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Sample records for agonist carbachol car

  1. Meclizine is an agonist ligand for mouse constitutive androstane receptor (CAR) and an inverse agonist for human CAR.

    PubMed

    Huang, Wendong; Zhang, Jun; Wei, Ping; Schrader, William T; Moore, David D

    2004-10-01

    The constitutive androstane receptor (CAR, NR1I3) is a key regulator of xenobiotic and endobiotic metabolism. The ligand-binding domains of murine (m) and human (h) CAR are divergent relative to other nuclear hormone receptors, resulting in species-specific differences in xenobiotic responses. Here we identify the widely used antiemetic meclizine (Antivert; Bonine) as both an agonist ligand for mCAR and an inverse agonist for hCAR. Meclizine increases mCAR transactivation in a dose-dependent manner. Like the mCAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, meclizine stimulates binding of steroid receptor coactivator 1 to the murine receptor in vitro. Meclizine administration to mice increases expression of CAR target genes in a CAR-dependent manner. In contrast, meclizine suppresses hCAR transactivation and inhibits the phenobarbital-induced expression of the CAR target genes, cytochrome p450 monooxygenase (CYP)2B10, CYP3A11, and CYP1A2, in primary hepatocytes derived from mice expressing hCAR, but not mCAR. The inhibitory effect of meclizine also suppresses acetaminophen-induced liver toxicity in humanized CAR mice. These results demonstrate that a single compound can induce opposite xenobiotic responses via orthologous receptors in rodents and humans. PMID:15272053

  2. The Cholinergic Agonist Carbachol Increases the Frequency of Spontaneous GABAergic Synaptic Currents in Dorsal Raphe Serotonergic Neurons in the Mouse

    PubMed Central

    Yang, Chun; Brown, Ritchie E.

    2013-01-01

    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 serotonin 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 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

  3. 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

  4. The novel β3-adrenoceptor agonist mirabegron reduces carbachol-induced contractile activity in detrusor tissue from patients with bladder outflow obstruction with or without detrusor overactivity.

    PubMed

    Svalø, Julie; Nordling, Jørgen; Bouchelouche, Kirsten; Andersson, Karl-Erik; Korstanje, Cees; Bouchelouche, Pierre

    2013-01-15

    β(3)-Adrenoceptors are major players in detrusor relaxation and have been suggested as a new putative target for the treatment of overactive bladder syndrome. We determined the effects of mirabegron (YM178), a novel β(3)-adrenoceptor agonist, on carbachol-induced tone in isolated human detrusor preparations from patients with bladder outflow obstruction (BOO) with and without detrusor overactivity (DO), and from patients with normal bladder function. We compared the effects to those of isoprenaline, a non-selective β-adrenoceptor agonist. Detrusor specimens were obtained from patients with benign prostatic hyperplasia undergoing cystoscopy and from patients undergoing radical prostatectomy/cystectomy (in total 33 donors). Detrusor contractility was evaluated by organ bath studies and strips were incubated with carbachol (1μM) to induce and enhance tension. Both mirabegron and isoprenaline reduced carbachol-induced tone in tissues from all groups. Isoprenaline decreased tension with higher potency than mirabegron in normal, BOO and BOO+DO detrusor strips with pIC(50) values of 7.49 ± 0.16 vs. 6.23 ± 0.26 (P=0.0002), 6.89 ± 0.34 vs. 6.04 ± 0.31 (P=0.01), and 6.57 ± 0.20 vs. 5.41 ± 0.08 (P<0.0001, n=4), respectively. The maximal relaxant effect of isoprenaline and mirabegron in the normal, BOO and BOO+DO detrusor was 37.7 ± 14.4% and 36.1 ± 23.3%, 14.4 ± 12.2% vs. 33.4 ± 21.0% and 18.3 ± 10.0% vs. 28.3 ± 12.2% (n=4, P>0.05), respectively. Mirabegron and isoprenaline reduced carbachol-induced tone in both normal bladders and obstructed bladder with and without DO. Isoprenaline had higher potency than mirabegron, but the efficacy of mirabegron effect was the same as that of isoprenaline. PMID:23246623

  5. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice.

    PubMed

    Wagner, Martin; Halilbasic, Emina; Marschall, Hanns-Ulrich; Zollner, Gernot; Fickert, Peter; Langner, Cord; Zatloukal, Kurt; Denk, Helmut; Trauner, Michael

    2005-08-01

    Induction of hepatic phase I/II detoxification enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate involved enzymes and transporters, we aimed to induce adaptive alternative pathways with different CAR and PXR agonists in vivo. Mice were treated with the CAR agonists phenobarbital and 1,4-bis-[2-(3,5-dichlorpyridyloxy)]benzene, as well as the PXR agonists atorvastatin and pregnenolone-16alpha-carbonitrile. Hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Cyp3a11, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Ntcp, Oatp1,2,4, Bsep, Mrp2-4, Mdr2, Abcg5/8, Asbt) in the liver and kidney were analyzed via reverse-transcriptase polymerase chain reaction and Western blotting. Potential functional relevance was tested in common bile duct ligation (CBDL). CAR agonists induced Mrp2-4 and Oatp2; PXR agonists induced only Mrp3 and Oatp2. Both PXR and CAR agonists profoundly stimulated bile acid-hydroxylating/detoxifying enzymes Cyp3a11 and Cyp2b10. In addition, CAR agonists upregulated bile acid-sulfating Sult2a1 and bilirubin-glucuronidating Ugt1a1. These changes were accompanied by reduced serum levels of bilirubin and bile acids in healthy and CBDL mice and by increased levels of polyhydroxylated bile acids in serum and urine of cholestatic mice. Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other transporters and enzymes were moderately affected. In conclusion, administration of specific CAR or PXR ligands results in coordinated stimulation of major hepatic bile acid/bilirubin metabolizing and detoxifying enzymes and hepatic key alternative efflux systems, effects that are predicted to counteract cholestasis. PMID:15986414

  6. The Use of the LanthaScreen TR-FRET CAR Coactivator Assay in the Characterization of Constitutive Androstane Receptor (CAR) Inverse Agonists

    PubMed Central

    Carazo, Alejandro; Pávek, Petr

    2015-01-01

    The constitutive androstane receptor (CAR) is a critical nuclear receptor in the gene regulation of xenobiotic and endobiotic metabolism. The LanthaScreenTM TR-FRET CAR coactivator assay provides a simple and reliable method to analyze the affinity of a ligand to the human CAR ligand-binding domain (LBD) with no need to use cellular models. This in silico assay thus enables the study of direct CAR ligands and the ability to distinguish them from the indirect CAR activators that affect the receptor via the cell signaling-dependent phosphorylation of CAR in cells. For the current paper we characterized the pharmacodynamic interactions of three known CAR inverse agonists/antagonists—PK11195, clotrimazole and androstenol—with the prototype agonist CITCO (6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime) using the TR-FRET LanthaScreenTM assay. We have confirmed that all three compounds are inverse agonists of human CAR, with IC50 0.51, 0.005, and 0.35 μM, respectively. All the compounds also antagonize the CITCO-mediated activation of CAR, but only clotrimazole was capable to completely reverse the effect of CITCO in the tested concentrations. Thus this method allows identifying not only agonists, but also antagonists and inverse agonists for human CAR as well as to investigate the nature of the pharmacodynamic interactions of CAR ligands. PMID:25905697

  7. The hypothermic action of carbachol in the rat brain periaqueductal grey area may involve neurotensin.

    PubMed Central

    Griffiths, E. C.; Slater, P.; Widdowson, P. S.

    1986-01-01

    Neurotensin (NT) and carbachol both caused hypothermia when injected into the periaqueductal grey area (PAG) of rat brain. Atropine prevented carbachol- but not NT-induced hypothermia. NT-induced hypothermia was unaffected by various neurotransmitter agonists and antagonists in the PAG. Both NT antibodies and thyrotrophin releasing hormone prevented carbachol hypothermia. It is concluded that the hypothermic action of carbachol in the PAG is mediated via endogenous NT. PMID:3742153

  8. 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.

  9. Novel cell-based reporter assay system using epitope-tagged protein for the identification of agonistic ligands of constitutive androstane receptor (CAR).

    PubMed

    Imai, Jun; Yamazoe, Yasushi; Yoshinari, Kouichi

    2013-01-01

    Constitutive androstane receptor (CAR) plays vital roles in multiple liver functions including xenobiotic and energy metabolisms, and also in hepatocarcinogenesis. CAR shows species-dependent ligand selectivity, leading to species differences in the actions of xenobiotics. Thus, to know whether a compound of interest activates human CAR or not is helpful for the chemical safety evaluation. However, it is very difficult to observe clear ligand response for CAR in cell-based assays, because of its high basal transcriptional activity in the absence of its ligands. In this study, we found that reporter assays using HepG2 cells human and mouse CAR fused with an epitope-tag at its C-terminus showed low basal activity and high response to the corresponding agonists but not to their indirect activator, phenobarbital. Using this system, 176 industrial chemicals were screened for their abilities to activate human and mouse CAR, and 6 compounds moderately or strongly activated human and/or mouse CAR. The CAR-mediated transcriptions induced by these compounds were blocked by clotrimazole or androstanol, the human and mouse CAR inverse agonists, respectively, suggesting that the newly identified CAR activators are agonistic ligands of CAR. Taken together, our reporter assay system may be a promising tool to assess chemicals' agonistic activities toward CAR. PMID:23268926

  10. Carbachol models of REM sleep: recent developments and new directions.

    PubMed

    Kubin, L

    2001-02-01

    Since the early '60s, injections of a broad-spectrum muscarinic cholinergic agonist, carbachol, into the medial pontine reticular formation (mPRF) of cats have been extensively used as a tool with which to study the neural mechanisms of rapid eye movement (REM) sleep. During the last decade, new carbachol models of REM sleep were introduced, including chronically instrumented/behaving rats and "reduced" preparations such as decerebrate or anesthetized cats and rats. The combined results from these distinct models show interspecies similarities and differences. The dual nature, both REM sleep-promoting and wakefulness (or arousal)-promoting, of the cholinergic effects exerted within the mPRF is more strongly expressed in rats than in cats. This strengthens the possibility suggested by earlier central neuronal recordings that active wakefulness and REM sleep have extensive common neuronal substrates, and may have evolved from a common behavioral state. Carbachol studies using different intact and reduced models also suggest that powerful REM sleep episode-terminating effects originate in suprapontine structures. In contrast, the timing of REM sleep-like episodes in decerebrate models is determined by a pontomedullary neuronal network responsible for the generation of an ultradian cycle similar to the basic rest-activity cycle of N. Kleitman. Other presumed species differences, such as the more widespread distribution of carbachol-sensitive sites or the relative failure of carbachol to increase the duration of REM sleep episodes in rats when compared to cats, may be of a quantitative or technical nature. While carbachol and many other neurotransmitters and peptides microinjected into the mPRF evoke, enhance or suppress REM sleep, the most sensitive site(s) of their actions have not been fully mapped, and the nature of the cellular and neurochemical interactions taking place at the sites where carbachol triggers the REM sleep-like state remain largely unknown

  11. 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.

  12. Carbachol promotes gastrointestinal function during oral resuscitation of burn shock

    PubMed Central

    Hu, Sen; Che, Jin-Wei; Tian, Yi-Jun; Sheng, Zhi-Yong

    2011-01-01

    AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 h were subjected to 35% total body surface area full-thickness burns, and were divided into three groups: no fluid resuscitation (NR, n = 10), in which animals did not receive fluid by any means in the first 24 h post-burn; oral fluid resuscitation (OR, n = 8), in which dogs were gavaged with glucose-electrolyte solution (GES) with volume and rate consistent with the Parkland formula; and oral fluid with carbachol group (OR/CAR, n = 8), in which dogs were gavaged with GES containing carbachol (20 μg/kg), with the same volume and rate as the OR group. Twenty-four hours after burns, all animals were given intravenous fluid replacement, and 72 h after injury, they received nutritional support. Hemodynamic and gastrointestinal parameters were measured serially with animals in conscious and cooperative state. RESULTS: The mean arterial pressure, cardiac output and plasma volume dropped markedly, and gastrointestinal tissue perfusion was reduced obviously after the burn injury in all the three groups. Hemodynamic parameters and gastrointestinal tissue perfusion in the OR and OR/CAR groups were promoted to pre-injury level at 48 and 72 h, respectively, while hemodynamic parameters in the NR group did not return to pre-injury level till 72 h, and gastrointestinal tissue perfusion remained lower than pre-injury level until 120 h post-burn. CO2 of the gastric mucosa and intestinal mucosa blood flow of OR/CAR groups were 56.4 ± 4.7 mmHg and157.7 ± 17.7 blood perfusion units (BPU) at 24 h post-burn, respectively, which were significantly superior to those in the OR group (65.8 ± 5.8 mmHg and 127.7 ± 11.9 BPU, respectively, all P < 0.05). Gastric emptying and intestinal absorption rates of GES were significantly reduced to the lowest level (52.8% and

  13. Carbachol dimers as homobivalent modulators of muscarinic receptors.

    PubMed

    Matucci, Rosanna; Nesi, Marta; Martino, Maria Vittoria; Bellucci, Cristina; Manetti, Dina; Ciuti, Elisa; Mazzolari, Angelica; Dei, Silvia; Guandalini, Luca; Teodori, Elisabetta; Vistoli, Giulio; Romanelli, Maria Novella

    2016-05-15

    A series of homodimers of the well-known cholinergic agonist carbachol have been synthesized, showing the two agonist units symmetrically connected through a methylene chain of variable length. The new compounds have been tested on the five cloned muscarinic receptors (hM1-5) expressed in CHO cells by means of equilibrium binding studies, showing an increase in affinity by rising the number of methylene units up to 7 and 9. Functional experiments on guinea-pig ileum and assessment of ERK1/2 phosphorylation on hM1, hM2 and hM3 on CHO cells have shown that the new compounds are endowed with muscarinic antagonistic properties. Kinetic binding studies have revealed that some of the tested compounds are able to slow the rate of dissociation of NMS, suggesting a bitopic behavior. Docking simulations, performed on the hM1 and hM2 receptors, give a sound rationalization of the experimental data revealing how these compounds are able to interact with both orthosteric and allosteric binding sites depending on the length of their connecting chain. PMID:26996304

  14. Motoneuron properties during motor inhibition produced by microinjection of carbachol into the pontine reticular formation of the decerebrate cat.

    PubMed

    Morales, F R; Engelhardt, J K; Soja, P J; Pereda, A E; Chase, M H

    1987-04-01

    It is well established that cholinergic agonists, when injected into the pontine reticular formation in cats, produce a generalized suppression of motor activity (1, 3, 6, 14, 18, 27, 33, 50). The responsible neuronal mechanisms were explored by measuring ventral root activity, the amplitude of the Ia-monosynaptic reflex, and the basic electrophysiological properties of hindlimb motoneurons before and after carbachol was microinjected into the pontine reticular formation of decerebrate cats. Intrapontine microinjections of carbachol (0.25-1.0 microliter, 16 mg/ml) resulted in the tonic suppression of ventral root activity and a decrease in the amplitude of the Ia-monosynaptic reflex. An analysis of intracellular records from lumbar motoneurons during the suppression of motor activity induced by carbachol revealed a considerable decrease in input resistance and membrane time constant as well as a reduction in motoneuron excitability, as evidenced by a nearly twofold increase in rheobase. Discrete inhibitory postsynaptic potentials were also observed following carbachol administration. The changes in motoneuron properties (rheobase, input resistance, and membrane time constant), as well as the development of discrete inhibitory postsynaptic potentials, indicate that spinal cord motoneurons were postsynaptically inhibited following the pontine administration of carbachol. In addition, the inhibitory processes that arose after carbachol administration in the decerebrate cat were remarkably similar to those that are present during active sleep in the chronic cat. These findings suggest that the microinjection of carbachol into the pontine reticular formation activates the same brain stem-spinal cord system that is responsible for the postsynaptic inhibition of alpha-motoneurons that occurs during active sleep. PMID:3585456

  15. 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…

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

    PubMed

    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

  17. Dual agonist occupancy of AT1-R–α2C-AR heterodimers results in atypical Gs-PKA signaling

    PubMed Central

    Bellot, Morgane; Galandrin, Ségolène; Boularan, Cédric; Matthies, Heinrich J; Despas, Fabien; Denis, Colette; Javitch, Jonathan; Mazères, Serge; Sanni, Samra Joke; Pons, Véronique; Seguelas, Marie-Hélène; Hansen, Jakob L; Pathak, Atul; Galli, Aurelio; Sénard, Jean-Michel; Galés, Céline

    2015-01-01

    Hypersecretion of norepinephrine (NE) and angiotensin II (AngII) is a hallmark of major prevalent cardiovascular diseases that contribute to cardiac pathophysiology and morbidity. Herein, we explore whether heterodimerization of presynaptic AngII AT1 receptor (AT1-R) and NE α2C-adrenergic receptor (α2C-AR) could underlie their functional cross-talk to control NE secretion. Multiple bioluminescence resonance energy transfer and protein complementation assays allowed us to accurately probe the structures and functions of the α2C-AR–AT1-R dimer promoted by ligand binding to individual protomers. We found that dual agonist occupancy resulted in a conformation of the heterodimer different from that induced by active individual protomers and triggered atypical Gs-cAMP–PKA signaling. This specific pharmacological signaling unit was identified in vivo to promote not only NE hypersecretion in sympathetic neurons but also sympathetic hyperactivity in mice. Thus, we uncovered a new process by which GPCR heterodimerization creates an original functional pharmacological entity and that could constitute a promising new target in cardiovascular therapeutics. PMID:25706338

  18. Growling component of vocalization as a quantitative index of carbachol-induced emotional-defensive response in cats.

    PubMed

    Brudzyński, S M

    1981-01-01

    Vocalization and eye movements during emotional-defensive response evoked by unilateral intrahypothalamic carbachol injections (10 micrograms) were quantitatively determined. The growling episodes duration paralleled the development and the subsiding of the defensive behavior, while the changes of eye movements indicated rather a general arousal than the course of agonistic attitude. The growling component can be treated as (i) a specific form of vocalization for emotional-defensive response, (ii) quantitative intensity index of the response, and (iii) a value reflecting the dynamics and the time-course of the emotional state, unlike the hissing component which is inappropriate for quantitative determination. The results enable to treat the carbachol-induced response as a model for quantitative investigations on emotional-defensive states in cats. The vocalization changes compared with cardiovascular changes are discussed in terms of their usefulness in measurements of aversive emotional responses. PMID:7196680

  19. Cholinergic agonists transactivate EGFR and stimulate MAPK to induce goblet cell secretion.

    PubMed

    Kanno, Harumi; Horikawa, Yoshitaka; Hodges, Robin R; Zoukhri, Driss; Shatos, Marie A; Rios, Jose D; Dartt, Darlene A

    2003-04-01

    Conjunctival goblet cells are the primary source of mucins in the mucous layer, the innermost layer of the tear film. Conjunctival goblet cell mucin secretion is under neural control because exogenous addition of parasympathetic agonists stimulates goblet cell secretion. To elucidate the intracellular signal pathways used by cholinergic agonists to stimulate goblet cell mucin secretion, we determined whether p42/p44 mitogen-activated protein kinase (MAPK) is activated during cholinergic agonist-stimulated mucin secretion. Rat conjunctiva was removed, preincubated with or without antagonists, and stimulated with the cholinergic agonist carbachol (10(-4) M). Carbachol statistically significantly stimulated the phosphorylation of MAPK in a time- and concentration-dependent manner. U-0126, an inhibitor of MAPK activation, completely inhibited both the activation of MAPK and goblet cell secretion stimulated by carbachol. The M(1) muscarinic antagonist pirenzepine, the M(2) muscarinic antagonist gallamine, and the M(1)/M(3) muscarinic receptor antagonist N-(3-chloropropyl)-4-piperidinyl diphenylacetate (4-DAMP) also inhibited carbachol-stimulated MAPK activation. Increasing the intracellular Ca(2+) concentration with a Ca(2+) ionophore increased MAPK activation, and chelation of extracellular Ca(2+) inhibited carbachol-stimulated activation. Carbachol also increased tyrosine phosphorylation of Pyk2, p60Src, and the epidermal growth factor receptor (EGFR). The Src inhibitor PP1 and the EGFR inhibitor AG-1478 completely inhibited carbachol-stimulated MAPK activation. AG-1478 also inhibited goblet cell secretion. We conclude that carbachol transactivates the EGFR to activate MAPK, leading to conjunctival goblet cell secretion. In addition, carbachol also activates Pyk2 and p60Src that could play a role in the transactivation of the EGFR.

  20. 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. PMID:26670051

  1. 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.

  2. Carbachol and bradykinin elevate cyclic AMP and rapidly deplete ATP in cultured rat sympathetic neurons.

    PubMed Central

    Suidan, H S; Murrell, R D; Tolkovsky, A M

    1991-01-01

    The agonists carbachol (CCh) and bradykinin (BK) and 54 mM KCl (high K+) were among the most potent stimulants of cyclic AMP (cAMP) production in cultured rat sympathetic neurons, measured with the use of a high-fidelity assay developed for small samples. The rise in cAMP evoked by CCh (through muscarinic receptors), BK, and high K+ was inhibited in Ca2(+)-depleted medium (1.3 mM Ca2+ and 2 mM BAPTA or EGTA), which also prevented the sustained rise in [Ca2+]i evoked by each of these stimuli, showing that elevation of cAMP requires extracellular Ca2+ and, possibly, Ca2+ influx. Preliminary results obtained with the novel calmodulin inhibitor CGS 9343B, which blocked the elevation of cAMP, and with the cyclogenase inhibitor indomethacin, which partially blocked the actions of the agonists but not those of high K+, suggest that calmodulin and arachidonate metabolites may be two components of the signaling pathway. In addition to their effects on cAMP metabolism, CCh, muscarine, and BK, but not nicotine, caused a 30-40% decrease in ATP levels. This effect was much greater than that evoked by high K+ and was largely inhibited by CGS 9343B but slightly enhanced in the Ca(+)-depleted medium, showing that agonists are still active in the absence of [Ca2+]o. Thus, agonists that activate phosphoinositide metabolism can also increase cAMP production and substantially deplete cells of ATP. These novel actions may have to be taken into account when the mechanisms by which such agonists regulate cell function are being considered. PMID:1848792

  3. Activation of T84 cell chloride channels by carbachol involves a phosphoinositide-coupled muscarinic M3 receptor.

    PubMed

    Dickinson, K E; Frizzell, R A; Sekar, M C

    1992-04-10

    Muscarinic agonists stimulate Cl- secretion across monolayers of the colon tumor epithelial cell line, T84. The muscarinic receptor has been characterized in T84 cell homogenates by radioligand binding using [3H]N-methylscopolamine ([3H]NMS). [3H]NMS bound to a single population of sites at 25 degrees C in 100 mM NaCl, 20 mM HEPES, 10 mM MgCl2, pH 7.4 buffer, with calculated Kd = 278 (+/- 44) pM and Bmax = 40 (+/- 6) fmol/mg protein (n = 4). Binding was reversible (diss. t1/2 = 18 +/- 3 min) and stereoselective (dexetimide Ki = 0.3 nM) much greater than levetimide (Ki = 8300 nM). Antagonists exhibited the following rank order of potencies and Ki values (nM): atropine (0.54) greater than 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) (0.84) greater than dicyclomine (14) = hexahydrosiladifenidol (18) greater than pirenzepine (136) greater than AF-DX 116 (3610). The same sequence was observed for inhibition of carbachol-induced 125I efflux from T84 monolayers. This is indicative of an M3 'glandular' muscarinic receptor. Coupling to second messenger systems was examined by labelling monolayers with [14C]arachidonic acid (AA) or [3H]inositol. Carbachol (0.3 mM) did not release [14C]AA from labelled lipids, but ionomycin produced a dose-dependent increase in media [14C]AA. Carbachol (0.3 mM) elevated inositol monophosphate 14-fold. The results suggest that muscarinic agonists stimulate Cl- secretion by interacting with an M3 receptor coupled to inositide lipid hydrolysis. PMID:1379932

  4. 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. PMID:25997581

  5. 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.

  6. Renshaw cells are inactive during motor inhibition elicited by the pontine microinjection of carbachol.

    PubMed

    Morales, F R; Engelhardt, J K; Pereda, A E; Yamuy, J; Chase, M H

    1988-04-12

    The present study was undertaken to determine whether the postsynaptic inhibition of motoneurons that occurs following the pontine microinjection of carbachol in the decerebrate cat is due to the activity of Renshaw cells. Thirty-two out of 37 Renshaw cells (86%) were spontaneously active prior to the administration of carbachol, whereas only 2 out of 13 Renshaw cells (15%) discharged during carbachol-induced motor inhibition. In addition, discrete inhibitory synaptic potentials were observed in 33% of the Renshaw cells from which intracellular recordings were obtained after carbachol administration, indicating that these cells were actively inhibited. The finding that a population of Renshaw cells, which inhibit motoneurons, were themselves inhibited during a period of profound motoneuron inhibition was quite unexpected. These results support the conclusion that Renshaw cells are not the inhibitory interneurons that are responsible for the powerful inhibition of motoneurons that occurs following the pontine microinjection of carbachol. PMID:3380320

  7. Modeling carbachol-induced hippocampal network synchronization using hidden Markov models

    NASA Astrophysics Data System (ADS)

    Dragomir, Andrei; Akay, Yasemin M.; Akay, Metin

    2010-10-01

    In this work we studied the neural state transitions undergone by the hippocampal neural network using a hidden Markov model (HMM) framework. We first employed a measure based on the Lempel-Ziv (LZ) estimator to characterize the changes in the hippocampal oscillation patterns in terms of their complexity. These oscillations correspond to different modes of hippocampal network synchronization induced by the cholinergic agonist carbachol in the CA1 region of mice hippocampus. HMMs are then used to model the dynamics of the LZ-derived complexity signals as first-order Markov chains. Consequently, the signals corresponding to our oscillation recordings can be segmented into a sequence of statistically discriminated hidden states. The segmentation is used for detecting transitions in neural synchronization modes in data recorded from wild-type and triple transgenic mice models (3xTG) of Alzheimer's disease (AD). Our data suggest that transition from low-frequency (delta range) continuous oscillation mode into high-frequency (theta range) oscillation, exhibiting repeated burst-type patterns, occurs always through a mode resembling a mixture of the two patterns, continuous with burst. The relatively random patterns of oscillation during this mode may reflect the fact that the neuronal network undergoes re-organization. Further insight into the time durations of these modes (retrieved via the HMM segmentation of the LZ-derived signals) reveals that the mixed mode lasts significantly longer (p < 10-4) in 3xTG AD mice. These findings, coupled with the documented cholinergic neurotransmission deficits in the 3xTG mice model, may be highly relevant for the case of AD.

  8. Endothelial-dependent relaxant actions of carbachol and substance P in arterial smooth muscle.

    PubMed

    Bolton, T B; Clapp, L H

    1986-04-01

    In helical strips cut from the small mesenteric artery of guinea-pig (GPSMA) (0.3-0.6 mm o.d.) relaxations induced by substance P were more susceptible to damage of the endothelium by rubbing than were relaxations evoked by carbachol. Relaxations induced by 2-nicotin-amidoethyl nitrate (SG75) were unaffected by this procedure. Relaxations evoked by the calcium ionophore A23187 persisted when those to substance P had been abolished by rubbing the endothelium in GPSMA, rabbit mesenteric and rabbit ear arteries. In guinea-pig pulmonary artery and aorta relaxations to A23187 were lost after this treatment. Carbachol and SG75 were more effective in inhibiting phasic than tonic tension induced by noradrenaline in GPSMA, but substance P was more effective against tonic tension. In the GPSMA, carbachol and substance P inhibited tension produced by noradrenaline to similar extents. However, carbachol was less, and substance P much less effective in inhibiting tension evoked by high-potassium solution than by noradrenaline. Susceptibility of relaxations to blockade by haemoglobin in GPSMA was: substance P greater than carbachol greater than ATP greater than SG75. The membrane potential of smooth muscle cells in the media of the GPSMA was recorded by microelectrode. Carbachol, but not substance P, hyperpolarized the cells both in the presence and absence of noradrenaline at concentrations which relaxed the muscle. These results suggest a heterogeneity in the mechanisms of endothelial-dependent relaxations induced by various vascular relaxants. PMID:2423170

  9. REM sleep-like episodes of motoneuronal depression and respiratory rate increase are triggered by pontine carbachol microinjections in in situ perfused rat brainstem preparation.

    PubMed

    Brandes, Ivo F; Stettner, Georg M; Mörschel, Michael; Kubin, Leszek; Dutschmann, Mathias

    2011-05-01

    Hypoglossal nerve activity (HNA) controls the position and movements of the tongue. In persons with compromised upper airway anatomy, sleep-related hypotonia of the tongue and other pharyngeal muscles causes increased upper airway resistance, or total upper airway obstructions, thus disrupting both sleep and breathing. Hypoglossal nerve activity reaches its nadir, and obstructive episodes are longest and most severe, during rapid eye movement stage of sleep (REMS). Microinjections of a cholinergic agonist, carbachol, into the pons have been used in vivo to investigate the mechanisms of respiratory control during REMS. Here, we recorded inspiratory-modulated phrenic nerve activity and HNA and microinjected carbachol (25-50 nl, 10 mm) into the pons in an in situ perfused working heart-brainstem rat preparation (WHBP), an ex vivo model previously validated for studies of the chemical and reflex control of breathing. Carbachol microinjections were made into 40 sites in 33 juvenile rat preparations and, at 24 sites, they triggered depression of HNA with increased respiratory rate and little change of phrenic nerve activity, a pattern akin to that during natural REMS in vivo. The REMS-like episodes started 151 ± 73 s (SD) following microinjections, lasted 20.3 ± 4.5 min, were elicited most effectively from the dorsal part of the rostral nucleus pontis oralis, and were prevented by perfusion of the preparation with atropine. The WHBP offers a novel model with which to investigate cellular and neurochemical mechanisms of REMS-related upper airway hypotonia in situ without anaesthesia and with full control over the cellular environment.

  10. Changes in electrophysiological properties of cat hypoglossal motoneurons during carbachol-induced motor inhibition.

    PubMed

    Fung, S J; Yamuy, J; Xi, M C; Engelhardt, J K; Morales, F R; Chase, M H

    2000-12-01

    The control of hypoglossal motoneurons during sleep is important from a basic science perspective as well as to understand the bases for pharyngeal occlusion which results in the obstructive sleep apnea syndrome. In the present work, we used intracellular recording techniques to determine changes in membrane properties in adult cats in which atonia was produced by the injection of carbachol into the pontine tegmentum (AS-carbachol). During AS-carbachol, 86% of the recorded hypoglossal motoneurons were found to be postsynaptically inhibited on the basis of analyses of their electrical properties; the electrical properties of the remaining 14% were similar to motoneurons recorded during control conditions. Those cells that exhibited changes in their electrical properties during AS-carbachol also displayed large-amplitude inhibitory synaptic potentials. Following sciatic nerve stimulation, hypoglossal motoneurons which responded with a depolarizing potential during control conditions exhibited a hyperpolarizing potential during AS-carbachol. Both spontaneous and evoked inhibitory potentials recorded during AS-carbachol were comparable to those that have been previously observed in trigeminal and spinal cord motoneurons under similar experimental conditions as well as during naturally occurring active sleep. Calculations based on modeling the changes that we found in input resistance and membrane time constant with a three-compartment neuron model suggest that shunts are present in all three compartments of the hypoglossal motoneuron model. Taken together, these data indicate that postsynaptic inhibitory drives are widely distributed on the soma-dendritic tree of hypoglossal motoneurons during AS-carbachol. These postsynaptic inhibitory actions are likely to be involved in the pathophysiology of obstructive sleep apnea. PMID:11102580

  11. Selectivity of muscarinic agonists including (+/-)-aceclidine and antimuscarinics on the human intraocular muscles.

    PubMed

    Ishikawa, H; DeSantis, L; Patil, P N

    1998-08-01

    The average EC50 value and the maximum response of carbachol on the human circular ciliary muscle obtained within 24 h of postmortem hypoxia was 517 nmol/l and 135 mg, respectively. These values for carbachol did not differ significantly from that of the longitudinal ciliary muscle. However, when tested at 1 mumol/l of carbachol, the peak response of the longitudinal muscle occurred at 59 sec vs 173 sec for that of the circular muscle of 70 year old donors. The relative potency of the muscarinic agonists on the circular muscle was oxotremorine-M, 1 > carbachol, 1/4 > pilocarpine, 1/19 > aceclidine, 1/132. The relative order of potency of agonists was similar for the longitudinal muscle. Only pilocarpine and aceclidine were partial agonists which produced 80-85% of the maximum response. When compared with the EC50 values of aceclidine on the iris sphincter and the longitudinal ciliary muscles, the agonist potency was only 1/28 for the latter tissue. Implications of these findings in relation to the use of these agonists in glaucoma are discussed. The pKB values of muscarinic antagonists on the circular ciliary muscle were: atropine, 8.8; cyclopentolate, 7.8; tropicamide, 7.4; P.F. HHSiD, 7.0; pirenzepine, 6.4; and methoctramine, 5.7. Nearly equal pKB values of each antagonist were obtained for the longitudinal ciliary muscle and iris sphincter. Based on the affinity constants of various competitive antagonists, the human iris as well as ciliary muscles may contain M3, M2 or M4 subtypes of muscarinic receptors.

  12. The depolarizing action of acetylcholine or carbachol in intestinal smooth muscle.

    PubMed

    Bolton, T B

    1972-02-01

    1. The membrane potential of the longitudinal muscle of the guinea-pig ileum was recorded intracellularly with glass micro-electrodes.2. Acetylcholine or carbachol depolarized the membrane. The depolarization produced by 1.4 x 10(-6)M carbachol was only 3.6 mV less than that produced by 5.5 x 10(-5)M.3. When the change in size of the electrotonic potential was used to estimate the increase in membrane conductance produced by different concentrations of carbachol, the increase in conductance was about tenfold at 1.4 x 10(-6)M and about 100-fold at 5.5 x 10(-5)M. There was a significant (P < 0.025) regression of the change in size of the electrotonic potential on the logarithm of the concentration of carbachol over this dose range. This and other observations suggest that it is not the availability of receptors which curtails the depolarization produced by concentrations of carbachol in excess of 1.4 x 10(-6)M.4. Reducing the external sodium concentration shifted the level of peak depolarization produced by carbachol negatively, and increasing the external sodium concentration shifted it positively.5. Reducing the external chloride from 134 to 13 mM had no significant effect on the level of peak depolarization produced by carbachol. Reducing the external chloride to 7 mM shifted the level of peak depolarization 3.1 mV in a positive direction.6. Increasing the external potassium concentration had little effect on the level of peak depolarization produced by carbachol, and decreasing the external potassium shifted the level of peak depolarization positively.7. It was possible to account for the observed relationship between membrane potential and membrane conductance if the assumption was made that carbachol opens additional ion channels in the membrane which have an equilibrium potential of about -9 mV. It is suggested therefore that the depolarizing action of carbachol on this smooth muscle is limited by its equilibrium potential, and that the equilibrium potential

  13. Effect of calcium chloride on gross behavioural changes produced by carbachol and eserine in cats.

    PubMed

    Beleslin, D B; Samardzic, R; Krstić, S K; Strbac, M

    1982-01-01

    The effect of calcium chloride injected into the cerebral ventricles of group-housed unanaesthetized cats upon vocalization (rage, hissing and snarling), fighting (attack with paws and claws, defense with paws and claws and biting), mydriasis, tremor and clonic-tonic convulsions produced by carbachol and eserine injected similarly was investigated. Calcium chloride depressed or almost completely abolished the vocalization and fighting due to carbachol and eserine. On the other hand, mydriasis, tremor and clonic-tonic convulsions evoked by carbachol and eserine were not significantly changed by calcium chloride. It is apparent that calcium chloride can "dissociate" vocalization and fighting from autonomic and motor phenomena such as mydriasis, tremor and clonic-tonic convulsions caused by carbachol and eserine. Calcium chloride inhibited the vocalization and fighting produced by carbachol and eserine most probably by a nonspecific stabilizing action on central muscarinic cholinoceptive sites. These results further support the view that calcium ions in excess have an atropine-like action also in the central nervous system. PMID:6892185

  14. Increase in sensitivity of the baroreceptor reflex following microinjection of carbachol into the posterior hypothalamic nucleus of awake rats.

    PubMed

    Newey, C R; Martin, J R

    2016-01-01

    In a rat model, the baroreceptor reflex can be assessed by graded infusions of either phenylephrine or sodium nitroprusside with continuous hemodynamic monitoring. Microinjection of the cholinergic agonist carbachol (CCh) into the posterior hypothalamic nucleus (PHN) evokes an increase in mean arterial pressure and a change in heart rate. Lower doses of CCh evoke only tachycardia, whereas middle and higher doses evoke a biphasic change in heart rate of tachycardia followed by bradycardia. The bradycardia following the microinjection of CCh into the PHN can be attenuated by the previous administration of the vasopressin V1 receptor antagonist [d(CH2 )5 Tyr(Me)] arginine vasopressin (AVPX). Circulating arginine vasopressin (AVP) has been shown to increase the sensitivity of the baroreceptor reflex by stimulating vasopressin V1 receptors in the area postrema. The attenuation by AVPX of the bradycardia that results following the high doses of CCh suggests that AVP is released into the circulation following stimulation of cholinergic systems within the PHN. Thus, microinjection of a high dose of CCh (11 nmol) into the PHN alters the sensitivity of the baroreceptor reflex by increasing peripheral levels of AVP. PMID:27555117

  15. Electric cars

    SciTech Connect

    Worsnop, R.L.

    1993-07-09

    This article is devoted entirely to the subject of electric cars. Some of the topics covered are alternate fuels in relation to development of electric cars, the impact of zero-emission laws, the range and performance of electric cars, historical aspects, legislative incentives, and battery technology.

  16. Prostaglandins and muscarinic agonists induce cyclic AMP attenuation by two distinct mechanisms in the pregnant-rat myometrium. Interaction between cyclic AMP and Ca2+ signals.

    PubMed Central

    Goureau, O; Tanfin, Z; Harbon, S

    1990-01-01

    In pregnant-rat myometrium (day 21 of gestation), isoprenaline-induced cyclic AMP accumulation, resulting from receptor-mediated activation of adenylate cyclase, was negatively regulated by prostaglandins [PGE2, PGF2 alpha; EC50 (concn. giving 50% of maximal response) = 2 nM] and by the muscarinic agonist carbachol (EC50 = 2 microM). PG-induced inhibition was prevented by pertussis-toxin treatment, supporting the idea that it was mediated by the inhibitory G-protein Gi through the inhibitory pathway of the adenylate cyclase. Both isoprenaline-induced stimulation and PG-evoked inhibition of cyclic AMP were insensitive to Ca2+ depletion. By contrast, carbachol-evoked attenuation of cyclic AMP accumulation was dependent on Ca2+ and was insensitive to pertussis toxin. The inhibitory effect of carbachol was mimicked by ionomycin. Indirect evidence was thus provided for the enhancement of cyclic AMP degradation by a Ca2(+)-dependent phosphodiesterase activity in the muscarinic-mediated effect. The attenuation of cyclic AMP elicited by carbachol coincided with carbachol-stimulated inositol phosphate (InsP3, InsP2 and InsP) generation, which displayed an almost identical EC50 (3 microM) and was similarly unaffected by pertussis toxin. Both carbachol effects were reproduced by oxotremorine, whereas pilocarpine (a partial muscarinic agonist) failed to induce any decrease in cyclic AMP accumulation and concurrently was unable to stimulate the generation of inositol phosphates. These data support our proposal for a carbachol-mediated enhancement of a Ca2(+)-dependent phosphodiesterase activity, compatible with the rises in Ca2+ associated with muscarinic-induced increased generation of inositol phosphates. They further illustrate that a cross-talk between the two major transmembrane signalling systems contributed to an ultimate decrease in cyclic AMP in the pregnant-rat myometrium near term. PMID:1700899

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

    PubMed

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

    1996-06-25

    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

  18. Stretch-induced myogenic responses of airways after histamine and carbachol.

    PubMed

    Thulesius, O; Mustafa, S

    1994-03-01

    The purpose of the study described here was to determine the possible role of a myogenic response of bronchial smooth muscle in deep inspiration (DI)-induced bronchoconstriction. Model experiments were performed on sheep tracheal strips. The effect of sudden stepwise elongation on isometric tension of tracheal muscle was studied in the absence and presence of the bronchoconstrictors carbachol (10(-8) M) and histamine (10(-4) M). In control strips tension increased rapidly with stretch and was followed by stress relaxation which corresponds to creep or bronchial dilatation. In histamine- and carbachol-treated strips a reactive contraction with a rhythmic pattern interrupted the process of stress relaxation. These responses appeared after only 20% elongation and were characteristic of a myogenic contraction which in the in vivo situation would correspond to a bronchoconstriction. These findings are interpreted as a functional transformation of multiple- to single-unit smooth muscle due to the influence of carbachol and histamine. This suggests that stretching (DI) of bronchial smooth muscle in the presence of carbachol and histamine induces a protracted myogenic contraction, which may explain bronchoconstriction after DI in severe asthma. PMID:8205744

  19. Regional haemodynamic effects of carbachol injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats.

    PubMed

    Bachelard, H; Gardiner, S M; Kemp, P A; Bennett, T

    1994-06-01

    Carbachol was injected into the hypothalamic paraventricular nuclei (PVN) of conscious, unrestrained Long Evans rats, chronically instrumented with intravascular catheters and pulsed Doppler probes to assess changes in regional haemodynamics. Bilateral microinjections of carbachol (1 ng-1 microgram) produced increases in blood pressure, bradycardias and vasoconstrictions in renal, superior mesenteric and hindquarters vascular beds. In the presence of phentolamine, the bradycardic and hindquarters vasoconstrictor responses to carbachol were unchanged while the pressor response was smaller due to a reduction in the renal and the superior mesenteric vasoconstriction. In the presence of propranolol, the bradycardic response was reduced, but the pressor and renal vasoconstrictor responses were potentiated, whereas the superior mesenteric and hindquarter vasoconstrictions were not changed significantly. In the presence of phentolamine and propranolol, the heart rate and pressor responses, as well as the renal vasoconstriction, were unchanged, whereas the superior mesenteric vasoconstriction was reduced and the hindquarters vasoconstriction was potentiated. Together these results are consistent with an involvement of the sympathoadrenal system in the pressor response to carbachol injected into the PVN of untreated animals. They indicate that alpha-adrenoceptor-mediated vasoconstriction in the superior mesenteric vascular bed is a particularly important component in that regard. In the presence of the vasopressin antagonist, d(CH2)5(Tyr(Et))DAVP, alone or in combination with phentolamine and propranolol, the pressor response to carbachol was substantially reduced, while the renal and superior mesenteric vasoconstrictor effects were completely abolished; the bradycardia was not significantly affected by this treatment. These results indicate an important involvement of vasopressin in the cardiovascular responses to carbachol injected into the PVN of untreated animals

  20. The effect of M & B 22948 on carbachol-induced inositol trisphosphate accumulation and contraction in iris sphincter smooth muscle.

    PubMed

    Akhtar, R A; Abdel-Latif, A A

    1991-04-25

    The effect of a cyclic GMP phosphodiesterase inhibitor, M & B 22948, on carbachol-induced phosphatidylinositol 4,5-bis-phosphate (PIP2) breakdown and phosphatidic acid labeling, 1,4,5-inositol trisphosphate (IP3) accumulation and muscle contraction was studied in bovine iris sphincter smooth muscle. Addition of carbachol (10 microM) to 32P-labeled tissue resulted in increased labeling of phosphatidic acid and hydrolysis of PIP2. In myo[3H]inositol labeled tissue, carbachol caused rapid accumulation of IP3 which reached its maximum at about 2 min. Under identical experimental conditions, carbachol initiated a rapid increase in muscle contraction (phasic component) which was followed by a slightly lower contractile response (tonic component) that lasted for several minutes. Pretreatment of the iris sphincter with M & B 22948 did not alter carbachol-stimulated PIP2 breakdown and phosphatidic acid labeling, IP3 accumulation, or phasic component of the contractile response. However, the tonic component of the contractile response was increasingly attenuated by increasing concentrations of the drug. In conclusion, the data presented demonstrate a close correlation between carbachol-induced IP3 accumulation and muscle contraction, and that M & B 22948 does not inhibit carbachol-induced responses in the iris sphincter.

  1. From synapse to gene product: Prolonged expression of c-fos induced by a single microinjection of carbachol in the pontomesencephalic tegmentum

    PubMed Central

    Quattrochi, James J.; Bazalakova, Mihaela; Hobson, J. Allan

    2006-01-01

    It is not known how the brain modifies its regulatory systems in response to the application of a drug, especially over the long term of weeks and months. We have developed a model system approach to this question by manipulating cholinergic cell groups of the laterodorsal and pedunculopontine tegmental (LDT/PPT) nuclei in the pontomesencephalic tegmentum (PMT), which are known to be actively involved in the timing and quantity of rapid eye movement (REM) sleep. In a freely moving feline model, a single microinjection of the cholinergic agonist carbachol conjugated to a latex nanosphere delivery system into the caudolateral PMT elicits a long-term enhancement of one distinguishing phasic event of REM sleep, ponto-geniculo-occipital (PGO) waves, lasting 5 days but without any significant change in REM sleep or other behavioral state. Here, we test the hypothesis that cholinergic activation within the caudolateral PMT alters the postsynaptic excitability of the PGO network, stimulating the prolonged expression of c-fos that underlies this long-term PGO enhancement (LTPE) effect. Using quantitative Fos immunohistochemistry, we found that the number of Fos-immunoreactive (Fos-IR) neurons surrounding the caudolateral PMT injection site decreased sharply by postcarbachol day 03, while the number of Fos-IR neurons in the more rostral LDT/PPT increased >30-fold and remained at a high level following the course of LTPE. These results demonstrate a sustained c-fos expression in response to pharmacological stimulation of the brain and suggest that carbachol's acute effects induce LTPE via cholinergic receptors, with subsequent transsynaptic activation of the LDT/PPT maintaining the LTPE effect. PMID:15893601

  2. From synapse to gene product: prolonged expression of c-fos induced by a single microinjection of carbachol in the pontomesencephalic tegmentum.

    PubMed

    Quattrochi, James J; Bazalakova, Mihaela; Hobson, J Allan

    2005-05-20

    It is not known how the brain modifies its regulatory systems in response to the application of a drug, especially over the long term of weeks and months. We have developed a model system approach to this question by manipulating cholinergic cell groups of the laterodorsal and pedunculopontine tegmental (LDT/PPT) nuclei in the pontomesencephalic tegmentum (PMT), which are known to be actively involved in the timing and quantity of rapid eye movement (REM) sleep. In a freely moving feline model, a single microinjection of the cholinergic agonist carbachol conjugated to a latex nanosphere delivery system into the caudolateral PMT elicits a long-term enhancement of one distinguishing phasic event of REM sleep, ponto-geniculo-occipital (PGO) waves, lasting 5 days but without any significant change in REM sleep or other behavioral state. Here, we test the hypothesis that cholinergic activation within the caudolateral PMT alters the postsynaptic excitability of the PGO network, stimulating the prolonged expression of c-fos that underlies this long-term PGO enhancement (LTPE) effect. Using quantitative Fos immunohistochemistry, we found that the number of Fos-immunoreactive (Fos-IR) neurons surrounding the caudolateral PMT injection site decreased sharply by postcarbachol day 03, while the number of Fos-IR neurons in the more rostral LDT/PPT increased >30-fold and remained at a high level following the course of LTPE. These results demonstrate a sustained c-fos expression in response to pharmacological stimulation of the brain and suggest that carbachol's acute effects induce LTPE via cholinergic receptors, with subsequent transsynaptic activation of the LDT/PPT maintaining the LTPE effect.

  3. [The influence of L-glutamate and carbachol on burst firing of dopaminergic neurons in ventral tegmental area].

    PubMed

    Wang, Shan-shan; Wei, Chun-ling; Liu, Zhi-qiang; Ren, Wei

    2011-02-25

    Burst firing of dopaminergic neurons in ventral tegmental area (VTA) induces a large transient increase in synaptic dopamine (DA) release and thus is considered the reward-related signal. But the mechanisms of burst generation of dopaminergic neuron still remain unclear. This experiment investigated the burst firing of VTA dopaminergic neurons in rat midbrain slices perfused with carbachol and L-glutamate individually or simultaneously to understand the neurotransmitter mechanism underlying burst generation. The results showed that bath application of carbachol (10 μmol/L) and pulse application of L-glutamate (3 mmol/L) both induced burst firing in dopaminergic neuron. Co-application of carbachol and L-glutamate induced burst firing in VTA dopaminergic cells which couldn't be induced to burst by the two chemicals separately. The result indicates that carbachol and L-glutamate co-regulate burst firing of dopaminergic neuron.

  4. Effect of mineral salts, carbachol, and pilocarpine on nutrient digestibility and ruminal characteristics in cattle.

    PubMed

    Wiedmeier, R D; Arambel, M J; Lamb, R C; Marcinkowski, D P

    1987-03-01

    Fifty percent concentrate diets containing 2% sodium bicarbonate, sodium chloride, or no additional mineral salts were fed at a rate of 86 g dry matter/kg body weight X 75/d to three barren Holstein cows fitted with ruminal fistulas in a 3 X 3 Latin square design. Dietary adaptation was 14 d followed by 4 d collection. Ruminal pH, liquid volume, liquid dilution rate, and particulate rate of passage were increased with dietary mineral salts. Six Holstein cows fitted with ruminal fistulas were administered .01 mg carbachol/kg body weight/d, .10 mg pilocarpine/kg body weight/d, or saline placebo via subcutaneous, osmotically controlled pumps in a replicated 3 X 3 Latin square design. Treatments were administered for a 14-d adaptation period followed by an 8-d collection period. Both carbachol and pilocarpine increased liquid dilution rate, particulate rate of passage, and percent cellulolytic bacteria, whereas liquid volume was reduced.

  5. Relationships of nucleus reticularis pontis oralis neuronal discharge with sensory and carbachol evoked hippocampal theta rhythm.

    PubMed

    Nuñez, A; de Andrés, I; García-Austt, E

    1991-01-01

    The activity of 72 neurons recorded in the reticularis pontis oralis nucleus (RPO) was examined in anesthetized and curarized rats during hippocampal theta (theta) rhythm elicited by either sensory stimulation or carbachol microinjections. During hippocampal theta rhythm evoked by sensory stimulation, 63.9% of RPO neurons increased their discharge rate while the firing rate decreased in 20.8%. In all cases, the RPO neurons maintained a non-rhythmic discharge pattern. In 44% of the neurons the discharges tended to occur on the positive wave of the theta rhythm. Similar firing patterns were seen in 18 RPO neurons recorded during theta rhythm elicited by both, sensory stimulation and a carbachol microinjection; this effect was blocked by atropine. These results indicate that the RPO region contributes to the generation of hippocampal theta rhythm with a tonic and nonrhythmic outflow through a cholinergic system which may be muscarinic.

  6. 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!

  7. 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.

  8. 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.

  9. Car wars

    SciTech Connect

    Russell, D.

    1996-01-01

    With a 1998 deadline looming for electric vehicles to go into mass production (2% of all new cars sold in California, Massachusetts, and New York must not have tail pipe pollution), the major automakers and oil companies have started to attack. This article describes and evaluates charges used in the attacks and the alternative technology possibilities.

  10. C-fos expression in the pons and medulla of the cat during carbachol-induced active sleep.

    PubMed

    Yamuy, J; Mancillas, J R; Morales, F R; Chase, M H

    1993-06-01

    Microinjection of carbachol into the rostral pontine tegmentum of the cat induces a state that is comparable to naturally occurring active (REM, rapid eye movement) sleep. We sought to determine, during this pharmacologically induced behavioral state, which we refer to as active sleep-carbachol, the distribution of activated neuron within the pons and medulla using c-fos immunocytochemistry as a functional marker. Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited higher numbers of c-fos-expressing neurons in (1) the medial and portions of the lateral reticular formation of the pons and medulla, (2) nuclei in the dorsolateral rostral pons, (3) various raphe nuclei, including the dorsal, central superior, magnus, pallidus, and obscurus, (4) the medial and lateral vestibular, prepositus hypoglossi, and intercalatus nuclei, and (5) the abducens nuclei. On the other hand, the mean number of c-fos-expressing neurons found in the masseter, facial, and hypoglossal nuclei was lower in carbachol-injected than in control cats. The data indicate that c-fos expression can be employed as a marker of state-dependent neuronal activity. The specific sites in which there were greater numbers of c-fos-expressing neurons during active sleep-carbachol are discussed in relation to the state of active sleep, as well as the functional role that these sites play in generating the various physiological patterns of activity that occur during this state. PMID:8501533

  11. Gudden's dorsal tegmental nucleus is activated in carbachol-induced active (REM) sleep and active wakefulness.

    PubMed

    Torterolo, Pablo; Sampogna, Sharon; Morales, Francisco R; Chase, Michael H

    2002-07-19

    Previous studies have shown that GABAergic processes in the ponto-mesencephalic region of the brainstem are involved in the generation of wakefulness and active sleep (AS). The dorsal and ventral tegmental nuclei of Gudden (DTN and VTN, respectively) are known to contain a large population of GABAergic neurons. In the present study, utilizing Fos immunoreactivity as a marker of neuronal activity, it was determined that GABAergic DTN pars dorsalis neurons are active during active wakefulness and AS induced by carbachol, but not during quiet wakefulness or quiet sleep. In contrast, no differences in the number of Fos immunoreactive neurons were observed in the DTN pars ventralis and VTN across behavioral states.

  12. 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

  13. 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

  14. Mechanism of carbachol-evoked contractions of guinea-pig ileal smooth muscle close to freezing point.

    PubMed Central

    Blackwood, A. M.; Bolton, T. B.

    1993-01-01

    1. The effect of lowering the temperature to near freezing-point upon the contractions and [3H]-inositol phosphate responses to carbachol were investigated in longitudinal smooth muscle from the guinea-pig ileum. 2. The peak amplitude of the contraction to a single application of 100 microM carbachol was the same at 37 degrees C and temperatures near freezing-point. However, the sensitivity to carbachol was reduced upon lowering the temperature and the time to peak contraction was increased from 5-10 s to 2-10 min. Even when the temperature was maintained near freezing-point, washing off carbachol produced a relaxation and eventual return of tension to basal levels. 3. Incubating the tissue in 140 mM K+, calcium-free solution or in calcium channel antagonists significantly reduced the carbachol-induced contraction to 10-30% of the control at 37 degrees C and also at 3 degrees C. Thus the majority of the activator calcium required for contraction entered the tissue via voltage-dependent calcium channels (VDCs) at both 37 degrees C and 3 degrees C. 4. The contractions produced by high potassium solutions were less at temperatures close to freezing-point than those at 37 degrees C suggesting that voltage-dependent calcium entry was inhibited as the temperature was lowered. 5. A small part of the contractile response to 100 microM carbachol was resistant to the removal of extracellular calcium at both 37 degrees C and 3 degrees C and this component was increased under depolarizing conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8401915

  15. 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. PMID:27562702

  16. Fos expression in pontomedullary catecholaminergic cells following rapid eye movement sleep-like episodes elicited by pontine carbachol in urethane-anesthetized rats.

    PubMed

    Rukhadze, I; Fenik, V B; Branconi, J L; Kubin, L

    2008-03-01

    Pontine noradrenergic neurons of the locus coeruleus (LC) and sub-coeruleus (SubC) region cease firing during rapid eye movement sleep (REMS). This plays a permissive role in the generation of REMS and may contribute to state-dependent modulation of transmission in the CNS. Whether all pontomedullary catecholaminergic neurons, including those in the A1/C1, A2/C2 and A7 groups, have REMS-related suppression of activity has not been tested. We used Fos protein expression as an indirect marker of the level of neuronal activity and linear regression analysis to determine whether pontomedullary cells identified by tyrosine hydroxylase (TH) immunohistochemistry have reduced Fos expression following REMS-like state induced by pontine microinjections of a cholinergic agonist, carbachol in urethane-anesthetized rats. The percentage of Fos-positive TH cells was negatively correlated with the cumulative duration of REMS-like episodes induced during 140 min prior to brain harvesting in the A7 and rostral A5 groups bilaterally (P < 0.01 for both), and in SubC neurons on the side opposite to carbachol injection (P < 0.05). Dorsal medullary A2/C2 neurons did not exhibit such correlation, but their Fos expression (and that in A7, rostral A5 and SubC neurons) was positively correlated with the duration of the interval between the last REMS-like episode and the time of perfusion (P < 0.05). In contrast, neither of these correlations was significant for A1 /C1 or caudal A5 neurons. These findings suggest that, similar to the prototypic LC neurons, neurons of the A7, rostral A5 and A2/C2 groups have reduced or abolished activity during REMS, whereas A1 /IC1 and caudal A5 neurons do not have this feature. The reduced activity of A2/C2, A5 and A7 neurons during REMS, and the associated decrements in norepinephrine release, may cause state-dependent modulation of.transmission in brain somato- and viscerosensory, somatomotor, and cardiorespiratory pathways.

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

    PubMed

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

    2014-02-01

    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

  18. GABAergic neurons of the cat dorsal raphe nucleus express c-fos during carbachol-induced active sleep.

    PubMed

    Torterolo, P; Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    2000-11-24

    Serotonergic neurons of the dorsal raphe nucleus (DRN) cease firing during active sleep (AS, also called rapid-eye-movement sleep). This cessation of electrical activity is believed to play a 'permissive' role in the generation of AS. In the present study we explored the possibility that GABAergic cells in the DRN are involved in the suppression of serotonergic activity during AS. Accordingly, we examined whether immunocytochemically identified GABAergic neurons in the DRN were activated, as indicated by their expression of c-fos, during carbachol-induced AS (AS-carbachol). Three chronically-prepared cats were euthanized after prolonged episodes of AS that was induced by microinjections of carbachol into the nucleus pontis oralis. Another four cats (controls) were maintained 2 h in quiet wakefulness before being euthanized. Thereafter, immunocytochemical studies were performed on brainstem sections utilizing antibodies against Fos, GABA and serotonin. When compared with identically prepared tissue from awake cats, the number of Fos+ neurons was larger in the DRN during AS-carbachol (35.9+/-5.6 vs. 13.9+/-4.4, P<0.05). Furthermore, a larger number of GABA+ Fos+ neurons were observed during AS-carbachol than during wakefulness (24.8+/-3.3 vs. 4.0+/-1.0, P<0.001). These GABA+ Fos+ neurons were distributed asymmetrically with a larger number located ipsilaterally to the site of injection. There was no significant difference between control and experimental animals in the number of non-GABAergic neurons that expressed c-fos in the DRN. We therefore suggest that activated GABAergic neurons of the DRN are responsible for the inhibition of serotonergic neurons that occurs during natural AS. PMID:11082488

  19. The effect of sodium removal on the contractile response of the guinea-pig taenia coli to carbachol.

    PubMed Central

    Brading, A F; Burnett, M; Sneddon, P

    1980-01-01

    1. The effects of Na-free solutions (using Li, Tris, sucrose or Mg as Na substitutes) on the contractile responses, membrane depolarization and 42K efflux produced by carbachol in the smooth muscle of the guinea-pig taenia coli have been investigated. The effect of these Na-free solutions on intracellular ion content of the muscle has also been studied. 2. Na removal induced a pattern of changes in the tone of the muscle characteristic of the substitute used, probably reflecting changes in transmembrane Ca fluxes involving Na. 3. Contractile responses to 10 sec application of 5 x 10(-5) M-carbachol were greatly reduced in Na-free solutions with all the Na substitutes used. This did not correlate with reduction in membrane depolarization or 42K efflux produced by the drug in the various Na-free medial used. 4. Intracellular Na seems important for maintaining the contractile response, since in Na-free solutions cellular Na levels and contractile responses were better maintained at 13 degrees than 34 degrees C and in tissues stimulated with carbachol every 10 min the final magnitude of the response was related to cellular Na content. If, however, the tissues was left unstimulated in Na-free Mg or sucrose solution a large response could still be obtained when cellular Na content was very low. A model is described which could account for these results in terms of an intracellular Ca store released by carbachol and requiring intracellular Na. 5. In tissues continuously exposed to 10(-4) M-carbachol Na removal, even for only 10 sec, produced rapid relaxation, probably secondary to changes in electrical properties of the membrane caused by removal of external Na. PMID:7463367

  20. 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. PMID:8205484

  1. CD28z CARs and Armored CARs

    PubMed Central

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

    2015-01-01

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

  2. 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.

  3. 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

    1986-11-01

    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.

  4. Subclassification of muscarinic receptors in the heart, urinary bladder and sympathetic ganglia in the pithed rat. Selectivity of some classical agonists.

    PubMed

    van Charldorp, K J; de Jonge, A; Thoolen, M J; van Zwieten, P A

    1985-12-01

    In pithed normotensive rats muscarinic receptors were characterized in heart, urinary bladder and sympathetic ganglia; the selectivity of some classical muscarinic agents for these subtypes was investigated. The potencies in decreasing heart rate, increasing bladder pressure and increasing diastolic blood pressure were measured for the following, intraarterially administered cholinergic agonists: McN-A-343 ([4-m-chlorophenylcarbamoyloxy]-2-butynyltrimethylammonium), pilocarpine, carbachol, oxotremorine, arecoline, acetyl-beta-methylcholine and acetylcholine. The selective M1-antagonist pirenzepine, the mixed M1/M2-antagonist dexetimide and the cardioselective M2-antagonist gallamine were used as tools for identification of the receptors. All data were obtained after intravenous pretreatment with a high dose of atenolol to eliminate tachycardia induced by stimulating sympathetic ganglionic muscarinic receptors. Dexetimide strongly antagonized the bradycardia as well as the increase in bladder pressure induced by pilocarpine, carbachol, oxotremorine, arecoline, acetyl-beta-methylcholine and acetylcholine, whereas pirenzepine was much less effective. Gallamine antagonized the bradycardia, whereas no influence was found on the bladder contraction. Pilocarpine acted as a partial agonist in reducing heart rate as well as in increasing bladder pressure, whereas McN-A-343 was almost ineffective in doses up to 1 mg/kg. The hypertensive response to pilocarpine and carbachol was less pronounced than that produced by McN-A-343. Pirenzepine and dexetimide significantly antagonized the hypertensive response to McN-A-343 and pilocarpine, whereas gallamine was much less effective. The hypertensive response induced by carbachol was totally blocked by hexamethonium. The other agonists used in this study did not produce a significant increase in diastolic blood pressure in doses that produced a maximal effect on heart rate and urinary bladder pressure.(ABSTRACT TRUNCATED AT 250 WORDS

  5. Electrophysiological properties of lumbar motoneurons in the alpha-chloralose-anesthetized cat during carbachol-induced motor inhibition.

    PubMed

    Xi, M C; Liu, R H; Yamuy, J; Morales, F R; Chase, M H

    1997-07-01

    The present study was undertaken 1) to examine the neuronal mechanisms responsible for the inhibition of spinal cord motoneurons that occurs in alpha-chloralose-anesthetized cats following the microinjection of carbachol into the nucleus pontis oralis (NPO), and 2) to determine whether the inhibitory mechanisms are the same as those that are responsible for the postsynaptic inhibition of motoneurons that is present during naturally occurring active sleep. Accordingly, the basic electrophysiological properties of lumbar motoneurons were examined, with the use of intracellular recording techniques, in cats anesthetized with alpha-chloralose and compared with those present during naturally occurring active sleep. The intrapontine administration of carbachol resulted in a sustained reduction in the amplitude of the spinal cord Ia monosynaptic reflex. Discrete large-amplitude inhibitory postsynaptic potentials (IPSPs), which are only present during the state of active sleep in the chronic cat, were also observed in high-gain recordings from lumbar motoneurons after the injection of carbachol. During carbachol-induced motor inhibition, lumbar motoneurons exhibited a statistically significant decrease in input resistance, membrane time constant and a reduction in the amplitude of the action potential's afterhyperpolarization. In addition, there was a statistically significant increase in rheobase and in the delay between the initial-segment (IS) and somadendritic (SD) portions of the action potential (IS-SD delay). There was a significant increase in the mean motoneuron resting membrane potential (i.e., hyperpolarization). The preceding changes in the electrophysiological properties of motoneurons, as well as the development of discrete IPSPs, indicate that lumbar motoneurons are postsynaptically inhibited after the intrapontine administration of carbachol in cats that are anesthetized with alpha-chloralose. These changes in the electrophysiological properties of lumbar

  6. Consumer's electric car

    SciTech Connect

    Wakefield, E.H.

    1980-01-01

    Offers fascinating details about electric cars, how they work, their construction, their power sources and complete information on future prospects. Topics include: design of electric vehicles - present and future; efficiency comparisons of electric and gasoline cars; electric car battery and charging systems; alternate motors and controls; troubleshooting an electric car; and other propulsion energies. 88 figures.

  7. 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.

  8. c-fos Expression in mesopontine noradrenergic and cholinergic neurons of the cat during carbachol-induced active sleep: a double-labeling study.

    PubMed

    Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    1998-01-01

    The interaction of cholinergic and catecholaminergic mechanisms in the mesopontine region has been hypothesized as being critical for the generation and maintenance of active (REM) sleep. To further examine this hypothesis, we sought to determine the pattern of neuronal activation (via c-fos expression) of catecholaminergic and cholinergic neurons in this region during active sleep induced by the pontine microapplication of carbachol (designated as active sleep-carbachol). Accordingly, we used two sets of double-labeling techniques; the first to identify tyrosine hydroxylase-containing neurons (putative catecholaminergic cells) which also express the c-fos protein product Fos, and the second to reveal choline acetyltransferase-containing neurons (putative cholinergic cells) which also express Fos. Compared to control cats, active sleep-carbachol cats exhibited a significantly greater number of Fos-expressing neurons in the dorsolateral region of the pons, which encompasses the locus coeruleus, the lateral pontine reticular formation, the peribrachial nuclei and the latero-dorsal and pedunculo-pontine tegmental nuclei. However, both control and active sleep-carbachol cats exhibited a similar number of catecholaminergic and cholinergic neurons in those regions that expressed Fos (i.e., double-labeled cells). A large number of c-fos-expressing neurons in the active sleep-carbachol cats whose neurotransmitter phenotype was not identified suggests that non-catecholaminergic, non-cholinergic neuronal populations in mesopontine regions are involved in the generation and maintenance of active sleep. The lack of increased c-fos expression in catecholaminergic neurons during active sleep-carbachol confirms and extends previous data that indicate that these cells are silent during active sleep-carbachol and naturally-occurring active sleep. The finding that cholinergic neurons of the dorsolateral pons were not activated either during wakefulness or active sleep-carbachol

  9. c-fos Expression in mesopontine noradrenergic and cholinergic neurons of the cat during carbachol-induced active sleep: a double-labeling study.

    PubMed

    Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    1998-01-01

    The interaction of cholinergic and catecholaminergic mechanisms in the mesopontine region has been hypothesized as being critical for the generation and maintenance of active (REM) sleep. To further examine this hypothesis, we sought to determine the pattern of neuronal activation (via c-fos expression) of catecholaminergic and cholinergic neurons in this region during active sleep induced by the pontine microapplication of carbachol (designated as active sleep-carbachol). Accordingly, we used two sets of double-labeling techniques; the first to identify tyrosine hydroxylase-containing neurons (putative catecholaminergic cells) which also express the c-fos protein product Fos, and the second to reveal choline acetyltransferase-containing neurons (putative cholinergic cells) which also express Fos. Compared to control cats, active sleep-carbachol cats exhibited a significantly greater number of Fos-expressing neurons in the dorsolateral region of the pons, which encompasses the locus coeruleus, the lateral pontine reticular formation, the peribrachial nuclei and the latero-dorsal and pedunculo-pontine tegmental nuclei. However, both control and active sleep-carbachol cats exhibited a similar number of catecholaminergic and cholinergic neurons in those regions that expressed Fos (i.e., double-labeled cells). A large number of c-fos-expressing neurons in the active sleep-carbachol cats whose neurotransmitter phenotype was not identified suggests that non-catecholaminergic, non-cholinergic neuronal populations in mesopontine regions are involved in the generation and maintenance of active sleep. The lack of increased c-fos expression in catecholaminergic neurons during active sleep-carbachol confirms and extends previous data that indicate that these cells are silent during active sleep-carbachol and naturally-occurring active sleep. The finding that cholinergic neurons of the dorsolateral pons were not activated either during wakefulness or active sleep-carbachol

  10. Naloxone reduces the amplitude of IPSPs evoked in lumbar motoneurons by reticular stimulation during carbachol-induced motor inhibition.

    PubMed

    Xi, M C; Liu, R H; Yamuy, J; Morales, F R; Chase, M H

    1999-02-20

    During active sleep or carbachol-induced motor inhibition, electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) evoked large amplitude, glycinergic inhibitory postsynaptic potentials (IPSPs) in cat motoneurons. The present study was directed to determine whether these IPSPs, that are specific to the state of active sleep, are modulated by opioid peptides. Accordingly, intracellular recordings were obtained from lumbar motoneurons of acute decerebrate cats during carbachol-induced motor inhibition while an opiate receptor antagonist, naloxone, was microiontophoretically released next to the recorded cells. Naloxone reversibly reduced by 26% the mean amplitude of NRGc-evoked IPSPs (1.9+/-0.2 mV (S.E.M.) vs. 1.4+/-0.2 mV; n=11, control and naloxone, respectively, p<0.05), but had no effect on the other waveform parameters of these IPSPs (e.g., latency-to-onset, latency-to-peak, duration, etc.). The mean resting membrane potential, input resistance and membrane time constant of motoneurons following naloxone ejection were not statistically different from those of the control. These data indicate that opioid peptides have a modulatory effect on NRGc-evoked IPSPs during carbachol-induced motor inhibition. We therefore suggest that endogenous opioid peptides may act as neuromodulators to regulate inhibitory glycinergic synaptic transmission at motoneurons during active sleep. PMID:10082872

  11. Role of phosphatidic acid in carbachol-induced contraction in guinea pig Taenia coli.

    PubMed

    Ohata, H; Nobe, K; Momose, K

    1991-01-01

    Carbachol (CCh, 10(-8)-10(-4) M) increased in concentration-dependent manner the mass of phosphatidic acid (PA), but not the mass of diacylglycerol (DG) in the Taenia coli from guinea pig. The increase in the amount of PA caused by CCh was maintained for 20 min. Release of choline from choline phospholipids labeled with [methyl-3H]choline was not changed by CCh. A DG kinase inhibitor, R59022, inhibited the CCh-induced increase in the mass of PA. These results indicate that the increase in the mass of PA by CCh is due to immediate phosphorylation by DG kinase to PA, of the DG produced by phospholipase C (PLC). It is not due to formation of PA by the direct action of phospholipase D. CCh increased 45Ca2+ uptake into the tissue. R59022 inhibited the sustained phase of CCh-induced contraction and 45Ca2+ uptake into the tissue, but only slightly inhibited the initial phase of the CCh-induced contraction. This inhibition by R59022 may result from the inhibitory effect on the CCh-induced increase in PA. These results suggest that CCh activates both PLC and DG kinase and the resultant increase in the mass of PA contributes to the regulation of the sustained phase of CCh-induced contraction which is related to Ca2+ influx.

  12. 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

  13. 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…

  14. Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists.

    PubMed

    Wollheim, C B; Biden, T J

    1986-01-01

    The initial events in signal transduction in insulin-secreting cells are summarized in FIGURE 8. Both nutrient stimuli, such as glucose and amino acids and the muscarinic agonist carbachol (carbamylcholine) raise [Ca2+]i. Although the rise in [Ca2+]i precedes the stimulation of insulin release, it is not a moment-to-moment regulator of release. The metabolizable fuel stimuli cause Ca2+ influx through voltage-dependent Ca2+ channels following depolarization of the membrane potential. In contrast, carbachol, which does not depolarize, elicits Ptd Ins 4,5-P2 hydrolysis, a reaction catalyzed by phospholipase C. The generation of Ins 1,4,5-P3 in this instance is Ca2+ independent, but appears to involve a GTP-binding protein. However, this protein is not a substrate for pertussis toxin. The levels of Ins 1,4,5-P3, which releases Ca2+ from an ATP-dependent Ca2+ pool of the endoplasmic reticulum, are increased prior to the rise in [Ca2+]i. The mitochondria may take up Ca2+ after large increases in [Ca2+]i. A previously proposed second messenger, arachidonic acid, is much less selective than Ins 1,4,5-P3 in that it releases Ca2+ from mitochondria as well as from the endoplasmic reticulum in a slow and irreversible manner. As Ins 1,4,5-P3 is also generated during glucose stimulation of islets, albeit in a Ca2+-dependent manner, this metabolite could mediate not only the action of carbachol but also contribute to amplifying the [Ca2+]i rise in response to glucose.

  15. 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.

  16. Fos and serotonin immunoreactivity in the raphe nuclei of the cat during carbachol-induced active sleep: a double-labeling study.

    PubMed

    Yamuy, J; Sampogna, S; López-Rodríguez, F; Luppi, P H; Morales, F R; Chase, M H

    1995-07-01

    The microinjection of carbachol into the nucleus pontis oralis produces a state which is polygraphically and behaviorally similar to active sleep (rapid eye movement sleep). In the present study, using double-labeling techniques for serotonin and the protein product of c-fos (Fos), we sought to examine whether immunocytochemically identified serotonergic neurons of the raphe nuclei of the cat were activated, as indicated by their expression of c-fos, during this pharmacologically-induced behavioral state (active sleep-carbachol). Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited a significantly greater number of c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus. Whereas most of the c-fos-expressing neurons in the raphe dorsalis were small, those in the raphe magnus were medium-sized and in the raphe pallidus they were small and medium-sized. The mean number of serotonergic neurons that expressed c-fos (i.e. double-labeled cells) was similar in control and active sleep-carbachol cats. These data indicate that there is an increased number of non-serotonergic, c-fos-expressing neurons in the raphe dorsalis, magnus and pallidus during the carbachol-induced state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7477901

  17. Contribution of Ih to the relative facilitation of synaptic responses induced by carbachol in the entorhinal cortex during repetitive stimulation of the parasubiculum.

    PubMed

    Sparks, D W; Chapman, C A

    2014-10-10

    Neurons in the superficial layers of the entorhinal cortex provide the hippocampus with the majority of its cortical sensory input, and also receive the major output projection from the parasubiculum. This puts the parasubiculum in a position to modulate the activity of entorhinal neurons that project to the hippocampus. These brain areas receive cholinergic projections that are active during periods of theta- and gamma-frequency electroencephalographic (EEG) activity. The purpose of this study was to investigate how cholinergic receptor activation affects the strength of repetitive synaptic responses at these frequencies in the parasubiculo-entorhinal pathway and the cellular mechanisms involved. Whole-cell patch-clamp recordings of rat layer II medial entorhinal neurons were conducted using an acute slice preparation, and responses to 5-pulse trains of stimulation at theta- and gamma-frequency delivered to the parasubiculum were recorded. The cholinergic agonist carbachol (CCh) suppressed the amplitude of single synaptic responses, but also produced a relative facilitation of synaptic responses evoked during stimulation trains. The N-methyl-d-aspartate (NMDA) glutamate receptor blocker APV did not significantly reduce the relative facilitation effect. However, the hyperpolarization-activated cationic current (Ih) channel blocker ZD7288 mimicked the relative facilitation induced by CCh, suggesting that CCh-induced inhibition of Ih could produce the effect by increasing dendritic input resistance (Rin). Inward-rectifying and leak K(+) currents are known to interact with Ih to affect synaptic excitability. Application of the K(+) channel antagonist Ba(2+) depolarized neurons and enhanced temporal summation, but did not block further facilitation of train-evoked responses by ZD7288. The Ih-dependent facilitation of synaptic responses can therefore occur during reductions in inward-rectifying potassium current (IKir) associated with dendritic depolarization. Thus, in

  18. GABAergic neurons of the laterodorsal and pedunculopontine tegmental nuclei of the cat express c-fos during carbachol-induced active sleep.

    PubMed

    Torterolo, P; Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    2001-02-23

    The laterodorsal and pedunculopontine tegmental nuclei (LDT-PPT) are involved in the generation of active sleep (AS; also called REM or rapid eye movement sleep). Although the LDT-PPT are composed principally of cholinergic neurons that participate in the control of sleep and waking states, the function of the large number of GABAergic neurons that are also located in the LDT-PPT is unknown. Consequently, we sought to determine if these neurons are activated (as indicated by their c-fos expression) during active sleep induced by the microinjection of carbachol into the rostro-dorsal pons (AS-carbachol). Accordingly, immunocytochemical double-labeling techniques were used to identify GABA and Fos protein, as well as choline acetyltransferase (ChAT), in histological sections of the LDT-PPT. Compared to control awake cats, there was a larger number of GABAergic neurons that expressed c-fos during AS-carbachol (31.5+/-6.1 vs. 112+/-15.2, P<0.005). This increase in the number of GABA+Fos+ neurons occurred on the ipsilateral side relative to the injection site; there was a small decrease in GABA+Fos+ cells in the contralateral LDT-PPT. However, the LDT-PPT neurons that exhibited the largest increase in c-fos expression during AS-carbachol were neither GABA+ nor ChAT+ (47+/-22.5 vs. 228.7+/-14.0, P<0.0005). The number of cholinergic neurons that expressed c-fos during AS-carbachol was not significantly different compared to wakefulness. These data demonstrate that, during AS-carbachol, GABAergic as well as an unidentified population of neurons are activated in the LDT-PPT. We propose that these non-cholinergic LDT-PPT neurons may participate in the regulation of active sleep. PMID:11172778

  19. GABAergic neurons of the laterodorsal and pedunculopontine tegmental nuclei of the cat express c-fos during carbachol-induced active sleep.

    PubMed

    Torterolo, P; Yamuy, J; Sampogna, S; Morales, F R; Chase, M H

    2001-02-23

    The laterodorsal and pedunculopontine tegmental nuclei (LDT-PPT) are involved in the generation of active sleep (AS; also called REM or rapid eye movement sleep). Although the LDT-PPT are composed principally of cholinergic neurons that participate in the control of sleep and waking states, the function of the large number of GABAergic neurons that are also located in the LDT-PPT is unknown. Consequently, we sought to determine if these neurons are activated (as indicated by their c-fos expression) during active sleep induced by the microinjection of carbachol into the rostro-dorsal pons (AS-carbachol). Accordingly, immunocytochemical double-labeling techniques were used to identify GABA and Fos protein, as well as choline acetyltransferase (ChAT), in histological sections of the LDT-PPT. Compared to control awake cats, there was a larger number of GABAergic neurons that expressed c-fos during AS-carbachol (31.5+/-6.1 vs. 112+/-15.2, P<0.005). This increase in the number of GABA+Fos+ neurons occurred on the ipsilateral side relative to the injection site; there was a small decrease in GABA+Fos+ cells in the contralateral LDT-PPT. However, the LDT-PPT neurons that exhibited the largest increase in c-fos expression during AS-carbachol were neither GABA+ nor ChAT+ (47+/-22.5 vs. 228.7+/-14.0, P<0.0005). The number of cholinergic neurons that expressed c-fos during AS-carbachol was not significantly different compared to wakefulness. These data demonstrate that, during AS-carbachol, GABAergic as well as an unidentified population of neurons are activated in the LDT-PPT. We propose that these non-cholinergic LDT-PPT neurons may participate in the regulation of active sleep.

  20. Rational Quantitative Structure-Activity Relationship (RQSAR) Screen for PXR and CAR Isoform-Specific Nuclear Receptor Ligands

    PubMed Central

    Dring, Ann M.; Anderson, Linnea E.; Qamar, Saima; Stoner, Matthew A.

    2010-01-01

    Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related orphan nuclear receptor proteins that share several ligands and target overlapping sets of genes involved in homeostasis and all phases of drug metabolism. CAR and PXR are involved in the development of certain diseases, including diabetes, metabolic syndrome and obesity. Ligand screens for these receptors so far have typically focused on steroid hormone analogs with pharmacophore-based approaches, only to find relatively few new hits. Multiple CAR isoforms have been detected in human liver, with the most abundant being the constitutively active reference, CAR1, and the ligand-dependent isoform CAR3. It has been assumed that any compound that binds CAR1 should also activate CAR3, and so CAR3 can be used as a ligand-activated surrogate for CAR1 studies. The possibility of CAR3-specific ligands has not, so far, been addressed. To investigate the differences between CAR1, CAR3 and PXR, and to look for more CAR ligands that may be of use in quantitative structure-activity relationship (QSAR) studies, we performed a luciferase transactivation assay screen of 60 mostly non-steroid compounds. Known active compounds with different core chemistries were chosen as starting points and structural variants were rationally selected for screening. Distinct differences in agonist versus inverse agonist/antagonist effects were seen in 49 compounds that had some ligand effect on at least one receptor and 18 that had effects on all three receptors; eight were CAR1 ligands only, three were CAR3 only ligands and four affected PXR only. This work provides evidence for new CAR ligands, some of which have CAR3-specific effects, and provides observational data on CAR and PXR ligands with which to inform in silico strategies. Compounds that demonstrated unique activity on any one receptor are potentially valuable diagnostic tools for the investigation of in vivo molecular targets. PMID:20869355

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

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

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

  2. 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

  3. 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

  4. 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.…

  5. 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.

  6. Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR).

    PubMed

    Chang, Thomas K H; Waxman, David J

    2006-01-01

    Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are members of the nuclear receptor superfamily. These transcription factors are predominantly expressed in the liver, where they are activated by structurally diverse compounds, including many drugs and endogenous substances. CAR and PXR regulate the expression of a broad range of genes, which contribute to transcellular transport, bioactivation, and detoxification of numerous xenochemicals and endogenous substances. This article discusses the importance of these receptors for pharmacology and toxicology, emphasizing the role of individual drugs and natural products as agonists, indirect activators, inverse agonists, and antagonists of CAR and PXR. PMID:16684648

  7. Electrophysiological characterization of neurons in the dorsolateral pontine REM sleep induction zone of the rat: intrinsic membrane properties and responses to carbachol and orexins

    PubMed Central

    Brown§, Ritchie E.; Winston, Stuart; Basheer, Radhika; Thakkar, Mahesh M; McCarley, Robert W.

    2006-01-01

    Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (Subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study. We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean diameter 30 and 27μm) were tentatively identified as cholinergic (rostral SubC) and noradrenergic (caudal SubC) neurons. SubC reticular neurons (non-cholinergic, non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing current pulses and often had a rebound depolarization (low-threshold spike, LTS). During depolarizing current pulses they exhibited little adaptation and fired maximally at 30–90 Hz. Those SubC reticular neurons excited by carbachol (n=27) fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied widely in size (17–42 μm). Carbachol-inhibited SubC reticular neurons were medium-sized (15–25 μm) and constituted two groups. The larger group (n=22) was silent at rest and possessed a prominent LTS and associated 1–4 action potentials. The second, smaller group (n=8) had a delayed return to baseline at the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons. SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (> 50 %), the majority of which demonstrated a prominent LTS and may correspond to PGO-on neurons

  8. Electrophysiological characterization of neurons in the dorsolateral pontine rapid-eye-movement sleep induction zone of the rat: Intrinsic membrane properties and responses to carbachol and orexins.

    PubMed

    Brown, R E; Winston, S; Basheer, R; Thakkar, M M; McCarley, R W

    2006-12-01

    Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study. We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean diameter 30 and 27 mum) were tentatively identified as cholinergic (rostral SubC) and noradrenergic (caudal SubC) neurons. SubC reticular neurons (non-cholinergic, non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing current pulses and often had a rebound depolarization (low-threshold spike, LTS). During depolarizing current pulses they exhibited little adaptation and fired maximally at 30-90 Hz. Those SubC reticular neurons excited by carbachol (n=27) fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied widely in size (17-42 mum). Carbachol-inhibited SubC reticular neurons were medium-sized (15-25 mum) and constituted two groups. The larger group (n=22) was silent at rest and possessed a prominent LTS and associated one to four action potentials. The second, smaller group (n=8) had a delayed return to baseline at the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons. SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (>50%), the majority of which demonstrated a prominent LTS and may correspond to pontine

  9. Modeling the Mousetrap Car

    NASA Astrophysics Data System (ADS)

    Jumper, William D.

    2012-03-01

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

  10. 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)

  11. How do CARs work?

    PubMed Central

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

    2012-01-01

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

  12. Pharmacological estimation of agonist affinity: detection of errors that may be caused by the operation of receptor isomerisation or ternary complex mechanisms.

    PubMed

    Leff, P; Harper, D; Dainty, I A; Dougall, I G

    1990-09-01

    1. Recent theoretical studies have questioned the pharmacological estimation of agonist affinity. They showed that when receptor isomerisation or ternary complex mechanisms operate, the receptor inactivation method can substantially overestimate affinity, whereas methods for partial agonist analysis are more accurate. We previously suggested that the operation of such mechanisms and therefore the presence of errors could be detected by analysing the same partial agonist by the receptor inactivation and comparative methods. This paper describes the practical application of this test. 2. The ternary complex mechanism was simulated for a partial agonist under various conditions relating receptor (R) and transducer (T) concentrations, one of which also corresponds to the receptor isomerisation mechanism. The theoretical data so generated were then analysed by the inactivation and comparative methods to quantify the magnitude of error of affinity estimation that could occur. 3. This analysis showed that for a partial agonist with approximately 85% of the activity of a full agonist, the inactivation method could produce an affinity (pKA) estimate up to 0.7 log10 units higher than that produced by the comparative method. This difference would occur when the total receptor concentration ([R0]) is less than or equal to the total transducer concentration ([T0]). It also showed that the overestimation of affinity by the inactivation method was accompanied by drastic overestimation of Em, the maximal effect parameter. 4. The test was then exemplified using the muscarinic receptor system in the guinea-pig isolated left atrial preparation, where there is evidence that a ternary complex mechanism operates. The test agonist was pilocarpine, which produced on average 83% of the activity of the full agonist, carbachol. Pilocarpine was analysed in comparison with carbachol and by receptor inactivation in the same tissue resulting in small and statistically insignificant differences

  13. A natural history of "agonist".

    PubMed

    Russo, Ruth

    2002-01-01

    This paper constructs a brief history of the biochemical term agonist by exploring the multiple meanings of the root agôn in ancient Greek literature and describing how agonist first appeared in the scientific literature of the 20th century in the context of neurophysiologists' debates about the existence and properties of cellular receptors. While the narrow scientific definition of agonist may appear colorless and dead when compared with the web of allusions spun by the ancient Greek agôn, the scientific power and creativity of agonist actually resides precisely in its exact, restricted meaning for biomedical researchers.

  14. Physics in a Bouncing Car.

    ERIC Educational Resources Information Center

    Bartlett, Albert A.

    1984-01-01

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

  15. Determination of mass changes in phosphatidylinositol 4,5-bisphosphate and evidence for agonist-stimulated metabolism of inositol 1,4,5-trisphosphate in airway smooth muscle.

    PubMed Central

    Chilvers, E R; Batty, I H; Challiss, R A; Barnes, P J; Nahorski, S R

    1991-01-01

    Stimulation of muscarinic receptors in bovine tracheal smooth muscle (BTSM) causes a sustained increase in muscle tone, but a transient increase in the second messenger Ins(1,4,5)P3. To examine whether this brief increase in Ins(1,4,5)P3 mass results from transient formation or is due to agonist-stimulation of Ins(1,4,5)P3 metabolism, we have studied the relationship between mass changes in PtdIns(4,5)P2 and Ins(1,4,5)P3 accumulation, and changes in [3H]InsP3, [3H]PtdIns, [3H]PtdInsP1 and [3H]PtdInsP2 in carbachol-stimulated myo-[3H]inositol-prelabelled BTSM slices. Carbachol (0.1 mM) caused a rapid transient increase in Ins(1,4,5)P3 concentration (basal, 12.9 +/- 0.8 pmol/mg of protein; 5 s carbachol treatment, 27.1 +/- 1.5 pmol/mg of protein), with values returning to basal levels by 30 s, but a sustained accumulation of total [3H]InsP3s, with [3H]Ins(1,3,4)P3 being the predominant isomer present at later time points. In contrast, PtdIns(4,5)P2 mass, determined by radioreceptor assay of Ins(1,4,5)P3 in desalted alkaline hydrolysates of acidified chloroform/methanol tissue extracts, declined rapidly (basal, 941 +/- 22 pmol/mg of protein; 120 s carbachol, 365 +/- 22 pmol/mg of protein; t1/2 14 s) and remained at this new steady-state level for at least 20 min in the continued presence of carbachol. Addition of 10 microM-atropine 2 min after carbachol caused a prompt return of PtdIns(4,5)P2 concentration to prestimulated values (t1/2 210 s). Ongoing resynthesis of PtdIns(4,5)P2 after carbachol stimulation was demonstrated in [3H]inositol-labelled tissue by observing a persistent increase in the specific radioactivity of [3H]PtdInsP2, shown to be exclusively [3H]PtdIns(4,5)P2, over a 10 min period. These findings strongly suggest the occurrence of persistent receptor-mediated increases in PtdIns(4,5)P2 hydrolysis and Ins(1,4,5)P3 formation which, in conjunction with the transient accumulation of Ins(1,4,5)P3 observed, provide evidence that regulation of the

  16. Aerodynamics of Race Cars

    NASA Astrophysics Data System (ADS)

    Katz, Joseph

    2006-01-01

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

  17. 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.

  18. 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. PMID:27110632

  19. 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. PMID:26567724

  20. 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

  1. Changes in the contractile responses to carbachol and in the inhibitory effects of verapamil and nitrendipine on isolated smooth muscle preparations from rats subchronically exposed to Pb2+ and Zn2+.

    PubMed

    Vassilev, P P; Venkova, K; Pencheva, N; Radomirov, R; Staneva-Stoytcheva, D

    1994-01-01

    Male Wistar rats were exposed to Pb2+ or Zn2+ and to Pb2+ + Zn2+, receiving Pb(CH3COO)2 or/and ZnSO4 with drinking water for 30 days. Cumulative concentration-effect curves for carbachol were obtained in ileum and trachea isolated from control and heavy metal-treated rats. The effect of the Ca2+ channel blockers on the carbachol-induced contractions was studied by addition of increasing concentrations of verapamil or nitrendipine to the bath solution 20 min. prior to carbachol. The results showed that exposure of rats to heavy metals in doses which did not change the body weight and behaviour, altered the contractile responses to carbachol. The sensitivity to carbachol was higher in preparations from the ileum of Zn(2+)-exposed rats as compared to controls, while a tendency towards decreasing this sensitivity was observed in ileal preparations from Pb(2+)-treated animals. The concentration-effect curves for carbachol in ileal preparations from Pb2+ + Zn(2+)-treated rats did not differ from those in the preparations from untreated rats. The inhibitory effect of the Ca2+ channel blockers on the contractility of ileal and tracheal preparations from treated rats was weaker as compared to that in controls.

  2. 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

  3. 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…

  4. Characterization and agonist regulation of muscarinic ([3H]N-methyl scopolamine) receptors in isolated ventricular myocytes from rat.

    PubMed

    Horackova, M; Robinson, B; Wilkinson, M

    1990-11-01

    Cell surface muscarinic cholinergic receptors have been characterized and quantified for the first time, in intact, isolated adult rat cardiomyocytes. The cells were previously established as functionally fully compatible with cellular responses in intact cardiac tissue. The specific binding of the hydrophilic radioligand, [3H]-NMS, (N-methyl-[3H]-scopolamine methylchloride) was found to be stereo-specific, saturable, reversible and of high affinity. Binding of [3H]-NMS demonstrated appropriate drug specificity and was positively correlated with increasing cell concentrations. Bmax for [3H]-NMS binding to ventricular myocytes, enzymatically dissociated from adult male rats, was 15.8 +/- 1.03 fmol/25 x 10(3) cells (at 4 degrees C) and KD was 0.27 +/- 0.05 nM (n = 14). Binding assays performed at a higher incubation temperature (30 degrees C) yielded a higher Bmax value (22.1 +/- 1.6 fmol/25 x 10(3) cells; n = 11; P less than 0.005 vs. Bmax at 4 degrees C) but an unchanged KD (0.23 +/- 0.06 nM). Pretreatment of myocytes with the muscarinic agonist carbachol (1 mM) at 37 degrees C resulted in a reduction (down-regulation) in specific binding of the hydrophilic ligand [3H]-NMS. The magnitude of this reduction and its rate of recovery were dependent on the time of the exposure to carbachol. Exposures of 30-60 min elicited down-regulated by 35% (Bmax = 14.29 +/- 1.66 changed to 9.5 +/- 1.79 fmol/25 x 10(3) cells, without change in KD P less than 0.01, n = 4). The down-regulation of the muscarinic receptors by carbachol was insensitive to application of bacitracin - an inhibitor of endocytosis. On the other hand preincubation with 10(-9)M atropine, a muscarinic antagonist, hindered the agonist-induced receptor "loss" from the cell surface confirming the muscarinic nature of these receptors. We conclude that our preparation of intact, isolated ventricular cardiomyocytes is ideally suited for the study of cell surface muscarinic receptor regulation under physiological and

  5. Characterization and agonist regulation of muscarinic ([3H]N-methyl scopolamine) receptors in isolated ventricular myocytes from rat.

    PubMed

    Horackova, M; Robinson, B; Wilkinson, M

    1990-11-01

    Cell surface muscarinic cholinergic receptors have been characterized and quantified for the first time, in intact, isolated adult rat cardiomyocytes. The cells were previously established as functionally fully compatible with cellular responses in intact cardiac tissue. The specific binding of the hydrophilic radioligand, [3H]-NMS, (N-methyl-[3H]-scopolamine methylchloride) was found to be stereo-specific, saturable, reversible and of high affinity. Binding of [3H]-NMS demonstrated appropriate drug specificity and was positively correlated with increasing cell concentrations. Bmax for [3H]-NMS binding to ventricular myocytes, enzymatically dissociated from adult male rats, was 15.8 +/- 1.03 fmol/25 x 10(3) cells (at 4 degrees C) and KD was 0.27 +/- 0.05 nM (n = 14). Binding assays performed at a higher incubation temperature (30 degrees C) yielded a higher Bmax value (22.1 +/- 1.6 fmol/25 x 10(3) cells; n = 11; P less than 0.005 vs. Bmax at 4 degrees C) but an unchanged KD (0.23 +/- 0.06 nM). Pretreatment of myocytes with the muscarinic agonist carbachol (1 mM) at 37 degrees C resulted in a reduction (down-regulation) in specific binding of the hydrophilic ligand [3H]-NMS. The magnitude of this reduction and its rate of recovery were dependent on the time of the exposure to carbachol. Exposures of 30-60 min elicited down-regulated by 35% (Bmax = 14.29 +/- 1.66 changed to 9.5 +/- 1.79 fmol/25 x 10(3) cells, without change in KD P less than 0.01, n = 4). The down-regulation of the muscarinic receptors by carbachol was insensitive to application of bacitracin - an inhibitor of endocytosis. On the other hand preincubation with 10(-9)M atropine, a muscarinic antagonist, hindered the agonist-induced receptor "loss" from the cell surface confirming the muscarinic nature of these receptors. We conclude that our preparation of intact, isolated ventricular cardiomyocytes is ideally suited for the study of cell surface muscarinic receptor regulation under physiological and

  6. Fatal Car Occupant Injuries after Car Lorry Collisions

    PubMed Central

    Gissane, William; Bull, John

    1973-01-01

    All deaths from road accidents in certain areas and periods were studied. Analysis of 224 deaths to car occupants from collisions between cars and lorries showed that such accidents were the commonest cause of death for car occupants on motorways and link roads. The impacts were such that relatively poor protection could be given by occupant restraint systems. Collisions of cars into the rear of lorries caused the most severe injuries; most of these accidents occurred at night. The traffic characteristics of cars and lorries are largely incompatible and increase the likelihood of collisions and of extremely severe injuries to car occupants. Some reduction in deaths may be expected from making lorries more conspicuous and eliminating the rear overhang. More fundamental measures are segregation of lorries from cars and return of traffic to railways. ImagesFIG. 1FIG. 2FIG. 3 PMID:20791870

  7. 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.

  8. All purpose railroad car

    SciTech Connect

    Terlecky, B.S.

    1987-01-13

    An all purpose railroad car is described for transporting wheeled trailers and containers, the car comprising an elongated frame supported by wheel trucks, combined hitch and bolster means adjacent one end of the frame for selectively receiving and releasably retaining a trailer king pin and one end of a container. A means is spaced from the combined hitch and bolster means for selectively receiving and supporting the wheels of a wheeled trailer and the other end of a container. The combined hitch and bolster means is an integral rigid structure with the hitch fixed in spaced relationship to the bolster with both the hitch and the bolster permanently disposed in operative position to respectively receive and retain a trailer king pin and a container.

  9. Modulation of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) by 6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives, ligands of peripheral benzodiazepine receptor (PBR).

    PubMed

    Anderson, Linnea E; Dring, Ann M; Hamel, Laura D; Stoner, Matthew A

    2011-04-25

    Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate xenobiotic sensing and metabolism through interactions with multiple exogenous and endogenous chemicals. Compounds that activate CAR are often ligands of PXR; attention is therefore given to discovery of new, receptor-specific chemical entities that may be exploited for therapeutic and basic research purposes. Recently, ligands of the peripheral benzodiazepine receptor (PBR), PK11195 and FGIN-1-27, were shown to modulate both CAR and PXR. PBR is a mitochondrial transport protein responsible for multiple regulatory functions, including heme biosynthesis, a major component in cytochrome P450 (CYP) enzymes. To investigate possible new roles for PBR involvement in metabolic regulation, expression of the CAR and PXR target genes, CYP2B6 and CYP3A4, was measured in human hepatocytes following treatment with a targeted PBR ligand set. Luciferase reporter assays with transiently expressed wild-type CAR (CAR1), splice variant CAR3, or PXR in HuH-7 cells were used to further study activation of these receptors. Four structurally related PBR ligands (benzothiazepines) differentially modulate CAR1, CAR3 and PXR activity. Benzothiazepine NF49 is an agonist ligand of CAR3, a partial agonist of PXR, exhibits greater inverse agonist activity on CAR1 than does PK11195, and is a new tool for studying these closely related nuclear receptors.

  10. Hydraulic motor for cars

    SciTech Connect

    Gagnon, D.C.

    1986-09-02

    A hydraulic motor for a car is described comprising, in combination, an automotive vehicle engine for travel self-propulsion, including a block, a plurality of cylinders in the block, a piston slidable in each cylinder, a crankshaft in the block, a piston rod connected between the crankshaft and each of the pistons, a power take-off gear on the crankshaft for the travel self-propulsion, and the engine including a hydraulic means for driving the pistons in the cylinders.

  11. 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.

  12. Scrap car recycling in Taiwan

    SciTech Connect

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

    1997-12-31

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

  13. Mechanisms involved in carbachol-induced Ca2+ sensitization of contractile elements in rat proximal and distal colon

    PubMed Central

    Takeuchi, Tadayoshi; Kushida, Masahiko; Hirayama, Nobue; Kitayama, Muneyoshi; Fujita, Akikazu; Hata, Fumiaki

    2004-01-01

    Mechanisms involved in Ca2+ sensitization of contractile elements induced by the activation of muscarinic receptors in membrane-permeabilized preparations of the rat proximal and distal colon were studied. In α-toxin-permeabilized preparations from the rat proximal and distal colon, Ca2+ induced a rapid phasic and subsequent tonic component. After Ca2+-induced contraction reached a plateau, guanosine 5′-triphosphate (GTP) and carbachol (CCh) in the presence of GTP further contracted preparations of both the proximal and distal colon (Ca2+ sensitization). Y-27632, a rho-kinase inhibitor, inhibited GTP plus CCh-induced Ca2+ sensitization more significantly in the proximal colon than in the distal colon. Y-27632 at 10 μM had no effect on Ca2+-induced contraction or slightly inhibited phorbol-12,13-dibutyrate-induced Ca2+ sensitization in either proximal or distal colon. Chelerythrine, a protein kinase C inhibitor, inhibited GTP plus CCh-induced Ca2+ sensitization in the distal colon, but not in the proximal colon. The component of Ca2+ sensitization that persisted after the chelerythrine treatment was completely inhibited by Y-27632. In β-escin-permeabilized preparations of the proximal colon, C3 exoenzyme completely inhibited GTP plus CCh-induced Ca2+ sensitization, but PKC(19–31) did not. In the distal colon, C3 exoenzyme abolished GTP-induced Ca2+ sensitization. It inhibited CCh-induced sensitization by 50 % and the remaining component was inhibited by PKC(19–31). These results suggest that both protein kinase C and rho pathways in parallel mediate the Ca2+ sensitization coupled to activation of muscarinic receptors in the rat distal colon, whereas the rho pathway alone mediates this action in the proximal colon. PMID:15159278

  14. Diminished agonist-stimulated inositol trisphosphate generation blocks stimulus-secretion coupling in mouse pancreatic acini during diet-induced experimental pancreatitis

    SciTech Connect

    Powers, R.E.; Saluja, A.K.; Houlihan, M.J.; Steer, M.L.

    1986-05-01

    Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet rapidly develop acute hemorrhagic pancreatitis. We have observed that pancreatic acini prepared from these mice are unable to secrete amylase in response to addition of the cholinergic agonist carbachol, although they retain the ability to secrete amylase in response to the Ca2+ ionophore A23187. The CDE diet does not alter the binding characteristics (Kd or the maximal number of binding sites) for muscarinic cholinergic receptors as tested using the antagonist (/sup 3/H)N-methylscopolamine nor the competition for this binding by carbachol. Addition of carbachol to acini prepared from mice fed the CDE diet does not result in as marked an increase in cytosolic free Ca2+ levels as that noted in control samples (evaluated using quin2 fluorescence). These observations indicate that the CDE diet interferes with stimulus-secretion coupling in mouse pancreatic acini at a step subsequent to hormone-receptor binding and prior to Ca2+ release. This conclusion is confirmed by our finding that the hormone-stimulated generation of (/sup 3/H)inositol phosphates (inositol trisphosphate, inositol bisphosphate, and inositol monophosphate) from acini labeled with (/sup 3/H)myoinositol is markedly reduced in acini prepared from mice fed the CDE diet. This reduction is not due to a decrease in phosphatidylinositol-4,5-bisphosphate. This communication represents the first report of a system in which a blockade of inositol phosphate generation can be related to a physiologic defect and pathologic lesion.

  15. Agonist-trafficking and hallucinogens.

    PubMed

    González-Maeso, Javier; Sealfon, Stuart C

    2009-01-01

    Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different agonists sometimes elicit a different relative activation of two signaling pathways downstream of the same receptor has led to a revision of the ternary complex model. According to this agonist- trafficking model, agonists stabilize distinct activated receptor conformations that preferentially activate specific signaling pathways. Hallucinogenic drugs and non-hallucinogenic drugs represent an attractive experimental system with which to study agonist-trafficking of receptor signaling. Thus many of the behavioral responses induced by hallucinogenic drugs, such as lysergic acid diethylamide (LSD), psilocybin or mescaline, depend on activation of serotonin 5-HT(2A) receptors (5-HT2ARs). In contrast, this neuropsychological state in humans is not induced by closely related chemicals, such as lisuride or ergotamine, despite their similar in vitro activity at the 5-HT2AR. In this review, we summarize the current knowledge, as well as unresolved questions, regarding agonist-trafficking and the mechanism of action of hallucinogenic drugs.

  16. 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

    2014-09-01

    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.

  17. On the nature of the oscillations of the membrane potential (slow waves) produced by acetylcholine or carbachol in intestinal smooth muscle.

    PubMed

    Bolton, T B

    1971-07-01

    1. Intracellular recording was made with glass micro-electrodes from cells of the longitudinal muscle of the guinea-pig ileum in isotonic and in hypertonic solution.2. In isotonic solution spontaneous bursts of electrical activity occurred; these consisted of a slow potential component which carried a burst of spike action potentials. Acetylcholine increased the size (and the frequency) of the slow potential component. This had the effect of first reducing and then abolishing the spike potentials; continuous slow wave activity was thus produced. Slow waves were about 1 sec in duration and up to 50 mV in size in isotonic solution.3. In hypertonic solution the membrane potential was stable. There were no spontaneous spikes and no slow potentials. However, spikes, but not slow potentials, were elicited by depolarizing current. Carbachol (or acetylcholine) reduced the membrane potential and initiated spikes and oscillations of the membrane potential (slow waves). Slow waves were 2-5 sec in duration and 10-40 mV in size in hypertonic solution.4. The response to carbachol in hypertonic solution was unaffected by surgical denervation of the tissue, by tetrodotoxin, or by ganglion blocking agents, indicating that muscarinic stimulants produced their effects by acting directly on the smooth muscle cell.5. In hypertonic solution slow waves occurred only in the presence of a muscarinic stimulant and could not be elicited with depolarizing current (unless carbachol was present) nor by increasing the external potassium concentration.6. In hypertonic solution slow waves were abolished by hyperpolarizing the membrane and their rate of rise was proportional to the level of the membrane potential from which they arose. The membrane resistance was reduced at the peak of the slow wave. Slow waves were rapidly abolished by sodium-deficient solutions but spikes were not.7. It is suggested that slow waves represent an inward current through a slow, sodium-sensitive and voltage

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Beta 1- and beta 2-adrenoceptor antagonist activities of ICI-215001, a putative beta 3-adrenoceptor agonist.

    PubMed Central

    Tesfamariam, B.; Allen, G. T.

    1994-01-01

    1. The present study was undertaken to characterize the beta 3-adrenoceptor agonist activity of ICI-215001 and to determine whether it exhibits additional activities on beta 1- and beta 2-adrenoceptors in isolated spontaneously beating atrium, trachea and ileum of guinea-pig. 2. In guinea-pig atrium, isoprenaline, a non-selective beta-adrenoceptor agonist, caused concentration-dependent, positive chronotropic effects that were inhibited by atenolol, a selective beta 1-antagonist. ICI-215001 also competitively antagonized the increase in heart rate caused by isoprenaline. 3. ICI-215001 exhibited low intrinsic activity at increasing the beating rate of atrium and no activity on resting or induced tone of tracheal strips. 4. In strips of guinea-pig trachea, contracted submaximally with carbachol, isoprenaline, caused concentration-dependent relaxations. Both ICI-118551, a selective beta 2-adrenoceptor antagonist, and ICI-215001 competitively inhibited the relaxations caused by isoprenaline. 5. In isolated strips of guinea-pig ileum longitudinal smooth muscle contracted with histamine, isoprenaline and ICI-215001 caused relaxations which were inhibited by alprenolol, a beta-adrenoceptor antagonist with modest affinity for beta 3-adrenoceptors, but were resistant to ICI-118551 and atenolol. 6. These results indicate that ICI-215001 exhibits beta 3-adrenoceptor agonist activity as demonstrated by relaxations mediated via atypical beta-adrenoceptors in the longitudinal smooth muscle of guinea-pig ileum. Further, the studies demonstrate that ICI-215001 can act as an antagonist at beta 1- and beta 2-adrenoceptors in situations where its intrinsic agonist activity is low. PMID:7913381

  3. 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...

  4. 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...

  5. 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...

  6. 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) (b) After Division 6.1 (poisonous) materials are unloaded from a rail car, that car must be thoroughly cleaned unless the car...

  7. 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...

  8. Changes in the contractile responses to carbachol and in the inhibitory effects of verapamil and nitrendipine on isolated smooth muscle preparations from rats subchronically exposed to Co2+ and Ni2+.

    PubMed

    Vassilev, P P; Venkova, K; Pencheva, N; Staneva-Stoytcheva, D

    1993-01-01

    Male Wistar rats were exposed to subtoxic doses of Co2+ or Ni2+, receiving Co(NO3)2 or NiSO4 with drinking water for 30 days. No significant differences in the body weight and no visible changes in the behaviour of the controls and experimental animals were established. Cumulative concentration-effect curves for carbachol were obtained in ileum and trachea isolated from control and Co(2+)- or Ni(2+)-treated rats. The effect of the Ca2+ antagonists on the carbachol-induced contractions was studied by adding increasing concentrations of verapamil or nitrendipine to the bath solution 20 min prior to carbachol. The results showed that exposure of rats to subtoxic doses of Co(NO3)2 or NiSO4 altered the contractile responses to carbachol. The changes in the pD2 values and the shift to the left of the concentration-effect curves suggest a higher sensitivity to carbachol in preparations from the ileum of Co(2+)- or Ni(2+)-exposed rats. The tracheal strips isolated from control and heavy metal-treated rats showed a less potent sensitiveness to carbachol as compared to the ileal segments. An opposite tendency for decreased cholinergic reactivity was observed in tracheal strips from Co(2+)- and Ni(2+)-treated animals. The inhibitory effect of the Ca(2+)-antagonists on the contractility of ileal preparations from Co(2+)-treated rats increased at all concentrations of verapamil and at the highest concentration of nitrendipine, but decreased at lower concentrations of nitrendipine. The effect of verapamil on the preparations from Ni(2+)-exposed rats was unchanged or even decreased at higher verapamil concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Car insurance and the risk of car crash injury.

    PubMed

    Blows, Stephanie; Ivers, Rebecca Q; Connor, Jennie; Ameratunga, Shanthi; Norton, Robyn

    2003-11-01

    Despite speculation about the role of vehicle insurance in road traffic accidents, there is little research estimating the direction or extent of the risk relationship. Data from the Auckland Car Crash Injury Study (1998-1999) were used to examine the association between driving an uninsured motor vehicle and car crash injury. Cases were all cars involved in crashes in which at least one occupant was hospitalized or killed anywhere in the Auckland region. Controls were 588 drivers of randomly selected cars on Auckland roads. Participants completed a structured interview. Uninsured drivers had significantly greater odds of car crash injury compared to insured drivers after adjustment for age, sex, level of education, and driving exposure (odds ratio 4.77, 95% confidence interval 2.94-7.75). The causal mechanism for insurance and car crash injury is not easily determined. Although we examined the effects of multiple potential confounders in our analysis including socioeconomic status and risk-taking behaviours, both of which have been previously observed to be associated with both insurance status and car crash injury, residual confounding may partly explain this association. The estimated proportion of drivers who are uninsured is between 5 and 15% in developed countries, representing a significant public health problem worthy of further investigation. PMID:12971933

  10. 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.

  11. 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.

  12. The action of cholinergic agonists on the squid stellate ganglion giant synapse.

    PubMed

    Stanley, E F

    1984-07-01

    Although the giant synapse in the squid stellate ganglion has served as a model in the understanding of the ionic and electrical changes that occur during the release of transmitter from nerve terminals, little is known about the pharmacology of this synapse or the identity of its neurotransmitter. In the present study, the suggestion that acetylcholine (ACh) is the excitatory transmitter at this synapse was tested by exploring the actions of cholinergic agents on the pre- and postsynaptic giant axons and on the excitatory postsynaptic potential (EPSP). A novel arterial perfusion technique that circumvents the diffusion barrier from the bathing medium to the synapse has been used to demonstrate a depolarizing action of ACh and its agonist carbachol on the post- but not the presynaptic axon. The cholinergic receptors are distinct from receptors activated by amino acids, such as glutamate, have a reversal potential of about -48 mV, are anion-permeable, and desensitize without blocking the EPSP. It is concluded that these receptors are involved in an inhibitory input onto the postsynaptic giant axon and, therefore, that ACh is most probably not the transmitter at the squid giant synapse.

  13. Inhibition of Rho-associated kinase blocks agonist-induced Ca2+ sensitization of myosin phosphorylation and force in guinea-pig ileum

    PubMed Central

    Swärd, Karl; Dreja, Karl; Susnjar, Marija; Hellstrand, Per; Hartshorne, David J; Walsh, Michael P

    2000-01-01

    Ca2+ sensitization of smooth muscle contraction involves the small GTPase RhoA, inhibition of myosin light chain phosphatase (MLCP) and enhanced myosin regulatory light chain (LC20) phosphorylation. A potential effector of RhoA is Rho-associated kinase (ROK).The role of ROK in Ca2+ sensitization was investigated in guinea-pig ileum.Contraction of permeabilized muscle strips induced by GTPγS at pCa 6.5 was inhibited by the kinase inhibitors Y-27632, HA1077 and H-7 with IC50 values that correlated with the known Ki values for inhibition of ROK. GTPγS also increased LC20 phosphorylation and this was prevented by HA1077. Contraction and LC20 phosphorylation elicited at pCa 5.75 were, however, unaffected by HA1077.Pre-treatment of intact tissue strips with HA1077 abolished the tonic component of carbachol-induced contraction and the sustained elevation of LC20 phosphorylation, but had no effect on the transient or sustained increase in [Ca2+]i induced by carbachol.LC20 phosphorylation and contraction dynamics suggest that the ROK-mediated increase in LC20 phosphorylation is due to MLCP inhibition, not myosin light chain kinase activation.In the absence of Ca2+, GTPγS stimulated 35S incorporation from [35S]ATPγS into the myosin targeting subunit of MLCP (MYPT). The enhanced thiophosphorylation was inhibited by HA1077. No thiophosphorylation of LC20 was detected.These results indicate that ROK mediates agonist-induced increases in myosin phosphorylation and force by inhibiting MLCP activity through phosphorylation of MYPT. Under Ca2+-free conditions, ROK does not appear to phosphorylate LC20in situ, in contrast to its ability to phosphorylate myosin in vitro. In particular, ROK activation is essential for the tonic phase of agonist-induced contraction. PMID:10618150

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Plastic cars for developing nations

    SciTech Connect

    Ashley, S.

    1997-11-01

    Plastic automobiles may have passed a milestone on the long road to commercial reality with the development of Composite Concept Vehicle (CCV) from Chrysler Corp. in Auburn Hills, Mich. This basic compact car--so basic it could be called bare bones--is built by attaching an injection-molded thermoplastic polyester body onto a tubular steel chassis. The 1,200-pound CCV, which is expected to require one-third the labor and investment needed to build a conventional small car, was designed for new buyers in the emerging economies of China, India, and Southeast Asia. If commercialized, the car would likely cost about $6,000--halfway between a motorcycle and an entry-level auto. The small car was unveiled in September 1996 at the Frankfurt Auto Show in Germany.

  2. SRC-3 is required for CAR-regulated hepatocyte proliferation and drug metabolism

    PubMed Central

    Chen, Tenghui; Chen, Qiang; Xu, Yixiang; Zhou, Qiling; Zhu, Jingwei; Zhang, Hao; Wu, Qiao; Xu, Jianming; Yu, Chundong

    2011-01-01

    Background & Aims Nuclear receptors such as pregnane X receptor and constitutive androstane receptor (CAR) are important regulators of drug-metabolizing systems such as P450s enzymes and modulate xenobiotic metabolism as well as hepatocellular proliferation. Binding of CAR to NR response elements alone is not sufficient to activate gene expression. Here we investigate the role of steroid receptor coactivator (SRC) family members in CAR-mediated hepatocyte proliferation and drug metabolism. Methods The role of SRCs in CAR activation was assessed in cell-based transfection assays and protein-protein interaction assays. The in vivo role of SRCs in CAR-mediated hepatocyte proliferation and drug metabolism was examined by using mice deficient in SRCs. Results SRC-3 displayed the highest coactivating activity to CAR compared with SRC-1 and SRC-2 in a cell-based reporter assay. Knockout of SRC-3 in mice attenuated hepatic hyperplasia induced by a CAR agonist 1,4-bis-[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), which was associated with a reduced expression of c-Myc and Foxm-1. In contrast, knockout of SRC-1 or SRC-2 in mice did not affect TCPOBOP-induced hepatic hyperplasia. SRC-3-deficient mice were hypersensitive to zoxazolamine-induced paralysis, but were resistant to acetaminophen hepatotoxicity induced by TCPOBOP, whereas mutant mice deficient in SRC-1 or SRC-2 exhibited severe acetaminophen hepatotoxicity similar to wild-type controls. Accordingly, deficiency in SRC-3, but not SRC-1 or SRC-2, resulted in a reduced CAR-mediated expression of drug metabolism-related genes in the liver. Conclusions Our study demonstrates that SRC-3 is the predominant transcriptional coactivator among the three SRC family members for CAR activation to promote hepatocyte proliferation and drug metabolism. PMID:21827731

  3. Phase dependency of long-term potentiation induction during the intermittent bursts of carbachol-induced β oscillation in rat hippocampal slices.

    PubMed

    Nishimura, Motoshi; Nakatsuka, Hiroki; Natsume, Kiyohisa

    2012-01-01

    The rodent hippocampus possesses theta (θ) and beta (β) rhythms, which occur intermittently as bursts. Both rhythms are related to spatial memory processing in a novel environment. θ rhythm is related to spatial memory encoding process. β rhythm is related to the match/mismatch process. In the match/mismatch process, rodent hippocampus detects a representation matching sensory inputs of the current place among the retrieved internal representations of places. Long-term synaptic potentiation (LTP) is induced in both processes. The cholinergic agent carbachol induces intermittent θ and β oscillations in in vitro slices similar to in vivo bursts. LTP is facilitated during the generation of θ oscillation, suggesting that the facilitation of LTP is dependent upon the phases of intermittent burst (burst phases) of the oscillation. However, whether this is the case for β oscillation has not yet been studied. In the present study, LTP-inducing θ-burst stimulation was administered at the different burst phases of carbachol-induced β oscillations (CIBO), and the synaptic changes were measured at CA3-CA3 pyramidal cell synapses (CA3 synapse) and at CA3-CA1 pyramidal cell synapses (CA1 synapse). At the CA3 synapse, the largest magnitude of LTP was induced at the late burst phases of CIBO. At the CA1 synapse, LTP was induced only at the late burst phases. Modulation of LTP was suppressed when CIBO was blocked by the application of atropine at both synapses. The results suggest that the bursts of hippocampal β rhythm can determine the optimal temporal period for completing with the match/mismatch process.

  4. The Role of Rac1 on Carbachol-induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin-induced Diabetic Rats.

    PubMed

    Evcim, Atiye Sinem; Micili, Serap Cilaker; Karaman, Meral; Erbil, Guven; Guneli, Ensari; Gidener, Sedef; Gumustekin, Mukaddes

    2015-06-01

    This study was designed to determine the role of the small GTPase Rac1 on carbachol-induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)-induced diabetic rat model, three study groups were composed of control, diabetic and insulin-treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8-12 weeks after STZ injection. Carbachol (CCh) (10(-9) -10(-4) M) concentration-response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 μM). Diabetes-related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose-dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh-induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin-treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh-induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes-related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity.

  5. 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

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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....

  11. 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...

  12. 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...

  13. 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...

  14. 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…

  15. 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....

  16. 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...

  17. 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....

  18. 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...

  19. 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...

  20. 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…

  1. Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR).

    PubMed

    Hernandez, J P; Mota, L C; Huang, W; Moore, D D; Baldwin, W S

    2009-02-01

    The constitutive androstane receptor (CAR) is a xenosensing nuclear receptor and regulator of cytochrome P450s (CYPs). However, the role of CAR as a basal regulator of CYP expression nor its role in sexually dimorphic responses have been thoroughly studied. We investigated basal regulation and sexually dimorphic regulation and induction by the potent CAR activator TCPOBOP and the moderate CAR activator Nonylphenol (NP). NP is an environmental estrogen and one of the most commonly found environmental toxicants in Europe and the United States. Previous studies have demonstrated that NP induces several CYPs in a sexually dimorphic manner, however the role of CAR in regulating NP-mediated sexually dimorphic P450 expression and induction has not been elucidated. Therefore, wild-type and CAR-null male and female mice were treated with honey as a carrier, NP, or TCPOBOP and CYP expression monitored by QPCR and Western blotting. CAR basally regulates the expression of Cyp2c29, Cyp2b13, and potentially Cyp2b10 as demonstrated by QPCR. Furthermore, we observed a shift in the testosterone 6alpha/15alpha-hydroxylase ratio in untreated CAR-null female mice to the male pattern, which indicates an alteration in androgen status and suggests a role for androgens as CAR inverse agonists. Xenobiotic-treatments with NP and TCPOBOP induced Cyp2b10, Cyp2c29, and Cyp3a11 in a CAR-mediated fashion; however NP only induced these CYPs in females and TCPOBOP induced these CYPs in both males and females. Interestingly, Cyp2a4, was only induced in wild-type male mice by TCPOBOP suggesting Cyp2a4 induction is not sensitive to CAR-mediated induction in females. Overall, TCPOBOP and NP show similar CYP induction profiles in females, but widely different profiles in males potentially related to lower sensitivity of males to either indirect or moderate CAR activators such as NP. In summary, CAR regulates the basal and chemically inducible expression of several sexually dimorphic xenobiotic

  2. [What pediatricians should know about car seats?: car safety seats].

    PubMed

    Navarro, Lucas David

    2013-06-01

    In Argentina more than 7,000 people die each year due to traffic injuries. It is an endemic disease, a serious public health problem. There are evidence-based recommendations about how children should ride safety in cars; children through 8 years or 4 feet 9 inches cannot be fastened by the seat belt so they should ride in a child restraint system. These devices significantly reduce the chances of suffering serious injuries and fatalities. Although in our country the use of car safety seats is not yet legislated nor compulsory, pediatricians should recommend parents how and why to use them. PMID:23732352

  3. Seatbelts in CAR therapy: How Safe Are CARS?

    PubMed Central

    Minagawa, Kentaro; Zhou, Xiaoou; Mineishi, Shin; Di Stasi, Antonio

    2015-01-01

    T-cells genetically redirected with a chimeric antigen receptor (CAR) to recognize tumor antigens and kill tumor cells have been infused in several phase 1 clinical trials with success. Due to safety concerns related to on-target/off-tumor effects or cytokine release syndrome, however, strategies to prevent or abate serious adverse events are required. Pharmacologic therapies; suicide genes; or novel strategies to limit the cytotoxic effect only to malignant cells are under active investigations. In this review, we summarize results and toxicities of investigations employing CAR redirected T-cells, with a focus on published strategies to grant safety of this promising cellular application. PMID:26110321

  4. 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...

  5. Microsaccades generated during car driving.

    PubMed

    Miki, Shuntaro; Hirata, Yutaka

    2013-01-01

    Microsaccades together with drift and tremor are fixational eye movements that are generated when we try to fixate our gaze on a visual target. Besides their function in vision to prevent neural adaptation to unchanging retinal image, microsaccades have been studied in neuroscience as an indicator of attentional states for the last decade. Most of microsaccade researches have been conducted in unnatural laboratory environments, using controlled artificial visual stimuli. Thus, little is known about the characteristics of microsaccades in natural viewing conditions. Here we attempted to evaluate microsaccades during car driving condition in the aim of estimating driver's spatial attention. We demonstrate that microsaccades are generated during car driving, and the rate of microsaccade generation is modulated by road conditions such as appearance of pedestrians or/and other cars.

  6. Environmental implications of electric cars

    SciTech Connect

    Lave, L.B.; Hendrickson, C.T.; McMichael, F.C.

    1995-05-19

    California and the Northeast states have passed laws requiring 2% of 1998 cars be `0` emissions vehicles such as electric cars. Electric vehicle technology also can move emissions to less crowd and less polluted locations. However, some other problems remain. The authors focus on the environmental consequences of producing and reprocessing large quantities of batteries to power electric cars, including discussions of both characteristics of Electric Vehicles and batteries and the life cycle of lead and the problems of environmental releases. The authors conclude that electric vehicles will not be in the public interest until they pose no greater threat to public health and the environment than do alternative technologies such as vehicles using low-emission gasoline. 19 refs., 1 tab.

  7. [Adrenergic beta-agonist intoxication].

    PubMed

    Carrola, Paulo; Devesa, Nuno; Silva, José Manuel; Ramos, Fernando; Alexandrino, Mário B; Moura, José J

    2003-01-01

    The authors describe two clinical cases (father and daughter), observed in the Hospital Urgency with distal tremors, anxiety, palpitations, nausea, headaches and dizziness, two hours after ingestión of cow liver. They also had leucocytosis (with neutrophylia), hypokalemia and hyperglycaemia. After treatment with potassium i.v. and propranolol, the symptoms disappeared. The symptoms recurred at home because the patients didn't take the prescribed medication and persisted for five days, with spontaneous disappearance. The serum of both patients revealed the presence of clenbuterol (65 hg/ml - father and 58 hg/ml - daughter). The animal's liver had a concentration of 1,42 mg/kg. Clenbuterol is a ß-adrenergic agonist with low specificity, with some veterinary indications. However, this substance has been illegally used as a growth's promotor. We intend to alert doctors for this problem, particularly those that work in the Urgency.

  8. 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.

  9. β2-agonist therapy in lung disease.

    PubMed

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  10. Method for loading coal into railroad cars

    SciTech Connect

    Moon, J.L.; Tompkins, J.C.

    1984-07-17

    A system for loading coal or other particles into railroad cars wherein every other railroad car is designated an EVEN railroad car and the remaining every other railroad cars are designated ODD railroad cars. Each EVEN railroad car is weighed after being filled with coal and before the initiation of the loading of coal into the next EVEN railroad car to determine a filled weight. The filled weight of each EVEN railroad car is compared to a predetermined control weight and, in response to this determination, the termination of the loading of coal into the next EVEN railroad car controllably is varied to bring the filled weight closer to control weight. In a like manner, each ODD railroad car is weighed after being filled with coal and before the initiation of the loading of coal into the next ODD railroad car to determine a filled weight. The filled weight of each ODD railroad car is compared to the predetermined control weight and, in response to this determination, the termination of the loading of coal into the next ODD railroad car controllably is varied to bring the filled weight closer to the control weight.

  11. 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.

  12. 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…

  13. 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…

  14. Physics Fun with Toy Cars

    ERIC Educational Resources Information Center

    Herald, Christine

    2010-01-01

    According to the National Science Education Standards, students should be able to describe an object by its position, direction of motion, and speed (NRC 1996). During a unit on motion, the author decided to use Hot Wheels cars as the object students would describe. The first two activities are used to introduce students to the equipment and the…

  15. Power unit for electric cars

    SciTech Connect

    Ishikawa, Masami; Minezawa, Yukihiro.

    1993-07-06

    A power unit for mounting on the body of an electric car is described, comprising: a sensor for detecting a running condition of the car; a first power supply mounted on the electric car body; a second power supply module; means for detachably mounting different, interchangeable types of the second power supply module on the electric car body; a motor control circuit, including a computer, connected to the first power supply and the second power supply module for feeding a current to a motor as commanded by the computer; the computer including control means for determining (1) whether the second power supply module is mounted or not and (2) for determining the type of second power supply module mounted; setting means for connecting the first power supply and the second power supply module with the motor control circuit, in parallel or in series, responsive to the detected running condition; and the computer controlling the motor control circuit according to determinations of the control means.

  16. 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…

  17. 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…

  18. The evolution of beta2-agonists.

    PubMed

    Sears, M R

    2001-08-01

    Beta-agonists have been widely used in the treatment of asthma for many years Although concerns have been expressed over their safety based largely upon epidemics of increased mortality in asthmatics associated with high doses of isoprenaline in the 1960s and fenoterol in the 1970s and 1980s, the specific beta2-agonists are vital drugs in asthma management. The short-acting beta2-agonists have an important prophylactic role in the prevention of exercise-induced bronchoconstriction, and are essential in the emergency treatment of severe asthma. However, little if any benefit seems to be derived from regular use of short-acting beta2-agonists and regular or frequent use can increase the severity of the condition. The development of beta2-agonists with long-acting properties, such as salmeterol and formoterol, has provided advantages over short-acting beta-agonists, such as prolonged bronchodilation, reduced day- and night-time symptoms and improved quality of sleep, and has reduced the requirement for short-acting beta2-agonists as relief medication. Both drugs are well tolerated and, when added to inhaled corticosteroids, produce greater mprovement in lung function than increased steroid dose alone. Because of its rapid onset of action, formoterol also has the potential to be used for as-needed bronchodilator therapy in asthma.

  19. 49 CFR 1037.2 - Cars.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is not in suitable condition for the transportation of bulk grain and grain products when it is...

  20. 49 CFR 1037.2 - Cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... GENERAL RULES AND REGULATIONS BULK GRAIN AND GRAIN PRODUCTS-LOSS AND DAMAGE CLAIMS § 1037.2 Cars. A car is not in suitable condition for the transportation of bulk grain and grain products when it is...

  1. 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)

  2. 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.

  3. Aspirin metabolites are GPR35 agonists.

    PubMed

    Deng, Huayun; Fang, Ye

    2012-07-01

    Aspirin is widely used as an anti-inflammatory, anti-platelet, anti-pyretic, and cancer-preventive agent; however, the molecular mode of action is unlikely due entirely to the inhibition of cyclooxygenases. Here, we report the agonist activity of several aspirin metabolites at GPR35, a poorly characterized orphan G protein-coupled receptor. 2,3,5-Trihydroxybenzoic acid, an aspirin catabolite, was found to be the most potent GPR35 agonist among aspirin metabolites. Salicyluric acid, the main metabolite of aspirin, was also active. These results suggest that the GPR35 agonist activity of certain aspirin metabolites may contribute to the clinical features of aspirin. PMID:22526472

  4. 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.

  5. 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....

  6. 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....

  7. 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...

  8. 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...

  9. 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....

  10. 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...

  11. 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...

  12. 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....

  13. 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...

  14. 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....

  15. 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)

  16. 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.

  17. Monoterpenoid agonists of TRPV3

    PubMed Central

    Vogt-Eisele, A K; Weber, K; Sherkheli, M A; Vielhaber, G; Panten, J; Gisselmann, G; Hatt, H

    2007-01-01

    Background and purpose: Transient receptor potential (TRP) V3 is a thermosensitive ion channel expressed predominantly in the skin and neural tissues. It is activated by warmth and the monoterpene camphor and has been hypothesized to be involved in skin sensitization. A selection of monoterpenoid compounds was tested for TRPV3 activation to establish a structure-function relationship. The related channel TRPM8 is activated by cool temperatures and a number of chemicals, among them the monoterpene (-)-menthol. The overlap of the receptor pharmacology between the two channels was investigated. Experimental approach: Transfected HEK293 cells were superfused with the test substances. Evoked currents were measured in whole cell patch clamp measurements. Dose-response curves for the most potent agonists were obtained in Xenopus laevis oocytes. Key results: Six monoterpenes significantly more potent than camphor were identified: 6-tert-butyl-m-cresol, carvacrol, dihydrocarveol, thymol, carveol and (+)-borneol. Their EC50 is up to 16 times lower than that of camphor. All of these compounds carry a ring-located hydroxyl group and neither activates TRPM8 to a major extent. Conclusions and implications: Terpenoids have long been recognized as medically and pharmacologically active compounds, although their molecular targets have only partially been identified. TRPV3 activation may be responsible for several of the described effects of terpenoids. We show here that TRPV3 is activated by a number of monoterpenes and that a secondary hydroxyl-group is a structural requirement. PMID:17420775

  18. Agonist-sensitive calcium pool in the pancreatic acinar cell. I. Permeability properties

    SciTech Connect

    Muallem, S.; Schoeffield, M.S.; Fimmel, C.J.; Pandol, S.J.

    1988-08-01

    45Ca2+ fluxes and free cytosolic Ca2+ (( Ca2+)i) were used to describe the Ca2+ permeability and Ca2+ reloading of the agonist-sensitive pool at rest, during stimulation, and at termination of stimulation. A sequence of stimulation with carbachol, inhibition with atropine (cycling), and restimulation with cholecystokinin octapeptide (CCK-8) was used to follow Ca2+ reloading. Reloading of the pool required extracellular Ca2+ and was measured as an increased rate and extent of 45Ca2+ uptake into the acini. The 45Ca2+ incorporated into cycled acini could be completely released with CCK-8. The dose-response curves for 45Ca uptake and release were identical to those of the hormonally evoked (Ca2+)i increase. The increased 45Ca2+ uptake during reloading was not due to an expansion of any intracellular pool size but reflects the labeling of the pool to isotopic equilibrium in cycled acini. The rate constant of Ca2+ efflux from the pool of resting cells was approximately 0.67 +/- 0.01/h. With stimulation, the Ca2+ permeability of the pool membrane rapidly increased, resulting in Ca2+ release into the cytosol and an increase in (Ca2+)i. With termination of stimulation, the Ca2+ permeability of the pool membrane rapidly decreased while the pool continued to reload with extracellular Ca2+. Labeling of the pool to isotopic equilibrium allowed determination of the amount of Ca2+ released from the pool, which was 2.94 +/- 0.06 nmol/mg protein. This indicates that total Ca2+ concentration in the pool is in the millimolar range.

  19. 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.

  20. 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.

  1. Entwurfskonzept einer Car2Car-Multiband-Dachantenne

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Reit, M.; Mathis, W.

    2012-09-01

    Due to the vastly increasing use of wireless services in the car, such as WiFi, Car2Car and LTE, the requirements on bandwidth and radiation pattern of the roof antenna systems become more challenging. In this work, a design concept for multi-band roof antenna systems is presented. We aim to get a higher bandwidth and an almost circular radiation pattern on the horizontal plane. Moreover, the antenna length is considered in order to fulfill the requirements set by construction ECE-regulations (ECE, 2010). The applicability of the design concept is not limited to multi-band roof antennas, it can also be used for a general wideband antenna design. For illustration of this concept, a multi-band roof antenna with a bandwidth of 780 MHz to 5.9 GHz and a near circular radiation pattern with an average gain of G = 3 dBi (at 5.9 GHz) on the horizontal plane is designed. The simulation and measurement results are presented.

  2. [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.

  3. Modulation of NMDA effects on agonist-stimulated phosphoinositide turnover by memantine in neonatal rat cerebral cortex.

    PubMed Central

    Mistry, R; Wilke, R; Challiss, R A

    1995-01-01

    1. The ability of memantine (1-amino-3,5-dimethyladamantane) to antagonize the modulatory effects of N-methyl-D-aspartate (NMDA) on phosphoinositide turnover stimulated by muscarinic cholinoceptor- and metabotropic glutamate receptor-agonists has been examined in neonatal rat cerebral cortex slices. 2. Memantine antagonized the inhibitory effect of NMDA (100 microM) on both total [3H]-inositol phosphate ([3H]-InsPx) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) mass accumulations stimulated by carbachol (1 mM) with EC50 values of 21 and 16 microM respectively. 3. Memantine concentration-dependently antagonized (IC50 24 microM) the ability of NMDA (10 microM) to potentiate [3H]-InsPx accumulation in response to a sub-maximal concentration of the metabotropic glutamate receptor agonist, 1S,3R-ACPD (10 microM). 4. The small (approx. 3 fold), concentration-dependent increase in [3H]-InsPx accumulation stimulated by NMDA was completely antagonized by the prototypic NDMA receptor-channel blocker, MK-801 (1 microM) at all concentrations of NDMA studied (1-1000 microM). In contrast, antagonism by memantine (100 microM) was observed only at low concentrations of NMDA (1-10 microM), whilst [3H]-InsPx accumulation stimulated by high concentrations of NMDA (300-1000 microM) was markedly enhanced by memantine. 5. Assessment of the incorporation of [3H]-inositol into inositol phospholipids revealed that memantine (100 microM) caused an approximate 2 fold increase in the labelling of phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7773540

  4. RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions.

    PubMed

    Broad, John; Takahashi, Nobuyuki; Tajimi, Masaomi; Sudo, Masaki; Góralczyk, Adam; Parampalli, Umesh; Mannur, Kesava; Yamamoto, Toshinori; Sanger, Gareth J

    2016-02-01

    The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically-mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ-00201894 0.1-30 μM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 μM this activity was usually prolonged. At higher concentrations (3-30 μM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 μM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying. PMID:26685754

  5. CAR-T cells are serial killers

    PubMed Central

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

    2015-01-01

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

  6. Electric cars shift into second gear

    SciTech Connect

    Silber, K.

    1994-05-09

    High cost and poor performance have hurt the market for electric cars, but more states are passing emission control regulations that will make electric cars more attractive. Federal funding also will promote research on electric vehicle technologies. There is much work to do on battery recharging, range expansion, and weight to make electric cars desirable to the public. The auto industry is lobbying against the regulations because it fears electric cars will not be commercially viable by the deadlines. Other alternatives for reducing auto emissions are explored. The ultimate fate of electric cars will be decided by consumers.

  7. Dopamine receptor partial agonists and addiction.

    PubMed

    Moreira, Fabricio A; Dalley, Jeffrey W

    2015-04-01

    Many drugs abused by humans acutely facilitate, either directly or indirectly, dopamine neurotransmission in the mesolimbic pathway. As a consequence dopamine receptor agonists and antagonists have been widely investigated as putative pharmacological therapies for addiction. This general strategy, however, has had only limited success due in part to poor treatment adherence and efficacy and the significant adverse effects of dopaminergic medications. In this perspective, we discuss the potential therapeutic use of dopamine receptor partial agonists in addiction, developed initially as antipsychotic agents. Recent research indicates that the dopamine D2 receptor partial agonists, such as aripiprazole, also shows useful ancillary efficacy in several animal models of psychostimulant and opioid addiction. Notably, these findings suggest that unlike full dopamine receptor agonists and antagonists these compounds have low abuse liability and are generally well tolerated. Indeed, partial dopamine agonists attenuate the rewarding properties of opioids without interfering with their analgesic effects. Herein we discuss the utility and potential of dopamine receptor partial agonists as treatments for both stimulant and non-stimulant drug addiction.

  8. PPAR Agonists and Cardiovascular Disease in Diabetes.

    PubMed

    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, PPARalpha 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 PPARgamma agonists, and more recently dual PPARalpha/gamma coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPARgamma 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.

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. Inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release evoked by metabotropic agonists and backpropagating action potentials in hippocampal CA1 pyramidal neurons.

    PubMed

    Nakamura, T; Nakamura, K; Lasser-Ross, N; Barbara, J G; Sandler, V M; Ross, W N

    2000-11-15

    We examined the properties of [Ca(2+)](i) changes that were evoked by backpropagating action potentials in pyramidal neurons in hippocampal slices from the rat. In the presence of the metabotropic glutamate receptor (mGluR) agonists t-ACPD, DHPG, or CHPG, spikes caused Ca(2+) waves that initiated in the proximal apical dendrites and spread over this region and in the soma. Consistent with previously described synaptic responses (Nakamura et al., 1999a), pharmacological experiments established that the waves were attributable to Ca(2+) release from internal stores mediated by the synergistic effect of receptor-mobilized inositol 1,4, 5-trisphosphate (IP(3)) and spike-evoked Ca(2+). The amplitude of the changes reached several micromoles per liter when detected with the low-affinity indicators fura-6F, fura-2-FF, or furaptra. Repetitive brief spike trains at 30-60 sec intervals generated increases of constant amplitude. However, trains at intervals of 10-20 sec evoked smaller increases, suggesting that the stores take 20-30 sec to refill. Release evoked by mGluR agonists was blocked by MCPG, AIDA, 4-CPG, MPEP, and LY367385, a profile consistent with the primacy of group I receptors. At threshold agonist concentrations the release was evoked only in the dendrites; threshold antagonist concentrations were effective only in the soma. Carbachol and 5-HT evoked release with the same spatial distribution as t-ACPD, suggesting that the distribution of neurotransmitter receptors was not responsible for the restricted range of regenerative release. Intracellular BAPTA and EGTA were approximately equally effective in blocking release. Extracellular Cd(2+) blocked release, but no single selective Ca(2+) channel blocker prevented release. These results suggest that IP(3) receptors are not associated closely with specific Ca(2+) channels and are not close to each other.

  17. High-viscosity carboxymethylcellulose reduces carbachol-stimulated intestinal chloride secretion in weaned piglets fed a diet based on skimmed milk powder and maltodextrin.

    PubMed

    Lallès, Jean-Paul; Boudry, Gaëlle; Favier, Christine; Sève, Bernard

    2006-03-01

    High-viscosity carboxymethylcellulose (CMC) promotes gastrointestinal disorders, tissue alterations and bacterial overgrowth in pigs. The impact of CMC on intestinal absorptive and secretory physiology is not known. We hypothesised that CMC consumption alters intestinal Na-dependent glucose absorption and stimulates electrogenic chloride secretion. For testing this hypothesis, twenty-four piglets were weaned at 21 d of age and pair-fed for 13 d a starter diet based on skimmed milk powder and maltodextrin containing cellulose (control) or CMC. Body weight and faecal total aerobe and coliform counts were measured kinetically. At slaughter, digesta were weighed and characterised for viscosity and pH. Gastrointestinal tissues were weighed and sampled for physiology in Ussing chambers, morphometry and enzymology. Glucose absorption tended to be higher (P = 0.08) and carbachol-stimulated chloride secretion was lower (P = 0.01) with CMC in the small intestine, without changes in the colon. Aerobes were transiently higher at day 7 (P < 0.05) but coliform counts remained unchanged (P = 0.78) and beta-haemolitic Escherichia coli were virtually absent. Stomach and small-intestinal segments were heavier, and viscosity higher with CMC (0.001 < P < 0.05). The pH in the stomach was higher, and in the caecum and proximal colon lower with CMC (0.001 < P < 0.05). Jejunal villus area was slightly reduced with CMC (P < 0.05) without effects on enzyme activities (P > 0.10). In conclusion, CMC supplementation had pro-absorptive effects on the small intestine, possibly due to the absence of pathogenic E. coli in the present study.

  18. 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.

  19. beta2-Agonists at the Olympic Games.

    PubMed

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  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. 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.

  2. 49 CFR 173.314 - Compressed gases in tank cars and multi-unit tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Compressed gases in tank cars and multi-unit tank... Compressed gases in tank cars and multi-unit tank cars. (a) Definitions. For definitions of compressed gases... any material that meets the criteria of Division 2.1 or 2.3 must have gaskets for manway cover...

  3. 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.

  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. 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. PMID:18606288

  6. 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...

  7. 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...

  8. 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...

  9. Identification of Selective ERRγ Inverse Agonists.

    PubMed

    Kim, Jina; Im, Chun Young; Yoo, Eun Kyung; Ma, Min Jung; Kim, Sang-Bum; Hong, Eunmi; Chin, Jungwook; Hwang, Hayoung; Lee, Sungwoo; Kim, Nam Doo; Jeon, Jae-Han; Lee, In-Kyu; Jeon, Yong Hyun; Choi, Hueng-Sik; Kim, Seong Heon; Cho, Sung Jin

    2016-01-12

    GSK5182 (4) is currently one of the lead compounds for the development of estrogen-related receptor gamma (ERRγ) inverse agonists. Here, we report the design, synthesis, pharmacological and in vitro absorption, distribution, metabolism, excretion, toxicity (ADMET) properties of a series of compounds related to 4. Starting from 4, a series of analogs were structurally modified and their ERRγ inverse agonist activity was measured. A key pharmacophore feature of this novel class of ligands is the introduction of a heterocyclic group for A-ring substitution in the core scaffold. Among the tested compounds, several of them are potent ERRγ inverse agonists as determined by binding and functional assays. The most promising compound, 15g, had excellent binding selectivity over related subtypes (IC50 = 0.44, >10, >10, and 10 μM at the ERRγ, ERRα, ERRβ, and ERα subtypes, respectively). Compound 15g also resulted in 95% transcriptional repression at a concentration of 10 μM, while still maintaining an acceptable in vitro ADMET profile. This novel class of ERRγ inverse agonists shows promise in the development of drugs targeting ERRγ-related diseases.

  10. 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

  11. FXR agonist activity of conformationally constrained analogs of GW 4064

    SciTech Connect

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Navas, III, Frank; Parks, Derek J.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce

    2010-09-27

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  12. FXR agonist activity of conformationally constrained analogs of GW 4064.

    PubMed

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

    2009-08-15

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  13. 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.

  14. Tragic Car Accident Involves ESO Employees

    NASA Astrophysics Data System (ADS)

    2000-06-01

    Saturday, May 27, turned into a tragic day for ESO. The team installing TIMMI2 at La Silla, went on an excursion to the Elqui valley, 70 km east of the city of La Serena and suffered a serious car accident, crashing against another car driving from the opposite direction.

  15. 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.

  16. 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, ...

  17. 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.)

  18. Driving an improved CAR for cancer immunotherapy.

    PubMed

    Huang, Xiaopei; Yang, Yiping

    2016-08-01

    The recent clinical success of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies represents a paradigm shift in cancer immunotherapy. Unfortunately, application of CAR T cell-mediated therapy for solid tumors has so far been disappointing, and the reasons for this poor response in solid tumors remain unknown. In this issue of the JCI, Cherkassky and colleagues report on their use of a murine model of human pleural mesothelioma to explore potential factors that limit CAR T cell efficacy. Their studies have uncovered the importance of the tumor microenvironment in the inhibition of CAR T cell functions, revealed a critical role for the programmed death-1 (PD-1) pathway in CAR T cell exhaustion within the tumor microenvironment, and demonstrated improved antitumor effects with a CAR T cell-intrinsic PD-1 blockade strategy using a dominant negative form of PD-1. Together, the results of this study lay the groundwork for further evaluation of mechanisms underlying CAR T cell immune evasion within the tumor microenvironment for the improvement of CAR T cell-mediated therapy for solid tumors.

  19. Driving an improved CAR for cancer immunotherapy.

    PubMed

    Huang, Xiaopei; Yang, Yiping

    2016-08-01

    The recent clinical success of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies represents a paradigm shift in cancer immunotherapy. Unfortunately, application of CAR T cell-mediated therapy for solid tumors has so far been disappointing, and the reasons for this poor response in solid tumors remain unknown. In this issue of the JCI, Cherkassky and colleagues report on their use of a murine model of human pleural mesothelioma to explore potential factors that limit CAR T cell efficacy. Their studies have uncovered the importance of the tumor microenvironment in the inhibition of CAR T cell functions, revealed a critical role for the programmed death-1 (PD-1) pathway in CAR T cell exhaustion within the tumor microenvironment, and demonstrated improved antitumor effects with a CAR T cell-intrinsic PD-1 blockade strategy using a dominant negative form of PD-1. Together, the results of this study lay the groundwork for further evaluation of mechanisms underlying CAR T cell immune evasion within the tumor microenvironment for the improvement of CAR T cell-mediated therapy for solid tumors. PMID:27454296

  20. Designing CAR T cells for glioblastoma

    PubMed Central

    Maus, Marcela V

    2015-01-01

    Chimeric antigen receptor (CAR)-modified T cells directed against CD19 can mediate long-term durable remissions in B cell malignancies, but bringing a new target antigen to the clinic requires extensive modeling to avoid on-target and off-target toxicity. We recently described a systematic approach to test a new CAR directed against EGFR variant III. PMID:26587317

  1. 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.

  2. Apparatus for controlling electric cars

    SciTech Connect

    Naruto, M.

    1987-01-06

    An apparatus is described for controlling electric cars comprising: d-c shunt-wound motors adapted to be connected to a d-c source and having armatures and field windings; first chopper circuit means connected in series with the armatures of the d-c shunt-wound motors and controlling the flow of armature currents in both directions upon receipt of timing signals; second chopper circuit means connected in series with the field windings of the d-c shunt-wound motors and controlling the flow of field currents in both directions upon receipt of timing signals; reactors having first and second coils, the first coils being connected in series with the armatures, and the second coils being connected in series with the field windings. The first coils and second coils and magnetically coupled together maintaining such a relation that the field currents decrease with the decrease in the armature currents.

  3. 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

  4. 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.

  5. 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.

  6. The passenger car and the greenhouse effect

    SciTech Connect

    Amann, C.A.

    1990-01-01

    This paper reports that concern is mounting over the possibility of global warming from the greenhouse effect. Carbon dioxide from the combustion of fossil fuel is a major greenhouse gas, and automobile exhaust is one of the contributors. The only way to decrease carbon dioxide emissions from a car consuming carbonaceous fuel is to decrease its fuel consumption. The best alternative fossil fuels offer a carbon dioxide reduction of about 20%. Without introducing any new greenhouse-gas controls, it is projected that the total greenhouse-gas contribution of the average car will be halved from recent levels just through fleet turnover and already planned elimination of the current air-conditioning refrigerant. If global warming develops into a serious problem, cars can be operated without fossil fuel. Leading options include battery-electric cars using nuclear power and engine-propelled cars burning biomass-derived alcohol or hydrogen extracted from water with solar cells or nuclear power.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. The benefits of improved car secondary safety.

    PubMed

    Broughton, Jeremy

    2003-07-01

    The term 'secondary safety' refers to the protection that a vehicle provides its occupants when involved in an accident. This paper studies information from the British database of road accident reports between 1980 and 1998, to estimate the reduction in the number of occupant casualties over these years which may be attributed to improvements to secondary safety in cars. The paper shows that the proportion of driver casualties who are killed or seriously injured (KSI) is lower for modern cars than for older cars. The reduction of this proportion is used to assess the improvement in secondary safety. Statistical models are developed to represent the proportion with 'year of first registration' as one of the independent variables, although only an incomplete assessment of the benefits of improved secondary safety can be made with the available data. The assessment compares the number of casualties that would have been expected if secondary safety had remained at the level found in cars first registered in 1980 with the actual casualty numbers. It is estimated that improved secondary safety reduced the number of drivers KSI by at least 19.7% in 1998, in comparison with what might have occurred if all cars had had that lower level of secondary safety. This figure relates to all cars on the road in 1998, and rises to 33%, when confined to the most modern cars (those which were first registered in 1998).

  14. Recent advances in the discovery of alpha1-adrenoceptor agonists.

    PubMed

    Bishop, Michael J

    2007-01-01

    The alpha(1) adrenoceptors are three of nine well-characterized receptors that are activated by epinephrine and norepinephrine. Agonists acting at the alpha(1) adrenoceptors produce numerous physiological effects, and are used therapeutically for several indications. Many known alpha(1) adrenoceptor agonists are alpha(1A) selective, but the discovery of highly selective alpha(1B) and alpha(1D) adrenoceptor agonists has proven to be an extremely difficult goal to achieve. This review will focus on recent advances in the discovery, development and clinical utility of subtype-specific alpha(1) agonists as well as contributions to our understanding of agonist-receptor interactions.

  15. Increased agonist affinity at the mu-opioid receptor induced by prolonged agonist exposure

    PubMed Central

    Birdsong, William T.; Arttamangkul, Seksiri; Clark, Mary J.; Cheng, Kejun; Rice, Kenner C.; Traynor, John R.; Williams, John T.

    2013-01-01

    Prolonged exposure to high-efficacy agonists results in desensitization of the mu opioid receptor (MOR). Desensitized receptors are thought to be unable to couple to G-proteins, preventing downstream signaling, however the changes to the receptor itself are not well characterized. In the current study, confocal imaging was used to determine whether desensitizing conditions cause a change in agonist-receptor interactions. Using rapid solution exchange, the binding kinetics of fluorescently labeled opioid agonist, dermorphin Alexa594 (derm A594), to MORs was measured in live cells. The affinity of derm A594 binding increased following prolonged treatment of cells with multiple agonists that are known to cause receptor desensitization. In contrast, binding of a fluorescent antagonist, naltrexamine Alexa 594, was unaffected by similar agonist pre-treatment. The increased affinity of derm A594 for the receptor was long-lived and partially reversed after a 45 min wash. Treatment of the cells with pertussis toxin did not alter the increase in affinity of the derm A594 for MOR. Likewise the affinity of derm A594 for MORs expressed in mouse embryonic fibroblasts derived from arrestin 1 and 2 knockout animals increased following treatment of the cells with the desensitization protocol. Thus, opioid receptors were “imprinted” with a memory of prior agonist exposure that was independent of G-protein activation or arrestin binding that altered subsequent agonist-receptor interactions. The increased affinity suggests that acute desensitization results in a long lasting but reversible conformational change in the receptor. PMID:23447620

  16. 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.

  17. PC-based car license plate reader

    NASA Astrophysics Data System (ADS)

    Hwang, Chung-Mu; Shu, Shyh-Yeong; Chen, Wen-Yu; Chen, Yie-Wern; Wen, Kuang-Pu

    1992-11-01

    A car license plate reader (CLPR) using fuzzy inference and neural network algorithm has been developed in Industrial Technology Research Institute (ITRI) and installed in highway toll stations to identify stolen cars. It takes an average of 0.7 seconds to recognize a car license plate by using a PC with 80486-50 CPU. The recognition rate of the system is about 97%. The techniques of CLPR include vehicle sensing, image grab control, optic pre- processing, lighting, and optic character recognition (OCR). The CLPR can be used in vehicle flow statistics, the checking of stolen vehicles, automatic charging systems in parking lots or garage management, and so on.

  18. Multimodal CARS microscopy of structured carbohydrate biopolymers

    PubMed Central

    Slepkov, Aaron D.; Ridsdale, Andrew; Pegoraro, Adrian F.; Moffatt, Douglas J.; Stolow, Albert

    2010-01-01

    We demonstrate the utility of multimodal coherent anti-Stokes Raman scattering (CARS) microscopy for the study of structured condensed carbohydrate systems. Simultaneous second-harmonic generation (SHG) and spectrally-scanned CARS microscopy was used to elucidate structure, alignment, and density in cellulose cotton fibers and in starch grains undergoing rapid heat-moisture swelling. Our results suggest that CARS response of the O-H stretch region (3000 cm−1–3400 cm−1), together with the commonly-measured C-H stretch (2750 cm−1–2970 cm−1) and SHG provide potentially important structural information and contrast in these materials. PMID:21258555

  19. Signal Use by Octopuses in Agonistic Interactions.

    PubMed

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

    2016-02-01

    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. PMID:26832440

  20. Signal Use by Octopuses in Agonistic Interactions.

    PubMed

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

    2016-02-01

    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.

  1. First car-to-car crashes involving young adult drivers: main patterns and their relation to car and driver characteristics.

    PubMed

    Laflamme, L; Hasselberg, M; Kullgren, A; Vaez, M

    2006-09-01

    The primary objective of the study was to examine the relationship between patterns in car-to-car crashes involving young drivers and car and driver characteristics and the research design was a national register-based prospective cohort study. Individual records in a cohort born 1970-1972 are linked to road-traffic-crash data (1988-2000). Subjects' first police-registered two-car crash leading to severe or fatal injury (n = 4875) are identified. Typical crash patterns are highlighted and associations between pattern and both car and individual socio-demographic characteristics are tested. Four crash patterns are highlighted. Male drivers and those with lower educational attainment are over-represented in all patterns. Pattern-based risk levels vary considerably according to car safety level and driver's age at time of injury and socio-economic status. Crash patterns might be considered in young adult driver education systems, bearing in mind the consistent higher risks of male drivers and of drivers with lower educational attainment. PMID:16943161

  2. 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. PMID:27231717

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

    PubMed Central

    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. PMID:27231717

  4. 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.)

  5. CAR therapy: the CD19 paradigm

    PubMed Central

    Sadelain, Michel

    2015-01-01

    Twenty-five years after its inception, the genetic engineering of T cells is now a therapeutic modality pursued at an increasing number of medical centers. This immunotherapeutic strategy is predicated on gene transfer technology to instruct T lymphocytes to recognize and reject tumor cells. Chimeric antigen receptors (CARs) are synthetic receptors that mediate antigen recognition, T cell activation, and — in the case of second-generation CARs — costimulation to augment T cell functionality and persistence. We demonstrated over a decade ago that human T cells engineered with a CD19-specific CAR eradicated B cell malignancies in mice. Several phase I clinical trials eventually yielded dramatic results in patients with leukemia or lymphoma, especially acute lymphoblastic leukemia (ALL). This review recounts the milestones of CD19 CAR therapy and summarizes lessons learned from the CD19 paradigm. PMID:26325036

  6. 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..

  7. 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..

  8. 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.

  9. Predicting Turning Points for Toy Cars

    NASA Astrophysics Data System (ADS)

    Ramsdell, M. W.; Wick, D. P.

    2005-10-01

    A simple experiment can be performed to estimate a toy car's effective coefficient of friction without the use of sophisticated equipment. The results can be used to predict the car's turning points when traveling on an arbitrarily shaped track containing multiple hills and valleys in a 2-D vertical plane. This activity is based on a team-oriented modeling-based project conducted at Clarkson University, which was published in the American Journal of Physics.

  10. Analysis of car-3-en-5-hydroperoxide.

    PubMed

    Lehnert, Nicole; Krings, Ulrich; Berger, Ralf G

    2011-09-01

    HRGC-MS, using split/splitless injection (230 degrees C), showed that a dioxygenase from Pleurotus sapidus regio-selectively transformed (+)-car-3-ene to car-3-en-5-one as the major volatile product to minor amounts of the corresponding alcohol, and to some other volatiles. Thus, the reaction was assumed to be radical mediated and similar to the lipoxygenase catalyzed peroxidation of polyunsaturated fatty acids, but the expected car-3-ene-hydroperoxides were not detected. TLC of the reaction products, followed by hydroperoxide specific staining, visually indicated the presence of hydroperoxides. TLC spots were eluted and re-analyzed using cool on-column injection, but only tailing peaks showing a mixed mass spectrum of car-3-en-5-ol/one were obtained. An unequivocal identification of car-3-en-5-hydroperoxides was achieved only after using APCI(+)-LC-MS. Upon structural confirmation, the car-3-en-5-hydroperoxide was accumulated by preparative HPLC, re-injected cool on-column, and the continuing degradation of the hydroperoxide to monoterpene ketone and alcohol during chromatography was verified. It was concluded that terpene hydroperoxides may occur in essential oils more frequently than anticipated, but are not recognized due to the principal blindness of capillary gas chromatography techniques and UV/vis LC-detectors.

  11. 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.

  12. 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.

  13. 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...

  14. 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....

  15. 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...

  16. 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....

  17. 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...

  18. 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...

  19. 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....

  20. 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...

  1. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... (1) Market rate cars shall not be subject to prescribed rates or to the provisions of 49 CFR 1039.14... 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)...

  2. 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....

  3. 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)...

  4. 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...

  5. 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....

  6. 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...

  7. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... (1) Market rate cars shall not be subject to prescribed rates or to the provisions of 49 CFR 1039.14... 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)...

  8. 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....

  9. 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....

  10. 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....

  11. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... (1) Market rate cars shall not be subject to prescribed rates or to the provisions of 49 CFR 1039.14... 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)...

  12. 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...

  13. 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....

  14. 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)...

  15. 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...

  16. 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)...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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....

  2. 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....

  3. 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...

  4. 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)...

  5. 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...

  6. 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....

  7. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... (1) Market rate cars shall not be subject to prescribed rates or to the provisions of 49 CFR 1039.14... 49 Transportation 8 2010-10-01 2010-10-01 false Car hire rates. 1033.1 Section 1033.1... OF TRANSPORTATION GENERAL RULES AND REGULATIONS CAR SERVICE § 1033.1 Car hire rates. (a)...

  8. 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...

  9. 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...

  10. 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...

  11. 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....

  12. 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...

  13. 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....

  14. 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...

  15. 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....

  16. 49 CFR 1033.1 - Car hire rates.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... (1) Market rate cars shall not be subject to prescribed rates or to the provisions of 49 CFR 1039.14... 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)...

  17. 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...

  18. 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)...

  19. 49 CFR 173.319 - Cryogenic liquids in tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... cars. (a) General requirements. (1) A tank car containing a flammable cryogenic liquid may not be... notify the Federal Railroad Administration whenever a tank car containing any flammable cryogenic liquid....330 of this subchapter. (b) When a tank car containing a flammable cryogenic liquid is offered...

  20. 49 CFR 173.319 - Cryogenic liquids in tank cars.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... cars. (a) General requirements. (1) A tank car containing a flammable cryogenic liquid may not be... notify the Federal Railroad Administration whenever a tank car containing any flammable cryogenic liquid....330 of this subchapter. (b) When a tank car containing a flammable cryogenic liquid is offered...

  1. 49 CFR 173.319 - Cryogenic liquids in tank cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... cars. (a) General requirements. (1) A tank car containing a flammable cryogenic liquid may not be... notify the Federal Railroad Administration whenever a tank car containing any flammable cryogenic liquid....330 of this subchapter. (b) When a tank car containing a flammable cryogenic liquid is offered...

  2. Effect of droplet-induced breakdown on CARS temperature measurements

    SciTech Connect

    Dunn-Rankin, D. ); Switzer, G.L. ); Obringer, C.A.; Jackson, T. )

    1990-07-20

    This research examines the potential for coherent anti-Stokes Raman scattering (CARS) to rovide reliable gas temperature measurements in the presence of liquid droplets. The droplets cause dielectric breakdown by focusing the CARS laser beams. This breakdown produces a plasma that can disrupt or obscure the CARS signal. Specifically, we examine the influence of laser induced breakdown on the CARS signal, and we determine the importance of droplet position relative to the CARS focal volume and droplet concentration on the reliability of CARS temperature measurements in droplet-laden flows. In addition, we propose a reliable data reduction procedure to minimize the disruptive influence of laser induced breakdown on CARS temperature.

  3. 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

  4. 49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  5. 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...

  6. 49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  7. 49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  8. Agonist-Directed Desensitization of the β2-Adrenergic Receptor

    PubMed Central

    Goral, Vasiliy; Jin, Yan; Sun, Haiyan; Ferrie, Ann M.; Wu, Qi; Fang, Ye

    2011-01-01

    The β2-adrenergic receptor (β2AR) agonists with reduced tachyphylaxis may offer new therapeutic agents with improved tolerance profile. However, receptor desensitization assays are often inferred at the single signaling molecule level, thus ligand-directed desensitization is poorly understood. Here we report a label-free biosensor whole cell assay with microfluidics to determine ligand-directed desensitization of the β2AR. Together with mechanistic deconvolution using small molecule inhibitors, the receptor desensitization and resensitization patterns under the short-term agonist exposure manifested the long-acting agonism of salmeterol, and differentiated the mechanisms of agonist-directed desensitization between a full agonist epinephrine and a partial agonist pindolol. This study reveals the cellular mechanisms of agonist-selective β2AR desensitization at the whole cell level. PMID:21541288

  9. Sports doping: emerging designer and therapeutic β2-agonists.

    PubMed

    Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

    2013-10-21

    Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future.

  10. Pathophysiological factors affecting CAR gene expression.

    PubMed

    Pascussi, Jean Marc; Dvorák, Zdenek; Gerbal-Chaloin, Sabine; Assenat, Eric; Maurel, Patrick; Vilarem, Marie José

    2003-11-01

    The body defends itself against potentially harmful compounds, such as drugs and toxic endogenous compounds and their metabolites, by inducing the expression of enzymes and transporters involved in their metabolism and elimination. The orphan nuclear receptor CAR (NR1I3 controls phase I (CYP2B, CYP2C, CYP3A), phase II (UGT1A1), and transporter (SLC21A6, MRP2) genes involved in drug metabolism and bilirubin clearance. Constitutive androstane receptor (CAR) is activated by xenobiotics, such as phenobarbital, but also by toxic endogenous compounds such as bilirubin metabolite(s). To better understand the inter- and intravariability in drug detoxification, we studied the molecular mechanisms involved in CAR gene expression in human hepatocytes. We clearly identified CAR as a glucocorticoid receptor (GR) target gene, and we proposed the hypothesis of a signal transduction where the activation of GR plays a critical function in CAR-mediated cellular response. According to our model, chemicals or pathophysiological factors that affect GR function should decrease CAR function. To test this hypothesis, we recently investigated the effect of microtubule disrupting agents (MIAs) or proinflammatory cytokines. These compounds are well-known inhibitors of GR transactivation property. MIAs activate c-Jun N-terminal kinase (JNK), which phosphorylates and inactivates GR, whereas proinflammatory cytokines, such as IL-6 or IL1beta, induce AP-1 or NF-kB activation, respectively, leading to GR inhibition. As expected, we observed that these molecules inhibit both CAR gene expression and phenobarbital-mediated CYP gene expression in human hepatocytes. PMID:14705859

  11. 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.

  12. 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.

  13. 49 CFR 173.314 - Compressed gases in tank cars and multi-unit tank cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... exceeding 1.52 mm (0.060 inch) diameter must be equipped with excess flow valves. For single unit tank cars... fiber placed over 5.08 cm (2 inches) of ceramic fiber. Tank cars must have excess flow valves on the... containing hydrogen chloride, refrigerated liquid must have the auxiliary valve on the pressure relief...

  14. Modulation of Innate Immune Responses via Covalently Linked TLR Agonists

    PubMed Central

    2015-01-01

    We present the synthesis of novel adjuvants for vaccine development using multivalent scaffolds and bioconjugation chemistry to spatially manipulate Toll-like receptor (TLR) agonists. TLRs are primary receptors for activation of the innate immune system during vaccination. Vaccines that contain a combination of small and macromolecule TLR agonists elicit more directed immune responses and prolong responses against foreign pathogens. In addition, immune activation is enhanced upon stimulation of two distinct TLRs. Here, we synthesized combinations of TLR agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. We covalently conjugated three TLR agonists (TLR4, 7, and 9) to a small molecule core to probe the spatial arrangement of the agonists. Treating immune cells with the linked agonists increased activation of the transcription factor NF-κB and enhanced and directed immune related cytokine production and gene expression beyond cells treated with an unconjugated mixture of the same three agonists. The use of TLR signaling inhibitors and knockout studies confirmed that the tri-agonist molecule activated multiple signaling pathways leading to the observed higher activity. To validate that the TLR4, 7, and 9 agonist combination would activate the immune response to a greater extent, we performed in vivo studies using a vaccinia vaccination model. Mice vaccinated with the linked TLR agonists showed an increase in antibody depth and breadth compared to mice vaccinated with the unconjugated mixture. These studies demonstrate how activation of multiple TLRs through chemically and spatially defined organization assists in guiding immune responses, providing the potential to use chemical tools to design and develop more effective vaccines. PMID:26640818

  15. Small Molecule Bax Agonists for Cancer Therapy

    PubMed Central

    Xin, Meiguo; Li, Rui; Xie, Maohua; Park, Dongkyoo; Owonikoko, Taofeek K.; Sica, Gabriel L.; Corsino, Patrick E.; Zhou, Jia; Ding, Chunyong; White, Mark A.; Magis, Andrew T.; Ramalingam, Suresh S.; Curran, Walter J.; Khuri, Fadlo R.; Deng, Xingming

    2014-01-01

    Bax, a central death regulator, is required at the decisional stage of apoptosis. We recently identified serine 184 (S184) of Bax as a critical functional switch controlling its proapoptotic activity. Here, we employed the structural pocket around S184 as a docking site to screen the NCI library of small molecules using the UCSF-DOCK program suite. Three compounds, small molecule Bax agonists SMBA1, SMBA2 and SMBA3, induce conformational changes in Bax by blocking S184 phosphorylation, facilitating Bax insertion into mitochondrial membranes and forming Bax oligomers. The latter leads to cytochrome c release and apoptosis in human lung cancer cells, which occurs in a Bax- but not Bak-dependent fashion. SMBA1 potently suppresses lung tumor growth via apoptosis by selectively activating Bax in vivo without significant normal tissue toxicity. Development of Bax agonists as a new class of anti-cancer drugs offers a strategy for the treatment of lung cancer and other Bax-expressing malignancies. PMID:25230299

  16. Separation of CARS image contributions with a Gaussian mixture model.

    PubMed

    Vogler, Nadine; Bocklitz, Thomas; Mariani, Melissa; Deckert, Volker; Markova, Aneta; Schelkens, Peter; Rösch, Petra; Akimov, Denis; Dietzek, Benjamin; Popp, Jürgen

    2010-06-01

    Coherent anti-Stokes Raman scattering (CARS) gained a lot of importance in chemical imaging. This is due to the fast image acquisition time, the high spatial resolution, the non-invasiveness, and the molecular sensitivity of this method. By using the single-line CARS in contrast to the multiplex CARS, different signal contributions stemming from resonant and non-resonant light-matter interactions are indistinguishable. Here a numerical method is presented in order to extract more information from univariate CARS images: vibrational composition, morphological information, and contributions from index-of-refraction steps can be separated from single-line CARS images. The image processing algorithm is based on the physical properties of CARS process as reflected in the shape of the intensity histogram of univariate CARS images. Because of this the comparability of individual CARS images recorded with different experimental parameters is achieved. The latter is important for a quantitative evaluation of CARS images. PMID:20508705

  17. 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.

  18. Aerodynamic characteristics of the Fiat UNO car

    SciTech Connect

    Costelli, A.F.

    1984-01-01

    The purpose of this article is to describe the work conducted in the aerodynamic field throughout the 4-year development and engineering time span required by the project of the UNO car. A description is given of all the parametric studies carried out. Through these studies two types of cars at present in production were defined and the characteristics of a possible future sports version laid down. A movable device, to be fitted in the back window, was also set up and patented. When actuated it reduces soiling of back window. A description is also provided of the measurements made in the car flow field and some considerations are outlined about the method applied. This method is still in development phase but it already permits some considerations and in-depth investigations to be made on the vehicle wake.

  19. 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.

  20. Online monitoring of torpedo car shells

    NASA Astrophysics Data System (ADS)

    Botelho, Romero A.; Calente, Aderaldo

    2001-03-01

    The on-line monitoring of temperature permits increasing the campaign and operational stability of the torpedo cars, as well as optimizing the consumption of refractory, thus reducing maintenance costs. It has become an indispensable tool in the productive process at Companhia Siderurgica de Tubarao - CST. This technique was implemented in 1996 with the purpose of following up the evolution of refractory wear in the torpedo cars, using two fixed thermographic cameras (infrared sensors) with a scanning system. The system captures, records and transmits the thermal images of the body surfaces for analysis by computer, besides sounding the alarm when the temperature reaches pre- set values.

  1. 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.

  2. Occupant safety in modern passenger cars.

    PubMed

    Fildes, B N; Vulcan, A P; Lenard, J

    1992-06-01

    A study was undertaken recently for the Federal Office of Road Safety in Australia of 150 modern vehicle crashes where at least one of the vehicle occupants was admitted to hospital. The types of injuries sustained by occupants of modern Australian passenger cars involved in road crashes (including points of contact within the vehicle) were assessed to provide direction for future improvements in occupant protection. Seat belt performance in all seating positions was of particular interest. While the limited number of cases did not permit a full and detailed statistical analysis of these data, the findings nevertheless show there is scope for improving occupant protection for drivers and passengers of modern passenger cars.

  3. Physical Chemistry to the Rescue: Differentiating Nicotinic and Cholinergic Agonists

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Researches suggest that two agonists can bind to the same binding site of an important transmembrane protein and elicit a biological response through strikingly different binding interactions. Evidence is provided which suggests two possible types of nicotinic acetylcholine receptor agonist binding like acetlycholine (cholinergic) or like nicotine…

  4. GLP-1 agonist treatment: implications for diabetic retinopathy screening.

    PubMed

    Varadhan, Lakshminarayanan; Humphreys, Tracy; Hariman, Christian; Walker, Adrian B; Varughese, George I

    2011-12-01

    Rapid improvement in glycaemic control induced by GLP-1 agonist therapy could be yet another illustration of transient or permanent progression of diabetic retinopathy, similar to documented examples such as pregnancy and continuous subcutaneous insulin infusion. Specific guidelines would be needed to monitor this paradoxical phenomenon during treatment with GLP-1 agonists. PMID:21906831

  5. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  6. Interactions between cannabinoid receptor agonists and mu opioid receptor agonists in rhesus monkeys discriminating fentanyl.

    PubMed

    Maguire, David R; France, Charles P

    2016-08-01

    Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Δ(9)-THC) enhance some (antinociceptive) but not other (positive reinforcing) effects of mu opioid receptor agonists, suggesting that cannabinoids might be combined with opioids to treat pain without increasing, and possibly decreasing, abuse. The degree to which cannabinoids enhance antinociceptive effects of opioids varies across drugs insofar as Δ(9)-THC and the synthetic cannabinoid receptor agonist CP55940 increase the potency of some mu opioid receptor agonists (e.g., fentanyl) more than others (e.g., nalbuphine). It is not known whether interactions between cannabinoids and opioids vary similarly for other (abuse-related) effects. This study examined whether Δ(9)-THC and CP55940 differentially impact the discriminative stimulus effects of fentanyl and nalbuphine in monkeys (n=4) discriminating 0.01mg/kg of fentanyl (s.c.) from saline. Fentanyl (0.00178-0.0178mg/kg) and nalbuphine (0.01-0.32mg/kg) dose-dependently increased drug-lever responding. Neither Δ(9)-THC (0.032-1.0mg/kg) nor CP55940 (0.0032-0.032mg/kg) enhanced the discriminative stimulus effects of fentanyl or nalbuphine; however, doses of Δ(9)-THC and CP55940 that shifted the nalbuphine dose-effect curve markedly to the right and/or down were less effective or ineffective in shifting the fentanyl dose-effect curve. The mu opioid receptor antagonist naltrexone (0.032mg/kg) attenuated the discriminative stimulus effects of fentanyl and nalbuphine similarly. These data indicate that the discriminative stimulus effects of nalbuphine are more sensitive to attenuation by cannabinoids than those of fentanyl. That the discriminative stimulus effects of some opioids are more susceptible to modification by drugs from other classes has implications for developing maximally effective therapeutic drug mixtures with reduced abuse liability. PMID:27184925

  7. 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…

  8. Inflation Rates, Car Devaluation, and Chemical Kinetics.

    ERIC Educational Resources Information Center

    Pogliani, Lionello; Berberan-Santos, Mario N.

    1996-01-01

    Describes the inflation rate problem and offers an interesting analogy with chemical kinetics. Presents and solves the car devaluation problem as a normal chemical kinetic problem where the order of the rate law and the value of the rate constant are derived. (JRH)

  9. Technology, Linear Equations, and Buying a Car.

    ERIC Educational Resources Information Center

    Sandefur, James T.

    1992-01-01

    Discusses the use of technology in solving compound interest-rate problems that can be modeled by linear relationships. Uses a graphing calculator to solve the specific problem of determining the amount of money that can be borrowed to buy a car for a given monthly payment and interest rate. (MDH)

  10. 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.

  11. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (ii) The Freight Car Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223... Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223), Safety Appliance Standards (49 CFR part 231) and Power Brake Standards (49 CFR part 232), to make reports of...

  12. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (ii) The Freight Car Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223... Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223), Safety Appliance Standards (49 CFR part 231) and Power Brake Standards (49 CFR part 232), to make reports of...

  13. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (ii) The Freight Car Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223... Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223), Safety Appliance Standards (49 CFR part 231) and Power Brake Standards (49 CFR part 232), to make reports of...

  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. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (ii) The Freight Car Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223... Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223), Safety Appliance Standards (49 CFR part 231) and Power Brake Standards (49 CFR part 232), to make reports of...

  16. 49 CFR 212.217 - Car inspector.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (ii) The Freight Car Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223... Safety Standards (49 CFR part 215), Safety Glazing Standards (49 CFR part 223), Safety Appliance Standards (49 CFR part 231) and Power Brake Standards (49 CFR part 232), to make reports of...

  17. 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" magazine. (AM)

  18. Aerodynamic Noise Generated by Shinkansen Cars

    NASA Astrophysics Data System (ADS)

    KITAGAWA, T.; NAGAKURA, K.

    2000-03-01

    The noise value (A -weighted sound pressure level, SLOW) generated by Shinkansen trains, now running at 220-300 km/h, should be less than 75 dB(A) at the trackside. Shinkansen noise, such as rolling noise, concrete support structure noise, and aerodynamic noise are generated by various parts of Shinkansen trains. Among these aerodynamic noise is important because it is the major contribution to the noise generated by the coaches running at high speed. In order to reduce the aerodynamic noise, a number of improvements to coaches have been made. As a result, the aerodynamic noise has been reduced, but it still remains significant. In addition, some aerodynamic noise generated from the lower parts of cars remains. In order to investigate the contributions of these noises, a method of analyzing Shinkansen noise has been developed and applied to the measured data of Shinkansen noise at speeds between 120 and 315 km/h. As a result, the following conclusions have been drawn: (1) Aerodynamic noise generated from the upper parts of cars was reduced considerably by smoothing car surfaces. (2) Aerodynamic noise generated from the lower parts of cars has a major influence upon the wayside noise.

  19. Burn injuries following explosion of car heaters.

    PubMed

    Alonso, D; Valero-Gasalla, J; Arnaiz, M; Martelo, F

    1998-09-01

    We report four cases of burn injuries inflicted by hot coolant after the explosion of the heating unit in four motor-vehicles of the same make and version, in similar circumstances while the patients were driving their cars. Burns of this type can cause considerable morbidity with an accompanying high risk of a traffic accident. PMID:9776101

  20. Child Dies in Hot Car Almost Once a Week

    MedlinePlus

    ... gov/news/fullstory_160479.html Child Dies in Hot Car Almost Once a Week Safe Kids Worldwide ... being left in a car that got too hot, according to Safe Kids Worldwide. Sometimes parents forget ...

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Stress Markers During a Rally Car Competition.

    PubMed

    Del Rosso, Sebastián; Abreu, Laurinda; Webb, Heather E; Zouhal, Hassane; Boullosa, Daniel A

    2016-03-01

    The aim of the study was to assess the stress responses in drivers during an official rally car race and the influence of fitness and body composition on stress hormones. Fitness and body composition were assessed in 9 rally car drivers with an incremental exercise test for determination of maximum aerobic speed (MAS) and 6-site skinfold method, respectively. Before (pre) and after (post) the first stage of an official rally car race, data were collected for heart rate (HR), blood samples were collected for analysis of hormones (i.e., epinephrine [EPI], norepinephrine [NE], cortisol, and aldosterone) and metabolites (i.e., lactate [LA], glucose, and ammonia). There were significant (p ≤ 0.05) increases in all assessed variables except glucose at postrace. Heart rate increased 93% (p ≤ 0.05) at the end of the race stage, reaching 88.77 ± 4.96% of HRpeak. Also, EPI and NE significantly (p = 0.001) increased by 45 and 65%, respectively, and LA increased by 395% (p < 0.001). Significant correlations between percent body fat (%BF) and postrace EPI (r = 0.95; p < 0.001), and percentage change of EPI (r = 0.83; p = 0.012) were observed. The MAS was not associated to any metabolic or hormonal variable. These results suggest that psycho-physiological stress induced by the race elicited important changes in hormonal and metabolic variables and that %BF could be an important mediator of psycho-physiological stress in rally car drivers. Specific programs, including both strength and aerobic training, and nutritional plans should be implemented for appropriate conditioning of rally car drivers.

  8. 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.

  9. 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.

  10. 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. PMID:27530964

  11. Parents Smoking in Their Cars With Children Present

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. CARS detection of ClO[sub 2

    SciTech Connect

    Zhang, J.X.; Aker, P.M. )

    1994-01-20

    Coherent anti-Stokes Raman scattering (CARS) spectroscopy has been used to detect the v[sub 1] fundamental of gas-phase ClO[sub 2]. CARS detection limits are reported. The results show that the CARS technique is ideally suited for gas-phase ClO[sub 2] photodissociation dynamics studies. 25 refs., 1 fig.

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. 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 much one…

  20. 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... cars built or rebuilt prior to July 1, 1980, shall be equipped with certified glazing in all windows and a minimum of four emergency windows after June 30, 1984. (d) Each passenger car subject to...

  1. 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... cars built or rebuilt prior to July 1, 1980, shall be equipped with certified glazing in all windows and a minimum of four emergency windows after June 30, 1984. (d) Each passenger car subject to...

  2. 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...

  3. 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...

  4. 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...

  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. 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...

  7. 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

  8. 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...

  9. 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...

  10. 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...

  11. 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....

  12. 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...

  13. 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....

  14. 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...

  15. 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...

  16. 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...

  17. 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....

  18. 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...

  19. 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...

  20. 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,...

  1. 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...

  2. 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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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....

  10. 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...

  11. 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,...

  12. 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,...

  13. 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...

  14. 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....

  15. 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...

  16. 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...

  17. 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....

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 77 FR 50763 - Notice of National Grain Car Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-22

    ... 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 section 10(a)(2) of the Federal...

  4. 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....

  5. 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...

  6. 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...

  7. 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...

  8. 75 FR 53736 - Notice of National Grain Car Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-01

    ... 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 section 10(a)(2) of the Federal...

  9. 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...

  10. 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...

  11. 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....

  12. 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...

  13. 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...

  14. 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...

  15. 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…

  16. 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...

  17. 49 CFR 232.305 - Single car air brake tests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain a copy of the incorporated document from the... 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...

  18. 40 CFR 201.13 - Standard for rail car operations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 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...

  19. 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...

  20. 76 FR 53717 - Notice of National Grain Car Council Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-29

    ... Surface Transportation Board Notice of National Grain Car Council Meeting AGENCY: Surface Transportation Board. 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...

  1. 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...

  2. 49 CFR 238.413 - End structures of trailer cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 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...

  3. 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...

  4. 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...

  5. 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,...

  6. CarD: a new RNA polymerase modulator in mycobacteria.

    PubMed

    Stallings, Christina L; Glickman, Michael S

    2011-01-01

    Mycobacteria CarD is an essential RNAP binding protein that regulates many transcripts including rRNA. This article will review our present state of knowledge regarding CarD and compare the known functions of CarD with other RNAP binding proteins in E. coli, emphasizing how this information can guide future investigations.

  7. 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

  8. Induction of bilirubin clearance by the constitutive androstane receptor (CAR).

    PubMed

    Huang, Wendong; Zhang, Jun; Chua, Steven S; Qatanani, Mohammed; Han, Yunqing; Granata, Riccarda; Moore, David D

    2003-04-01

    Bilirubin clearance is one of the numerous important functions of the liver. Defects in this process result in jaundice, which is particularly common in neonates. Elevated bilirubin levels can be decreased by treatment with phenobarbital. Because the nuclear hormone receptor constitutive androstane receptor (CAR) mediates hepatic effects of this xenobiotic inducer, we hypothesized that CAR could be a regulator of bilirubin clearance. Activation of the nuclear hormone receptor CAR increases hepatic expression of each of five components of the bilirubin-clearance pathway. This induction is absent in homozygous CAR null mice but is observed in mice expressing human CAR instead of mouse CAR. Pretreatment with xenobiotic inducers markedly increases the rate of clearance of an exogenous bilirubin load in wild-type but not CAR knockout animals. Bilirubin itself can also activate CAR, and mice lacking CAR are defective in clearing chronically elevated bilirubin levels. Unexpectedly, CAR expression is very low in livers of neonatal mice and humans. We conclude that CAR directs a protective response to elevated bilirubin levels and suggest that a functional deficit of CAR activity may contribute to neonatal jaundice. PMID:12644704

  9. 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....

  10. 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...

  11. 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,...

  12. 49 CFR 173.31 - Use of tank cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 49 CFR 238.413 - End structures of trailer cars.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain a copy of the incorporated document from the... 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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....

  6. 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...

  7. The cardiovascular effects of peroxisome proliferator-activated receptor agonists.

    PubMed

    Friedland, Sayuri N; Leong, Aaron; Filion, Kristian B; Genest, Jacques; Lega, Iliana C; Mottillo, Salvatore; Poirier, Paul; Reoch, Jennifer; Eisenberg, Mark J

    2012-02-01

    Although peroxisome proliferator-activated receptor agonists are prescribed to improve cardiovascular risk factors, their cardiovascular safety is controversial. We therefore reviewed the literature to identify landmark randomized controlled trials evaluating the effect of peroxisome proliferator-activated receptor gamma agonists (pioglitazone and rosiglitazone), alpha agonists (fenofibrate and gemfibrozil), and pan agonists (bezafibrate, muraglitazar, ragaglitazar, tesaglitazar, and aleglitazar) on cardiovascular outcomes. Pioglitazone may modestly reduce cardiovascular events but also may increase the risk of bladder cancer. Rosiglitazone increases the risk of myocardial infarction and has been withdrawn in European and restricted in the United States. Fibrates improve cardiovascular outcomes only in select subgroups: fenofibrate in diabetic patients with metabolic syndrome, gemfibrozil in patients with dyslipidemia, and bezafibrate in patients with diabetes or metabolic syndrome. The cardiovascular safety of the new pan agonist aleglitazar, currently in phase II trials, remains to be determined. The heterogenous effects of peroxisome proliferator-activated receptor agonists to date highlight the importance of postmarketing surveillance. The critical question of why peroxisome proliferator-activated receptor agonists seem to improve cardiovascular risk factors without significantly improving cardiovascular outcomes requires further investigation. PMID:22269613

  8. [PPAR receptors and insulin sensitivity: new agonists in development].

    PubMed

    Pégorier, J-P

    2005-04-01

    Thiazolidinediones (or glitazones) are synthetic PPARgamma (Peroxisome Proliferator-Activated Receptors gamma) ligands with well recognized effects on glucose and lipid metabolism. The clinical use of these PPARgamma agonists in type 2 diabetic patients leads to an improved glycemic control and an inhanced insulin sensitivity, and at least in animal models, to a protective effect on pancreatic beta-cell function. However, they can produce adverse effects, generally mild or moderate, but some of them (mainly peripheral edema and weight gain) may conduct to treatment cessation. Several pharmacological classes are currently in pre-clinical or clinical development, with the objective to retain the beneficial metabolic properties of PPARgamma agonists, either alone or in association with the PPARalpha agonists (fibrates) benefit on lipid profile, but devoid of the side-effects on weight gain and fluid retention. These new pharmacological classes: partial PPARgamma agonists, PPARgamma antagonists, dual PPARalpha/PPARgamma agonists, pan PPARalpha/beta(delta)/gamma agonists, RXR receptor agonists (rexinoids), are presented in this review. Main results from in vitro cell experiments and animal model studies are discussed, as well as the few published short-term studies in type 2 diabetic patients. PMID:15959400

  9. 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....

  10. 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....

  11. 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...

  12. 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…

  13. Antifertility effects of luteinizing hormone-releasing hormone (LHRH) agonists.

    PubMed

    Labrie, F; Bélanger, A; Kelly, P A; Séguin, C; Cusan, L; Lefebvre, F A; Reeves, J J; Lemay, A; Faure, N; Gourdeau, Y; Raynaud, J P

    1981-01-01

    This paper reviews the mechanisms responsible for the antifertility effects of luteinizing hormone-releasing hormone (LHRH) agonists. Large doses of the LHRH agonist LHRH-EA lead to a marked reduction of testicular and secondary sex organ weight, LH receptor levels, and plasma testosterone concentration. A marked inhibition of basal testicular and testosterone concentrations is obtained after daily administration of the LHRH agonists at doses greater than 10 ng. Treatment with low doses of the LHRH agonist can lead to an increased steroidogenic response to LH. Treatment with low doses of LHRH agonists could stimulate Leydig cell function while high doses are history. A study of the effects of longterm treatment with an LHRH agonsist on spermatogenesis revelaed that testis, prostate, and seminal vesicle weight decreased and plasma LH and FSH levels increased over 12 weeks. Comparison of the effects of increasing doses of LHRH agonist on testicular and ovarian gonadotropin receptors and steroidogenesis in male rats indicates that single or repeated administration of LHRH agonists can lead to loss of testicular LH receptors in the absence of the pituitary gland. The loss of ovarian gonadotropin receptors in female rats is also investigated. Antifertility effects of LHRH ethylamide are accompanied by a marked loss of LH/hCG and FSH receptors in ovarian tissue. The injection of 1,3, or 10 ng LHRH-EA in intact rats has no significant effect on ovarian LH receptor levels. A study of the direct action of LHRH agonists at the ovarian level demonstrates a close relationship between the binding activity of a large series of LHRH agonists and antagonists in the anterior pituitary gland and the ovary. Inhibition of testicular steroidogenesis in man by treatment with a potent LHRH agonist is also demonstrated. Intranasal administration of LHRH ethylamide has luteolytic effects in normal women. Daily administration of LHRH-EA inhibited ovulation in all but 2 of 89 treatment

  14. Monitoring Car Drivers' Condition Using Image Processing

    NASA Astrophysics Data System (ADS)

    Adachi, Kazumasa; Yamamto, Nozomi; Yamamoto, Osami; Nakano, Tomoaki; Yamamoto, Shin

    We have developed a car driver monitoring system for measuring drivers' consciousness, with which we aim to reduce car accidents caused by drowsiness of drivers. The system consists of the following three subsystems: an image capturing system with a pulsed infrared CCD camera, a system for detecting blinking waveform by the images using a neural network with which we can extract images of face and eye areas, and a system for measuring drivers' consciousness analyzing the waveform with a fuzzy inference technique and others. The third subsystem extracts three factors from the waveform first, and analyzed them with a statistical method, while our previous system used only one factor. Our experiments showed that the three-factor method we used this time was more effective to measure drivers' consciousness than the one-factor method we described in the previous paper. Moreover, the method is more suitable for fitting parameters of the system to each individual driver.

  15. 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.

  16. 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

  17. 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).

  18. CARS imaging with a single laser pulse

    NASA Astrophysics Data System (ADS)

    Heinrich, Christoph; Bernet, Stefan; Ritsch-Marte, Monika

    2005-09-01

    We report coherent anti-Stokes Raman scattering (CARS) microscopy with ns-pulses. The chosen wide-field geometry allows imaging of the whole field of view at once, without scanning of the sample. Tuning the difference of the two incident laser frequencies overlapping at the sample to a specific vibrational level, one can map the spatial distribution of selected Raman active molecules. Both the CARS signal of the surrounding solvent can be excited (negative contrast) as well as the signal of the structure embedded by the solvent (positive contrast). As a biological sample we used slices of a sunflower seed and tuned to the vibrational transition of its ingredient - linoleic acid - at 2870 cm-1 which corresponds to the strongest C-H stretching vibration. Even with a single pair of laser pulses of 3 ns duration it was possible to acquire a rough, but still meaningful image.

  19. Single-beam heterodyne FAST CARS microscopy.

    PubMed

    Shen, Yujie; Voronine, Dmitri V; Sokolov, Alexei V; Scully, Marlan O

    2016-09-19

    We demonstrate, for the first time, single-beam heterodyne FAST CARS imaging without data post-processing and with nonresonant background subtraction in a simple setup via the real-time piezo modulation of the probe delay. Our fast signal acquisition scheme does not require a spatial light modulator in the pulse shaper, and is suitable for high-resolution imaging and time-resolved dynamics. In addition, the spectral detection of the back-scattered FAST CARS signal is incorporated into the pulse shaper, allowing for a compact and more efficient design. Such epi-detection capability is demonstrated by imaging Si and MoS2 microstructures. PMID:27661903

  20. A broken heart in a broken car.

    PubMed

    Schlossbauer, Susanne Anna; Ghadri, Jelena-Rima; Cammann, Victoria Lucia; Maier, Willibald; Lüscher, Thomas F; Templin, Christian

    2016-01-01

    Takotsubo syndrome (TTS) is still a relatively understudied and often undetected disease. It is usually preceded by emotional or physical triggers. We here report a case of TTS following a car accident. Typical apical ballooning with moderate reduction of left ventricular ejection fraction (LVEF) and increased level of pro-B-type natriuretic peptide (BNP) as well as slightly increased creatine kinase and troponin T values were found in this 76-year-old female patient, 6 h after a car accident. At 10 weeks follow-up, we observed a normalization of regional wall motion, LVEF, electrocardiogram and pro-BNP. TTS is an acute heart failure syndrome and an important differential diagnosis of acute coronary syndrome. PMID:27377800