with the altered testicular BA homeostasis and the production of intermediate metabolites of BAs which led to the modulation of CAR signaling pathways within the testis. The role of the CAR signaling pathways within testis was validated using specific CAR agonist (TCPOBOP) and inverse agonist (androstanol) that respectively inhibited or reproduced the phenotype observed in Fxrα-/- males fed BA-diet. These data open interesting perspectives to better define how BA homeostasis contributes to physiological or pathophysiological conditions via the modulation of CAR activity. PMID:28181583

  17. Cortisol awakening response (CAR)'s flexibility leads to larger and more consistent associations with psychological factors than CAR magnitude.

    PubMed

    Mikolajczak, Moïra; Quoidbach, Jordi; Vanootighem, Valentine; Lambert, Florence; Lahaye, Magali; Fillée, Catherine; de Timary, Philippe

    2010-06-01

    The cortisol awakening response (CAR) is increasingly recognized as a potential biological marker of psychological and physical health status. Yet, the CAR literature is replete with contradictory results: both supposedly protective and vulnerability psychosocial factors have been associated with both increased and decreased CAR. In this study, we tested the hypothesis that the CAR flexibility would be a better indicator of psychological status than CAR magnitude. Forty-two men measures of happiness, perceived stress and neuroticism, and took saliva samples immediately on awakening, then at 15, 30, 45 and 60min post-awakening on three study days (i.e., Sunday, Monday and Tuesday). When considering the CAR magnitude, our effects perfectly reflect the inconsistencies previously observed in the literature (i.e., the main effects of the psychological predictors are not consistent with each other, and the effect of one predictor on a given day contradicts the effect of the same predictor on another day). However, considering the CAR flexibility leads to a fully consistent pattern: protective factors (i.e., high happiness, low stress, low neurotiscim) are associated with a flexible CAR (i.e., lower CAR during weekends compared to workdays) whereas vulnerability factors (i.e., low happiness, high stress, high neurotiscim) are associated with a stiff CAR (i.e., same magnitude during weekends and workdays). We conclude that considering the CAR flexibility (e.g., between weekends and workdays) rather than the traditional CAR magnitude might be a way to understand the apparent conflicts in the CAR literature.

  18. The specificity of some agonists and antagonists for nicotine-sensitive receptors in ganglia

    PubMed Central

    Barlow, R.B.; Bowman, Frances; Ison, R.R.; McQueen, D.S.

    1974-01-01

    1 The guinea-pig isolated ileum has been used to estimate the ability of substituted phenylalkylonium salts (related to nicotine) to stimulate or block receptors in ganglia. The effects of hexamethonium were used to indicate which were the most specific ganglion stimulants; these were tested on the blood-pressure of pithed rats and for neuromuscular blocking activity on the rat diaphragm preparation. 2 m-Hydroxyphenylpropyltrimethylammonium and 3,4-dihydroxyphenethyltrimethylammonium (coryneine, `quaternary dopamine') were the most active and specific ganglion stimulants but their usefulness in vivo may be limited by their neuromuscular blocking activity. The analogous tertiary compounds are being investigated. 3 The affinities of substances which were blocking agents at ganglionic receptors were measured on the isolated ileum with m-hydroxyphenylpropyltrimethylammonium as agonist. The affinities of selected compounds for postganglionic receptors were measured in experiments on the ileum in the presence of hexamethonium and with carbachol as agonist. Some of the compounds were tested for neuromuscular blocking activity on the rat diaphragm. 4 Phenylbutyldiethylamine had ganglion-blocking activity greater than pempidine and little postganglionic blocking or neuromuscular blocking activity. Its triethylammonium analogue had higher ganglion-blocking activity but had appreciable neuromuscular blocking activity. 5 The aromatic ring system is not essential either for activity or affinity and the effects of substituents are not related to their effects on electron distribution. Stimulant activity is enhanced only by hydroxyl or amino groups in suitable positions; it is not improved by the presence of rigid features (double or triple bonds or a cyclopropane ring) in the side chain. Affinity is slightly increased by chloro or bromo groups in suitable positions but the unsubstituted compounds are among those with the highest affinity. Substituents have similar effects on

  19. The role of TRPP2 in agonist-induced gallbladder smooth muscle contraction.

    PubMed

    Zhong, Xingguo; Fu, Jie; Song, Kai; Xue, Nairui; Gong, Renhua; Sun, Dengqun; Luo, Huilai; He, Wenzhu; Pan, Xiang; Shen, Bing; Du, Juan

    2016-04-01

    TRPP2 channel protein belongs to the superfamily of transient receptor potential (TRP) channels and is widely expressed in various tissues, including smooth muscle in digestive gut. Accumulating evidence has demonstrated that TRPP2 can mediate Ca(2+) release from Ca(2+) stores. However, the functional role of TRPP2 in gallbladder smooth muscle contraction still remains unclear. In this study, we used Ca(2+) imaging and tension measurements to test agonist-induced intracellular Ca(2+) concentration increase and smooth muscle contraction of guinea pig gallbladder, respectively. When TRPP2 protein was knocked down in gallbladder muscle strips from guinea pig, carbachol (CCh)-evoked Ca(2+) release and extracellular Ca(2+) influx were reduced significantly, and gallbladder contractions induced by endothelin 1 and cholecystokinin were suppressed markedly as well. CCh-induced gallbladder contraction was markedly suppressed by pretreatment with U73122, which inhibits phospholipase C to terminate inositol 1,4,5-trisphosphate receptor (IP3) production, and 2-aminoethoxydiphenyl borate (2APB), which inhibits IP3 recepor (IP3R) to abolish IP3R-mediated Ca(2+) release. To confirm the role of Ca(2+) release in CCh-induced gallbladder contraction, we used thapsigargin (TG)-to deplete Ca(2+) stores via inhibiting sarco/endoplasmic reticulum Ca(2+)-ATPase and eliminate the role of store-operated Ca(2+) entry on the CCh-induced gallbladder contraction. Preincubation with 2 μmol L(-1) TG significantly decreased the CCh-induced gallbladder contraction. In addition, pretreatments with U73122, 2APB or TG abolished the difference of the CCh-induced gallbladder contraction between TRPP2 knockdown and control groups. We conclude that TRPP2 mediates Ca(2+) release from intracellular Ca(2+) stores, and has an essential role in agonist-induced gallbladder muscle contraction.

  20. Symmetry in the Car Park

    ERIC Educational Resources Information Center

    Hancock, Karen

    2007-01-01

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

  1. Automated Car Park Management System

    NASA Astrophysics Data System (ADS)

    Fabros, J. P.; Tabañag, D.; Espra, A.; Gerasta, O. J.

    2015-06-01

    This study aims to develop a prototype for an Automated Car Park Management System that will increase the quality of service of parking lots through the integration of a smart system that assists motorist in finding vacant parking lot. The research was based on implementing an operating system and a monitoring system for parking system without the use of manpower. This will include Parking Guidance and Information System concept which will efficiently assist motorists and ensures the safety of the vehicles and the valuables inside the vehicle. For monitoring, Optical Character Recognition was employed to monitor and put into list all the cars entering the parking area. All parking events in this system are visible via MATLAB GUI which contain time-in, time-out, time consumed information and also the lot number where the car parks. To put into reality, this system has a payment method, and it comes via a coin slot operation to control the exit gate. The Automated Car Park Management System was successfully built by utilizing microcontrollers specifically one PIC18f4550 and two PIC16F84s and one PIC16F628A.

  2. Car Hits Boy on Bicycle

    ERIC Educational Resources Information Center

    Ruiz, Michael J.

    2005-01-01

    In this article we present the fascinating reconstruction of an accident where a car hit a boy riding his bicycle. The boy dramatically flew several metres through the air after the collision and was injured, but made a swift and complete recovery from the accident with no long-term after-effects. Students are challenged to determine the speed of…

  3. Friction in a Moving Car

    ERIC Educational Resources Information Center

    Goldberg, Fred M.

    1975-01-01

    Describes an out-of-doors, partially unstructured experiment to determine the coefficient of friction for a moving car. Presents the equation which relates the coefficient of friction to initial velocity, distance, and time and gives sample computed values as a function of initial speed and tire pressure. (GS)

  4. Restoring a Classic Electric Car

    ERIC Educational Resources Information Center

    Kraft, Thomas E.

    2012-01-01

    One hundred years ago, automobiles were powered by steam, electricity, or internal combustion. Female drivers favored electric cars because, unlike early internal-combustion vehicles, they did not require a crank for starting. Nonetheless, internal-combustion vehicles came to dominate the industry and it's only in recent years that the electrics…

  5. The Speeding Car Design Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2009-01-01

    All too often, one reads about high-speed police chases in pursuit of stolen cars that result in death and injury to people and innocent bystanders. Isn't there another way to accomplish the apprehension of the thieves that does not put people at such great risk? This article presents a classroom challenge to use technology to remotely shutdown…

  6. Coke quench car emission control system

    SciTech Connect

    Baum, J.P.

    1983-07-19

    A coke quench car emission control system includes a coke car and a filter car connected in tandem for joint movement on rails disposed adjacent a coke oven. A hood and recuperator are mounted on a third car disposed on auxiliary rails which extend longitudinally along the upper portions of both the quench car and the filter car and in end-wise alignment. The hood is adapted to be coupled to the coke oven for receiving coke during a pushing operation. The recuperation has an inlet coupled to the hood for receiving emissions and withdrawing heat therefrom. The recuperator also has an outlet which is disposed adjacent the inlet of a filter system mounted on the filter car, when the third car is positioned atop the quench car. The third car is sized so that it can be moved on the auxiliary rails from a position atop the quench car to a position atop the filter car whereby the quench car can be exposed for a quenching operation.

  7. Synergistic acceleration of thyroid hormone degradation by phenobarbital and the PPAR{alpha} agonist WY14643 in rat hepatocytes

    SciTech Connect

    Wieneke, N.; Neuschaefer-Rube, F.; Bode, L.M.; Kuna, M.; Andres, J.; Carnevali, L.C.; Hirsch-Ernst, K.I.; Pueschel, G.P.

    2009-10-01

    Energy balance is maintained by controlling both energy intake and energy expenditure. Thyroid hormones play a crucial role in regulating energy expenditure. Their levels are adjusted by a tight feedback-controlled regulation of thyroid hormone production/incretion and by their hepatic metabolism. Thyroid hormone degradation has previously been shown to be enhanced by treatment with phenobarbital or other antiepileptic drugs due to a CAR-dependent induction of phase II enzymes of xenobiotic metabolism. We have recently shown, that PPAR{alpha} agonists synergize with phenobarbital to induce another prototypical CAR target gene, CYP2B1. Therefore, it was tested whether a PPAR{alpha} agonist could enhance the phenobarbital-dependent acceleration of thyroid hormone elimination. In primary cultures of rat hepatocytes the apparent half-life of T3 was reduced after induction with a combination of phenobarbital and the PPAR{alpha} agonist WY14643 to a larger extent than after induction with either compound alone. The synergistic reduction of the half-life could be attributed to a synergistic induction of CAR and the CAR target genes that code for enzymes and transporters involved in the hepatic elimination of T3, such as OATP1A1, OATP1A3, UGT1A3 and UGT1A10. The PPAR{alpha}-dependent CAR induction and the subsequent induction of T3-eliminating enzymes might be of physiological significance for the fasting-induced reduction in energy expenditure by fatty acids as natural PPAR{alpha} ligands. The synergism of the PPAR{alpha} agonist WY14643 and phenobarbital in inducing thyroid hormone breakdown might serve as a paradigm for the synergistic disruption of endocrine control by other combinations of xenobiotics.

  8. Novel diazabicycloalkane delta opioid agonists.

    PubMed

    Loriga, Giovanni; Lazzari, Paolo; Manca, Ilaria; Ruiu, Stefania; Falzoi, Matteo; Murineddu, Gabriele; Bottazzi, Mirko Emilio Heiner; Pinna, Giovanni; Pinna, Gérard Aimè

    2015-09-01

    Here we report the investigation of diazabicycloalkane cores as potential new scaffolds for the development of novel analogues of the previously reported diazatricyclodecane selective delta (δ) opioid agonists, as conformationally constrained homologues of the reference δ agonist (+)-4-[(αR)-α((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80). In particular, we have simplified the diazatricyclodecane motif of δ opioid agonist prototype 1a with bridged bicyclic cores. 3,6-diazabicyclo[3.1.1]heptane, 3,8-diazabicyclo[3.2.1]octane, 3,9-diazabicyclo[3.3.1]nonane, 3,9-diazabicyclo[4.2.1]nonane, and 3,10-diazabicyclo[4.3.1]decane were adopted as core motifs of the novel derivatives. The compounds were synthesized and biologically assayed as racemic (3-5) or diastereoisomeric (6,7) mixtures. All the novel compounds 3-7 showed δ agonism behaviour and remarkable affinity to δ receptors. Amongst the novel derivatives, 3,8-diazabicyclo[3.2.1]octane based compound 4 evidenced improved δ affinity and selectivity relative to SNC80.

  9. Inflation Rates, Car Devaluation, and Chemical Kinetics

    NASA Astrophysics Data System (ADS)

    Pogliani, Lionello; Berberan-Santos, Màrio N.

    1996-10-01

    The inflation rate problem of a modern economy shows quite interesting similarities with chemical kinetics and especially with first-order chemical reactions. In fact, capital devaluation during periods of rather low inflation rates or inflation measured over short periods shows a dynamics formally similar to that followed by first-order chemical reactions and they can thus be treated by the aid of the same mathematical formalism. Deviations from this similarity occurs for higher inflation rates. The dynamics of price devaluation for two different types of car, a compact car and a luxury car, has been followed for seven years long and it has been established that car devaluation is a process that is formally similar to a zeroth-order chemical kinetic process disregarding the type of car, if car devaluation is much faster than money devaluation. In fact, expensive cars devaluate with a faster rate than inexpensive cars.

  10. A Demonstration of Car Braking Instabilities.

    ERIC Educational Resources Information Center

    Irwin, Jack; Swinson, Derek

    1990-01-01

    Detailed are the construction of a demonstration car, apparatus and procedures used in the demonstration, and the analysis of the effects of car braking. The cases of rear-wheel and front-wheel braking are considered. (CW)

  11. Solar-powered car. Final report

    SciTech Connect

    Plank, D.

    1982-03-30

    The work reported was to modify a commercially available electric vehicle to use power generated by solar cells. Besides the technical and financial aspects of constructing the car, media publicity and public showings of the car are discussed. (LEW)

  12. Pharmacological Profiles of Alpha 2 Adrenergic Receptor Agonists Identified Using Genetically Altered Mice and Isobolographic Analysis

    PubMed Central

    Fairbanks, Carolyn A.; Stone, Laura S.; Wilcox, George L.

    2009-01-01

    Endogenous, descending noradrenergic fibers convey powerful analgesic control over spinal afferent circuitry mediating the rostrad transmission of pain signals. These fibers target alpha 2 adrenergic receptors (α2ARs) on both primary afferent terminals and secondary neurons, and their activation mediates substantial inhibitory control over this transmission, rivaling that of opioid receptors which share similar a similar pattern of distribution. The terminals of primary afferent nociceptive neurons and secondary spinal dorsal horn neurons express α2AAR and α2CAR subtypes, respectively. Spinal delivery of these agents serves to reduce their side effects, which are mediated largely at supraspinal sites, by concentrating the drugs at the spinal level. Targeting these spinal α2ARs with one of five selective therapeutic agonists, clonidine, dexmedetomidine, brimonidine, ST91 and moxonidine, produces significant antinociception that can work in concert with opioid agonists to yield synergistic antinociception. Application of several genetically altered mouse lines had facilitated identification of the primary receptor subtypes that likely mediate the antinociceptive effects of these agents. This review provides first an anatomical description of the localization of the three subtypes in the central nervous system, second a detailed account of the pharmacological history of each of these six primary agonists, and finally a comprehensive report of the specific interactions of other GPCR agonists with each of the six principal α2AR agonists featured. PMID:19393691

  13. Shuttle-Car System for Continuous Mining

    NASA Technical Reports Server (NTRS)

    Collins, E. R., Jr.

    1984-01-01

    Buffer storage catches coal production between loadings. Telescoping reservoir filled continuously. With tailgate down, shuttle car slides into place along sides and bottom of reservoir. Reservoir retracts along inside of car and out through tailgate, leaving coal behind in car. System not restricted to coal mining and may prove economical for hauling other solid materials.

  14. Determining the Air Drag on a Car.

    ERIC Educational Resources Information Center

    Farr, John E.

    1983-01-01

    Students' cars and wristwatches are used as "apparatus" to introduce and demonstrate Newton's second law of motion. Forces acting on cars are discussed and typical student data (for different makes of cars) are provided. Data could also be used in discussions of work, horsepower, efficiency, and energy cost. (JN)

  15. Video monitoring system for car seat

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

  16. Car Ownership and Welfare-to-Work

    ERIC Educational Resources Information Center

    Ong, Paul M.

    2002-01-01

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

  17. 49 CFR 174.57 - Cleaning cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  18. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  19. 49 CFR 174.110 - Car magazine.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 49 CFR 174.110 - Car magazine.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  1. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  2. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  3. 49 CFR 174.110 - Car magazine.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  4. 49 CFR 174.57 - Cleaning cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  5. 49 CFR 174.57 - Cleaning cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  6. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  7. 49 CFR 174.57 - Cleaning cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  8. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  9. 49 CFR 174.110 - Car magazine.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  10. 49 CFR 174.57 - Cleaning cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  11. 49 CFR 174.110 - Car magazine.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  12. Regulation of membrane cholecystokinin-2 receptor by agonists enables classification of partial agonists as biased agonists.

    PubMed

    Magnan, Rémi; Masri, Bernard; Escrieut, Chantal; Foucaud, Magali; Cordelier, Pierre; Fourmy, Daniel

    2011-02-25

    Given the importance of G-protein-coupled receptors as pharmacological targets in medicine, efforts directed at understanding the molecular mechanism by which pharmacological compounds regulate their presence at the cell surface is of paramount importance. In this context, using confocal microscopy and bioluminescence resonance energy transfer, we have investigated internalization and intracellular trafficking of the cholecystokinin-2 receptor (CCK2R) in response to both natural and synthetic ligands with different pharmacological features. We found that CCK and gastrin, which are full agonists on CCK2R-induced inositol phosphate production, rapidly and abundantly stimulate internalization. Internalized CCK2R did not rapidly recycle to plasma membrane but instead was directed to late endosomes/lysosomes. CCK2R endocytosis involves clathrin-coated pits and dynamin and high affinity and prolonged binding of β-arrestin1 or -2. Partial agonists and antagonists on CCK2R-induced inositol phosphate formation and ERK1/2 phosphorylation did not stimulate CCK2R internalization or β-arrestin recruitment to the CCK2R but blocked full agonist-induced internalization and β-arrestin recruitment. The extreme C-terminal region of the CCK2R (and more precisely phosphorylatable residues Ser(437)-Xaa(438)-Thr(439)-Thr(440)-Xaa(441)-Ser(442)-Thr(443)) were critical for β-arrestin recruitment. However, this region and β-arrestins were dispensable for CCK2R internalization. In conclusion, this study allowed us to classify the human CCK2R as a member of class B G-protein-coupled receptors with regard to its endocytosis features and identified biased agonists of the CCK2R. These new important insights will allow us to investigate the role of internalized CCK2R·β-arrestin complexes in cancers expressing this receptor and to develop new diagnosis and therapeutic strategies targeting this receptor.

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

    PubMed

    Whitworth, D E; Hodgson, D A

    2001-11-01

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

  14. [Vision and car driving ability].

    PubMed

    Wilhelm, Helmut

    2011-05-01

    Visual functions relevant for car driving are: Visual acuity, contrast and twilight vision, visual field, ocular motility and alignment and colour vision. Generally accepted and standardized tests are available for visual acuity and visual field. Maximum permissible values have been defined arbitrarily and are hardly supported by studies. European standards have been published comprising also contrast and twilight vision. When examining driving ability progressive and treatable ocular disorders such as cataract and glaucoma have to be considered.

  15. CAR-T cells are serial killers.

    PubMed

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

    2015-12-01

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

  16. S-branch CARS applicability to thermometry

    SciTech Connect

    Akihama, K.; Asai, T. )

    1990-07-20

    The pressure and temperature dependence of background-free {ital S}-branch CARS spectra of N{sub 2} are investigated in the temperature range of 300--700 K for pressures of 1--20 atm. Collisional narrowing for {ital S}-branch CARS spectra is proved to be negligible. Individual {ital S}-branch lines are clearly resolved in the entire range, enabling unequivocal determination of temperatures by their peak ratios. Advantages and disadvantages of {ital S}-branch CARS thermometry are discussed on the basis of experimental results. The dual narrowband Stokes CARS technique is also discussed as a practical method of {ital S}-branch CARS thermometry.

  17. S-branch CARS applicability to thermometry.

    PubMed

    Akihama, K; Asai, T

    1990-07-20

    The pressure and temperature dependence of background-free S-branch CARS spectra of N(2) are investigated in the temperature range of 300-700 K for pressures of 1-20 atm. Collisional narrowing for S-branch CARS spectra is proved to be negligible. Individual S-branch lines are clearly resolved in the entire range, enabling unequivocal determination of temperatures by their peak ratios. Advantages and disadvantages of S-branch CARS thermometry are discussed on the basis of experimental results. The dual narrowband Stokes CARS technique is also discussed as a practical method of S-branch CARS thermometry.

  18. Kappa Opioid Receptor Agonist and Brain Ischemia

    PubMed Central

    Chunhua, Chen; Chunhua, Xi; Megumi, Sugita; Renyu, Liu

    2014-01-01

    Opioid receptors, especially Kappa opioid receptor (KOR) play an important role in the pathophysiological process of cerebral ischemia reperfusion injury. Previously accepted KOR agonists activity has included anti-nociception, cardiovascular, anti-pruritic, diuretic, and antitussive effects, while compelling evidence from various ischemic animal models indicate that KOR agonist have neuroprotective effects through various mechanisms. In this review, we aimed to demonstrate the property of KOR agonist and its role in global and focal cerebral ischemia. Based on current preclinical research, the KOR agonists may be useful as a neuroprotective agent. The recent discovery of salvinorin A, highly selective non-opioid KOR agonist, offers a new tool to study the role of KOR in brain HI injury and the protective effects of KOR agonist. The unique pharmacological profile of salvinorin A along with the long history of human usage provides its high candidacy as a potential alternative medication for brain HI injury. PMID:25574482

  19. 49 CFR 232.305 - Single car air brake tests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 49 CFR 232.305 - Single car air brake tests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  1. 49 CFR 232.305 - Single car air brake tests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  2. 49 CFR 215.121 - Defective car body.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  3. 49 CFR 215.121 - Defective car body.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  4. 49 CFR 232.305 - Single car air brake tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Single car air brake tests. 232.305 Section 232... car air brake tests. (a) Single car air brake tests shall be performed by a qualified person in... single car air brake test on a car when: (1) A car has its brakes cut-out or inoperative when...

  5. 49 CFR 215.121 - Defective car body.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  6. 49 CFR 215.121 - Defective car body.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  7. 49 CFR 232.305 - Single car air brake tests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Single car air brake tests. 232.305 Section 232... car air brake tests. (a) Single car air brake tests shall be performed by a qualified person in... single car air brake test on a car when: (1) A car has its brakes cut-out or inoperative when...

  8. 49 CFR 215.121 - Defective car body.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  9. Inositol 1,3,4,5-tetrakisphosphate and not phosphatidylinositol 3,4-bisphosphate is the probable precursor of inositol 1,3,4-trisphosphate in agonist-stimulated parotid gland.

    PubMed Central

    Downes, C P; Hawkins, P T; Irvine, R F

    1986-01-01

    When [3H]inositol-prelabelled rat parotid-gland slices were stimulated with carbachol, noradrenaline or Substance P, the major inositol trisphosphate produced with prolonged exposure to agonists was, in each case, inositol 1,3,4-trisphosphate. Much lower amounts of radioactivity were present in the inositol 1,4,5-trisphosphate fraction separated by anion-exchange h.p.l.c. Analysis of the inositol trisphosphate head group of phosphatidylinositol bisphosphate in [32P]Pi-labelled parotid glands showed the presence of phosphatidylinositol 4,5-bisphosphate, but no detectable phosphatidylinositol 3,4-bisphosphate. Carbachol-stimulated [3H]inositol-labelled parotid glands contained an inositol polyphosphate with the chromatographic properties and electrophoretic mobility of an inositol tetrakisphosphate, the probable structure of which was determined to be inositol 1,3,4,5-tetrakisphosphate. Since an enzyme in erythrocyte membranes is capable of degrading this tetrakisphosphate to inositol 1,3,4-trisphosphate, it is suggested to be the precursor of inositol 1,3,4-trisphosphate in parotid glands. PMID:2432882

  10. PLC-γ directly binds activated c-Src, which is necessary for carbachol-mediated inhibition of NHE3 activity in Caco-2/BBe cells.

    PubMed

    Zachos, Nicholas C; Lee, Luke J; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark

    2013-08-01

    Elevated levels of intracellular Ca(2+) ([Ca(2+)]i) inhibit Na(+)/H(+) exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca(2+)]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca(2+) signaling proteins necessary for regulation of NHE3 activity. [Ca(2+)]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca(2+)]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y(416) phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca(2+)]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca(2+)]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca(2+)]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3.

  11. An improved car-following model considering the immediately ahead car's velocity difference

    NASA Astrophysics Data System (ADS)

    Yu, Shaowei; Zhao, Xiangmo; Xu, Zhigang; Shi, Zhongke

    2016-11-01

    The field car-following data at a signalized intersection of Jinan in China are collected for data mining. An improved car-following model considering the immediately ahead car's velocity difference on a single-lane road was proposed, calibrated and verified based on full velocity difference model. The results of some numerical simulations indicate that the immediately ahead car's velocity difference has significant effects on the following car's motion, that the improved car-following model fits the measured data well and can qualitatively describe the impacts of the immediately ahead car's velocity difference on traffic flow, and that modeling the car-following behavior considering the immediately ahead car's velocity difference can improve the stability of the simulated traffic flow.

  12. Dopamine receptor agonists, partial agonists and psychostimulant addiction.

    PubMed

    Pulvirenti, L; Koob, G F

    1994-10-01

    Despite the epidemic growth of psychostimulant addiction over the past years, few pharmacological means of intervention are available to date for clinical treatment. This is of importance since the withdrawal syndrome that follows abstinence from drugs such as cocaine and the amphetamines is characterized, among other symptoms, by intense craving for the abused drug, and this is considered a critical factor leading into relapse of drug use. In this article, Luigi Pulvirenti and George Koob focus on the modulatory role shown by drugs acting at the dopamine receptor on the various phases of psychostimulant dependence in preclinical models and in human studies, and suggest that a class of compounds with partial agonist properties at the dopamine receptor may have therapeutic potential.

  13. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s disease

    PubMed Central

    Fisher, Abraham; Bezprozvanny, Ilya; Wu, Lili; Ryskamp, Daniel A.; Bar-Ner, Nira; Natan, Niva; Brandeis, Rachel; Elkon, Hanoch; Nahum, Victoria; Gershonov, Eitan; LaFerla, Frank M.; Medeiros, Rodrigo

    2015-01-01

    We previously developed orthosteric M1 muscarinic agonists (e.g., AF102B, AF267B, and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (phopho-ERK1/2, phospho-CREB). AF710B (1–30 µg/kg, po) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its anti-amnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice AF710B (10 µg/kg, ip/daily/2 months) – i) mitigated cognitive impairments in Morris water maze; ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1, M1 muscarinic (orthosteric, allosteric or bi-topic) or σ1/muscarinic agonists. These results highlight AF710B as a potential treatment for AD (e.g., improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies. PMID:26606130

  14. Beta-agonists and animal welfare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  15. Research and Development Trends of Car Networking

    NASA Astrophysics Data System (ADS)

    He, Wei; Li, Zhixiong; Xie, Guotao

    With the rapid development of the world economy, road transport has become increasingly busy. An unexpected incident would cause serious traffic disaster due to traffic accidents. To solve this problem, the intelligent transportation system (ITS), which is important for the health developments of the city transportation, has become a hot topic. The car networking provides a new way for intelligent transportation system. It can ensure intelligent control and monitoring of urban road with high performance. This paper described the concept of car networking and related technology both in oversea and domestic. The importance of car networking to achieve vehicle and details of the car networking related technologies were illustrated firstly. Then, attentions focus on the research nodus of the car networking. Lastly, the development trend of car networking research was discussed.

  16. Small molecule fluoride toxicity agonists.

    PubMed

    Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

    2015-04-23

    Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride.

  17. Small Molecule Fluoride Toxicity Agonists

    PubMed Central

    Nelson1, James W.; Plummer, Mark S.; Blount, Kenneth F.; Ames, Tyler D.; Breaker, Ronald R.

    2015-01-01

    SUMMARY Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch-reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. PMID:25910244

  18. Collisions with passenger cars and moose, Sweden.

    PubMed Central

    Björnstig, U; Eriksson, A; Thorson, J; Bylund, P O

    1986-01-01

    The number of collisions between motor vehicles and moose is increasing in many countries. Collisions with large, high animals such as moose cause typical rear- and downward deformation of the windshield pillars and front roof, most pronounced for small passenger cars; the injury risk increases with the deformation of the car. A strengthening of the windshield pillars and front roof and the use of antilacerative windshields would reduce the injury risk to car occupants. PMID:3953927

  19. Heterodyne effect in Hybrid CARS

    NASA Astrophysics Data System (ADS)

    Wang, Xi; Zhang, Aihua; Zhi, Miaochan; Sokolov, Alexei; Welch, George; Scully, Marlan

    2009-10-01

    We study the interaction between the resonant Raman signal and non-Raman field, either the concomitant nonresonant four-wave-mixing (FWM) background or an applied external field, in our recently developed scheme of coherent Anti-Stokes Raman scattering, a hybrid CARS. Our technique combines instantaneous coherent excitation of several characteristic molecular vibrations with subsequent probing of these vibrations by an optimally shaped, time-delayed, narrowband laser pulse. This pulse configuration mitigates the non-resonant FWM background while maximizing the Raman-resonant signal, and allows rapid and highly specific detection even in the presence of multiple scattering. We apply this method to non-invasive monitoring of blood glucose levels. Under certain conditions we find that the measured signal is linearly proportional to the glucose concentration due to optical interference with the residual background light, which allows reliable detection of spectral signatures down to medically-relevant glucose levels. We also study the interference between the CARS field and an external field (the local oscillator) by controlling their relative phase and amplitude. This control allows direct observation of the real and imaginary components of the third-order nonlinear susceptibility (χ^(3)) of the sample. We demonstrate that the heterodyne method can be used to amplify the signal and thus increase detection sensitivity.

  20. Stock-car racing makes intuitive physicists

    NASA Astrophysics Data System (ADS)

    Gwynne, Peter

    2008-03-01

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

  1. CARS thermometry in high temperature gradients

    NASA Astrophysics Data System (ADS)

    Zhu, J. Y.; Dunn-Rankin, D.

    1993-01-01

    CARS is an effective non-intrusive technique for measuring gas temperature in combustion environments. In regions of high temperature gradient, however, the CARS signal is complicated by contributions from gas at different temperature. This paper examines theoretically the uncertainty associated with CARS thermometry in steep temperature gradients. In addition, the work compares the temperature predicted from CARS with the adiabatic mixed temperature of the gas resident in the measurement volume. This comparison helps indicate the maximum sample volume size allowed for accurate temperature measurements.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    NASA Astrophysics Data System (ADS)

    Yu, Shao-Wei; Shi, Zhong-Ke

    2015-01-01

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

  4. Car driver casualty rates in Great Britain by type of car.

    PubMed

    Broughton, Jeremy

    2008-07-01

    Since 1989, the British STATS19 national road accident reporting system has included the Vehicle Registration Mark (VRM). This allows the basic vehicle record to be augmented with details such as the date of first registration and codes that specify the vehicle's make and model. In order to examine the influence of car type upon the driver casualty rate, this paper groups car models into six types, ranging from 'Minis and Superminis' to '4x4s and people carriers (pc)'. Exploratory analyses of data from accidents that occurred between 2001 and 2005 show that the driver casualty rate falls markedly with size of car. In car-car collisions, the rate also rises markedly with the size of the other car. The car's year of first registration also influences the casualty rate, and represents the influence of changes in the characteristics of new cars. Statistical models are fitted to identify the separate influences on a driver's risk of injury in a car-car collision of the type and registration year of the driver's car and the type and registration year of the other car in the collision. The analysis is extended to include collisions with other vehicles such as lorries and buses.

  5. Functional crosstalk of CAR-LXR and ROR-LXR in drug metabolism and lipid metabolism.

    PubMed

    Xiao, Lei; Xie, Xinni; Zhai, Yonggong

    2010-10-30

    Nuclear receptor crosstalk represents an important mechanism to expand the functions of individual receptors. The liver X receptors (LXR, NR1H2/3), both the α and β isoforms, are nuclear receptors that can be activated by the endogenous oxysterols and other synthetic agonists. LXRs function as cholesterol sensors, which protect mammals from cholesterol overload. LXRs have been shown to regulate the expression of a battery of metabolic genes, especially those involved in lipid metabolism. LXRs have recently been suggested to play a novel role in the regulation of drug metabolism. The constitutive androstane receptor (CAR, NR1I3) is a xenobiotic receptor that regulates the expression of drug-metabolizing enzymes and transporters. Disruption of CAR alters sensitivity to toxins, increasing or decreasing it depending on the compounds. More recently, additional roles for CAR have been discovered. These include the involvement of CAR in lipid metabolism. Mechanistically, CAR forms an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the LXRs, in exerting its effect on lipid metabolism. Retinoid-related orphan receptors (RORs, NR1F1/2/3) have three isoforms, α, β and γ. Recent reports have shown that loss of RORα and/or RORγ can positively or negatively influence the expression of multiple drug-metabolizing enzymes and transporters in the liver. The effects of RORs on expression of drug-metabolizing enzymes were reasoned to be, at least in part, due to the crosstalk with LXR. This review focuses on the CAR-LXR and ROR-LXR crosstalk, and the implications of this crosstalk in drug metabolism and lipid metabolism.

  6. Agonist activation of cytosolic Ca2+ in subfornical organ cells projecting to the supraoptic nucleus

    NASA Technical Reports Server (NTRS)

    Johnson, R. F.; Beltz, T. G.; Sharma, R. V.; Xu, Z.; Bhatty, R. A.; Johnson, A. K.

    2001-01-01

    The subfornical organ (SFO) is sensitive to both ANG II and ACh, and local application of these agents produces dipsogenic responses and vasopressin release. The present study examined the effects of cholinergic drugs, ANG II, and increased extracellular osmolarity on dissociated, cultured cells of the SFO that were retrogradely labeled from the supraoptic nucleus. The effects were measured as changes in cytosolic calcium in fura 2-loaded cells by using a calcium imaging system. Both ACh and carbachol increased intracellular ionic calcium concentration ([Ca2+]i). However, in contrast to the effects of muscarinic receptor agonists on SFO neurons, manipulation of the extracellular osmolality produced no effects, and application of ANG II produced only moderate effects on [Ca2+]i in a few retrogradely labeled cells. The cholinergic effects on [Ca2+]i could be blocked with the muscarinic receptor antagonist atropine and with the more selective muscarinic receptor antagonists pirenzepine and 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP). In addition, the calcium in the extracellular fluid was required for the cholinergic-induced increase in [Ca2+]i. These findings indicate that ACh acts to induce a functional cellular response in SFO neurons through action on a muscarinic receptor, probably of the M1 subtype and that the increase of [Ca2+]i, at least initially, requires the entry of extracellular Ca2+. Also, consistent with a functional role of M1 receptors in the SFO are the results of immunohistochemical preparations demonstrating M1 muscarinic receptor-like protein present within this forebrain circumventricular organ.

  7. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  8. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  9. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  10. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  11. 49 CFR 238.311 - Single car test.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  12. 49 CFR 180.507 - Qualification of tank cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  13. 49 CFR 238.311 - Single car test.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  14. 49 CFR 180.507 - Qualification of tank cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  15. 49 CFR 180.507 - Qualification of tank cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  16. 49 CFR 238.311 - Single car test.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  17. 49 CFR 238.311 - Single car test.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  18. 49 CFR 180.507 - Qualification of tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  19. 49 CFR 180.507 - Qualification of tank cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 49 CFR 238.311 - Single car test.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  1. Investigation of the mechanism of agonist and inverse agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Lin, Hong; Strange, Philip G

    2004-05-01

    This study investigated, for the D2 dopamine receptor, the relation between the ability of agonists and inverse agonists to stabilise different states of the receptor and their relative efficacies. Ki values for agonists were determined in competition versus the binding of the antagonist [3H]spiperone. Competition data were fitted best by a two-binding site model (with the exception of bromocriptine, for which a one-binding site model provided the best fit) and agonist affinities for the higher (Kh) (G protein-coupled) and lower affinity (Kl) (G protein-uncoupled) sites determined. Ki values for agonists were also determined in competition versus the binding of the agonist [3H]N-propylnorapomorphine (NPA) to provide a second estimate of Kh. Maximal agonist effects (Emax) and their potencies (EC50) were determined from concentration-response curves for agonist stimulation of guanosine-5'-O-(3-[32S]thiotriphosphate) ([35S]GTPgammaS) binding. The ability of agonists to stabilise the G protein-coupled state of the receptor (Kl/Kh determined from ligand-binding assays) did not correlate with either of two measures of relative efficacy (relative Emax, Kl/EC50) of agonists determined in [35S]GTPgammaS-binding assays, when the data for all of the compounds tested were analysed. For a subset of compounds, however, there was a relation between Kl/Kh and Emax. Competition-binding data versus [3H]spiperone and [3H]NPA for a range of inverse agonists were fitted best by a one-binding site model. Ki values for the inverse agonists tested were slightly lower in competition versus [3H]NPA compared to [3H]spiperone. These data do not provide support for the idea that inverse agonists act by binding preferentially to the ground state of the receptor.

  2. Car Stopping Distance on a Tabletop

    ERIC Educational Resources Information Center

    Haugland, Ole Anton

    2013-01-01

    Stopping distances in car braking can be an intriguing topic in physics teaching. It illustrates some basic principles of physics, and sheds valuable light on students' attitude towards aggressive driving. Due to safety considerations, it can be difficult to make experiments with actual car braking. (Contains 2 figures.)

  3. Smart CARs Engineered for Cancer Immunotherapy

    PubMed Central

    Priceman, Saul J.; Forman, Stephen J.; Brown, Christine E.

    2015-01-01

    Purpose Chimeric antigen receptors (CARs) are synthetic immunoreceptors that can redirect T cells to selectively kill tumor cells, and as “living-drugs” have the potential to generate long-term anti-tumor immunity. Given their recent clinical successes for the treatment of refractory B-cell malignancies, there is a strong push toward advancing this immunotherapy to other hematological diseases and solid cancers. Here, we summarize the current state of the field, highlighting key variables for the optimal application of CAR T cells for cancer immunotherapy. Recent Findings Advances in CAR T cell therapy have highlighted intrinsic CAR design and T cell manufacturing methods as critical components for maximal therapeutic success. Similarly, addressing the unique extrinsic challenges of each tumor type, including overcoming the immunosuppressive tumor microenvironment and tumor heterogeneity, as well as mitigating potential toxicity, will dominate the next wave of CAR T cell development. Summary CAR T cell therapeutic optimization, including intrinsic and extrinsic factors, is critical to developing effective CAR T cell therapies for cancer. The excitement of CAR T cell immunotherapy has just begun, and will continue with new insights revealed in laboratory research and in ongoing clinical investigations. PMID:26352543

  4. A Radio-Controlled Car Challenge

    ERIC Educational Resources Information Center

    Roman, Harry T.

    2010-01-01

    Watching a radio-controlled car zip along a sidewalk or street has become a common sight. Within this toy are the basic ingredients of a mobile robot, used by industry for a variety of important and potentially dangerous tasks. In this challenge, students consider modifying an of-the-shelf, radio-controlled car, adapting it for a robotic task.

  5. CRISPR Meets CAR T-cell Therapy.

    PubMed

    2017-03-21

    Using CRISPR/Cas9 technology, researchers have devised a method to deliver a CAR gene to a specific locus, TRAC, in T cells. This targeted approach yielded therapeutic cells that were more potent even at low doses; in a mouse model of acute lymphoblastic leukemia, they outperformed CAR T cells created with a randomly integrating retroviral vector.

  6. Rear-facing car seat (image)

    MedlinePlus

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

  7. Automated Coal-Mine Shuttle Car

    NASA Technical Reports Server (NTRS)

    Collins, E. R., Jr.

    1984-01-01

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

  8. Zoom Zoom: racing CARs for multiple myeloma.

    PubMed

    Maus, Marcela V; June, Carl H

    2013-04-15

    Chimeric antigen receptors redirect T cells to surface antigens. Discovery and validation of appropriate target antigens expand the possible indications for chimeric-antigen receptor (CAR)-T cells. B-cell maturation antigen (BCMA) is expressed only on mature B cells and plasma cells and promotes their survival. BCMA is a promising target for CAR-T cells in multiple myeloma.

  9. Constitutive androstane receptor (CAR) as a potential sensing biomarker of persistent organic pollutants (POPs) in aquatic mammal: molecular characterization, expression level, and ligand profiling in Baikal seal (Pusa sibirica).

    PubMed

    Sakai, Hiroki; Iwata, Hisato; Kim, Eun-Young; Tsydenova, Oyuna; Miyazaki, Nobuyuki; Petrov, Evgeny A; Batoev, Valeriy B; Tanabe, Shinsuke

    2006-11-01

    To characterize the function of constitutive active/androstane receptor (CAR) in aquatic mammals, CAR complementary DNA (cDNA) was cloned from the liver of Baikal seal (Pusa sibirica) from Lake Baikal, Russia, and the messenger RNA (mRNA) expression levels in various tissues/organs of the wild population and the CAR ligand profiles were investigated. The seal CAR cDNA had an open reading frame of 1047 bp encoding 348 amino acids that revealed 74-84% amino acid identities with CARs from rodents and human. The mRNA expression profile of tissues/organs represented that Baikal seal CAR was predominantly expressed in the liver followed by heart and intestine. The expression analysis of hepatic CAR mRNA showed no correlation with expression of cytochrome P450 (CYP) 1A, 1B, 2B, 2C, and 3A-like proteins, indicating that the CAR expression level may not be the sole determinant of the regulation of these CYP expressions in the seal liver. There was no significant correlation between CAR expression and any of the persistent organic pollutants (POPs) levels. Furthermore, we performed an in vitro CAR transactivation assay using MCF-7 cells transfected with Baikal seal CAR expression plasmid and (NR1)(3)-luciferase reporter gene plasmid. In the transactivation analysis of Baikal seal CAR, neither repression by androstanol and androstenol, nor activation by estrone and estradiol, which are recognized as endogenous ligands for mouse and human CARs, was detected. On the other hand, bile acids such as chenodeoxycholic acid, deoxycholic acid, and lithocholic acid activated the seal CAR as well as mouse CAR. As for exogenous chemicals, the seal CAR was transactivated by a human CAR agonist, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime), but not by a mouse CAR agonist, (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene). In addition, the seal CAR was also activated by polychlorinated biphenyls (PCBs) (Kanechlor-500, International Union of Pure and

  10. Entertainment and Pacification System For Car Seat

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

    An entertainment and pacification system for use with a child car seat has speakers mounted in the child car seat with a plurality of audio sources and an anti-noise audio system coupled to the child car seat. A controllable switching system provides for, at any given time, the selective activation of i) one of the audio sources such that the audio signal generated thereby is coupled to one or more of the speakers, and ii) the anti-noise audio system such that an ambient-noise-canceling audio signal generated thereby is coupled to one or more of the speakers. The controllable switching system can receive commands generated at one of first controls located at the child car seat and second controls located remotely with respect to the child car seat with commands generated by the second controls overriding commands generated by the first controls.

  11. The kinematic advantage of electric cars

    NASA Astrophysics Data System (ADS)

    Meyn, Jan-Peter

    2015-11-01

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

  12. Coal cars - the first three hundred years

    SciTech Connect

    Martin Robert Karig III

    2007-12-15

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

  13. Car size or car mass: which has greater influence on fatality risk?

    PubMed Central

    Evans, L; Frick, M C

    1992-01-01

    OBJECTIVES. Proposed increases in corporate average fuel economy standards would probably lead to lighter cars. Well-established relationships between occupant risk and car mass predict consequent additional casualties. However, if size, not mass, is the causative factor in these relationships, then decreasing car mass need not increase risk. This study examines whether mass or size is the causative factor. METHODS. Data from the Fatal Accident Reporting System are used to explore relationships between car mass, car size (as represented by wheelbase), and driver fatality risk in two-car crashes. RESULTS. When cars of identical (or similar) wheelbase but different mass crash into each other, driver fatality risk depends strongly on mass; the relationship is quantitatively similar to that found in studies that ignore wheelbase. On the other hand, when cars of similar mass but different wheelbase crash into each other, the data reveal no dependence of driver fatality risk on wheelbase. CONCLUSIONS. Mass is the dominant causative factor in relationships between driver risk and car size in two-car crashes, with size, as such, playing at most a secondary role. Reducing car mass increases occupant risk. PMID:1636830

  14. [Safety of beta-agonists in asthma].

    PubMed

    Oscanoa, Teodoro J

    2014-01-01

    Beta 2 agonist bronchodilators (β2A) are very important part in the pharmacotherapy of bronchial asthma, a disease that progresses in the world in an epidemic way. The β2A are prescribed to millions of people around the world, therefore the safety aspects is of public interest. Short-Acting β2 Agonists (SABAs), such as albuterol inhaler, according to current evidence, confirming its safety when used as a quick-relief or rescue medication. The long-acting β2 agonists (LABAs) The long-acting bronchodilators β2A (Long acting β2 Agonists or LABAs) are used associated with inhaled corticosteroids as controller drugs for asthma exacerbationsaccess, for safety reasons LABAs are not recommended for use as monotherapy.

  15. 1. GENERAL VIEW OF TIPPLE LOOKING NORTHWEST, SHOWING LARRY CARS ...

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

    1. GENERAL VIEW OF TIPPLE LOOKING NORTHWEST, SHOWING LARRY CARS BELOW HOPPER BIN. GRAY FITZSIMONS, HAER HISTORIAN, IS STANDING ON PLATFORM NEXT TO LARRY CARS - Lucernemines Coke Works, Larry Car Tipple, East of Lucerne, Lucerne Mines, Indiana County, PA

  16. 7. VAL CAMERA CAR, DETAIL OF 'FLARE' OR TRAJECTORY CAMERA ...

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

    7. VAL CAMERA CAR, DETAIL OF 'FLARE' OR TRAJECTORY CAMERA INSIDE CAMERA CAR. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  17. 5. VAL CAMERA CAR, DETAIL OF HOIST AT SIDE OF ...

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

    5. VAL CAMERA CAR, DETAIL OF HOIST AT SIDE OF BRIDGE AND ENGINE CAR ON TRACKS, LOOKING NORTHEAST. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  18. 6. VAL CAMERA CAR, DETAIL OF COMMUNICATION EQUIPMENT INSIDE CAMERA ...

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

    6. VAL CAMERA CAR, DETAIL OF COMMUNICATION EQUIPMENT INSIDE CAMERA CAR WITH CAMERA MOUNT IN FOREGROUND. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  19. Differential regulation by agonist and phorbol ester of cloned m1 and m2 muscarinic acetylcholine receptors in mouse Y1 adrenal cells and in Y1 cells deficient in cAMP-dependent protein kinase

    SciTech Connect

    Scherer, N.M.; Nathanson, N.M. )

    1990-09-11

    Cloned muscarinic acetylcholine m1 and m2 receptors were expressed in stably transfected mouse Y1 adrenal cells and in a variant Y1 line, Kin-8, which is deficient in cAMP-dependent protein kinase activity (PKA{sup {minus}}). m1 and m2 receptors were rapidly internalized following exposure of transfected PKA{sup +} or PKA{sup {minus}} cells to the muscarinic agonist carbachol. Thus, agonist-dependent internalization of m1 and m2 did not require PKA activity. A differential effect of PKA on regulation by agonist of the m2 receptor, but not the m1 receptor, was unmasked in PKA{sup {minus}} cells. These data indicate that the basal activity of PKA may modulate the agonist-dependent internalization of the m2 receptor, but not the m1 receptor. The internalization of the m1 and m2 receptors in both PKA{sup +} and PKA{sup {minus}} cells was accompanied by desensitization of functional responses. Exposure of PKA{sup +} cells to 10{sup {minus}7} M phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, resulted in a 30 {plus minus} 9% decrease in the number of m1 receptors on the cell surface. The m2 receptor was not internalized following treatment of either PKA{sup +} or PKA{sup {minus}} cells with PMA. Thus, the m1 and m2 receptors show differential sensitivity to internalization by PMA. Agonist-dependent internalization of the m1 receptor appeared to be independent of activation of PKC because (1) agonist-dependent internalization of m1 was not attenuated in PKA{sup {minus}} cells, (2) the rate and extent of internalization of m1 in cells exposed to PMA were less than those in cells exposed to agonist, and (3) treatment of cells with concanavalin A selectivity blocked internalization of m1 in cells exposed to PMA, but not to agonist. The effects of agonist and PMA on receptor internalization were not additive. Exposure of PKA{sup +} or PKA{sup {minus}} cells to PMA reduced the magnitude of pilocarpine-stimulated PI hydrolysis by about 25%.

  20. PPAR Agonists and Cardiovascular Disease in Diabetes

    PubMed Central

    Calkin, Anna C.; Thomas, Merlin C.

    2008-01-01

    Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPARα agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPARγ agonists, and more recently dual PPARα/γ coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARγ receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease. PMID:18288280

  1. Long-term studies of dopamine agonists.

    PubMed

    Hubble, Jean P

    2002-02-26

    Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

  2. A CARS solution with high temporal resolution

    NASA Astrophysics Data System (ADS)

    Landwehr, Stefanie; Lurquin, Vanessa; Hay, William C.; Krishnamachari, Vishnu; Schwarz, Ulf

    2011-03-01

    Confocal and multiphoton microscopy are powerful fluorescence techniques for morphological and dynamics studies of labeled elements. For non-fluorescent components, CARS (Coherent Anti-Stokes Raman Scattering) microscopy can be used for imaging various elements of cells such as lipids, proteins, DNA, etc. This technique is based on the intrinsic vibrational properties of the molecules. Leica Microsystems has combined CARS technology with its TCS SP5 II confocal microscope to provide several advantages for CARS imaging. The Leica TCS CARS combines two technologies in one system: a conventional scanner for maximum accuracy and a resonant scanner for highly time resolved imaging. For CARS microscopy, two picosecond near-infrared lasers are overlapped tightly, spatially and temporally, and sent directly into the confocal system. The conventional scanner can be used for morphological studies and the resonant scanner for following dynamic processes of unstained living cells. The fast scanner has several advantages over other solutions. First, the sectioning is truly confocal and does not suffer from spatial leakage. Second, the high speed (29 images/sec @ 512x512 pixels) provides fast data acquisition at video rates, allowing studies at the sub-cellular level. In summary, CARS microscopy combined with the tandem scanner makes the Leica TCS CARS a powerful tool for multimodal and three-dimensional imaging of chemical and biological sample.

  3. Monoclonal antibody against mouse CAR following genetic immunization.

    PubMed

    Carson, Steven D; Switzer, Barbara L; Tracy, Steven M; Chapman, Nora M

    2004-02-01

    To broaden our repertoire of monoclonal antibodies against CAR (coxsackievirus and adenovirus receptor), we inoculated mice with an expression vector containing the cDNA encoding human CAR extracellular and transmembrane sequence, and boosted the response by inoculation with soluble human CAR protein produced in E. coli. Of the hybridomas obtained following this immunization protocol, one secreted IgG with exceptional reactivity against mouse CAR. Since CAR has been shown to form dimers, expression of human CAR in cells that express mouse CAR may have stimulated the host immune system to recognize endogenous CAR in heterodimers.

  4. The human controller in car following

    NASA Technical Reports Server (NTRS)

    Burnham, G. O.; Bekey, G. A.

    1975-01-01

    The man machine interface between the human driver and his automobile during car following tasks was examined. A direct connection between models of the human operator and the theory of optimal control was established for car following situations involving both linear and nonlinear car dynamics. Results obtained from several types of mathematical models are discussed. Conventional parameter identification techniques were used to obtain the parameters of these models by comparing their performance to data obtained by aerial photogrammetry. The results indicate that there are two general classes of model structures: models assumed to have preview information and models without preview.

  5. CAR models: next-generation CAR modifications for enhanced T-cell function.

    PubMed

    Abate-Daga, Daniel; Davila, Marco L

    2016-01-01

    T cells genetically targeted with a chimeric antigen receptor (CAR) to B-cell malignancies have demonstrated tremendous clinical outcomes. With the proof in principle for CAR T cells as a therapy for B-cell malignancies being established, current and future research is being focused on adapting CAR technology to other cancers, as well as enhancing its efficacy and/or safety. The modular nature of the CAR, extracellular antigen-binding domain fused to a transmembrane domain and intracellular T-cell signaling domains, allows for optimization by replacement of the various components. These modifications are creating a whole new class of therapeutic CARs. In this review, we discuss the recent major advances in CAR design and how these modifications will impact its clinical application.

  6. The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor.

    PubMed

    Warne, Tony; Moukhametzianov, Rouslan; Baker, Jillian G; Nehmé, Rony; Edwards, Patricia C; Leslie, Andrew G W; Schertler, Gebhard F X; Tate, Christopher G

    2011-01-13

    β-adrenergic receptors (βARs) are G-protein-coupled receptors (GPCRs) that activate intracellular G proteins upon binding catecholamine agonist ligands such as adrenaline and noradrenaline. Synthetic ligands have been developed that either activate or inhibit βARs for the treatment of asthma, hypertension or cardiac dysfunction. These ligands are classified as either full agonists, partial agonists or antagonists, depending on whether the cellular response is similar to that of the native ligand, reduced or inhibited, respectively. However, the structural basis for these different ligand efficacies is unknown. Here we present four crystal structures of the thermostabilized turkey (Meleagris gallopavo) β(1)-adrenergic receptor (β(1)AR-m23) bound to the full agonists carmoterol and isoprenaline and the partial agonists salbutamol and dobutamine. In each case, agonist binding induces a 1 Å contraction of the catecholamine-binding pocket relative to the antagonist bound receptor. Full agonists can form hydrogen bonds with two conserved serine residues in transmembrane helix 5 (Ser(5.42) and Ser(5.46)), but partial agonists only interact with Ser(5.42) (superscripts refer to Ballesteros-Weinstein numbering). The structures provide an understanding of the pharmacological differences between different ligand classes, illuminating how GPCRs function and providing a solid foundation for the structure-based design of novel ligands with predictable efficacies.

  7. Policy: A challenging future for cars

    NASA Astrophysics Data System (ADS)

    Howey, David A.

    2012-01-01

    The rising demand for road vehicles increases Europe's oil dependency and carbon emissions. Switching to alternative cars and fuels can help energy security and climate change policy, if consumers can be persuaded.

  8. Binarity of the LBV HR Car

    NASA Astrophysics Data System (ADS)

    Rivinius, Th.; Boffin, H. M. J.; de Wit, W. J.; Mehner, A.; Martayan, Ch.; Guieu, S.; Le Bouquin, J.-B.

    2015-01-01

    VLTI/AMBER and VLTI/PIONIER observations of the LBV HR Car show an interferometric signature that could not possibly be explained by an extended wind, more or less symmetrically distributed around a single object. Instead, observations both in the Brγ line and the H-band continuum are best explained by two point sources (or alternatively one point source and one slightly extended source) at about 2 mas separation and a contrast ratio of about 1:5. These observations establish that HR Car is a binary, but further interpretation will only be possible with future observations to constrain the orbit. Under the assumption that the current separation is close to the maximum one, the orbital period can be estimated to be of the order of 5 years, similar as in the η Car system. This would make HR Car the second such LBV binary.

  9. How to Buy a Car 101

    ERIC Educational Resources Information Center

    Flores, Charity A.

    2006-01-01

    This article elaborates on the basics of problem-based learning units and tips for implementation. The problem-based learning unit described focuses on the course of action involved in purchasing a new car. (Contains 2 figures.)

  10. CAR-T Cell Therapy for Lymphoma.

    PubMed

    Ramos, Carlos A; Heslop, Helen E; Brenner, Malcolm K

    2016-01-01

    Lymphomas arise from clonal expansions of B, T, or NK cells at different stages of differentiation. Because they occur in the immunocyte-rich lymphoid tissues, they are easily accessible to antibodies and cell-based immunotherapy. Expressing chimeric antigen receptors (CARs) on T cells is a means of combining the antigen-binding site of a monoclonal antibody with the activating machinery of a T cell, enabling antigen recognition independent of major histocompatibility complex restriction, while retaining the desirable antitumor properties of a T cell. Here, we discuss the basic design of CARs and their potential advantages and disadvantages over other immune therapies for lymphomas. We review current clinical trials in the field and consider strategies to improve the in vivo function and safety of immune cells expressing CARs. The ultimate driver of CAR development and implementation for lymphoma will be the demonstration of their ability to safely and cost-effectively cure these malignancies.

  11. CAR-T Cell Therapy for Lymphoma

    PubMed Central

    Ramos, Carlos A.; Heslop, Helen E.; Brenner, Malcolm K.

    2016-01-01

    Lymphomas arise from clonal expansions of B, T, or NK cells at different stages of differentiation. Because they occur in the immunocyte-rich lymphoid tissues, they are easily accessible to antibodies and cell-based immunotherapy. Expressing chimeric antigen receptors (CARs) on T cells is a means of combining the antigen-binding site of a monoclonal antibody with the activating machinery of a T cell, enabling antigen recognition independent of major histocompatibility complex restriction, while retaining the desirable antitumor properties of a T cell. Here, we discuss the basic design of CARs and their potential advantages and disadvantages over other immune therapies for lymphomas. We review current clinical trials in the field and consider strategies to improve the in vivo function and safety of immune cells expressing CARs. The ultimate driver of CAR development and implementation for lymphoma will be the demonstration of their ability to safely and cost-effectively cure these malignancies. PMID:26332003

  12. Aryl hydrocarbon receptor agonists trigger avoidance of novel food in rats.

    PubMed

    Mahiout, Selma; Pohjanvirta, Raimo

    2016-12-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of dioxins, but also plays important physiological roles, which are only beginning to unfold. Previous studies have surprisingly unveiled that low doses of the potent AHR agonist TCDD induce a strong and persistent avoidance of novel food items in rats. Here, we further examined the involvement of the AHR in the avoidance response in Sprague-Dawley rats with three established AHR agonists: 6-formylindolo(3,2-b)carbazole (FICZ), β-naphthoflavone (BNF) and benzo[a]pyrene (BaP); with a novel selective AHR modulator (C2); and with an activator of another nuclear receptor, CAR: 2,4,6-tryphenyldioxane-1,3 (TPD). As sensitive indices of AHR or CAR activity, we used Cyp1a1 and Cyp2b1 gene expression, as they are, respectively, the drug-metabolizing enzymes specifically regulated by them. We further attempted to address the roles played by enhanced neophobia and conditioned taste aversion (CTA) in the avoidance behaviour. All AHR agonists triggered practically total avoidance of novel chocolate, but the durations varied. Likewise, acutely subtoxic doses of C2, differing by 25-fold, all elicited a similar outcome. In contrast, TPD did not influence chocolate consumption at all. If rats were initially accustomed to chocolate for 6h after single FICZ or BNF exposure, avoidance was still clearly present two weeks later when chocolate was offered again. Hence, the avoidance response appears to specifically involve the AHR instead of being triggered by induction of intestinal or hepatic nuclear receptor signalling in general. It is also shared by both endogenous and exogenous AHR activators. Moreover, this behavioural change in rats seems to contain elements of both CTA and enhanced neophobia, but further clarification of this is still required.

  13. CARS Diagnostics of High Pressure Combustion.

    DTIC Science & Technology

    1982-11-01

    e) 8. CONTRACT OR GRANT NUMBER(e) J. H. Stufflebeam t JDAAG29- 79-C-0008J %A,, Shirley R,,. Hall 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10...also the work in N2 at elevated tem- perature up to 30 atmospheres. John H. Stufflebeam continued the high pressure CARS work under the contract...Spectroscopy, Bordeaux, France, September 1982. 12. J. H. Stufflebeam , J. F. Verdieck, and R. J. Hall: CARS Diagnostics of High Pressure and

  14. EcoCAR Challenge Profile: Virginia Tech

    SciTech Connect

    Gantt, Lynn

    2011-01-01

    Since childhood, Lynn Gantt has had a deep seeded passion for cars and the mechanics that drive them. The Virginia native spent his weekends rebuilding antique tractors with his dad to race at tractor pulls across the state, and now the Virginia Tech graduate student is the proud team co-leader of Virginia Tech's EcoCAR Challenge team -- the winners of the three-year long competition, as announced last night at an awards ceremony in Washington, D.C..

  15. The Goods Upstairs Car Innovative Design

    NASA Astrophysics Data System (ADS)

    Wang, Feng-Lan; Zhang, Bo; Gao, Bo; Liu, Yan-Xin; Gao, Bo

    2016-05-01

    The design is a new kind of cars used for loading goods when you upstairs. The cars -- ones are very safe and convenient --consist of body, chassis, bottom, round, object, stage, upstairs, train wheels, handles, storage tank, security fence etc. The design, composed of combination of each structure, achieves the purpose of loading goods and even some large potted plants when you go upstairs or downstairs very flatly.

  16. EcoCAR Challenge Profile: Virginia Tech

    ScienceCinema

    Gantt, Lynn

    2016-07-12

    Since childhood, Lynn Gantt has had a deep seeded passion for cars and the mechanics that drive them. The Virginia native spent his weekends rebuilding antique tractors with his dad to race at tractor pulls across the state, and now the Virginia Tech graduate student is the proud team co-leader of Virginia Tech's EcoCAR Challenge team -- the winners of the three-year long competition, as announced last night at an awards ceremony in Washington, D.C..

  17. Car radiator burns: a prevention issue.

    PubMed

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

    2004-01-01

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

  18. Car drivers' attitudes towards motorcyclists: a survey.

    PubMed

    Crundall, David; Bibby, Peter; Clarke, David; Ward, Patrick; Bartle, Craig

    2008-05-01

    Motorcyclists are over-represented in UK traffic accident statistics. Many car-motorcycle accidents are however due to the inappropriate actions of car drivers. It is predicted that car drivers at risk of collision with motorcycles have divergent attitudes and beliefs about motorcyclists compared to safer drivers, which may lead to a deficient mental model guiding their interactions with motorcyclists. To assess car drivers' attitudes towards motorcyclists, a survey was undertaken. Respondents filled in 26 general and motorcycle-related items and the 24 items of the reduced Driver Behaviour Questionnaire. Compared to an experienced dual driver group (who both drive cars and ride motorcycles), all other drivers showed divergent beliefs and attitudes. Four factors were extracted from the motorcycle items: negative attitudes, empathic attitudes, awareness of perceptual problems, and spatial understanding. Car drivers with a moderate amount of experience (between 2 and 10 years driving) held the most negative views and reported the most violations. The results have lead to several suggestions for interventions aimed at decreasing the divergence between drivers' perceptions of motorcyclists, and the perceptions of experienced dual drivers.

  19. Macroscopic car condensation in a parking garage.

    PubMed

    Ha, Meesoon; Den Nijs, Marcel

    2002-09-01

    An asymmetric exclusion process type process, where cars move forward along a closed road that starts and terminates at a parking garage, displays dynamic phase transitions into two types of condensate phases where the garage becomes macroscopically occupied. The total car density rho(o) and the exit probability alpha from the garage are the two control parameters. At the transition, the number of parked cars N(p) diverges in both cases, with the length of the road N(s), as N(p) approximately N(y(p))(s) with y(p)=1/2. Towards the transition, the number of parked cars vanishes as N(p) approximately epsilon(beta) with beta=1, epsilon=/alpha-alpha(*)/ or epsilon=|rho(*)(o)-rho(o)/ being the distance from the transition. The transition into the normal phase represents also the onset of transmission of information through the garage. This gives rise to unusual parked car autocorrelations and car density profiles near the garage, which depend strongly on the group velocity of the fluctuations along the road.

  20. Pyrene is a Novel Constitutive Androstane Receptor (CAR) Activator and Causes Hepatotoxicity by CAR.

    PubMed

    Zhang, Xiao-Jie; Shi, Zhe; Lyv, Jing-Xi; He, Xuyan; Englert, Neal A; Zhang, Shu-Yun

    2015-10-01

    Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous persistent environmental pollutants which are primarily formed from the incomplete combustion of organic materials. Many potential sources of human exposure to PAHs exist, including daily exposures from the ambient environment or occupational settings. PAHs have been found to cause harmful effects on human health. Here, we evaluated the adverse effects of pyrene, a common PAH, on the liver. The present study demonstrates that pyrene is able to activate mouse constitutive androstane receptor (CAR). CAR protein, as measured by Western blot analysis, was observed to translocate into the nucleus from the cytoplasm in mouse liver after exposure to pyrene. Utilizing CAR null mice, we identified that CAR mediates pyrene-induced hepatotoxicity. Increased relative liver weight, hepatocellular hypertrophy, and elevated serum alanine aminotransferase levels were found in wild-type but not CAR null mice after orally administered pyrene. We further show that pyrene induced the expression of mouse liver metabolism enzymes including CYP2B10, CYP3A11, GSTm1, GSTm3, and SULT1A1, and caused hepatic glutathione depletion in wild-type but not CAR null mice. Moreover, by luciferase reporter assay and quantitative real-time PCR analysis, pyrene was found to be a potential inducer of CYP2B6 expression via activation of human CAR in HepG2 cells and human primary hepatocytes. Our observations suggest that pyrene is a novel CAR activator and that CAR is essential for mediating pyrene-induced liver injury.

  1. 30 CFR 57.19079 - Blocking mine cars.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  2. 19 CFR 151.26 - Molasses in tank cars.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  3. 36 CFR 1192.109 - Between-car barriers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  4. 49 CFR 215.119 - Defective freight car truck.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  5. 49 CFR 223.15 - Requirements for existing passenger cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built...

  6. 49 CFR 38.109 - Between-car barriers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  7. 49 CFR 215.303 - Stenciling of restricted cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  8. 30 CFR 57.19079 - Blocking mine cars.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  9. 49 CFR 215.119 - Defective freight car truck.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  10. 49 CFR 215.303 - Stenciling of restricted cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  11. 49 CFR 223.15 - Requirements for existing passenger cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built...

  12. 49 CFR 218.80 - Movement of occupied camp cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Movement of occupied camp cars. 218.80 Section 218... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Occupied Camp Cars § 218.80 Movement of occupied camp cars. Occupied cars may not be humped or flat switched unless coupled...

  13. 30 CFR 56.19079 - Blocking mine cars.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  14. 49 CFR 173.10 - Tank car shipments.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  15. 49 CFR 223.15 - Requirements for existing passenger cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built...

  16. 49 CFR 223.15 - Requirements for existing passenger cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built...

  17. 49 CFR 223.15 - Requirements for existing passenger cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built...

  18. 49 CFR 38.109 - Between-car barriers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  19. 49 CFR 218.80 - Movement of occupied camp cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of occupied camp cars. 218.80 Section 218... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Occupied Camp Cars § 218.80 Movement of occupied camp cars. Occupied cars may not be humped or flat switched unless coupled...

  20. 36 CFR 1192.109 - Between-car barriers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  1. 19 CFR 151.26 - Molasses in tank cars.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  2. 49 CFR 218.80 - Movement of occupied camp cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Movement of occupied camp cars. 218.80 Section 218... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Occupied Camp Cars § 218.80 Movement of occupied camp cars. Occupied cars may not be humped or flat switched unless coupled...

  3. 49 CFR 215.119 - Defective freight car truck.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  4. 30 CFR 57.19079 - Blocking mine cars.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  5. 49 CFR 218.80 - Movement of occupied camp cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Movement of occupied camp cars. 218.80 Section 218... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Occupied Camp Cars § 218.80 Movement of occupied camp cars. Occupied cars may not be humped or flat switched unless coupled...

  6. 36 CFR 1192.109 - Between-car barriers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  7. 19 CFR 151.26 - Molasses in tank cars.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  8. 19 CFR 151.26 - Molasses in tank cars.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  9. 49 CFR 215.119 - Defective freight car truck.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  10. 49 CFR 38.109 - Between-car barriers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  11. 30 CFR 56.19079 - Blocking mine cars.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  12. 30 CFR 57.19079 - Blocking mine cars.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  13. 49 CFR 38.109 - Between-car barriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  14. 49 CFR 215.303 - Stenciling of restricted cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  15. 30 CFR 56.19079 - Blocking mine cars.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  16. 49 CFR 215.303 - Stenciling of restricted cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  17. 36 CFR 1192.109 - Between-car barriers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  18. 49 CFR 218.80 - Movement of occupied camp cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Movement of occupied camp cars. 218.80 Section 218... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Occupied Camp Cars § 218.80 Movement of occupied camp cars. Occupied cars may not be humped or flat switched unless coupled...

  19. 30 CFR 56.19079 - Blocking mine cars.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  20. 49 CFR 38.109 - Between-car barriers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  1. 49 CFR 215.303 - Stenciling of restricted cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  2. 19 CFR 151.26 - Molasses in tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  3. 30 CFR 57.19079 - Blocking mine cars.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  4. 49 CFR 215.119 - Defective freight car truck.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  5. 36 CFR 1192.109 - Between-car barriers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  6. 30 CFR 56.19079 - Blocking mine cars.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

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

    PubMed

    Ansong, Michael; Pickering, Catherine

    2013-01-01

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

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

    PubMed Central

    Ansong, Michael; Pickering, Catherine

    2013-01-01

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

  9. Muscimol as an ionotropic GABA receptor agonist.

    PubMed

    Johnston, Graham A R

    2014-10-01

    Muscimol, a psychoactive isoxazole from Amanita muscaria and related mushrooms, has proved to be a remarkably selective agonist at ionotropic receptors for the inhibitory neurotransmitter GABA. This historic overview highlights the discovery and development of muscimol and related compounds as a GABA agonist by Danish and Australian neurochemists. Muscimol is widely used as a ligand to probe GABA receptors and was the lead compound in the development of a range of GABAergic agents including nipecotic acid, tiagabine, 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, (Gaboxadol(®)) and 4-PIOL.

  10. Defining the mammalian CArGome

    PubMed Central

    Sun, Qiang; Chen, Guang; Streb, Jeffrey W.; Long, Xiaochun; Yang, Yumei; Stoeckert, Christian J.; Miano, Joseph M.

    2006-01-01

    Serum response factor (SRF) binds a 1216-fold degenerate cis element known as the CArG box. CArG boxes are found primarily in muscle- and growth-factor-associated genes although the full spectrum of functional CArG elements in the genome (the CArGome) has yet to be defined. Here we describe a genome-wide screen to further define the functional mammalian CArGome. A computational approach involving comparative genomic analyses of human and mouse orthologous genes uncovered >100 hypothetical SRF-dependent genes, including 10 previously identified SRF targets, harboring a conserved CArG element within 4000 bp of the annotated transcription start site (TSS). We PCR-cloned 89 hypothetical SRF targets and subjected each of them to at least two of several validations including luciferase reporter, gel shift, chromatin immunoprecipitation, and mRNA expression following RNAi knockdown of SRF; 60/89 (67%) of the targets were validated. Interestingly, 26 of the validated SRF target genes encode for cytoskeletal/contractile or adhesion proteins. RNAi knockdown of SRF diminishes expression of several SRF-dependent cytoskeletal genes and elicits an attending perturbation in the cytoarchitecture of both human and rodent cells. These data illustrate the power of integrating existing algorithms to interrogate the genome in a relatively unbiased fashion for cis-regulatory element discovery. In this manner, we have further expanded the mammalian CArGome with the discovery of an array of cyto-contractile genes that coordinate normal cytoskeletal homeostasis. We suggest one function of SRF is that of an ancient master regulator of the actin cytoskeleton. PMID:16365378

  11. 49 CFR 180.519 - Periodic retest and inspection of tank cars other than single-unit tank car tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Periodic retest and inspection of tank cars other... of Tank Cars § 180.519 Periodic retest and inspection of tank cars other than single-unit tank car... devices must be retested periodically as specified in Retest Table 1 of paragraph (b)(5) of this...

  12. 49 CFR 173.314 - Compressed gases in tank cars and multi-unit tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... trichloride Note 3 105, 106 Carbon dioxide, refrigerated liquid Note 5 105 Chlorine Note 6 105 105J600I 125... requirements for carbon dioxide, refrigerated liquid and nitrous oxide, refrigerated liquid. Each tank car must... for nitrosyl chloride. Single unit tank cars and their associated service equipment, such as...

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Meinrenken, Christoph J.; Lackner, Klaus S.

    2011-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Meinrenken, Christoph; Lackner, Klaus S.

    2012-02-01

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

  16. Characterization of three-color CARS in a two-pulse broadband CARS spectrum.

    PubMed

    Lee, Young Jong; Liu, Yuexin; Cicerone, Marcus T

    2007-11-15

    We demonstrate that a broadband coherent anti-Stokes Raman scattering (CARS) spectrum generated with a typical two-pulse scheme contains two distinct, significant signals: '2-color' CARS, where the pump and probe are provided by a narrowband pulse and the continuum pulse constitutes the Stokes light, and '3-color' CARS, where the pump and Stokes are provided by two different frequency components in the continuum pulse and the narrowband pulse serves as the probe. The CARS spectra from the two different mechanisms show distinct characteristics in Raman shift range, laser power dependence, and chirping dependence. We discuss the potential for a 3-color CARS signal to cover the fingerprint region with reduced photodamage of live cells. Official contribution of the National Institute of Standards and Technology; not subject to copyright in the United States.

  17. A CARS solution with high temporal resolution

    NASA Astrophysics Data System (ADS)

    Lurquin, Vanessa; Hay, William C.; Landwehr, Stefanie; Krishnamachari, Vishnu

    2010-02-01

    Confocal and multiphoton microscopy are powerful fluorescence techniques for morphological and dynamics studies of labeled elements. For non-fluorescent components, CARS (Coherent Anti-Stokes Raman Scattering) microscopy can be used for imaging various elements of cells such as lipids, proteins, DNA, etc. This technique is based on the intrinsic vibrational properties of the molecules. Leica Microsystems has combined CARS technology with its TCS SP5 II confocal microscope to provide several advantages for CARS imaging. The Leica TCS SP5 II combines two technologies in one system: a conventional scanner for maximum resolution and a resonant scanner for high time resolution. For CARS microscopy, two picosecond near-infrared lasers are tightly overlapped spatially and temporally and sent directly into the confocal system. The conventional scanner can be used for morphological studies and the resonant scanner for following dynamic processes of unstained living cells. The fast scanner has several advantages over other solutions. First, the sectioning is truly confocal and does not suffer from spatial leakage. Second, the high speed (29 images/sec @ 512×512 pixels) provides fast data acquisition at video rates, allowing studies at the sub-cellular level. In summary, CARS microscopy combined with the tandem scanner makes the Leica TCS SP5 II a powerful tool for multi-modal and three-dimensional imaging of chemical and biological samples. We will present our solution and show results from recent studies with the Leica instrument to illustrate the high flexibility of our system.

  18. Corepressors of agonist-bound nuclear receptors

    SciTech Connect

    Gurevich, Igor; Aneskievich, Brian J.

    2007-09-15

    Nuclear receptors (NRs) rely on coregulator proteins to modulate transcription of target genes. NR coregulators can be broadly subdivided into coactivators which potentiate transcription and corepressors which silence gene expression. The prevailing view of coregulator action holds that in the absence of agonist the receptor interacts with a corepressor via the corepressor nuclear receptor (CoRNR, 'corner') box motifs within the corepressor. Upon agonist binding, a conformational change in the receptor causes the shedding of corepressor and the binding of a coactivator which interacts with the receptor via NR boxes within the coregulator. This view was challenged with the discovery of RIP140 which acts as a NR corepressor in the presence of agonist and utilizes NR boxes. Since then a number of other corepressors of agonist-bound NRs have been discovered. Among them are LCoR, PRAME, REA, MTA1, NSD1, and COPR1 Although they exhibit a great diversity of structure, mechanism of repression and pathophysiological function, these corepressors frequently have one or more NR boxes and often recruit histone deacetylases to exert their repressive effects. This review highlights these more recently discovered corepressors and addresses their potential functions in transcription regulation, disease pharmacologic responses and xenobiotic metabolism.

  19. Multiple tyrosine metabolites are GPR35 agonists

    PubMed Central

    Deng, Huayun; Hu, Haibei; Fang, Ye

    2012-01-01

    Both kynurenic acid and 2-acyl lysophosphatidic acid have been postulated to be the endogenous agonists of GPR35. However, controversy remains whether alternative endogenous agonists exist. The molecular targets accounted for many nongenomic actions of thyroid hormones are mostly unknown. Here we report the agonist activity of multiple tyrosine metabolites at the GPR35. Tyrosine metabolism intermediates that contain carboxylic acid and/or catechol functional groups were first selected. Whole cell dynamic mass redistribution (DMR) assays enabled by label-free optical biosensor were then used to characterize their agonist activity in native HT-29. Molecular assays including β-arrestin translocation, ERK phosphorylation and receptor internalization confirmed that GPR35 functions as a receptor for 5,6-dihydroxyindole-2-carboxylic acid, 3,3′,5′-triiodothyronine, 3,3′,5-triiodothyronine, gentisate, rosmarinate, and 3-nitrotyrosine. These results suggest that multiple tyrosine metabolites are alternative endogenous ligands of GPR35, and GPR35 may represent a druggable target for treating certain diseases associated with abnormality of tyrosine metabolism. PMID:22523636

  20. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

    SciTech Connect

    Rogue, Alexandra; Anthérieu, Sébastien; Vluggens, Aurore; Umbdenstock, Thierry; Claude, Nancy; Moureyre-Spire, Catherine de la; Weaver, Richard J.; Guillouzo, André

    2014-04-01

    Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control

  1. Detection and measurement of the agonistic activities of PCBs and mono-hydroxylated PCBs to the constitutive androstane receptor using a recombinant yeast assay.

    PubMed

    Kamata, Ryo; Shiraishi, Fujio; Kageyama, Shiho; Nakajima, Daisuke

    2015-10-01

    Polychlorinated biphenyls (PCBs) are thought to exert their toxicities mainly by binding to the aryl hydrocarbon receptor and by stimulating transcription of various genes, notably metabolizing enzymes including the cytochrome P450 (CYP) 1 family. However, PCBs and their metabolites could have potential to activate other nuclear receptors and subsequent events. We focused on the constitutive androstane receptor (CAR) inducing CYP2B and measured the agonistic activity of PCBs and mono-hydroxylated PCBs (OH-PCBs) to the CAR using yeast cells transduced with the human CAR and its response pathway. Twenty-nine of 34 tested PCBs and 72 of 91 OH-PCBs exhibited CAR agonistic effects. Of 41 OH-PCBs that had the same chlorination patterns as the tested PCBs, 9 had activities more than twice those of their non-hydroxylated analogs. In particular, 2',4',6'-trichlorobiphenyl-4-ol and 2,2',4',6'-tetrachlorobiphenyl-4-ol were 332- and 22-fold more potent than their analogs and were 15 times and 2.8 times, respectively, as active as a reference substance, 4-tert-octylphenol. The activities of 17 of the OH-PCBs were reduced to less than half those of their non-hydroxylated analogs. Four OH-PCBs derived from 3 active PCBs were inactive. However, a consistent relationship between hydroxyl substituent position and activity could not be discerned. Comprehensive evaluation of the toxic potential of PCBs and their hydroxylated metabolites and their concentrations in the environment are required.

  2. ChemMatCARS Data Archive

    DOE Data Explorer

    ChemMatCARS is a high-brilliance national synchrotron x-ray facility dedicated primarily to static and dynamic condensed matter chemistry and materials science. The scientific focus of the facility includes the study of surface and interfacial properties of liquids and solids as well as their bulk structure at atomic, molecular and mesoscopic length scales with high spatial and energy resolution. Experimental techniques supported by the facility include: 1) Liquid Surface X-ray Scattering; 2) Solid Surface X-ray Scattering; 3) Time-Resolved Crystallography; 4) Micro-Crystal Diffraction; 5) Small and Wide-angle X-ray Scattering. The data archive referenced here contains data for various components along the beamline within the First Optics Enclosure and is intended to be input or parameter data. See the Science Nuggets at http://cars9.uchicago.edu/chemmat/pages/nuggets.html for leads to some of the research conducted at the ChemMatCARS beamline.

  3. Track-train dynamics. [railroad car design

    NASA Technical Reports Server (NTRS)

    Abbott, P. W.; Morosow, G.; Macpherson, J.

    1975-01-01

    The purpose of this paper is to outline one of the serious dynamic problems involving railroad cars and to propose an orderly approach to the definition of a dynamic model through analysis and testing that can be used to investigate various fixes. The problem in question is the hunting phenomenon involving lateral instability of the car suspension (trucks). This phenomenon has been recognized as a major contributing factor in a significant number of derailments causing millions of dollars in losses. This paper expounds on the mechanics and characteristics of hunting. The planned solution is outlined as a building block approach directed at formulating a test verified dynamic model of an open hopper freight car-truck assembly. Results obtained to date are presented together with conclusions related to the program.

  4. Serotonergic agonists behave as partial agonists at the dopamine D2 receptor.

    PubMed

    Rinken, A; Ferré, S; Terasmaa, A; Owman, C; Fuxe, K

    1999-02-25

    RAT dopamine D2short receptors expressed in CHO cells were characterized by activation of [35S]GTPgammaS binding. There were no significant differences between the maximal effects seen in activation of [35S]GTPgammaS binding caused by dopaminergic agonists, but the effects of 5-HT, 8OH-DPAT and 5-methoxytryptamine amounted to 47 +/- 7%, 43 +/- 5% and 70 +/- 7% of the dopamine effect, respectively. The dopaminergic antagonist (+)butaclamol inhibited activations of both types of ligands with equal potency (pA2 = 8.9 +/- 0.1), indicating that only one type of receptor is involved. In competition with [3H]raclopride binding, dopaminergic agonists showed 53 +/- 2% of the binding sites in the GTP-dependent high-affinity state, whereas 5-HT showed only 20 +/- 3%. Taken together, the results indicate that serotonergic agonists behave as typical partial agonists for D2 receptors with potential antiparkinsonian activity.

  5. Leica solution: CARS microscopy at video rates

    NASA Astrophysics Data System (ADS)

    Lurquin, V.

    2008-02-01

    Confocal and multiphoton microscopy are powerful techniques to study morphology and dynamics in cells and tissue, if fluorescent labeling is possible or autofluorescence is strong. For non-fluorescent molecules, Coherent anti-Stokes Raman scattering (CARS) microscopy provides chemical contrast based on intrinsic and highly specific vibrational properties of molecules eliminating the need for labeling. Just as other multiphoton techniques, CARS microscopy possesses three-dimensional sectioning capabilities. Leica Microsystems has combined the CARS imaging technology with its TCS SP5 confocal microscope to provide several advantages for CARS imaging. For CARS microscopy, two picosecond near-infrared lasers are overlapped spatially and temporally and sent into the scanhead of the confocal system. The software allows programmed, automatic switching between these light sources for multi-modal imaging. Furthermore the Leica TCS SP5 can be equipped with a non-descanned detector which will significantly enhance the signal. The Leica TCS SP5 scanhead combines two technologies in one system: a conventional scanner for maximum resolution and a resonant scanner for high time resolution. The fast scanner allows imaging speeds as high as 25 images/per second at a resolution of 512×512 pixel. This corresponds to true video-rate allowing to follow processes at these time-scales as well as the acquisition of three-dimensional stacks in a few seconds. This time resolution is critical to study live animals or human patients for which heart beat and muscle movements lead to a blurring of the image if the acquisition time is high. Furthermore with the resonant scanhead the sectioning is truly confocal and does not suffer from spatial leakage. In summary, CARS microscopy combined with the tandem scanner makes the Leica TCS SP5 a powerful tool for three-dimensional, label-free imaging of chemical and biological samples in vitro and in vivo.

  6. CARS system for turbulent flame measurements

    NASA Technical Reports Server (NTRS)

    Antcliff, R. R.; Jarrett, O., Jr.; Rogers, R. C.

    1984-01-01

    Simultaneous nitrogen number density and rotational-vibrational temperatures were measured in a turbulent diffusion flame with a Coherent Anti-Stokes Raman Scattering (CARS) instrument. The fuel jet was diluted with nitrogen (20 percent by volume) to allow temperature measurements across the entire jet mixing region. These measurements were compared with fluid dynamics computations. The CARS system incorporated a neodymium YAG laser, an intensified silicon photodiode array detector, and unique dynamic range enhancement methods. Theoretical calculations were based on a parabolic Navier-Stokes computer code. The comparison of these techniques will aid their development in the study of complex flowfields.

  7. Polyphenols in alcoholic beverages activating constitutive androstane receptor CAR.

    PubMed

    Yao, Ruiqing; Yasuoka, Akihito; Kamei, Asuka; Kitagawa, Yoshinori; Rogi, Tomohiro; Taieishi, Norifumi; Tsuruoka, Nobuo; Kiso, Yoshionobu; Misaka, Takumi; Abe, Keiko

    2011-01-01

    The constitutive androstane receptor CAR is a xenosensing nuclear receptor that can be activated by natural polyphenols such as flavonoids and catechins. We examined alcoholic beverage phytochemicals for their ability to activate CAR. HepG2 cells were transfected with CAR expression vector and its reporter gene, and then treated with trans-resveratrol, ellagic acid, β-caryophyllene, myrcene, and xanthohumol. A luciferase assay revealed that ellagic acid and trans-resveratrol activated both human and mouse CAR. Since CAR regulates many genes involved in energy metabolism, the possibility exists that these polyphenols would reduce the risk of certain alcohol-induced metabolic disorders with the help of CAR.

  8. CARS Diagnostics for Solid Propellant Combustion Investigations

    DTIC Science & Technology

    1992-01-29

    100 micron), near-surface reaction zone. Dual broadband CARS of HCN, H2CO and CH 4 was utilized to observe the com- petition between two major... reaction mechanisms; they determine the speed of the overall reaction . Resolution of the temperature and species profiles in the reaction zone, required for...Equilibrium ........... ...................... 5 Near-Surface Reactions ........... ......................... 5 Surface Gradients of Temperature and

  9. Electric hybrid module based specialty car design

    SciTech Connect

    Bohan, K.R.

    1995-12-31

    The vast majority of automobiles made in the United states today are manufactured by one of three major auto manufacturers. It is intrinsic in their nature to act conservatively. The big three`s large production runs represents a huge amount of capitalization. The amount of capital being invested is the real driving factor behind the conservative nature of these companies. In the computer industries we have seen a significant number of small start up companies as the driving force behind technological change. If a large company does not do it, a small venture capital company will certainly fill the vacuum. Unfortunately, the existing auto industry does not have a strong startup company presence. Even into the 1920`s, the specialty car or custom coach work manufactures represented a lively part of the auto economy. It was not until the coming of the great depression that the small specialty car manufacture was virtually eliminated. Today we see the beginnings of a comeback of the specialty car manufacturer in the kit car industry of today.

  10. Picasso, Car Classics, and the Engineers.

    ERIC Educational Resources Information Center

    Wosk, Julie H.

    1982-01-01

    Describes a college course which introduces engineering and business students to abstract art. Students study the relationships between abstract styles in painting and abstract styles in twentieth-century architecture and industrial design. The relevance of abstract design principles is shown by referring students to "Car and Driver"…

  11. 75 FR 10567 - Commerce Acquisition Regulation (CAR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-08

    ...We, the Department of Commerce, issue a final rule to bring the Commerce Acquisition Regulation in alignment with the Federal Acquisition Regulation (FAR) and to streamline DOC's internal policy and guidance. This final rule updates the entire CAR through FAC 2005-...

  12. What Happens at a Car Wash?

    ERIC Educational Resources Information Center

    Gallick, Barbara; Lee, Lisa

    2010-01-01

    A class of 3- to 5-year-old children in a child care center in the midwestern United States chose to study a car wash as a group project. This article discusses how the project evolved, describes the three phases of the project, and provides the teachers' reflections on the project. Photos taken during the project and children's sketches are…

  13. Costimulation Engages the Gear in Driving CARs.

    PubMed

    Abken, Hinrich

    2016-02-16

    In this issue of Immunity,Kawalekar et al. (2016) find that costimulation by a chimeric antigen receptor (CAR) can control T cell metabolism and balance the response toward long-lived memory or short-lived effector cells. The results provide a rationale of how to tune cancer immunotherapy more effectively in a hostile tumor environment.

  14. Colleges Drive Research on Electric Cars

    ERIC Educational Resources Information Center

    Basken, Paul

    2009-01-01

    As the General Motors Corporation shuts assembly plants and veers toward bankruptcy, the lonely remnants of one of its top technological achievements--the first modern mass-produced electric car--lie scattered across a few dozen American college campuses. GM produced and leased to customers more than 1,000 "EV1" automobiles beginning in 1996. In…

  15. Agonistic and reproductive interactions in Betta splendens.

    PubMed

    Bronstein, P M

    1984-12-01

    Reproductive and agonistic behaviors in Siamese fighting fish were investigated in eight experiments, and some consequences and determinants of these sequences were isolated. First, fights and the formation of dominance-subordinancy relations were studied. Second, it was determined that large body size as well as males' prior residency in a tank produced an agonistic advantage; the magnitude of this advantage was positively related to the duration of residency. Third, the prior-residency effect in Bettas was determined by males' familiarity with visual and/or tactile cues in their home tanks. Fourth, dominant males had greater access to living space and were more likely to display at a mirror, build nests, and approach females than were subordinates. Finally, it was discovered that chemical cues associated with presumedly inert plastic tank dividers influence Bettas' social behavior.

  16. Agonists block currents through acetylcholine receptor channels.

    PubMed Central

    Sine, S M; Steinbach, J H

    1984-01-01

    We have examined the effects of high concentrations of cholinergic agonists on currents through single acetylcholine receptor (AChR) channels on clonal BC3H1 cells. We find that raised concentrations of acetylcholine (ACh; above 300 microM) or carbamylcholine (Carb; above 1,000 microM) produce a voltage- and concentration-dependent reduction in the mean single-channel current. Raised concentrations of suberyldicholine (Sub; above 3 microM) produce a voltage- and concentration-dependent increase in the number of brief duration low-conductance interruptions of open-channel currents. These observations can be quantitatively described by a model in which agonist molecules enter and transiently occlude the ion-channel of the AChR. PMID:6478036

  17. Ropinirole, a non-ergoline dopamine agonist.

    PubMed

    Jost, Wolfgang H; Angersbach, Dieter

    2005-01-01

    Dopamine agonists have become indispensable in the treatment of Parkinson's disease. In every-day practice, however, the decision to select the best compound for an individual patient is rendered difficult because of the large number of substances available on the market. This review article provides a closer look at the experimental and clinical studies with ropinirole published so far. Ropinirole is a non-ergoline dopamine agonist which has been proven to be effective in both, monotherapy and combination therapy of idiopathic Parkinson's disease. In addition to ameliorating bradykinesia, rigor, and tremor, ropinirole facilitates the daily life and improves depressive moods of patients with Parkinson's disease. The long-term complications of levodopa are avoided, and problems commonly associated with levodopa treatment are reduced. Ropinirole appears to have a neuroprotective effect. In addition to Parkinson's disease, ropinirole has also been used successfully in the treatment of restless legs syndrome.

  18. Effect of interferences on indoor visible light car-to-car communication systems

    NASA Astrophysics Data System (ADS)

    Kim, Jong-Young; Park, Bong-Seok; Choi, Hyun-Sik; Kim, So Eun; Moon, Inkyu; Lee, Chung Ghiu

    2016-04-01

    We report the effect of interferences on visible light car-to-car communication system. The interferences from floor reflections and fluorescent lamps are taken into account for indoor car-to-car visible light communication (VLC) systems. The system is composed of a white LED lamp as a VLC transmitter and a photo-receiver with an appropriate optical filter as a VLC receiver. The signal power distribution patterns are measured and analyzed at a transmission distance, considering the positions of the transmitter and receiver. Generally, the light from fluorescent lamps in indoor environment affects the DC level of the received signal power, which is more significant at higher receiver positions. The measurements show that the indoor VLC communication performance can be varied depending on floor reflections. Also, the fluorescent ceiling illuminations affect the DC level change of the received VLC signal waveforms.

  19. Can a road-driven car outrace a free-falling car?

    NASA Astrophysics Data System (ADS)

    Castaño, Diego J.

    2011-11-01

    Motivated by an advertising scenario in which a luxury sports sedan races against a similar car falling under the influence of gravity, a calculation using undergraduate physics and calculus is performed to theoretically predict the outcome.

  20. Cellular automaton model considering the velocity effect of a car on the successive car.

    PubMed

    Li, X; Wu, Q; Jiang, R

    2001-12-01

    In this paper we present a cellular automata model for one-lane traffic flow. The update rules of velocity of a car depend not only on the positions of this car and the car ahead of it, but also on the velocities of the two cars. Using computer simulations we obtain some basic qualitative results and the fundamental diagram of the proposed model. In comparison with those of the existing models in the literature, we find that the fundamental diagram of the proposed model is more consistent with the results measured in the real traffic, and the model is able to reproduce some relevant macroscopic states that are found in the real traffic flow but cannot be predicted by the existing models.

  1. The identification of orally bioavailable thrombopoietin agonists.

    PubMed

    Munchhof, Michael J; Antipas, Amy S; Blumberg, Laura C; Brissette, William H; Brown, Matthew F; Casavant, Jeffrey M; Doty, Jonathan L; Driscoll, James; Harris, Thomas M; Wolf-Gouveia, Lilli A; Jones, Christopher S; Li, Qifang; Linde, Robert G; Lira, Paul D; Marfat, Anthony; McElroy, Eric; Mitton-Fry, Mark; McCurdy, Sandra P; Reiter, Lawrence A; Ripp, Sharon L; Shavnya, Andrei; Thomasco, Lisa M; Trevena, Kristen A

    2009-03-01

    Recently, we disclosed a series of potent pyrimidine benzamide-based thrombopoietin receptor agonists. Unfortunately, the structural features required for the desired activity conferred physicochemical properties that were not favorable for the development of an oral agent. The physical properties of the series were improved by replacing the aminopyrimidinyl group with a piperidine-4-carboxylic acid moiety. The resulting compounds possessed favorable in vivo pharmacokinetic properties, including good bioavailability.

  2. 27. BOILER HOUSE, GENERAL VIEW LOOKING SOUTH, PAST COAL CAR ...

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

    27. BOILER HOUSE, GENERAL VIEW LOOKING SOUTH, PAST COAL CAR No. 9 TOWARD COAL CARS No. 11 & 8 - Delaware County Electric Company, Chester Station, Delaware River at South end of Ward Street, Chester, Delaware County, PA

  3. 130. Photocopied July 1978. 'CAR NO. 8 PARKED AT QUINCY ...

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

    130. Photocopied July 1978. 'CAR NO. 8 PARKED AT QUINCY NO. 2 SHAFT.' CAR NO. 8 CARRIED BUREAU OF MINES EMERGENCY TEAM TO QUINCY TO HELP FIGHT AN UNDERGROUND FIRE. JULY 1927. - Quincy Mining Company, Hancock, Houghton County, MI

  4. 10. VIEW OF BOILER SHOP FROM TOP OF BOX CAR ...

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

    10. VIEW OF BOILER SHOP FROM TOP OF BOX CAR WITH CIRCULAR CAR SHOP IN BACKGROUND LOOKING NORTHEAST. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

  5. CAR MACHINE SHOP, SECOND FLOOR, LYE TANKS FOR CLEANING METAL ...

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

    CAR MACHINE SHOP, SECOND FLOOR, LYE TANKS FOR CLEANING METAL PRIOR TO PLATING, LOOKING SOUTH FROM ATTIC. - Southern Pacific, Sacramento Shops, Car Machine Shop, 111 I Street, Sacramento, Sacramento County, CA

  6. 33. VAL, DETAIL OF PERSONNEL CAR AT THE TOP OF ...

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

    33. VAL, DETAIL OF PERSONNEL CAR AT THE TOP OF THE COUNTERWEIGHT SLAB WITH THE COUNTERWEIGHT CAR IN DISTANCE LOOKING NORTH. - Variable Angle Launcher Complex, Variable Angle Launcher, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  7. West view; Street Car Waiting House, east elevation North ...

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

    West view; Street Car Waiting House, east elevation - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  8. Detail; Street Car Waiting House, support for exterior light fixture ...

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

    Detail; Street Car Waiting House, support for exterior light fixture - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  9. East yard, north elevation of car department tool house (converted ...

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

    East yard, north elevation of car department tool house (converted from express car). - Chesapeake & Ohio Railroad, Thurmond Yards, East side New River, mouths of Arbuckle & Dunlop Circles, Thurmond, Fayette County, WV

  10. 14. AERIAL VIEW OF ENGINE DISPLAY INSIDE PASSENGER CAR SHOP ...

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

    14. AERIAL VIEW OF ENGINE DISPLAY INSIDE PASSENGER CAR SHOP (NOW A TRANSPORTATION MUSEUM) - Baltimore & Ohio Railroad, Mount Clare Passenger Car Shop, Southwest corner of Pratt & Poppleton Streets, Baltimore, Independent City, MD

  11. 20. TURNTABLE WITH CABLE CAR BAY & TAYLOR: View ...

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

    20. TURNTABLE WITH CABLE CAR - BAY & TAYLOR: View to northwest of the Bay and Taylor turntable. The gripman and conductor are turning the car around. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  12. 3. GENERAL VIEW OF PASSENGER CAR SHOP; RAILROAD TRACKS IN ...

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

    3. GENERAL VIEW OF PASSENGER CAR SHOP; RAILROAD TRACKS IN FOREGROUND - Baltimore & Ohio Railroad, Mount Clare Passenger Car Shop, Southwest corner of Pratt & Poppleton Streets, Baltimore, Independent City, MD

  13. 11. VIEW OF CIRCULAR CAR SHOP OVER TOPS OF BOX ...

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

    11. VIEW OF CIRCULAR CAR SHOP OVER TOPS OF BOX CARS LOOKING NORTHEAST. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

  14. Inside the covered hopper car loading dock at railroad level, ...

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

    Inside the covered hopper car loading dock at railroad level, looking east from the 1945 elevator into the 1913 elevator, control for the railroad car puller in background - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  15. CAR MACHINE SHOP, SECOND FLOOR, PAINT SPRAY ROOM EXTERIOR AND ...

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

    CAR MACHINE SHOP, SECOND FLOOR, PAINT SPRAY ROOM EXTERIOR AND ATTIC FLOOR SUPPORT COLUMNS AND BEAMS, LOOKING WEST. - Southern Pacific, Sacramento Shops, Car Machine Shop, 111 I Street, Sacramento, Sacramento County, CA

  16. CAR MACHINE SHOP, FIRST FLOOR, DETAIL OF WOOD COLUMN AND ...

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

    CAR MACHINE SHOP, FIRST FLOOR, DETAIL OF WOOD COLUMN AND INVERTED KING-POST TRUSS TO PROVIDE INCREASED SPAN BETWEEN COLUMNS, LOOKING SOUTH. - Southern Pacific, Sacramento Shops, Car Machine Shop, 111 I Street, Sacramento, Sacramento County, CA

  17. 31. REAR OF CAR BARN DURING RECONSTRUCTION: Photocopy of July ...

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

    31. REAR OF CAR BARN DURING RECONSTRUCTION: Photocopy of July 1908 photograph showing west rear of powerhouse and car barn. View from the north. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  18. Interior view; Street Car Waiting House North Philadelphia Station, ...

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

    Interior view; Street Car Waiting House - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  19. CAR MACHINE SHOP, SECOND FLOOR, LYE TANKS FOR CLEANING METAL ...

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

    CAR MACHINE SHOP, SECOND FLOOR, LYE TANKS FOR CLEANING METAL PRIOR TO PLATING, LOOKING SOUTHWEST FROM ATTIC. - Southern Pacific, Sacramento Shops, Car Machine Shop, 111 I Street, Sacramento, Sacramento County, CA

  20. Detail; Street Car Waiting House window, north wall North ...

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

    Detail; Street Car Waiting House window, north wall - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  1. 8. VAL CAMERA CAR, CLOSEUP VIEW OF 'FLARE' OR TRAJECTORY ...

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

    8. VAL CAMERA CAR, CLOSE-UP VIEW OF 'FLARE' OR TRAJECTORY CAMERA ON SLIDING MOUNT. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

  2. 23. POWELLTYPE CAR THROUGH GRIP REMOVAL DOOR: View looking through ...

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

    23. POWELL-TYPE CAR THROUGH GRIP REMOVAL DOOR: View looking through grip removal door into interior of a Powell-type cable car. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  3. 35. EAST FRONT OF POWERHOUSE AND CAR BARN: East front ...

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

    35. EAST FRONT OF POWERHOUSE AND CAR BARN: East front of powerhouse and car barn. 'Annex' is right end of building. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  4. North view; Street Car Waiting House, south (front) elevation ...

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

    North view; Street Car Waiting House, south (front) elevation - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

  5. 26. VIEW OF TAINTER GATE HOIST CAR (LEFT FOREGROUND), BULKHEAD ...

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

    26. VIEW OF TAINTER GATE HOIST CAR (LEFT FOREGROUND), BULKHEAD HOIST CAR (LEFT BACKGROUND) AND FLATCAR ON DAM BRIDGE, LOOKING EAST - Upper Mississippi River 9-Foot Channel Project, Lock & Dam No. 5, Minneiska, Winona County, MN

  6. 5. VIEW OF CAR BARN PROPERTY AT THIRD AVENUE AND ...

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

    5. VIEW OF CAR BARN PROPERTY AT THIRD AVENUE AND PINE STREET, LOOKING SOUTH ALONG EAST SIDE OF CAR BARN TOWARD POWER SUBSTATION - Yakima Valley Transportation Company Interurban Railroad, Connecting towns of Yakima, Selah & Wiley City, Yakima, Yakima County, WA

  7. 8. VIEW OF CAR BARN PROPERTY AT THIRD AVENUE AND ...

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

    8. VIEW OF CAR BARN PROPERTY AT THIRD AVENUE AND PINE STREET, LOOKING NORTHEAST ADJACENT TO WAREHOUSE TOWARD CAR BARN - Yakima Valley Transportation Company Interurban Railroad, Connecting towns of Yakima, Selah & Wiley City, Yakima, Yakima County, WA

  8. 35. BOILER HOUSE, TRACK FOR COAL CARS LEADING TO COAL ...

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

    35. BOILER HOUSE, TRACK FOR COAL CARS LEADING TO COAL TOWER No. 2 (NOTE: SKYLIGHT ABOVE; COAL CARS IN FAR BACKGROUND) - Delaware County Electric Company, Chester Station, Delaware River at South end of Ward Street, Chester, Delaware County, PA

  9. Signal Use by Octopuses in Agonistic Interactions.

    PubMed

    Scheel, David; Godfrey-Smith, Peter; Lawrence, Matthew

    2016-02-08

    Cephalopods show behavioral parallels to birds and mammals despite considerable evolutionary distance [1, 2]. Many cephalopods produce complex body patterns and visual signals, documented especially in cuttlefish and squid, where they are used both in camouflage and a range of interspecific interactions [1, 3-5]. Octopuses, in contrast, are usually seen as solitary and asocial [6, 7]; their body patterns and color changes have primarily been interpreted as camouflage and anti-predator tactics [8-12], though the familiar view of the solitary octopus faces a growing list of exceptions. Here, we show by field observation that in a shallow-water octopus, Octopus tetricus, a range of visible displays are produced during agonistic interactions, and these displays correlate with the outcome of those interactions. Interactions in which dark body color by an approaching octopus was matched by similar color in the reacting octopus were more likely to escalate to grappling. Darkness in an approaching octopus met by paler color in the reacting octopus accompanied retreat of the paler octopus. Octopuses also displayed on high ground and stood with spread web and elevated mantle, often producing these behaviors in combinations. This study is the first to document the systematic use of signals during agonistic interactions among octopuses. We show prima facie conformity of our results to an influential model of agonistic signaling [13]. These results suggest that interactions have a greater influence on octopus evolution than has been recognized and show the importance of convergent evolution in behavioral traits.

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

    PubMed

    Laflamme, L; Vaez, M

    2007-03-01

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

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

    NASA Astrophysics Data System (ADS)

    Ispas, N.; Năstăsoiu, M.

    2016-08-01

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

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

    PubMed

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

    2014-01-01

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

  13. Stand-off detection of alcohol vapours in moving cars

    NASA Astrophysics Data System (ADS)

    Kopczyński, Krzysztof; Kubicki, Jan; Młyńczak, Jaroslaw; Mierczyk, Jadwiga; Hackiewicz, Klaudia

    2016-12-01

    In this article we present the research on optoelectronic system for stand-off detection of alcohol vapours in moving cars. The idea of using commercially available cascade lasers was presented. Special attention was paid to the optical characteristics of the car windowpanes. It was shown that using 3.45 μm and 3.59 μm wavelengths the alcohol vapours inside a car can be successfully detected even for cars with different windows

  14. Staying Safe in the Car and on the Bus

    MedlinePlus

    ... in the Operating Room? Staying Safe in the Car and on the Bus KidsHealth > For Kids > Staying Safe in the Car and on the Bus A A A What's ... re probably getting there by riding in a car or a school bus. Most kids spend some ...

  15. Buying a Car: Using On-Line Tools. Technology Update.

    ERIC Educational Resources Information Center

    McCoy, Kimberly

    This lesson plan was created to assist learners in adult basic and literacy education programs with the car-buying process. The goal for the lesson is to "effectively use the Internet to research necessary items before purchasing a car." These nine learning objectives are set: (1) determine what kind of car is needed; (2) determine how…

  16. 78 FR 20597 - New Car Assessment Program (NCAP)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... National Highway Traffic Safety Administration 49 CFR Part 575 New Car Assessment Program (NCAP) AGENCY... for comments. SUMMARY: The U.S. New Car Assessment Program (NCAP) provides comparative information on...: For crashworthiness issues, you may contact Ms. Jennifer N. Dang, Division Chief, New Car...

  17. 49 CFR 231.21 - Tank cars without underframes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... within thirty inches from side of car, except buffer block, brake shaft, brake-shaft brackets, brake... parallel with end of car and passing through the inside face of knuckle when closed with coupler horn against the buffer block or end sill, and no other part of end of car or fixtures on same, above end...

  18. 49 CFR 231.21 - Tank cars without underframes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... within thirty inches from side of car, except buffer block, brake shaft, brake-shaft brackets, brake... parallel with end of car and passing through the inside face of knuckle when closed with coupler horn against the buffer block or end sill, and no other part of end of car or fixtures on same, above end...

  19. 49 CFR 231.21 - Tank cars without underframes.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... within thirty inches from side of car, except buffer block, brake shaft, brake-shaft brackets, brake... parallel with end of car and passing through the inside face of knuckle when closed with coupler horn against the buffer block or end sill, and no other part of end of car or fixtures on same, above end...

  20. 49 CFR 231.21 - Tank cars without underframes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... within thirty inches from side of car, except buffer block, brake shaft, brake-shaft brackets, brake... parallel with end of car and passing through the inside face of knuckle when closed with coupler horn against the buffer block or end sill, and no other part of end of car or fixtures on same, above end...

  1. 49 CFR 231.21 - Tank cars without underframes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... within thirty inches from side of car, except buffer block, brake shaft, brake-shaft brackets, brake... parallel with end of car and passing through the inside face of knuckle when closed with coupler horn against the buffer block or end sill, and no other part of end of car or fixtures on same, above end...

  2. Car App's Persuasive Design Principles and Behavior Change

    ERIC Educational Resources Information Center

    Zhang, Chao; Wan, Lili; Min, Daihwan

    2016-01-01

    The emphasis of this study lies in behavior change after using car apps that assist users in using their vehicles and establishing a process for examining the interrelationship between car app's persuasive characteristics and behavior change. A categorizing method was developed and 697 car apps were investigated and classified into eight…

  3. 40 CFR 201.13 - Standard for rail car operations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Standard for rail car operations. 201... Interstate Rail Carrier Operations Standards § 201.13 Standard for rail car operations. Effective December 31, 1976, no carrier subject to this regulation shall operate any rail car or combination of rail...

  4. Engineering Analysis in the Chem-E-Car Competition

    ERIC Educational Resources Information Center

    Lewis, Randy S.; Moshfeghian, Aliakbar; Madihally, Sundararajan V.

    2006-01-01

    The AIChE Chem-E-Car competition provides students an opportunity to demonstrate their design and teamwork skills. Engineering analysis is not required at the national competition and is often not applied. This work describes an engineering analysis of a Chem-E-Car to predict the distance traveled by the car. Engineering analysis is advantageous…

  5. 40 CFR 201.13 - Standard for rail car operations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Standard for rail car operations. 201... Interstate Rail Carrier Operations Standards § 201.13 Standard for rail car operations. Effective December 31, 1976, no carrier subject to this regulation shall operate any rail car or combination of rail...

  6. 40 CFR 201.13 - Standard for rail car operations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Standard for rail car operations. 201... Interstate Rail Carrier Operations Standards § 201.13 Standard for rail car operations. Effective December 31, 1976, no carrier subject to this regulation shall operate any rail car or combination of rail...

  7. 40 CFR 201.13 - Standard for rail car operations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Standard for rail car operations. 201... Interstate Rail Carrier Operations Standards § 201.13 Standard for rail car operations. Effective December 31, 1976, no carrier subject to this regulation shall operate any rail car or combination of rail...

  8. 49 CFR 231.18 - Cars of special construction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Cars of special construction. 231.18 Section 231... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.18 Cars of special construction. Cars of construction not covered specifically in the foregoing sections in this part, relative...

  9. 36 CFR 1192.85 - Between-car barriers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  10. 49 CFR 231.22 - Operation of track motor cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Operation of track motor cars. 231.22 Section 231... motor cars. On and after August 1, 1963, it shall be unlawful for any railroad subject to the requirements of the Safety Appliance Acts to operate or permit to be operated on its line track motor cars...

  11. 49 CFR 1033.2 - Car service orders.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  12. 36 CFR 1192.85 - Between-car barriers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  13. 29 CFR 1917.124 - Dockboards (car and bridge plates).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Dockboards (car and bridge plates). 1917.124 Section 1917..., DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.124 Dockboards (car and bridge... and across openings. (b) (c) Dockboards (car and bridge plates). (1) Dockboards shall be strong...

  14. Looking north toward Locomotive Shop (2 tracks on left), Car ...

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

    Looking north toward Locomotive Shop (2 tracks on left), Car Shop on right, and flat car in foreground. Note locomotive and car tires leaning on stock shed at left - East Broad Top Railroad & Coal Company, State Route 994, West of U.S. Route 522, Rockhill Furnace, Huntingdon County, PA

  15. 19 CFR 123.61 - Baggage arriving in baggage car.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars....

  16. 19 CFR 123.61 - Baggage arriving in baggage car.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars....

  17. 49 CFR 38.85 - Between-car barriers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  18. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and...

  19. 49 CFR 37.93 - One car per train rule.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false One car per train rule. 37.93 Section 37.93... DISABILITIES (ADA) Acquisition of Accessible Vehicles By Public Entities § 37.93 One car per train rule. (a) The definition of accessible for purposes of meeting the one car per train rule is spelled out in...

  20. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at...

  1. 19 CFR 123.61 - Baggage arriving in baggage car.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars....

  2. 7 CFR 160.28 - Tank cars of turpentine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Tank cars of turpentine. 160.28 Section 160.28... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.28 Tank cars of turpentine. A tank car loaded for shipment with spirits of turpentine shall, after the same has been sampled...

  3. 49 CFR 38.63 - Between-car barriers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  4. 49 CFR 38.85 - Between-car barriers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  5. 75 FR 53736 - Notice of National Grain Car Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-01

    ...-No. 4)] Notice of National Grain Car Council Meeting AGENCY: Surface Transportation Board, DOT. ACTION: Notice of National Grain Car Council meeting. SUMMARY: Notice is hereby given of a meeting of the National Grain Car Council (NGCC), pursuant to section 10(a)(2) of the Federal Advisory Committee Act,...

  6. 40 CFR 201.15 - Standard for car coupling operations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Standard for car coupling operations... Interstate Rail Carrier Operations Standards § 201.15 Standard for car coupling operations. Effective January 15, 1984, no carrier subject to this regulation shall conduct car coupling operations that exceed...

  7. 36 CFR 1192.63 - Between-car barriers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  8. 19 CFR 123.61 - Baggage arriving in baggage car.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Baggage arriving in baggage car. 123.61 Section... OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.61 Baggage arriving in baggage car... cars....

  9. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at...

  10. 36 CFR 1192.63 - Between-car barriers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Between-car barriers. 1192.63... Rail Vehicles and Systems § 1192.63 Between-car barriers. (a) Requirement. Suitable devices or systems... between cars. Acceptable solutions include, but are not limited to, pantograph gates, chains,...

  11. 49 CFR 231.18 - Cars of special construction.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Cars of special construction. 231.18 Section 231... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.18 Cars of special construction. Cars of construction not covered specifically in the foregoing sections in this part, relative...

  12. 49 CFR 38.63 - Between-car barriers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  13. 78 FR 58383 - Renewal of National Grain Car Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... Surface Transportation Board Renewal of National Grain Car Council AGENCY: Surface Transportation Board... Board intends to renew the charter of the National Grain Car Council (NGCC). ADDRESSES: A copy of the... 14 members from the Class I railroads (one marketing and one car management representative from...

  14. 49 CFR 231.22 - Operation of track motor cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Operation of track motor cars. 231.22 Section 231... motor cars. On and after August 1, 1963, it shall be unlawful for any railroad subject to the requirements of the Safety Appliance Acts to operate or permit to be operated on its line track motor cars...

  15. 49 CFR 238.413 - End structures of trailer cars.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false End structures of trailer cars. 238.413 Section... II Passenger Equipment § 238.413 End structures of trailer cars. (a) Except as provided in paragraph (b) of this section, the end structure of a trailer car shall be designed to include the...

  16. 49 CFR 238.413 - End structures of trailer cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false End structures of trailer cars. 238.413 Section... II Passenger Equipment § 238.413 End structures of trailer cars. (a) Except as provided in paragraph (b) of this section, the end structure of a trailer car shall be designed to include the...

  17. 36 CFR 1192.85 - Between-car barriers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Between-car barriers. 1192.85... Rail Vehicles and Systems § 1192.85 Between-car barriers. Where vehicles operate in a high-platform... inadvertently stepping off the platform between cars. Appropriate devices include, but are not limited...

  18. 49 CFR 38.85 - Between-car barriers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  19. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and...

  20. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at...

  1. 36 CFR 1192.63 - Between-car barriers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  2. 40 CFR 201.15 - Standard for car coupling operations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Standard for car coupling operations... Interstate Rail Carrier Operations Standards § 201.15 Standard for car coupling operations. Effective January 15, 1984, no carrier subject to this regulation shall conduct car coupling operations that exceed...

  3. 49 CFR 38.63 - Between-car barriers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  4. 49 CFR 231.18 - Cars of special construction.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Cars of special construction. 231.18 Section 231... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.18 Cars of special construction. Cars of construction not covered specifically in the foregoing sections in this part, relative...

  5. 7 CFR 160.28 - Tank cars of turpentine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Tank cars of turpentine. 160.28 Section 160.28... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.28 Tank cars of turpentine. A tank car loaded for shipment with spirits of turpentine shall, after the same has been sampled...

  6. 36 CFR 1192.85 - Between-car barriers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  7. 19 CFR 123.61 - Baggage arriving in baggage car.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Baggage arriving in baggage car. 123.61 Section... car. An inward foreign manifest on Customs Form 7533 shall be used for all baggage arriving in baggage cars....

  8. 40 CFR 201.15 - Standard for car coupling operations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Standard for car coupling operations... Interstate Rail Carrier Operations Standards § 201.15 Standard for car coupling operations. Effective January 15, 1984, no carrier subject to this regulation shall conduct car coupling operations that exceed...

  9. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at...

  10. 7 CFR 160.28 - Tank cars of turpentine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Tank cars of turpentine. 160.28 Section 160.28... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.28 Tank cars of turpentine. A tank car loaded for shipment with spirits of turpentine shall, after the same has been sampled...

  11. 40 CFR 201.15 - Standard for car coupling operations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Standard for car coupling operations... Interstate Rail Carrier Operations Standards § 201.15 Standard for car coupling operations. Effective January 15, 1984, no carrier subject to this regulation shall conduct car coupling operations that exceed...

  12. 49 CFR 238.413 - End structures of trailer cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false End structures of trailer cars. 238.413 Section... II Passenger Equipment § 238.413 End structures of trailer cars. (a) Except as provided in paragraph (b) of this section, the end structure of a trailer car shall be designed to include the...

  13. 29 CFR 1917.124 - Dockboards (car and bridge plates).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Dockboards (car and bridge plates). 1917.124 Section 1917..., DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.124 Dockboards (car and bridge... and across openings. (b) (c) Dockboards (car and bridge plates). (1) Dockboards shall be strong...

  14. 75 FR 14496 - Commerce Acquisition Regulation (CAR); Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... CFR Part 1352 RIN 0605-AA26 Commerce Acquisition Regulation (CAR); Correction AGENCY: Department of...: On March 8, 2010, the Department of Commerce published a final rule to amend the CAR to update the regulations since its last revision on September 12, 1995. That rule updated the CAR to bring it...

  15. 49 CFR 38.63 - Between-car barriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  16. 49 CFR 231.18 - Cars of special construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Cars of special construction. 231.18 Section 231... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.18 Cars of special construction. Cars of construction not covered specifically in the foregoing sections in this part, relative...

  17. 36 CFR 1192.85 - Between-car barriers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  18. 30 CFR 56.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Coupling or uncoupling cars. 56.14215 Section... Equipment Safety Practices and Operational Procedures § 56.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and then moved at...

  19. 49 CFR 174.67 - Tank car unloading.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 29 CFR 1917.124 - Dockboards (car and bridge plates).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Dockboards (car and bridge plates). 1917.124 Section 1917..., DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.124 Dockboards (car and bridge... and across openings. (b) (c) Dockboards (car and bridge plates). (1) Dockboards shall be strong...

  1. 76 FR 59186 - Renewal of National Grain Car Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... Surface Transportation Board Renewal of National Grain Car Council AGENCY: Surface Transportation Board... Board intends to renew the charter of the National Grain Car Council (NGCC). ADDRESSES: A copy of the... marketing and one car management representative from each Class I), 7 representatives from Class II and...

  2. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and...

  3. 40 CFR 201.15 - Standard for car coupling operations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Standard for car coupling operations... Interstate Rail Carrier Operations Standards § 201.15 Standard for car coupling operations. Effective January 15, 1984, no carrier subject to this regulation shall conduct car coupling operations that exceed...

  4. 29 CFR 1917.124 - Dockboards (car and bridge plates).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Dockboards (car and bridge plates). 1917.124 Section 1917..., DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.124 Dockboards (car and bridge... and across openings. (b) (c) Dockboards (car and bridge plates). (1) Dockboards shall be strong...

  5. 49 CFR 1033.2 - Car service orders.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  6. 7 CFR 160.28 - Tank cars of turpentine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Tank cars of turpentine. 160.28 Section 160.28... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.28 Tank cars of turpentine. A tank car loaded for shipment with spirits of turpentine shall, after the same has been sampled...

  7. 49 CFR 38.85 - Between-car barriers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  8. 49 CFR 1033.2 - Car service orders.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  9. 7 CFR 160.28 - Tank cars of turpentine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Tank cars of turpentine. 160.28 Section 160.28... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.28 Tank cars of turpentine. A tank car loaded for shipment with spirits of turpentine shall, after the same has been sampled...

  10. 49 CFR 1033.2 - Car service orders.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  11. 49 CFR 38.85 - Between-car barriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  12. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and...

  13. 78 FR 52606 - Notice of National Grain Car Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... Surface Transportation Board Notice of National Grain Car Council Meeting AGENCY: Surface Transportation Board, DOT. ACTION: Notice of National Grain Car Council meeting. SUMMARY: Notice is hereby given of a meeting of the National Grain Car Council (NGCC), pursuant to the Federal Advisory Committee Act, 5...

  14. 49 CFR 231.18 - Cars of special construction.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Cars of special construction. 231.18 Section 231... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.18 Cars of special construction. Cars of construction not covered specifically in the foregoing sections in this part, relative...

  15. 49 CFR 37.93 - One car per train rule.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false One car per train rule. 37.93 Section 37.93... DISABILITIES (ADA) Acquisition of Accessible Vehicles By Public Entities § 37.93 One car per train rule. (a) The definition of accessible for purposes of meeting the one car per train rule is spelled out in...

  16. 49 CFR 37.93 - One car per train rule.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false One car per train rule. 37.93 Section 37.93... DISABILITIES (ADA) Acquisition of Accessible Vehicles By Public Entities § 37.93 One car per train rule. (a) The definition of accessible for purposes of meeting the one car per train rule is spelled out in...

  17. 49 CFR 231.22 - Operation of track motor cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Operation of track motor cars. 231.22 Section 231... motor cars. On and after August 1, 1963, it shall be unlawful for any railroad subject to the requirements of the Safety Appliance Acts to operate or permit to be operated on its line track motor cars...

  18. 49 CFR 37.93 - One car per train rule.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false One car per train rule. 37.93 Section 37.93... DISABILITIES (ADA) Acquisition of Accessible Vehicles By Public Entities § 37.93 One car per train rule. (a) The definition of accessible for purposes of meeting the one car per train rule is spelled out in...

  19. 49 CFR 38.63 - Between-car barriers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  20. 49 CFR 1033.2 - Car service orders.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  1. 30 CFR 57.14215 - Coupling or uncoupling cars.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Coupling or uncoupling cars. 57.14215 Section... and Equipment Safety Practices and Operational Procedures § 57.14215 Coupling or uncoupling cars. Prior to coupling or uncoupling cars manually, trains shall be brought to a complete stop, and...

  2. 49 CFR 37.93 - One car per train rule.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false One car per train rule. 37.93 Section 37.93... DISABILITIES (ADA) Acquisition of Accessible Vehicles By Public Entities § 37.93 One car per train rule. (a) The definition of accessible for purposes of meeting the one car per train rule is spelled out in...

  3. 29 CFR 1917.124 - Dockboards (car and bridge plates).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Dockboards (car and bridge plates). 1917.124 Section 1917..., DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.124 Dockboards (car and bridge... and across openings. (b) (c) Dockboards (car and bridge plates). (1) Dockboards shall be strong...

  4. 36 CFR 1192.63 - Between-car barriers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  5. 37. WEST REAR OF POWERHOUSE AND CAR BARN: West rear ...

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

    37. WEST REAR OF POWERHOUSE AND CAR BARN: West rear of powerhouse and car barn, showing the turntable and tracks used to move cars in and out of the building's repair and storage area. - San Francisco Cable Railway, Washington & Mason Streets, San Francisco, San Francisco County, CA

  6. 36 CFR 1192.63 - Between-car barriers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  7. Helical grip for the cable cars of San Francisco

    NASA Technical Reports Server (NTRS)

    Peyran, R. J.

    1979-01-01

    A helical cable car grip to minimize high maintenance costs of San Francisco's cable car operation is presented. The grip establishes a rolling contact between the cable and grip to reduce sliding friction and associated cable wear. The design, development, and testing of the helical cable car grip are described.

  8. Elevation (typical EBT Coal Hopper Car) with scale. 3 Bay ...

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

    Elevation (typical EBT Coal Hopper Car) with scale. 3 Bay Steel Hopper Car with side extensions raising coal carrying capacity to 80,000 pounds. Note cars on either side lack extensions limiting their coal capacity to 70,000 pounds - East Broad Top Railroad & Coal Company, State Route 994, West of U.S. Route 522, Rockhill Furnace, Huntingdon County, PA

  9. 49 CFR 231.22 - Operation of track motor cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Operation of track motor cars. 231.22 Section 231... motor cars. On and after August 1, 1963, it shall be unlawful for any railroad subject to the requirements of the Safety Appliance Acts to operate or permit to be operated on its line track motor cars...

  10. 49 CFR 231.22 - Operation of track motor cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Operation of track motor cars. 231.22 Section 231... motor cars. On and after August 1, 1963, it shall be unlawful for any railroad subject to the requirements of the Safety Appliance Acts to operate or permit to be operated on its line track motor cars...

  11. Conditional Ablation of Mediator Subunit MED1 (MED1/PPARBP) Gene in Mouse Liver Attenuates Glucocorticoid Receptor Agonist Dexamethasone-Induced Hepatic Steatosis

    PubMed Central

    JIA, YUZHI; VISWAKARMA, NAVIN; FU, TAO; YU, SONGTAO; RAO, M. SAMBASIVA; BORENSZTAJN, JAYME; REDDY, JANARDAN K.

    2009-01-01

    Glucocorticoid receptor (GR) agonist dexamethasone (Dex) induces hepatic steatosis and enhances constitutive androstane receptor (CAR) expression in the liver. CAR is known to worsen hepatic injury in nonalcoholic hepatic steatosis. Because transcription coactivator MED1/PPARBP gene is required for GR- and CAR-mediated transcriptional activation, we hypothesized that disruption of MED1/PPARBP gene in liver cells would result in the attenuation of Dex-induced hepatic steatosis. Here we show that liver-specific disruption of MED1 gene (MED1ΔLiv) improves Dex-induced steatotic phenotype in the liver. In wild-type mice Dex induced severe hepatic steatosis and caused reduction in medium- and short-chain acyl-CoA dehydrogenases that are responsible for mitochondrial β-oxidation. In contrast, Dex did not induce hepatic steatosis in mice conditionally null for hepatic MED1, as it failed to inhibit fatty acid oxidation enzymes in the liver. MED1ΔLiv livers had lower levels of GR-regulated CAR mRNA compared to wild-type mouse livers. Microarray gene expression profiling showed that absence of MED1 affects the expression of the GR-regulated genes responsible for energy metabolism in the liver. These results establish that absence of MED1 in the liver diminishes Dex-induced hepatic steatosis by altering the GR- and CAR-dependent gene functions. PMID:19630272

  12. 49 CFR 179.201 - Individual specification requirements applicable to non-pressure tank car tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... to non-pressure tank car tanks. 179.201 Section 179.201 Transportation Other Regulations Relating to... MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes... car tanks....

  13. 49 CFR 179.400 - General specification applicable to cryogenic liquid tank car tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... liquid tank car tanks. 179.400 Section 179.400 Transportation Other Regulations Relating to... MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specification for Cryogenic Liquid Tank Car Tanks and... liquid tank car tanks....

  14. 49 CFR 180.519 - Periodic retest and inspection of tank cars other than single-unit tank car tanks.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Periodic retest and inspection of tank cars other... § 180.519 Periodic retest and inspection of tank cars other than single-unit tank car tanks. (a) General... periodically as specified in Retest Table 1 of paragraph (b)(5) of this section. Retests may be made at...

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

    ERIC Educational Resources Information Center

    Highsmith, Joni Bitman

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

  16. [The compensatory light for car plate recognition].

    PubMed

    Yu, Chun-yu; Chang, Ben-kang; Wang, Qing-bao

    2005-07-01

    In the intelligent traffic system, the automatic recognition system of the car plate is an important development field. This system must satisfy the requirement of all-day long inspection. In the course of inspection, the lack of natural light(such as at night, in rainy day...) could be a problem, that is to say there could be backlighting problem, and this problem can be solved by using compensatory light. By now, the high-power floodlight has been adopted. Because of its own characteristics of the floodlight, the satisfied result cannot be obtained. In the present thesis, how to select the right light is analyzed, including car lights' spectra and visual response, and so on. The results of the practices are very satisfied.

  17. Unified spontaneous Raman and CARS system

    NASA Astrophysics Data System (ADS)

    Lederman, S.; Posillico, C.

    1981-06-01

    In order to provide a more universally applicable diagnostic apparatus, a novel device based on simultaneous LDV and spontaneous Raman diagnostics is proposed. The simplest configuration of the device uses a Q-switched ruby laser and a Raman cell filled with a gas of particular interest, the Stokes line of which is stimulated. When the line is colinearly mixed with the primary beam, a coherent anti-Stokes Raman scattering (CARS) signal is generated in a given flowfield. A part of the incident ruby laser is simultaneously utilized to obtain spontaneous Raman signals, yielding the advantages of both the spontaneous and the CARS techniques using only one ruby laser. Experimental results demonstrate that the system can provide data on most practical flowfields, whether they are clean or contaminated and environmentally friendly or hostile.

  18. Corporate ergonomics programme at Volvo Car Corporation.

    PubMed

    Munck-Ulfsfält, Ulla; Falck, Annki; Forsberg, Anette; Dahlin, Christer; Eriksson, Anders

    2003-01-01

    One of Volvo Car Corporation's core values is "Environmental Care". Volvo Cars has a tradition of attention to the work environment and has over the years developed a working environment management system, an organisational strategy for the participation of everyone, a working environment policy, standards/specifications and methods for efficient practical performance. The Production Ergonomics Project is an example of this. In order to achieve results in ergonomics one has to work comprehensively, which means working with the product, the process, the workplace, the individuals and the work organisation. The key to success is to train all categories concerned in load ergonomics and to perform methodical ergonomic work through the whole chain from design to production.

  19. Car Accident Reconstruction and Head Injury Correlation

    NASA Astrophysics Data System (ADS)

    Chawla, A.; Grover, V.; Mukherjee, S.; Hassan, A. M.

    2013-04-01

    Estimation of brain damage remains an elusive issue and controlled tests leading to brain damage cannot be carried out on volunteers. This study reconstructs real-world car accidents to estimate the kinematics of the head impact. This data is to be used to estimate the head injury measures through computer simulations and then correlate reported skull as well as brain damage to impact measures; whence validating the head FE model (Willinger, IJCrash 8:605-617, 2003). In this study, two crash cases were reconstructed. Injury correlation was successful in one of these cases in that the injuries to the brain of one of the car drivers could be correlated in terms of type, location and severity when compared with the tolerance limits of relevant injury parameters (Willinger, IJCrash 8:605-617, 2003).

  20. Engineering CAR-T Cells: Design Concepts

    PubMed Central

    Srivastava, Shivani; Riddell, Stanley R.

    2016-01-01

    Despite being empirically designed based on a simple understanding of TCR signaling, T cells engineered with chimeric antigen receptors (CARs) have been remarkably successful in treating patients with advanced refractory B cell malignancies. However, many challenges remain in improving the safety and efficacy of this therapy and extending it toward the treatment of epithelial cancers. Other aspects TCR signaling beyond those directly provided by CD3ζ and CD28 phosphorylation strongly influence a T cell’s ability to differentiate and acquire full effector functions. Here, we discuss how the principles of TCR recognition, including spatial constraints, Kon/Koff rates, and synapse formation, along with in-depth analysis of CAR signaling might be applied to develop safer and more effective synthetic tumor targeting receptors. PMID:26169254

  1. Simultaneous CARS and Interferometric Rayleigh Scattering

    NASA Technical Reports Server (NTRS)

    Bivolaru, Daniel; Danehy, Paul M.; Grinstead, Keith D., Jr.; Tedder, Sarah; Cutler, Andrew D.

    2006-01-01

    This paper reports for the first time the combination of a dual-pump coherent anti-Stokes Raman scattering system with an interferometric Rayleigh scattering system (CARS - IRS) to provide time-resolved simultaneous measurement of multiple properties in combustion flows. The system uses spectrally narrow green (seeded Nd:YAG at 532 nm) and yellow (552.9 nm) pump beams and a spectrally-broad red (607 nm) beam as the Stokes beam. A spectrometer and a planar Fabry-Perot interferometer used in the imaging mode are used to record the spectrally broad CARS spectra and the spontaneous Rayleigh scattering spectra, respectively. Time-resolved simultaneous measurement of temperature, absolute mole fractions of N2, O2, and H2, and two components of velocity in a Hencken burner flame were performed to demonstrate the technique.

  2. The muscarinic acetylcholine receptor agonist BuTAC mediates antipsychotic-like effects via the M4 subtype.

    PubMed

    Watt, Marla L; Rorick-Kehn, Linda; Shaw, David B; Knitowski, Karen M; Quets, Anne T; Chesterfield, Amy K; McKinzie, David L; Felder, Christian C

    2013-12-01

    The generation of muscarinic acetylcholine receptor (mAChR) subtype-selective compounds has been challenging, requiring use of nonpharmacological approaches, such as genetically engineered animals, to deepen our understanding of the potential that members of the muscarinic receptor subtype family hold as therapeutic drug targets. The muscarinic receptor agonist 'BuTAC' was previously shown to exhibit efficacy in animal models of psychosis, although the particular receptor subtype(s) responsible for such activity was unclear. Here, we evaluate the in vitro functional agonist and antagonist activity of BuTAC using an assay that provides a direct measure of G protein activation. In addition, we employ the conditioned avoidance response paradigm, an in vivo model predictive of antipsychotic activity, and mouse genetic deletion models to investigate which presynaptic mAChR subtype mediates the antipsychotic-like effects of BuTAC. Our results show that, in vitro, BuTAC acts as a full agonist at the M2AChR and a partial agonist at the M1 and M4 receptors, with full antagonist activity at M3- and M5AChRs. In the mouse conditioned avoidance response (CAR) assay, BuTAC exhibits an atypical antipsychotic-like profile by selectively decreasing avoidance responses at doses that do not induce escape failures. CAR results using M2(-/-), M4(-/-), and M2/M4 (M2/M4(-/-)) mice found that the effects of BuTAC were near completely lost in M2/M4(-/-) double-knockout mice and potency of BuTAC was right-shifted in M4(-/-) as compared with wild-type and M2(-/-) mice. The M2/M4(-/-) mice showed no altered sensitivity to the antipsychotic effects of either haloperidol or clozapine, suggesting that these compounds mediate their actions in CAR via a non-mAChR-mediated mechanism. These data support a role for the M4AChR subtype in mediating the antipsychotic-like activity of BuTAC and implicate M4AChR agonism as a potential novel therapeutic mechanism for ameliorating symptoms associated with

  3. Resonant CARS Detection of OH Radicals.

    DTIC Science & Technology

    1985-01-31

    pp. 3819-3825. 13. Bloembergen, N., U.L. Lotem, and 4. Eckbreth, A.C., G.M. Dobbs, J.H. R.T. Lynch, "Llneshapes in Coherent Stufflebeam , and P.A...Combustion Engine," Aplied Oprics, VnI. 18, 15 November, 1979, pp. 3819-3825. i4 4Eckbreth, A.C., Dobbs, G.M., Stufflebeam , 1.11., .x , P.A., "CARS

  4. Effects of motivation on car-following

    NASA Technical Reports Server (NTRS)

    Boesser, T.

    1982-01-01

    Speed- and distance control by automobile-drivers is described best by linear models when the leading vehicles speed varies randomly and when the driver is motivated to keep a large distance. A car-following experiment required subjects to follow at 'safe' or at 'close' distance. Transfer-characteristics of the driver were extended by 1 octave when following 'closely'. Nonlinear properties of drivers control-movements are assumed to reflect different motivation-dependent control strategies.

  5. Health Monitoring System for Car Seat

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

    A health monitoring system for use with a child car seat has sensors mounted in the seat to monitor one or more health conditions of the seat's occupant. A processor monitors the sensor's signals and generates status signals related to the monitored conditions. A transmitter wireless transmits the status signals to a remotely located receiver. A signaling device coupled to the receiver produces at least one sensory (e.g., visual, audible, tactile) output based on the status signals.

  6. Distributed wireless sensor for smart car seats

    NASA Astrophysics Data System (ADS)

    Baz, A.; Smoker, Jason

    2009-03-01

    A distributed wireless sensor network is embedded inside car seats to enable the measurements of the weight of the occupants, location of their center of gravity, and spatial orientation of their bodies. Based on these measurements, intelligent decisions can be made to ensure their comfort and safety particularly in case of accidents. Appropriate activation of the inflatable bags according to the weight and position of the occupants will be critical to avoiding unnecessary and undesirable injuries.

  7. Bessel beam CARS of axially structured samples

    NASA Astrophysics Data System (ADS)

    Heuke, Sandro; Zheng, Juanjuan; Akimov, Denis; Heintzmann, Rainer; Schmitt, Michael; Popp, Jürgen

    2015-06-01

    We report about a Bessel beam CARS approach for axial profiling of multi-layer structures. This study presents an experimental implementation for the generation of CARS by Bessel beam excitation using only passive optical elements. Furthermore, an analytical expression is provided describing the generated anti-Stokes field by a homogeneous sample. Based on the concept of coherent transfer functions, the underling resolving power of axially structured geometries is investigated. It is found that through the non-linearity of the CARS process in combination with the folded illumination geometry continuous phase-matching is achieved starting from homogeneous samples up to spatial sample frequencies at twice of the pumping electric field wave. The experimental and analytical findings are modeled by the implementation of the Debye Integral and scalar Green function approach. Finally, the goal of reconstructing an axially layered sample is demonstrated on the basis of the numerically simulated modulus and phase of the anti-Stokes far-field radiation pattern.

  8. Bessel beam CARS of axially structured samples.

    PubMed

    Heuke, Sandro; Zheng, Juanjuan; Akimov, Denis; Heintzmann, Rainer; Schmitt, Michael; Popp, Jürgen

    2015-06-05

    We report about a Bessel beam CARS approach for axial profiling of multi-layer structures. This study presents an experimental implementation for the generation of CARS by Bessel beam excitation using only passive optical elements. Furthermore, an analytical expression is provided describing the generated anti-Stokes field by a homogeneous sample. Based on the concept of coherent transfer functions, the underling resolving power of axially structured geometries is investigated. It is found that through the non-linearity of the CARS process in combination with the folded illumination geometry continuous phase-matching is achieved starting from homogeneous samples up to spatial sample frequencies at twice of the pumping electric field wave. The experimental and analytical findings are modeled by the implementation of the Debye Integral and scalar Green function approach. Finally, the goal of reconstructing an axially layered sample is demonstrated on the basis of the numerically simulated modulus and phase of the anti-Stokes far-field radiation pattern.

  9. New Life For The Cable Cars

    NASA Technical Reports Server (NTRS)

    1979-01-01

    NASA-Arnes' major recommendations involved ways of extending cable life in the interests of safety and economy. Other recommendations included redesign of the cablegripping device, substitution of modern braking mechanisms, improvements in cable pulleys and other components, and new inspection and repair procedures. Ames followed up by designing and installing new equipment to lengthen cable life, which averages only about two months. These cables-four of them for four different car routes--are endless belts, like ski lift cables, running from the downtown car barn to the end of each line. When a cable is installed, the loop is closed by splicing the ends together in a 72-footlong splice. The splice is the weakest part of the cable and a source of problems. When the car operator applies his grip while over a splice, the resulting friction sometimes causes the splice to "unbraid" and fail; this means shutting down the line until the splice can be repaired. Even when unbraiding does not occur, gripping a splice shortens cable life by friction wear. Worn cables are a safety hazard and must be replaced, which is expensive at $1.60 a foot for 10,000 to 20,000 feet of cable.

  10. Cognitive compatibility of motorcyclists and car drivers.

    PubMed

    Walker, Guy H; Stanton, Neville A; Salmon, Paul M

    2011-05-01

    Incompatibility between different types of road user is a problem that previous research has shown to be resistant to a range of interventions. Cars and motorcycles are particularly prone to this. Insight is provided in this paper by a naturalistic method using concurrent verbal protocols and an automatic, highly reliable semantic network creation tool. The method shows how the same road situation is interpreted differently by car drivers and motorcyclists in ways congruent with wider accident rates. Analysis of the structure and content of the semantic networks reveals a greater degree of cognitive compatibility on faster roads such as motorways, but evidence of more critical incompatibilities on country roads and junctions. Both of these road types are implicated in helping to activate cognitive schema which in turn generate stereotypical behaviors unfavourable to the anticipation of motorcyclists by car drivers. The results are discussed in terms of practical measures such as road signs which warn of events behind as well as in front, cross-mode training and the concept of route driveability.

  11. Bessel beam CARS of axially structured samples

    PubMed Central

    Heuke, Sandro; Zheng, Juanjuan; Akimov, Denis; Heintzmann, Rainer; Schmitt, Michael; Popp, Jürgen

    2015-01-01

    We report about a Bessel beam CARS approach for axial profiling of multi-layer structures. This study presents an experimental implementation for the generation of CARS by Bessel beam excitation using only passive optical elements. Furthermore, an analytical expression is provided describing the generated anti-Stokes field by a homogeneous sample. Based on the concept of coherent transfer functions, the underling resolving power of axially structured geometries is investigated. It is found that through the non-linearity of the CARS process in combination with the folded illumination geometry continuous phase-matching is achieved starting from homogeneous samples up to spatial sample frequencies at twice of the pumping electric field wave. The experimental and analytical findings are modeled by the implementation of the Debye Integral and scalar Green function approach. Finally, the goal of reconstructing an axially layered sample is demonstrated on the basis of the numerically simulated modulus and phase of the anti-Stokes far-field radiation pattern. PMID:26046671

  12. The Fuel Cell Powered Club Car Carryall

    NASA Technical Reports Server (NTRS)

    Eichenberg, Dennis J.

    2005-01-01

    The NASA Glenn Research Center initiated development of the Fuel Cell Powered Club Car Carryall as a way to reduce pollution in industrial settings, reduce fossil fuel consumption and reduce operating costs for transportation systems. The Club Car Carryall provides an inexpensive approach to advance the state of the art in electric vehicle technology in a practical application. The project transfers space technology to terrestrial use via non-traditional partners, and provides power system data valuable for future aeronautics and space applications. The work was done under the Hybrid Power Management (HPM) Program. The Carryall is a state of the art, dedicated, electric utility vehicle. Hydrogen powered proton exchange membrane (PEM) fuel cells are the primary power source. Ultracapacitors were used for energy storage as long life, maintenance free operation, and excellent low temperature performance is essential. Metal hydride hydrogen storage was used to store hydrogen in a safe and efficient low-pressure solid form. The report concludes that the Fuel Cell Powered Club Car Carryall can provide excellent performance, and that the implementation of fuel cells in conjunction with ultracapacitors in the power system can provide significant reliability and performance improvements.

  13. EcoCAR Challenge: Finish Line

    SciTech Connect

    2011-01-01

    The EcoCAR Challenege is a competition that challenges participating students from across North America to re-engineer a vehicle donated by General Motors. With the goal of minimizing the vehicle's fuel consumption and emissions, while maintaining its utility, safety and performance, teams had to find the best combination of cutting-edge technologies to meet these objectives. In the final year, the vehicles ran through a series of safety and technical tests at GM's Proving Ground in Milford, Michigan very similar to those GM's own production vehicles undergo. As EcoCAR wraps up, it is only the beginning for the next chapter in the DOE's 23-year history of advanced vehicle technology competitions. In April, Assistant Secretary for Policy and International Affairs David Sandalow announced the launch of EcoCAR 2: Plugging into the Future http://www.ecocar2.org/index.html . We look forward to seeing the new and innovative designs that students bring to this challenge and know they will find a way to exceed even our highest expectations.

  14. Burning Cars in a Parking Lot

    NASA Astrophysics Data System (ADS)

    Bertoin, Jean

    2011-08-01

    Knuth's parking scheme is a model in computer science for hashing with linear probing. One may imagine a circular parking lot with n sites; cars arrive at each site with unit rate. When a car arrives at a vacant site, it parks there; otherwise it turns clockwise and parks at the first vacant site which is found. We incorporate fires into this model by throwing Molotov cocktails on each site at a smaller rate n - α , where 0 < α < 1 is a fixed parameter. When a car is hit by a Molotov cocktail, it burns and the fire propagates to the entire occupied interval which turns vacant. We show that with high probability when n → ∞, the parking lot becomes saturated at a time close to 1 (i.e. as in the absence of fire) for α > 2/3, whereas for α < 2/3, the average occupation approaches 1 at time 1 but then quickly drops to 0 before the parking lot is ever saturated. Our study relies on asymptotics for the occupation of the parking lot without fires in certain regimes which may be of independent interest.

  15. CARS microscopy of Alzheimer's diseased brain tissue

    NASA Astrophysics Data System (ADS)

    Enejder, Annika; Kiskis, Juris; Fink, Helen; Nyberg, Lena; Thyr, Jakob; Li, Jia-Yi

    2014-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder currently without cure, characterized by the presence of extracellular plaques surrounded by dystrophic neurites. In an effort to understand the underlying mechanisms, biochemical analysis (protein immunoblot) of plaque extracts reveals that they consist of amyloid-beta (Aβ) peptides assembled as oligomers, protofibrils and aggregates. Their spatial distribution has been confirmed by Thioflavin-S or immuno-staining with fluorescence microscopy. However, it is increasingly understood that the protein aggregation is only one of several mechanism that causes neuronal dysfunction and death. This raises the need for a more complete biochemical analysis. In this study, we have complemented 2-photon fluorescence microscopy of Thioflavin-S and Aβ immuno-stained human AD plaques with CARS microscopy. We show that the chemical build-up of AD plaques is more complex and that Aβ staining does not provide the complete picture of the spatial distribution or the molecular composition of AD plaques. CARS images provide important complementary information to that obtained by fluorescence microscopy, motivating a broader introduction of CARS microscopy in the AD research field.

  16. EcoCAR Challenge: Finish Line

    ScienceCinema

    None

    2016-07-12

    The EcoCAR Challenege is a competition that challenges participating students from across North America to re-engineer a vehicle donated by General Motors. With the goal of minimizing the vehicle's fuel consumption and emissions, while maintaining its utility, safety and performance, teams had to find the best combination of cutting-edge technologies to meet these objectives. In the final year, the vehicles ran through a series of safety and technical tests at GM's Proving Ground in Milford, Michigan very similar to those GM's own production vehicles undergo. As EcoCAR wraps up, it is only the beginning for the next chapter in the DOE's 23-year history of advanced vehicle technology competitions. In April, Assistant Secretary for Policy and International Affairs David Sandalow announced the launch of EcoCAR 2: Plugging into the Future http://www.ecocar2.org/index.html . We look forward to seeing the new and innovative designs that students bring to this challenge and know they will find a way to exceed even our highest expectations.

  17. Development of an in vitro high content imaging assay for quantitative assessment of CAR-dependent mouse, rat, and human primary hepatocyte proliferation.

    PubMed

    Soldatow, Valerie; Peffer, Richard C; Trask, O Joseph; Cowie, David E; Andersen, Melvin E; LeCluyse, Edward; Deisenroth, Chad

    2016-10-01

    Rodent liver tumors promoted by constitutive androstane receptor (CAR) activation are known to be mediated by key events that include CAR-dependent gene expression and hepatocellular proliferation. Here, an in vitro high content imaging based assay was developed for quantitative assessment of nascent DNA synthesis in primary hepatocyte cultures from mouse, rat, and human species. Detection of DNA synthesis was performed using direct DNA labeling with the nucleoside analog 5-ethynyl-2'-deoxyuridine (EdU). The assay was multiplexed to enable direct quantitation of DNA synthesis, cytotoxicity, and cell count endpoints. An optimized defined medium cocktail was developed to sensitize hepatocytes to cell cycle progression. The baseline EdU response to defined medium was greatest for mouse, followed by rat, and then human. Hepatocytes from all three species demonstrated CAR activation in response to the CAR agonists TCPOBOP, CITCO, and phenobarbital based on increased gene expression for Cyp2b isoforms. When evaluated for a proliferation phenotype, TCPOBOP and CITCO exhibited significant dose-dependent increases in frequency of EdU labeling in mouse and rat hepatocytes that was not observed in hepatocytes from three human donors. The observed species differences are consistent with CAR activators inducing a proliferative response in rodents, a key event in the liver tumor mode of action that is not observed in humans.

  18. Regulation of gene expression by CAR: an update.

    PubMed

    Kobayashi, Kaoru; Hashimoto, Mari; Honkakoski, Paavo; Negishi, Masahiko

    2015-07-01

    The constitutive androstane receptor (CAR), a member of the nuclear receptor superfamily, is a well-known xenosensor that regulates hepatic drug metabolism and detoxification. CAR activation can be elicited by a large variety of xenobiotics, including phenobarbital (PB) which is not a directly binding CAR ligand. The mechanism of CAR activation is complex and involves translocation from the cytoplasm into the nucleus, followed by further activation steps in the nucleus. Recently, epidermal growth factor receptor (EGFR) has been identified as a PB-responsive receptor, and PB activates CAR by inhibiting the EGFR signaling. In addition to regulation of drug metabolism, activation of CAR has multiple biological end points such as modulation of xenobiotic-elicited liver injury, and the role of CAR in endobiotic functions such as glucose metabolism and cholesterol homeostasis is increasingly recognized. Thus, investigations on the molecular mechanism of CAR activation are critical for the real understanding of CAR-mediated processes. Here, we summarize the current understanding of mechanisms by which CAR activators regulate gene expression through cellular signaling pathways and the roles of CAR on xenobiotic-elicited hepatocellular carcinoma, liver injury, glucose metabolism and cholesterol homeostasis.

  19. Assessment of resist outgassing related EUV optics contamination for CAR and non-CAR material chemistries

    NASA Astrophysics Data System (ADS)

    Pollentier, I.; Neira, I.; Gronheid, R.

    2011-04-01

    EUV lithography is expected to be the key lithography option for sub-22nm device manufacturing. In order to meet the required imaging capability, resist performance improvements are being investigated by exploring both chemically amplified resists (CAR) and non-CAR chemistries. Another critical item related to resist chemistry is the EUV irradiation induced outgassing and its risk for optics contamination, especially towards high source power (pre-) productions tools. In this area it is important to characterize for the different chemistries which resist components are critical for EUV induced outgassing and - more important - which can result in non-cleanable mirror contamination. In this paper, we will explore the outgassing and contamination behavior of CAR and non-CAR resist by using Residual Gas Analysis (RGA) for identifying the resist outgassing characteristics, and by Witness Sample (WS) testing to evaluate the tendency for contamination. For CAR resists, it has been found that the PAG cation is a key component contributing to the contamination, but its impact can be changed by changing the resist formulation. In this investigation several model resists have been evaluated in order to understand which chemical components have - or don't have - an impact on the contamination. This has led to a proposal of a definition for a resist family. For non-CAR materials, the investigation has focused to a number of example resists. Most results are related to poly(-olefin sulfones), which have been proven to be good candidate materials for outgassing and contamination learning. The tests have confirmed that aromatic groups present in resist outgassing are playing an important role. As an opposite example of non-CAR material, the inorganic Inpria resist was tested, which revealed that its resist outgassing (water and oxygen) can remove carbon contamination. The combined work on CAR and non-CAR outgassing and contamination has learned significantly on the relationship

  20. Establishing guidelines for CAR-T cells: challenges and considerations.

    PubMed

    Wang, Wei; Qin, Di-Yuan; Zhang, Bing-Lan; Wei, Wei; Wang, Yong-Sheng; Wei, Yu-Quan

    2016-04-01

    T cells, genetically modified by chimeric antigen receptors (CAR-T), are endowed with specificity to a desired antigen and are cytotoxic to cells expressing the targeted antigen. CAR-T-based cancer immunotherapy is a promising therapy for curing hematological malignancy, such as acute lymphoid leukemia, and is promising for extending their efficacy to defeat solid tumors. To date, dozens of different CAR-T cells have been evaluated in clinical trials to treat tumors; this necessitates the establishment of guidelines for the production and application of CAR-T cells. However, it is challenging to standardize CAR-T cancer therapy because it involves a combination of gene therapy and cell therapy. In this review, we compare the existing guidelines for CAR-T cells and discuss the challenges and considerations for establishing guidance for CAR-T-based cancer immunotherapy.